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Sample records for prl toomas haldma

  1. Purification of PRL receptors from toad kidney: Comparisons with rabbit mammary PRL receptors

    SciTech Connect

    Dunand, M.; Kraehenbuhl, J.P.; Rossier, B.C.; Aubert, M.L. Univ. of Lausanne School of Medicine )

    1988-03-01

    The binding characteristics of the prolactin (PRL) receptors present in toad (Bufo marinus) kidneys were investigated and compared to those of PRL receptors present in rabbit mammary glands. The molecular characteristics of the Triton X-100 solubilized renal and mammary PRL receptors were assessed by gel filtration and by migration analysis on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) after affinity labeling of the binding sites with {sup 125}I-human growth hormone. Similar results were obtained for both receptors. Partial purification of the toad PRL receptor could be achieved by affinity chromatography. The molecular weight of this purified receptor could be determined by analysis of SDS-PAGE. With the use of a polyclonal antiserum raised against a purified preparation of rabbit mammary PRL receptor, one or several antigenic epitope(s) could be identified on the core of the toad renal PRL receptor. In conclusion, although the structure and the biological role(s) of PRL have substantially changed during evolution, the receptor for this hormone has retained many of its structural features as could be assessed between an amphibian and a mammalian species on functionally different target tissues.

  2. Therapeutic potential of PRL-3 targeting and clinical significance of PRL-3 genomic amplification in gastric cancer

    PubMed Central

    2011-01-01

    Background Phosphatase of regenerating liver-3 (PRL-3) has deserved attention as a crucial molecule in the multiple steps of metastasis. In the present study, we examined the mechanisms regulating PRL-3 expression, and assessed the clinical potential of PRL-3-targeted therapy in gastric cancer. Methods PRL-3 genomic amplification was analyzed using quantitative-polymerase chain reaction and/or fluorescence in situ hybridization in 77 primary gastric tumors. The anticancer activity of PRL-3 inhibitor (1-4-bromo-2-benzylidene rhodanine) treatment was evaluated against cancer cells with different genetic and expression status. Results PRL-3 genomic amplification was closely concordant with high level of its protein expression in cell lines, and was found in 20% (8/40) among human primary tumors with its expression, which were all stage III/IV disease (40%, 8/20), but in none (0/37) among those without expression. Additionally, PRL-3 genomic amplification was associated with metastatic lymph node status, leading to advanced stage and thereby poor outcomes in patients with lymph node metastasis (P = 0.021). PRL-3 small interfering RNA robustly repressed metastatic properties, including cell proliferation, invasion, and anchorage-independent colony formation. Although neither PRL-3 genomic amplification nor expression level was responsible for the sensitivity to PRL-3 inhibitor treatment, the inhibitor showed dose-dependent anticancer efficacy, and remarkably induced apoptosis on all the tested cell lines with PRL-3 expression. Conclusions We have for the first time, demonstrated that PRL-3 genomic amplification is one of the predominant mechanisms inducing its expression, especially in more advanced stage, and that PRL-3-targeted therapy may have a great potential against gastric cancer with its expression. PMID:21466710

  3. Prolactin (PRL) in adipose tissue: regulation and functions.

    PubMed

    Ben-Jonathan, Nira; Hugo, Eric

    2015-01-01

    New information concerning the effects of prolactin (PRL) on metabolic processes warrants reevaluation of its overall metabolic actions. PRL affects metabolic homeostasis by regulating key enzymes and transporters associated with glucose and lipid metabolism in several target organs. In the lactating mammary gland, PRL increases the production of milk proteins, lactose, and lipids. In adipose tissue, PRL generally suppresses lipid storage and adipokine release and affect adipogenesis. A specific case is made for PRL in the human breast and adipose tissues, where it acts as a circulating hormone and an autocrine/paracrine factor. Although its overall effects on body composition are both modest and species-specific, PRL may be involved in the manifestation of insulin resistance.

  4. Extra-pituitary prolactin (PRL) and prolactin-like protein (PRL-L) in chickens and zebrafish.

    PubMed

    Bu, Guixian; Liang, Xiaomeng; Li, Juan; Wang, Yajun

    2015-09-01

    It is generally believed that in vertebrates, prolactin (PRL) is predominantly synthesized and released by pituitary lactotrophs and plays important roles in many physiological processes via activation of PRL receptor (PRLR), including water and electrolyte balance, reproduction, growth and development, metabolism, immuno-modulation, and behavior. However, there is increasing evidence showing that PRL and the newly identified 'prolactin-like protein (PRL-L)', a novel ligand of PRL receptor, are also expressed in a variety of extra-pituitary tissues, such as the brain, skin, ovary, and testes in non-mammalian vertebrates. In this brief review, we summarize the recent research progress on the structure, biological activities, and extra-pituitary expression of PRL and PRL-L in chickens (Gallus gallus) and zebrafish (Danio rerio) from our and other laboratories and briefly discuss their potential paracrine/autocrine roles in non-mammalian vertebrates, which may promote us to rethink the broad spectrum of PRL actions previously attributed to pituitary PRL only.

  5. Characterization of a PRL protein tyrosine phosphatase from Plasmodium falciparum.

    PubMed

    Pendyala, Prakash Rao; Ayong, Lawrence; Eatrides, Jennifer; Schreiber, Melissa; Pham, Connie; Chakrabarti, Ratna; Fidock, David A; Allen, Charles M; Chakrabarti, Debopam

    2008-03-01

    Isoprenylated proteins have important functions in cell growth and differentiation of eukaryotic cells. Inhibitors of protein prenylation in malaria have recently shown strong promise as effective antimalarials. In studying protein prenylation in the malaria protozoan parasite Plasmodium falciparum, we have shown earlier that the incubation of P. falciparum cells with (3)H-prenol precursors resulted in various size classes of labeled proteins. To understand the physiological function of prenylated proteins of malaria parasites, that are targets of prenyltransferase inhibitors, we searched the PlasmoDB database for proteins containing the C-terminus prenylation motif. We have identified, among other potentially prenylated proteins, an orthologue of a PRL (protein of regenerating liver) subgroup protein tyrosine phosphatases, termed PfPRL. Here, we show that PfPRL is expressed in the parasite's intraerythrocytic stages, where it partially associates with endoplasmic reticulum and within a subcompartment of the food vacuole. Additionally, PfPRL targeting parallels that of apical membrane antigen-1 in developing merozoites. Recombinant PfPRL shows phosphatase activity that is preferentially inhibited by a tyrosine phosphatase inhibitor suggesting that PfPRL functions as a tyrosine phosphatase. Recombinant PfPRL can also be farnesylated in vitro. Inhibition of malarial farnesyltransferase activity can be achieved with the heptapetide RKCHFM, which corresponds to the C-terminus of PfPRL. This study provides the first evidence for expression of enzymatically active PRL-related protein tyrosine phosphatases in malarial parasites, and demonstrates the potential of peptides derived from Plasmodium prenylated proteins as malarial farnesyltransferase inhibitors.

  6. Bifidobacterium bifidum PRL2010 Modulates the Host Innate Immune Response

    PubMed Central

    Turroni, Francesca; Taverniti, Valentina; Ruas-Madiedo, Patricia; Duranti, Sabrina; Guglielmetti, Simone; Lugli, Gabriele Andrea; Gioiosa, Laura; Palanza, Paola; Margolles, Abelardo; van Sinderen, Douwe

    2014-01-01

    Here, we describe data obtained from transcriptome profiling of human cell lines and intestinal cells of a murine model upon exposure and colonization, respectively, with Bifidobacterium bifidum PRL2010. Significant changes were detected in the transcription of genes that are known to be involved in innate immunity. Furthermore, results from enzyme-linked immunosorbent assays (ELISAs) showed that exposure to B. bifidum PRL2010 causes enhanced production of interleukin 6 (IL-6) and IL-8 cytokines, presumably through NF-κB activation. The obtained global transcription profiles strongly suggest that Bifidobacterium bifidum PRL2010 modulates the innate immune response of the host. PMID:24242237

  7. Discovery and Evaluation of PRL Trimer Disruptors for Novel Anticancer Agents.

    PubMed

    Bai, Yunpeng; Yu, Zhi-Hong; Zhang, Zhong-Yin

    2016-01-01

    Overexpression of PRL phosphatases (PRL1, PRL2, and PRL3) has been found in a variety of late-stage tumors and their distant metastatic sites. Therefore, the oncogenic PRL phosphatases represent intriguing targets for cancer therapy. There is considerable interest in identifying small molecule inhibitors targeting PRLs as novel anticancer agents. However, it has been difficult to acquire phosphatase activity-based PRL inhibitors due to the unusual wide and shallow catalytic pockets of PRLs revealed by crystal structure studies. Here, we present a novel method to identify PRL1 inhibitors by targeting the PRL1 trimer interface and the procedure to characterize their biochemical and cellular activity. PMID:27514804

  8. Discovery and Evaluation of PRL Trimer Disruptors for Novel Anticancer Agents.

    PubMed

    Bai, Yunpeng; Yu, Zhi-Hong; Zhang, Zhong-Yin

    2016-01-01

    Overexpression of PRL phosphatases (PRL1, PRL2, and PRL3) has been found in a variety of late-stage tumors and their distant metastatic sites. Therefore, the oncogenic PRL phosphatases represent intriguing targets for cancer therapy. There is considerable interest in identifying small molecule inhibitors targeting PRLs as novel anticancer agents. However, it has been difficult to acquire phosphatase activity-based PRL inhibitors due to the unusual wide and shallow catalytic pockets of PRLs revealed by crystal structure studies. Here, we present a novel method to identify PRL1 inhibitors by targeting the PRL1 trimer interface and the procedure to characterize their biochemical and cellular activity.

  9. Role of phosphatase of regenerating liver 1 (PRL1) in spermatogenesis

    PubMed Central

    Bai, Yunpeng; Zhou, Hong-Ming; Zhang, Lujuan; Dong, Yuanshu; Zeng, Qi; Shou, Weinian; Zhang, Zhong-Yin

    2016-01-01

    The PRL phosphatases are oncogenic when overexpressed but their in vivo biological function is less well understood. Previous gene deletion study revealed a role for PRL2 in spermatogenesis. We report here the first knockout mice lacking PRL1, the most related homolog of PRL2. We found that loss of PRL1 does not affect spermatogenesis and reproductive ability of male mice, likely due to functional compensation by the relatively higher expression of PRL2 in the testes. However, PRL1−/−/PRL2+/− male mice show testicular atrophy phenotype similar to PRL2−/− mice. More strikingly, deletion of one PRL1 allele in PRL2−/− male mice causes complete infertility. Mechanistically, the total level of PRL1 and PRL2 is negatively correlated with the PTEN protein level in the testis and PRL1+/−/PRL2−/− mice have the highest level of PTEN, leading to attenuated Akt activation and increased germ cell apoptosis, effectively halting spermatozoa production. These results provide the first evidence that in addition to PRL2, PRL1 is also required for spermatogenesis by downregulating PTEN and promoting Akt signaling. The ability of the PRLs to suppress PTEN expression underscores the biochemical basis for their oncogenic potential. PMID:27666520

  10. Src-Mediated Phosphorylation of the Tyrosine Phosphatase PRL-3 Is Required for PRL-3 Promotion of Rho Activation, Motility and Invasion

    PubMed Central

    Fiordalisi, James J.; Dewar, Brian J.; Graves, Lee M.; Madigan, James P.; Cox, Adrienne D.

    2013-01-01

    The metastasis-associated tyrosine phosphatase PRL-3/PTP4A is upregulated in numerous cancers, but the mechanisms modulating PRL-3 activity other than its expression levels have not been investigated. Here we report evidence for both Src-dependent tyrosine phosphorylation of PRL-3 and Src-mediated regulation of PRL-3 biological activities. We used structural mutants, pharmacological inhibitors and siRNA to demonstrate Src-dependent phosphorylation of endogenous PRL-3 in SW480 colon cancer cells. We also demonstrated that PRL-3 was not tyrosine phosphorylated in SYF mouse embryo fibroblasts deficient in Src, Yes and Fyn unless Src was re-expressed. Further, we show that platelet-derived growth factor (PDGF) can stimulate PRL-3 phosphorylation in a Src-dependent manner. Finally, we show that PRL-3-induced cell motility, Matrigel invasion and activation of the cytoskeleton-regulating small GTPase RhoC were abrogated in the presence of the phosphodeficient PRL-3 mutant Y53F, or by use of a Src inhibitor. Thus, PRL-3 requires the activity of a Src kinase, likely Src itself, to promote these cancer-associated phenotypes. Our data establish a model for the regulation of PRL-3 by Src that supports the possibility of their coordinate roles in signaling pathways promoting invasion and metastasis, and supports simultaneous use of novel molecularly targeted therapeutics directed at these proteins. PMID:23691193

  11. PRL tyrosine phosphatases regulate rho family GTPases to promote invasion and motility.

    PubMed

    Fiordalisi, James J; Keller, Patricia J; Cox, Adrienne D

    2006-03-15

    Phosphatase found in regenerating liver (PRL)-1, PRL-2, and PRL-3 [also known as PTP4A1, PTP4A2, and PTP4A3, respectively] constitute a unique family of putative protein tyrosine phosphatases (PTPs) modified by farnesylation. PRL-3 is amplified and its message is up-regulated in colorectal carcinoma metastases. Its ectopic expression promotes invasive and metastatic properties, supporting a causal link between PRL-3 and late-stage cancer development. However, neither PRL phosphatase substrates nor their signaling pathways have been defined. To address possible mechanisms for the biological activity of PRL-3, we sought to identify its downstream targets, reasoning that regulators of motility and invasion, such as the Rho family of small GTPases, might be logical candidates. We found that levels of active RhoA and RhoC were increased 4- to 7-fold in SW480 colorectal carcinoma cells expressing exogenous PRL-1 and PRL-3, and that PRL-mediated motility and Matrigel invasion were blocked by pharmacologic inhibition of Rho kinase (ROCK), a key Rho effector. In contrast, the activity of Rac was reduced by PRL PTPs, whereas Cdc42 activity was unaffected. PRL-3 stimulated transcription driven by the serum response element in a Rho-dependent manner. We also confirmed that the ability of PRL PTPs to induce invasion and motility is dependent on farnesylation. Catalytic PRL-3 mutants (C104A or D72A) were impaired in PRL-3-induced invasion and Rho activation, indicating that these properties require phosphatase activity. We conclude that PRL PTPs stimulate Rho signaling pathways to promote motility and invasion. Characterization of PRL activity and regulatory pathways should enhance efforts to understand and interfere with PRL-mediated events in invasion and metastasis.

  12. PRL3-zumab, a first-in-class humanized antibody for cancer therapy

    PubMed Central

    Thura, Min; Al-Aidaroos, Abdul Qader Omer; Yong, Wei Peng; Kono, Koji; Gupta, Abhishek; Lin, You Bin; Mimura, Kousaku; Thiery, Jean Paul; Goh, Boon Cher; Tan, Patrick; Soo, Ross; Hong, Cheng William; Wang, Lingzhi; Lin, Suling Joyce; Chen, Elya; Rha, Sun Young; Chung, Hyun Cheol; Li, Jie; Nandi, Sayantani; Yuen, Hiu Fung; Zhang, Shu-Dong; Guan, Yeoh Khay; So, Jimmy

    2016-01-01

    Novel, tumor-specific drugs are urgently needed for a breakthrough in cancer therapy. Herein, we generated a first-in-class humanized antibody (PRL3-zumab) against PRL-3, an intracellular tumor-associated phosphatase upregulated in multiple human cancers, for unconventional cancer immunotherapies. We focused on gastric cancer (GC), wherein elevated PRL-3 mRNA levels significantly correlated with shortened overall survival of GC patients. PRL-3 protein was overexpressed in 85% of fresh-frozen clinical gastric tumor samples examined but not in patient-matched normal gastric tissues. Using human GC cell lines, we demonstrated that PRL3-zumab specifically blocked PRL-3+, but not PRL-3–, orthotopic gastric tumors. In this setting, PRL3-zumab had better therapeutic efficacy as a monotherapy, rather than simultaneous combination with 5-fluorouracil or 5-fluorouracil alone. PRL3-zumab could also prevent PRL-3+ tumor recurrence. Mechanistically, we found that intracellular PRL-3 antigens could be externalized to become “extracellular oncotargets” that serve as bait for PRL3-zumab binding to potentially bridge and recruit immunocytes into tumor microenvironments for killing effects on cancer cells. In summary, our results document a comprehensive cancer therapeutic approach to specific antibody-targeted therapy against the PRL-3 oncotarget as a case study for developing antibodies against other intracellular targets in drug discovery. PMID:27699276

  13. PRL3-zumab, a first-in-class humanized antibody for cancer therapy

    PubMed Central

    Thura, Min; Al-Aidaroos, Abdul Qader Omer; Yong, Wei Peng; Kono, Koji; Gupta, Abhishek; Lin, You Bin; Mimura, Kousaku; Thiery, Jean Paul; Goh, Boon Cher; Tan, Patrick; Soo, Ross; Hong, Cheng William; Wang, Lingzhi; Lin, Suling Joyce; Chen, Elya; Rha, Sun Young; Chung, Hyun Cheol; Li, Jie; Nandi, Sayantani; Yuen, Hiu Fung; Zhang, Shu-Dong; Guan, Yeoh Khay; So, Jimmy

    2016-01-01

    Novel, tumor-specific drugs are urgently needed for a breakthrough in cancer therapy. Herein, we generated a first-in-class humanized antibody (PRL3-zumab) against PRL-3, an intracellular tumor-associated phosphatase upregulated in multiple human cancers, for unconventional cancer immunotherapies. We focused on gastric cancer (GC), wherein elevated PRL-3 mRNA levels significantly correlated with shortened overall survival of GC patients. PRL-3 protein was overexpressed in 85% of fresh-frozen clinical gastric tumor samples examined but not in patient-matched normal gastric tissues. Using human GC cell lines, we demonstrated that PRL3-zumab specifically blocked PRL-3+, but not PRL-3–, orthotopic gastric tumors. In this setting, PRL3-zumab had better therapeutic efficacy as a monotherapy, rather than simultaneous combination with 5-fluorouracil or 5-fluorouracil alone. PRL3-zumab could also prevent PRL-3+ tumor recurrence. Mechanistically, we found that intracellular PRL-3 antigens could be externalized to become “extracellular oncotargets” that serve as bait for PRL3-zumab binding to potentially bridge and recruit immunocytes into tumor microenvironments for killing effects on cancer cells. In summary, our results document a comprehensive cancer therapeutic approach to specific antibody-targeted therapy against the PRL-3 oncotarget as a case study for developing antibodies against other intracellular targets in drug discovery.

  14. The posterior chamber phakic refractive lens (PRL): a review

    PubMed Central

    Pérez-Cambrodí, R J; Piñero, D P; Ferrer-Blasco, T; Cerviño, A; Brautaset, R

    2013-01-01

    Implantation of phakic intraocular lenses (pIOLs) is a reversible refractive procedure, preserving the patient's accommodative function with minimal induction of higher order aberrations compared with corneal photoablative procedures. Despite this, as an intraocular procedure, it has potential risks such as cataracts, chronic uveitis, pupil ovalization, corneal endothelial cell loss, pigmentary dispersion syndrome, pupillary block glaucoma, astigmatism, or endophthalmitis. Currently, only two models of posterior chamber pIOLs are commercially available, the implantable collammer lens (STAAR Surgical Co.) and the phakic refractive lens (PRL; Zeiss Meditec). The number of published reports on the latter is very low, and some concerns still remain about its long-term safety. The present article reviews the published literature on the outcomes after PRL implantation in order to provide a general overview and evaluate its real potential as a surgical refractive option. PMID:23222559

  15. Pleiotropic regulatory locus 2 exhibits unequal genetic redundancy with its homolog PRL1.

    PubMed

    Weihmann, Tabea; Palma, Kristoffer; Nitta, Yukino; Li, Xin

    2012-09-01

    In plants, signaling leading to resistance against biotrophic pathogens is complex. Perception of pathogenic microbes by resistance (R) proteins is relayed though successive activities of downstream components, in a network that is not well understood. PLEIOTROPIC REGULATORY LOCUS 1 (PRL1) and >20 other proteins are members of the MOS4-associated complex (MAC), a regulatory node in defense signaling. Of all characterized MAC members, mutations in PRL1 cause the most severe susceptibility towards both virulent and avirulent microbial pathogens. Genetic suppressors of prl1 represent new signaling elements and may aid in further unraveling of defense mechanisms. Our identification and characterization of a dominant suppressor of prl1 revealed a regulatory, gain-of-function mutation in PLEIOTROPIC REGULATORY LOCUS 2 (PRL2), a close homolog of PRL1. Loss-of-function mutants of PRL2 do not exhibit altered phenotypes; however, prl1 prl2 double mutants exhibit enhanced morphological defects consistent with unequal genetic redundancy between the homologs. Up-regulated gene expression mediated by the dominant prl2-1D allele completely suppresses disease susceptibility in the prl1 mutant background and also restores wild-type appearance, further supporting functional equivalence between the two PRL proteins. PMID:22813545

  16. Anti-Cytomegalovirus Activity of the Anthraquinone Atanyl Blue PRL

    PubMed Central

    Alam, Zohaib; Al-Mahdi, Zainab; Zhu, Yali; McKee, Zachary; Parris, Deborah S.; Parikh, Hardik I.; Kellogg, Glen E.; Kuchta, Alison; McVoy, Michael A.

    2014-01-01

    Human cytomegalovirus (CMV) causes significant disease in immunocompromised patients and serious birth defects if acquired in utero. Available CMV antivirals target the viral DNA polymerase, have significant toxicities, and suffer from resistance. New drugs targeting different pathways would be beneficial. The anthraquinone emodin is proposed to inhibit herpes simplex virus by blocking the viral nuclease. Emodin and related anthraquinones are also reported to inhibit CMV. In the present study, emodin reduced CMV infectious yield with an EC50 of 4.9 μM but was cytotoxic at concentrations only two-fold higher. Related anthraquinones acid blue 40 and alizarin violet R inhibited CMV at only high concentrations (238–265 μM) that were also cytotoxic. However, atanyl blue PRL inhibited infectious yield of CMV with an EC50 of 6.3 μM, significantly below its 50% cytotoxic concentration of 216 μM. Atanyl blue PRL reduced CMV infectivity and inhibited spread. When added up to one h after infection, it dramatically reduced CMV immediate early protein expression and blocked viral DNA synthesis. However, it had no antiviral activity when added 24 h after infection. Interestingly, atanyl blue PRL inhibited nuclease activities of purified CMV UL98 protein with IC50 of 4.5 and 9.3 μM. These results indicate that atanyl blue PRL targets very early post-entry events in CMV replication and suggest it may act through inhibition of UL98, making it a novel CMV inhibitor. This compound may provide valuable insights into molecular events that occur at the earliest times post-infection and serve as a lead structure for antiviral development. PMID:25499125

  17. Exploring Amino Acid Auxotrophy in Bifidobacterium bifidum PRL2010.

    PubMed

    Ferrario, Chiara; Duranti, Sabrina; Milani, Christian; Mancabelli, Leonardo; Lugli, Gabriele A; Turroni, Francesca; Mangifesta, Marta; Viappiani, Alice; Ossiprandi, Maria C; van Sinderen, Douwe; Ventura, Marco

    2015-01-01

    The acquisition and assimilation strategies followed by members of the infant gut microbiota to retrieve nitrogen from the gut lumen are still largely unknown. In particular, no information on these metabolic processes is available regarding bifidobacteria, which are among the first microbial colonizers of the human intestine. Here, evaluation of amino acid auxotrophy and prototrophy of Bifidobacterium bifidum, with particular emphasis on B. bifidum strain PRL2010 (LMG S-28692), revealed a putative auxotrophy for cysteine. In addition, we hypothesized that cysteine plays a role in the oxidative stress response in B. bifidum. The use of glutathione as an alternative reduced sulfur compound did not alleviate cysteine auxotrophy of this strain, though it was shown to stimulate expression of the genes involved in cysteine biosynthesis, reminiscent of oxidative stress response. When PRL2010 was grown on a medium containing complex substrates, such as whey proteins or casein hydrolysate, we noticed a distinct growth-promoting effect of these compounds. Transcriptional analysis involving B. bifidum PRL2010 cultivated on whey proteins or casein hydrolysate revealed that the biosynthetic pathways for cysteine and methionine are modulated by the presence of casein hydrolysate. Such findings support the notion that certain complex substrates may act as potential prebiotics for bifidobacteria in their ecological niche. PMID:26635786

  18. Exploring Amino Acid Auxotrophy in Bifidobacterium bifidum PRL2010

    PubMed Central

    Ferrario, Chiara; Duranti, Sabrina; Milani, Christian; Mancabelli, Leonardo; Lugli, Gabriele A.; Turroni, Francesca; Mangifesta, Marta; Viappiani, Alice; Ossiprandi, Maria C.; van Sinderen, Douwe; Ventura, Marco

    2015-01-01

    The acquisition and assimilation strategies followed by members of the infant gut microbiota to retrieve nitrogen from the gut lumen are still largely unknown. In particular, no information on these metabolic processes is available regarding bifidobacteria, which are among the first microbial colonizers of the human intestine. Here, evaluation of amino acid auxotrophy and prototrophy of Bifidobacterium bifidum, with particular emphasis on B. bifidum strain PRL2010 (LMG S-28692), revealed a putative auxotrophy for cysteine. In addition, we hypothesized that cysteine plays a role in the oxidative stress response in B. bifidum. The use of glutathione as an alternative reduced sulfur compound did not alleviate cysteine auxotrophy of this strain, though it was shown to stimulate expression of the genes involved in cysteine biosynthesis, reminiscent of oxidative stress response. When PRL2010 was grown on a medium containing complex substrates, such as whey proteins or casein hydrolysate, we noticed a distinct growth-promoting effect of these compounds. Transcriptional analysis involving B. bifidum PRL2010 cultivated on whey proteins or casein hydrolysate revealed that the biosynthetic pathways for cysteine and methionine are modulated by the presence of casein hydrolysate. Such findings support the notion that certain complex substrates may act as potential prebiotics for bifidobacteria in their ecological niche. PMID:26635786

  19. A comprehensive analysis of common genetic variation in prolactin (PRL) and PRL receptor (PRLR) genes in relation to plasma prolactin levels and breast cancer risk: the Multiethnic Cohort

    PubMed Central

    Lee, Sulggi A; Haiman, Christopher A; Burtt, Noel P; Pooler, Loreall C; Cheng, Iona; Kolonel, Laurence N; Pike, Malcolm C; Altshuler, David; Hirschhorn, Joel N; Henderson, Brian E; Stram, Daniel O

    2007-01-01

    Background Studies in animals and humans clearly indicate a role for prolactin (PRL) in breast epithelial proliferation, differentiation, and tumorigenesis. Prospective epidemiological studies have also shown that women with higher circulating PRL levels have an increase in risk of breast cancer, suggesting that variability in PRL may also be important in determining a woman's risk. Methods We evaluated genetic variation in the PRL and PRL receptor (PRLR) genes as predictors of plasma PRL levels and breast cancer risk among African-American, Native Hawaiian, Japanese-American, Latina, and White women in the Multiethnic Cohort Study (MEC). We selected single nucleotide polymorphisms (SNPs) from both the public (dbSNP) and private (Celera) databases to construct high density SNP maps that included up to 20 kilobases (kb) upstream of the transcription initiation site and 10 kb downstream of the last exon of each gene, for a total coverage of 59 kb in PRL and 210 kb in PRLR. We genotyped 80 SNPs in PRL and 173 SNPs in PRLR in a multiethnic panel of 349 unaffected subjects to characterize linkage disequilibrium (LD) and haplotype patterns. We sequenced the coding regions of PRL and PRLR in 95 advanced breast cancer cases (19 of each racial/ethnic group) to uncover putative functional variation. A total of 33 and 60 haplotype "tag" SNPs (tagSNPs) that allowed for high predictability (Rh2 ≥ 0.70) of the common haplotypes in PRL and PRLR, respectively, were then genotyped in a multiethnic breast cancer case-control study of 1,615 invasive breast cancer cases and 1,962 controls in the MEC. We also assessed the association of common genetic variation with circulating PRL levels in 362 postmenopausal controls without a history of hormone therapy use at blood draw. Because of the large number of comparisons being performed we used a relatively stringent type I error criteria (p < 0.0005) for evaluating the significance of any single association to correct for performing

  20. Overexpression of PRL7D1 in Leydig Cells Causes Male Reproductive Dysfunction in Mice.

    PubMed

    Liu, Yaping; Su, Xingyu; Hao, Jie; Chen, Maoxin; Liu, Weijia; Liao, Xiaogang; Li, Gang

    2016-01-01

    Prolactin family 7, subfamily d, member 1 (PRL7D1) is found in mouse placenta. Our recent work showed that PRL7D1 is also present in mouse testis Leydig cells, and the expression of PRL7D1 in the testis exhibits an age-related increase. In the present study, we generated transgenic mice with Leydig cell-specific PRL7D1 overexpression to explore its function during male reproduction. Prl7d1 male mice exhibited subfertility as reflected by reduced sperm counts and litter sizes. The testes from Prl7d1 transgenic mice appeared histologically normal, but the frequency of apoptotic germ cells was increased. Prl7d1 transgenic mice also had lower testosterone concentrations than wild-type mice. Mechanistic studies revealed that Prl7d1 transgenic mice have defects in the testicular expression of steroidogenic acute regulatory protein (STAR) and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase cluster (HSD3B). Further studies revealed that PRL7D1 overexpression affected the expression of transferrin (TF) in Sertoli cells. These results suggest that PRL7D1 overexpression could lead to increased germ cell apoptosis and exert an inhibitory effect on testosterone production in Leydig cells by reducing the expression of certain steroidogenic-related genes. In addition, PRL7D1 appears to have important roles in the function of Sertoli cells, which, in turn, affects male fertility. We conclude that the expression level of PRL7D1 is associated with the reproductive function of male mice. PMID:26771609

  1. Structural and ultrastructural study of GH, PRL and SMT cells in male goat by immunocytochemical methods.

    PubMed

    Gómez, M A; Garcés-Abadías, B; Muñoz, A; Vásquez, F; Serrano, J; Bernabé, A

    1999-01-01

    The structural and ultrastructural characteristics of adenohypophyseal growth hormone (GH)-, prolactin (PRL)- and GH-PRL (SMT)-secreting cells were studied using immunocytochemical techniques in two normal and one lactating male goat. SMT cells were found in both types of males, which showed the same characteristics as those reported for the female. PRL and SMT cells were more frequent in the lactating male, which reflects their greater galactopoietic activity. GH cells did not seem to influence this process significantly.

  2. Overexpression of PRL7D1 in Leydig Cells Causes Male Reproductive Dysfunction in Mice.

    PubMed

    Liu, Yaping; Su, Xingyu; Hao, Jie; Chen, Maoxin; Liu, Weijia; Liao, Xiaogang; Li, Gang

    2016-01-13

    Prolactin family 7, subfamily d, member 1 (PRL7D1) is found in mouse placenta. Our recent work showed that PRL7D1 is also present in mouse testis Leydig cells, and the expression of PRL7D1 in the testis exhibits an age-related increase. In the present study, we generated transgenic mice with Leydig cell-specific PRL7D1 overexpression to explore its function during male reproduction. Prl7d1 male mice exhibited subfertility as reflected by reduced sperm counts and litter sizes. The testes from Prl7d1 transgenic mice appeared histologically normal, but the frequency of apoptotic germ cells was increased. Prl7d1 transgenic mice also had lower testosterone concentrations than wild-type mice. Mechanistic studies revealed that Prl7d1 transgenic mice have defects in the testicular expression of steroidogenic acute regulatory protein (STAR) and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase cluster (HSD3B). Further studies revealed that PRL7D1 overexpression affected the expression of transferrin (TF) in Sertoli cells. These results suggest that PRL7D1 overexpression could lead to increased germ cell apoptosis and exert an inhibitory effect on testosterone production in Leydig cells by reducing the expression of certain steroidogenic-related genes. In addition, PRL7D1 appears to have important roles in the function of Sertoli cells, which, in turn, affects male fertility. We conclude that the expression level of PRL7D1 is associated with the reproductive function of male mice.

  3. Upregulation of metastasis-associated PRL-3 initiates chordoma in zebrafish.

    PubMed

    Li, Li; Shi, Hongshun; Zhang, Mingming; Guo, Xiaoling; Tong, Fang; Zhang, Wenliang; Zhou, Junyi; Wang, Haihe; Yang, Shulan

    2016-04-01

    The metastasis-associated phosphatase of regenerating liver-3 (PRL-3) plays multiple roles in progression of various human cancers; however, significance of its role during development has not been addressed. Here we cloned and characterized the expression pattern of zebrafish prl-3 transcript and showed that it is ubiquitiously expressed in the first 24 h of development with both maternal and zygotic expressions. The transcripts become progressively restricted to the notochord, vessels and the intestine by 96 h post-fertilization. Notably, overexpression of zebrafish Prl-3 (zPrl-3) and human PRL-3 induces notochord malformation in zebrafish. This phenotype resembles chordoma and is confirmed by associated misexpression of notochord-specific markers. Clinical significance of the PRL-3 in chordoma is strongly suggested by detection of PRL-3 antigen in clinical chordoma specimens. Collectively, our results uncovered that aberrant overexpression of PRL-3 could initiate chordoma in early development and suggest the use of PRL-3 could be used as a predictor and a therapeutic target for chordoma.

  4. PRL-3 promotes cell adhesion by interacting with JAM2 in colon cancer

    PubMed Central

    Lian, Shenyi; Meng, Lin; Xing, Xiaofang; Yang, Yongyong; Qu, Like; Shou, Chengchao

    2016-01-01

    Phosphatase of regenerating liver-3 (PRL-3), also termed PTP4A3, is a metastasis-related protein tyrosine phosphatase. Its expression levels are significantly correlated with the progression and survival of a wide range of malignant tumors. However, the mechanism by which PRL-3 promotes tumor invasion and metastasis is not clear. In the present study, the functions of PRL-3 were systemically analyzed in the key events of metastasis including, motility and adhesion. A cell wounding assay, cell spread assay and cell-matrix adhesion assay were carried out to analyze the cell movement and cell adhesion ability of colon cancer, immunoprecipitation and immunofluorescence assay was confirmed the interaction of PRL-3 and JAM2. It was demonstrated that PRL-3 promoted the motility of Flp-In-293 and LoVo colon cancer cells and increased the distribution of cell skeleton proteins on the cell protrusions. In addition, stably expressing PRL-3 reduced the spreading speed of colon cancer cells and cell adhesion on uncoated, fibronectin-coated and collagen I-coated plates. Mechanistically, junction adhesion molecular 2 (JAM2) was identified as a novel interacting protein of PRL-3. The findings of the present study revealed the roles of PRL-3 in cancer cell motility and adhesion process, and provided information on the possibility of PRL-3 increase cell-cell adhesion by associating with JAM2. PMID:27588115

  5. Differential expression and functional constraint of PRL-2 in hibernating bat.

    PubMed

    Yuan, Lihong; Chen, Jinping; Lin, Benfu; Zhang, Junpeng; Zhang, Shuyi

    2007-12-01

    Circannual hibernation is a biological adaptation to periods of cold and food shortage and the role of the brain in its control is poorly understood. An SSH library of hibernating bat brains (Rhinolophus ferrumequinum) was constructed in order to explore the molecular mechanism of hibernation. An up-regulated gene, PRL-2, was obtained from hibernating bat brains. PRL-2 is a member of PTP family and has an important function in controlling cell growth. Alignment of sequences showed that PRL-2 is highly conserved among species, including two species of hibernating bats (R. ferrumequinum and Myotis ricketti). Moreover, Maximum Likelihood Analysis suggested that it may experience strong selection pressure leading to functional constraint in evolution, which indicated the significance of PRL-2 in normal bio-function. RQ-PCR was performed and statistical analysis suggested that PRL-2 exhibited distinct differential expression patterns in different organs during hibernation. In heart, fat and brain tissue of hibernating bats, the transcriptional level of PRL-2 increased almost 170%, 35% and 12% respectively. However, in muscle it decreased nearly 70%. The change of mRNA level of PRL-2 in heart tissue of hibernating bats was significantly higher than that in heart tissue of active controls (P=0.043). However, the regulation mechanism of differential expression of PRL-2 and the signal pathway involved are still unknown. PMID:17683965

  6. Pharmacological activation of the GABAergic system does not affect GH and PRL release in acromegaly.

    PubMed

    Orio, F; Iovino, M; Monteleone, P; Agrusta, M; Steardo, L; Lombardi, G

    1988-11-01

    An extensive hypothalamic neurotransmitter impairment has been proposed in acromegaly. However, at the moment, the hypothalamic GABAergic system has been little investigated in this disorder. Since GABA has been shown to modulate growth hormone (GH) and prolactin (PRL) secretion in human subjects, it seemed reasonable to investigate hypothalamic GABAergic functioning through the assessment of basal GH and PRL responses to pharmacological activation of this system. 800 mg of sodium valproate (SV), a drug with GABA facilitating properties, were administered orally to 7 acromegalic patients and 9 healthy volunteers. Blood samples were collected before and after the drug administration for the measurement of plasma GH and PRL levels. SV induced a clear-cut rise in basal GH and a decrease in basal PRL in healthy subjects, but it did not induce any change in the basal levels of these hormones in acromegalics. These results suggest that the response of GH and PRL to SV in acromegaly is qualitatively different from normal controls.

  7. Expression of PRL proteins at invasive margin of rectal cancers in relation to preoperative radiotherapy

    SciTech Connect

    Wallin, Asa R.; Svanvik, Joar; Adell, Gunnar; Sun Xiaofeng . E-mail: xiasu@ibk.liu.se

    2006-06-01

    Purpose: PRL-3 (phosphatase of regenerating liver) is involved in metastasis of colorectal cancer; however, its therapeutic implication in cancer patients has not been studied. We investigated the relationships of PRL expression to radiotherapy (RT) in rectal cancer patients. Methods and Materials: Phosphatase of regenerating liver expression was immunohistochemically examined in distant (n = 36) and adjacent (n = 82) normal mucosa, primary tumor (n = 125), biopsy specimens (n = 96), and lymph node metastasis (n = 30) from rectal cancer patients participating in a clinical trial of preoperative RT. Results: Phosphatase of regenerating liver expression was increased from the distant to adjacent mucosa and to the primary tumor (p < 0.05). PRL was highly expressed at the invasive margin in 28% of the primary tumors and 26% of the metastases. In the RT group, strong PRL expression at the invasive margin was related to distant recurrence (p 0.006) and poor survival (p = 0.01), but not in the non-RT group. The survival significance remained even after adjusting for Dukes' stage and differentiation (p = 0.02). Additional multivariate analyses showed that the correlation with prognostic significance of PRL differed between the RT and non-RT groups (p = 0.01). Conclusion: Phosphatase of regenerating liver expression (rather than PRL-3 alone) at the invasive margin predicted resistance to RT and unfavorable survival in rectal cancer patients with preoperative RT.

  8. Somatomammotrophic cells in GH-secreting and PRL-secreting human pituitary adenomas.

    PubMed

    Bassetti, M; Brina, M; Spada, A; Giannattasio, G

    1989-11-01

    A morphological study has been carried out on 20 GH-secreting adenomas removed from acromegalic normoprolactinemic patients, on 29 PRL-secreting adenomas removed from hyperprolactinemic patients without signs of acromegaly and on one normal human anterior pituitary gland collected at autopsy. The protein A-gold immunoelectron microscopic technique has been utilized in order to verify the presence of mixed cells producing both GH and PRL (somatomammotrophs) in these pituitary tissues. In the normal pituitary a considerable number of somatomammotrophs (15-20%) was found, thus supporting the idea that these cells are normal components of the human anterior pituitary gland. In 10 GH-secreting adenomas and in 10 PRL-secreting adenomas somatomammotrophs were present in a variable number (from 4 to 20% of the whole cell population in GH adenomas and from 1 to 47% in PRL tumors). It can be concluded therefore that these cells, largely present in all GH/PRL-secreting adenomas, can also be found in GH-secreting and PRL-secreting tumors without clinical evidence of a mixed secretion. Adenomatous somatomammotrophs displayed ultrastructural features of adenomatous somatotrophs and mammotrophs (prominent Golgi complexes, abundant rough endoplasmic reticulum, irregular nuclei). The size and the number of granules were variable. In some cells GH and PRL were stored in distinct secretory granules, in others in mixed granules or both in mixed and distinct granules, thus suggesting that in adenomatous somatomammotrophs the efficiency of the mechanisms of sorting of the two hormones varies from one cell to another.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Structural and ultrastructural studies of GH, PRL and SMT cells in goat fetus (Capra hircus) using immunocytochemical methods.

    PubMed

    Vásquez, F A; Gómez, M A; Serrano, J; Bernabé, A

    2000-10-01

    The first data based on immunolabeling techniques of goat fetus adenohypophysis show that the structure and ultrastructure of growth hormone (GH)-, prolactin (PRL)-, and GH- plus PRL-secreting cells (SMT cells) in fetuses aged 100 days differ from those in the adult. Both cell number and cell size are smaller in the fetus, and the percentage of dark cells decreases with development. The data do not support the hypothesis that SMT cells represent the common origin of GH- and PRL-cells.

  10. The phosphatase of regenerating liver-3 (PRL-3) is important for IL-6-mediated survival of myeloma cells

    PubMed Central

    Slørdahl, Tobias S.; Abdollahi, Pegah; Vandsemb, Esten N.; Rampa, Christoph; Misund, Kristine; Baranowska, Katarzyna A.; Westhrin, Marita; Waage, Anders; Rø, Torstein B.; Børset, Magne

    2016-01-01

    Multiple myeloma (MM) is a neoplastic proliferation of bone marrow plasma cells. PRL-3 is a phosphatase induced by interleukin (IL)-6 and other growth factors in MM cells and promotes MM-cell migration. PRL-3 has also been identified as a marker gene for a subgroup of patients with MM. In this study we found that forced expression of PRL-3 in the MM cell line INA-6 led to increased survival of cells that were depleted of IL-6. It also caused redistribution of cells in cell cycle, with an increased number of cells in G2M-phase. Furthermore, forced PRL-3 expression significantly increased phosphorylation of Signal transducer and activator of transcription (STAT) 3 both in the presence and the absence of IL-6. Knockdown of PRL-3 with shRNA reduced survival in MM cell line INA-6. A pharmacological inhibitor of PRL-3 reduced survival in the MM cell lines INA-6, ANBL-6, IH-1, OH-2 and RPMI8226. The inhibitor also reduced survival in 9 of 9 consecutive samples of purified primary myeloma cells. Treatment with the inhibitor down-regulated the anti-apoptotic protein Mcl-1 and led to activation of the intrinsic apoptotic pathway. Inhibition of PRL-3 also reduced IL-6-induced phosphorylation of STAT3. In conclusion, our study shows that PRL-3 is an important mediator of growth factor signaling in MM cells and hence possibly a good target for treatment of MM. PMID:27036022

  11. PRL-3 promotes the proliferation of LoVo cells via the upregulation of KCNN4 channels.

    PubMed

    Lai, Wei; Chen, Shuang; Wu, Heng; Guan, Yufeng; Liu, Lu; Zeng, Yujie; Zhao, Haiyan; Jiang, Jianmin; Chu, Zhonghua

    2011-10-01

    Previous studies have shown that phosphatase of regenerating liver-3 (PRL-3) plays an important role in the metastasis and proliferation of tumor cells. However, the mechanism by which PRL-3 controls the cell cycle of tumor cells remains unknown. In the present study, considering that the K+ channels strictly control cell proliferation, we examined whether K+ channels participate in the proliferation of tumor cells induced by PRL-3. Interestingly, the expression of intermediate-conductance Ca2+-activated K+ channels (KCNN4) was upregulated in an NF-κB-dependent manner when PRL-3 was transfected into LoVo cells. Also, we identified two NF-κB binding sites in the promoter region of KCNN4. Use of the specific inhibitor 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34) significantly inhibited the proliferation induced by PRL-3 and blocked the cell cycle at the G2/M phase. Meanwhile, the level of phosphorylation of Cdc2 was increased in a dose-dependent manner. Furthermore, TRAM-34 also inhibited tumor formation of PRL-3 cell xenografts implanted by injection in nude mice. In conclusion, PRL-3 promoted the proliferation of LoVo cells through upregulation of KCNN4 channels which facilitated the G2/M transition.

  12. Overexpression and involvement in migration by the metastasis-associated phosphatase PRL-3 in human myeloma cells.

    PubMed

    Fagerli, Unn-Merete; Holt, Randi U; Holien, Toril; Vaatsveen, Thea K; Zhan, Fenghuang; Egeberg, Kjartan W; Barlogie, Bart; Waage, Anders; Aarset, Harald; Dai, Hong Yan; Shaughnessy, John D; Sundan, Anders; Børset, Magne

    2008-01-15

    Multiple myeloma (MM) is characterized by accumulation and dissemination of malignant plasma cells (PCs) in the bone marrow (BM). Gene expression profiling of 2 MM cell lines (OH-2 and IH-1) indicated that expression of PRL-3, a metastasis-associated tyrosine phosphatase, was induced by several mitogenic cytokines. Cytokine-driven PRL-3 expression could be shown in several myeloma cell lines at both the mRNA and protein levels. There was significantly higher expression of the PRL-3 gene in PCs from patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma (SMM), and myeloma than in PCs from healthy persons. Among 7 MM subgroups identified by unsupervised hierarchical cluster analysis, PRL-3 gene expression was significantly higher in the 3 groups denoted as "proliferation," "low bone disease," and "MMSET/FGFR3." PRL-3 protein was detected in 18 of 20 BM biopsies from patients with MM. Silencing of the PRL-3 gene by siRNA reduced cell migration in the MM cell line INA-6, but had no detectable effect on proliferation and cell-cycle phase distribution of the cells. In conclusion, PRL-3 is a gene product specifically expressed in malignant plasma cells and may have a role in migration of these cells. PMID:17934070

  13. Prolactin (PRL) induction of cyclooxygenase 2 (COX2) expression and prostaglandin (PG) production in hamster Leydig cells.

    PubMed

    Matzkin, María Eugenia; Ambao, Verónica; Carino, Mónica Herminia; Rossi, Soledad Paola; González, Lorena; Turyn, Daniel; Campo, Stella; Calandra, Ricardo Saúl; Frungieri, Mónica Beatriz

    2012-01-01

    Serum prolactin (PRL) variations play a crucial role in the photoperiodic-induced testicular regression-recrudescence transition in hamsters. We have previously shown that cyclooxygenase 2 (COX2), a key enzyme in the biosynthesis of prostaglandins (PGs), is expressed mostly in Leydig cells of reproductively active hamsters with considerable circulating and pituitary levels of PRL. In this study, we describe a stimulatory effect of PRL on COX2/PGs in hamster Leydig cells, which is mediated by IL-1β and prevented by P38-MAPK and JAK2 inhibitors. Furthermore, by preparative isoelectric focusing (IEF), we isolated PRL charge analogues from pituitaries of active [isoelectric points (pI): 5.16, 4.61, and 4.34] and regressed (pI: 5.44) hamsters. More acidic PRL charge analogues strongly induced COX2 expression, while less acidic ones had no effect. Our studies suggest that PRL induces COX2/PGs in hamster Leydig cells through IL-1β and activation of P38-MAPK and JAK2. PRL microheterogeneity detected in active/inactive hamsters may be responsible for the photoperiodic variations of COX2 expression in Leydig cells.

  14. Bifidobacterium asteroides PRL2011 Genome Analysis Reveals Clues for Colonization of the Insect Gut

    PubMed Central

    Bottacini, Francesca; Milani, Christian; Turroni, Francesca; Sánchez, Borja; Foroni, Elena; Duranti, Sabrina; Serafini, Fausta; Viappiani, Alice; Strati, Francesco; Ferrarini, Alberto; Delledonne, Massimo; Henrissat, Bernard; Coutinho, Pedro; Fitzgerald, Gerald F.; Margolles, Abelardo; van Sinderen, Douwe; Ventura, Marco

    2012-01-01

    Bifidobacteria are known as anaerobic/microaerophilic and fermentative microorganisms, which commonly inhabit the gastrointestinal tract of various animals and insects. Analysis of the 2,167,301 bp genome of Bifidobacterium asteroides PRL2011, a strain isolated from the hindgut of Apis mellifera var. ligustica, commonly known as the honey bee, revealed its predicted capability for respiratory metabolism. Conservation of the latter gene clusters in various B. asteroides strains enforces the notion that respiration is a common metabolic feature of this ancient bifidobacterial species, which has been lost in currently known mammal-derived Bifidobacterium species. In fact, phylogenomic based analyses suggested an ancient origin of B. asteroides and indicates it as an ancestor of the genus Bifidobacterium. Furthermore, the B. asteroides PRL2011 genome encodes various enzymes for coping with toxic products that arise as a result of oxygen-mediated respiration. PMID:23028506

  15. Inhibition of PRL-2·CNNM3 Protein Complex Formation Decreases Breast Cancer Proliferation and Tumor Growth*

    PubMed Central

    Kostantin, Elie; Hardy, Serge; Valinsky, William C.; Kompatscher, Andreas; de Baaij, Jeroen H. F.; Zolotarov, Yevgen; Landry, Melissa; Uetani, Noriko; Martínez-Cruz, Luis Alfonso; Hoenderop, Joost G. J.; Shrier, Alvin; Tremblay, Michel L.

    2016-01-01

    The oncogenic phosphatase of regenerating liver 2 (PRL-2) has been shown to regulate intracellular magnesium levels by forming a complex through an extended amino acid loop present in the Bateman module of the CNNM3 magnesium transporter. Here we identified highly conserved residues located on this amino acid loop critical for the binding with PRL-2. A single point mutation (D426A) of one of those critical amino acids was found to completely disrupt PRL-2·human Cyclin M 3 (CNNM3) complex formation. Whole-cell voltage clamping revealed that expression of CNNM3 influenced the surface current, whereas overexpression of the binding mutant had no effect, indicating that the binding of PRL-2 to CNNM3 is important for the activity of the complex. Interestingly, overexpression of the CNNM3 D426A-binding mutant in cancer cells decreased their ability to proliferate under magnesium-deprived situations and under anchorage-independent growth conditions, demonstrating a PRL-2·CNNM3 complex-dependent oncogenic advantage in a more stringent environment. We further confirmed the importance of this complex in vivo using an orthotopic xenograft breast cancer model. Finally, because molecular modeling showed that the Asp-426 side chain in CNNM3 buries into the catalytic cavity of PRL-2, we showed that a PRL inhibitor could abrogate complex formation, resulting in a decrease in proliferation of human breast cancer cells. In summary, we provide evidence that this fundamental regulatory aspect of PRL-2 in cancer cells could potentially lead to broadly applicable and innovative therapeutic avenues. PMID:26969161

  16. DGAT1, GH, GHR, PRL and PRLR polymorphism in water buffalo (Bubalus bubalis).

    PubMed

    Shi, D-S; Wang, J; Yang, Y; Lu, F-H; Li, X-P; Liu, Q-Y

    2012-04-01

    The polymorphism of several genes has been shown to affect the milk composition traits in dairy cattle, including DGAT1-exon8 K232A, GH-intron3 MspI, GH-exon5 AluI, GHR-exon8 F279Y, PRL-exon3 RsaI and PRLR-exon3 S18N. However, the polymorphism and effects of these genes on the milk traits of water buffalo are still unclear. In this study, four DNA pooling samples from Murrah, Nili-ravi, Murrah-Nili-Swamp crossbreed and Chinese swamp buffalo were constructed, respectively, and polymorphism of these sites was investigated using PCR-Single-strand conformation polymorphism and sequencing. Twenty-eight inter-specific single-nucleotide polymorphism (SNPs) were found in these six assayed gene fragments between buffalo and dairy cattle, including nine intra-specific SNPs among buffalo groups. All buffalo fixed a K allele genotype in DGAT1-exon8, MspI(+) restriction site(c nucleotide) and AluI(+) site(c nucleotide) at intron3 and exon5 of GH gene, F allele genotype of F279Y mutation in GHR gene, RsaI(-) restriction site at PRL-exon3/exon4 and N allele genotype of S18N mutation at PRLR-exon3. It provides an indirect evidence that water buffalo have fixed alleles with genotypes reported in dairy cattle, which is thought to be responsible for high milk fat, high protein content and low milk yield. Moreover, three new intra-specific SNPs were found including 275th bp (c/t) in DGAT1 of Murrah buffalo, 109th bp (t/a) in PRL-exon3/exon4 and 43rd bp (c/t) in PRLR-exon3 of Chinese swamp buffalo. Information provided in this study will be useful in further studies to improve buffalo breeding for better lactation performances.

  17. Modeling Prolactin Actions in Breast Cancer in vivo: Insights from the NRL-PRL Mouse

    PubMed Central

    O'Leary, Kathleen A.; Shea, Michael P.; Schuler, Linda A.

    2016-01-01

    Elevated exposure to prolactin is epidemiologically associated with an increased risk of aggressive ER+ breast cancer. To understand the underlying mechanisms and crosstalk with other oncogenic factors, we developed the NRL-PRL mouse. In this model, mammary expression of a rat prolactin transgene raises local exposure to prolactin without altering estrous cycling. Nulliparous females develop metastatic, histotypically diverse mammary carcinomas independent from ovarian steroids, and most are ER+. These characteristics resemble the human clinical disease, facilitating study of tumorigenesis, and identification of novel preventive and therapeutic approaches. PMID:25472540

  18. Increased serum interleukin-22 levels in patients with PRL-secreting and non-functioning pituitary macroadenomas.

    PubMed

    Cannavo, S; Ferrau, F; Cotta, O R; Saitta, S; Barresi, V; Cristani, M T; Saija, A; Ruggeri, R M; Trimarchi, F; Gangemi, S

    2014-02-01

    Cytokines' involvement in tumorigenesis has been hypothesized. Interleukin-22 (IL-22) is implicated in proliferative and anti-apoptotic pathways via its receptor IL-22R. Its role in pituitary adenomas has never been investigated. Twenty-seven patients with pituitary macroadenomas (PA, 21 males, mean age 53.8 ± 14.4 years) and 30 healthy controls (19 males, mean age 50.4 ± 8.4 years) were enrolled. Out of 27 PA patients, 17 had a non-functioning tumour (NFPA) and 10 a PRL-secreting adenoma (PRL-oma). Serum IL-22 levels were measured in both patients and controls. Immunohistochemical (IHC) tumoral IL-22R expression was evaluated in 10 patients with NFPA and 4 with PRL-oma. IL-22 levels were significantly higher in PA patients than in controls [32.47 (11.29-70.12) vs. 5.58 (0.19-21.46) pg/mL, p < 0.0001] but did not correlate with tumor maximum diameter and were not associated to pituitary function impairment. PRL-oma patients had significantly higher IL-22 levels than NFPA patients [37.18 (14.82-70.12) vs. 21.29 (11.29-56) pg/mL, p = 0.039]. IHC revealed a strong IL-22R staining in 100 % of PRL-omas and 60 % of NFPAs. We provide the first evidence of increased serum IL-22 levels in patients with pituitary macroadenoma, especially in PRL-omas, regardless of tumor size and/or degree of pituitary function impairment. We also demonstrated the expression of IL22R in all PRL-omas and in 60 % of NFPAs. PMID:23512698

  19. Identification and characterization of novel membrane-bound PRL protein tyrosine phosphatases from Setaria cervi, a bovine filarial parasite.

    PubMed

    Singh, Neetu; Yadav, Smita; Rathaur, Sushma

    2015-11-01

    A significant amount of protein tyrosine phosphatase (PTP) activity was detected in the detergent-soluble membrane-bound fraction of Setaria cervi, a bovine filarial parasite. The membrane-bound PTP activity was significantly inhibited when the adult parasites were exposed to compounds having antifilarial activity like aspirin and SK7 as well as phenylarsine oxide, a specific PTP inhibitor suggesting that this activity is stress regulated. Further, this enzyme was purified as a single protein of apparently 21 kDa using two different chromatographic techniques. The MALDI-MS/MS analysis of its peptides showed closest match with protein tyrosine phosphatase PRL (Aedes aegypti). This purified enzyme (named as PRL) showed maximum activity at pH 5.5/37 °C and hydrolysed para nitro phenyl phosphate (pNPP) at the highest rate followed by O-P-L-tyrosine and O-P-L-threonine. It showed significant inhibition by specific inhibitors of PTP such as sodium orthovanadate, phenylarsine oxide and ammonium molybdate and was activated by dithiothreitol (DTT). The active site modification studies suggested involvement of cysteine, arginine, histidine and aspartic acid in the catalytic activity of PRL. The activity of S. cervi PRL was also found to be resistant towards the external oxidative stress. Thus, S. cervi PRL could be taken as a potential target for the management of human lymphatic filariasis. PMID:26341797

  20. PRL1 modulates root stem cell niche activity and meristem size through WOX5 and PLTs in Arabidopsis.

    PubMed

    Ji, Hongtao; Wang, Shuangfeng; Li, Kexue; Szakonyi, Dóra; Koncz, Csaba; Li, Xia

    2015-02-01

    The stem cell niche in the root meristem maintains pluripotent stem cells to ensure a constant supply of cells for root growth. Despite extensive progress, the molecular mechanisms through which root stem cell fates and stem cell niche activity are determined remain largely unknown. In Arabidopsis thaliana, the Pleiotropic Regulatory Locus 1 (PRL1) encodes a WD40-repeat protein subunit of the spliceosome-activating Nineteen Complex (NTC) that plays a role in multiple stress, hormone and developmental signaling pathways. Here, we show that PRL1 is involved in the control of root meristem size and root stem cell niche activity. PRL1 is strongly expressed in the root meristem and its loss of function mutation results in disorganization of the quiescent center (QC), premature stem cell differentiation, aberrant cell division, and reduced root meristem size. Our genetic studies indicate that PRL1 is required for confined expression of the homeodomain transcription factor WOX5 in the QC and acts upstream of the transcription factor PLETHORA (PLT) in modulating stem cell niche activity and root meristem size. These findings define a role for PRL1 as an important determinant of PLT signaling that modulates maintenance of the stem cell niche and root meristem size.

  1. Mass spectrometry study of PRL-3 phosphatase inactivation by disulfide bond formation and cysteine into glycine conversion.

    PubMed

    Orsatti, Laura; Innocenti, Federica; Lo Surdo, Paola; Talamo, Fabio; Barbato, Gaetano

    2009-09-01

    The Phosphatase of Regenerating Liver-3 (PRL-3) is a cysteine-based phosphatase (CBP) that is highly over-expressed in liver metastasis in colorectal cancer and suspected to be involved in the progression from tumor to metastasis. During substrate-specificity studies based on the screening of PRL-3 phosphatase activity on several phosphorylated synthetic peptides, we observed a decrease in activity depending on sample aging and storage conditions. By liquid chromatography combined with selective alkylation and mass spectrometry, we found two main PRL-3 inactivation pathways: a disulfide bond formation between the catalytic C104 and C49, blocking the enzyme in an inactive oxidized form, or the conversion of the catalytic C104 into glycine. We also found that the disulfide formation and the cysteine into glycine conversion are catalyzed by cations present in the sample after protein purification through a nickel column. By adding a cation chelator such as EDTA and de-oxygenating the sample with argon, PRL-3 phosphatase activity was preserved. These findings suggest that PRL-3, like other CBPs, is sensitive to inactivation by catalytic cysteine oxidation and this has implications for future studies of its activity and specificity. PMID:19639556

  2. A novel method for detection of preferred retinal locus (PRL) through simple retinal image processing using MATLAB

    NASA Astrophysics Data System (ADS)

    Kalikivayi, V.; Pal, Sudip; Ganesan, A. R.

    2013-09-01

    simple and new technique for detection of `Preferred Retinal Locus' (PRL) in human eye is proposed in this paper. Simple MATLAB algorithms for estimating RGB pixel intensity values of retinal images were used. The technique proved non-existence of `S' cones in Fovea Centralis and also proposes that rods are involved in blue color perception. Retinal images of central vision loss and normal retina were taken for image processing. Blue minimum, Red maximum and Red+Green maximum were the three methods used in detecting PRL. Comparative analyses were also performed for these methods with patient's age and visual acuity.

  3. PRL-3 promotes the peritoneal metastasis of gastric cancer through the PI3K/Akt signaling pathway by regulating PTEN.

    PubMed

    Xiong, Jianbo; Li, Zhengrong; Zhang, Yang; Li, Daojiang; Zhang, Guoyang; Luo, Xianshi; Jie, Zhigang; Liu, Yi; Cao, Yi; Le, Zhibiao; Tan, Shengxing; Zou, Wenyu; Gong, Peitao; Qiu, Lingyu; Li, Yuanyuan; Wang, Huan; Chen, Heping

    2016-10-01

    Peritoneal metastasis is the most frequent cause of death in patients with advanced gastric carcinoma (GC). The phosphatase of regenerating liver-3 (PRL-3) is recognized as an oncogene and plays an important role in GC peritoneal metastasis. However, the mechanism of how PRL-3 regulates GC invasion and metastasis is unknown. In the present study, we found that PRL-3 presented with high expression in GC with peritoneal metastasis, but phosphatase and tensin homologue (PTEN) was weakly expressed. The p-PTEN/PTEN ratio was also higher in GC with peritoneal metastasis than that in the normal gastric tissues. We also found the same phenomenon when comparing the gastric mucosa cell line with the GC cell lines. After constructing a wild-type and a mutant-type plasmid without enzyme activity and transfecting them into GC SGC7901 cells, we showed that only PRL-3 had enzyme activity to downregulate PTEN and cause PTEN phosphorylation. The results also showed that PRL-3 increased the expression levels of MMP-2/MMP-9 and promoted the migration and invasion of the SGC7901 cells. Knockdown of PRL-3 decreased the expression levels of MMP-2/MMP-9 significantly, which further inhibited the migration and invasion of the GC cells. PRL-3 also increased the expression ratio of p-Akt/Akt, which indicated that PRL-3 may mediate the PI3K/Akt pathway to promote GC metastasis. When we transfected the PTEN siRNA plasmid into the PRL-3 stable low expression GC cells, the expression of p-Akt, MMP-2 and MMP-9 was reversed. In conclusion, our results provide a bridge between PRL-3 and PTEN; PRL-3 decreased the expression of PTEN as well as increased the level of PTEN phosphorylation and inactivated it, consequently activating the PI3K/Akt signaling pathway, and upregulating MMP-2/MMP-9 expression to promote GC cell peritoneal metastasis.

  4. PRL-3 promotes the peritoneal metastasis of gastric cancer through the PI3K/Akt signaling pathway by regulating PTEN

    PubMed Central

    Xiong, Jianbo; Li, Zhengrong; Zhang, Yang; Li, Daojiang; Zhang, Guoyang; Luo, Xianshi; Jie, Zhigang; Liu, Yi; Cao, Yi; Le, Zhibiao; Tan, Shengxing; Zou, Wenyu; Gong, Peitao; Qiu, Lingyu; Li, Yuanyuan; Wang, Huan; Chen, Heping

    2016-01-01

    Peritoneal metastasis is the most frequent cause of death in patients with advanced gastric carcinoma (GC). The phosphatase of regenerating liver-3 (PRL-3) is recognized as an oncogene and plays an important role in GC peritoneal metastasis. However, the mechanism of how PRL-3 regulates GC invasion and metastasis is unknown. In the present study, we found that PRL-3 presented with high expression in GC with peritoneal metastasis, but phosphatase and tensin homologue (PTEN) was weakly expressed. The p-PTEN/PTEN ratio was also higher in GC with peritoneal metastasis than that in the normal gastric tissues. We also found the same phenomenon when comparing the gastric mucosa cell line with the GC cell lines. After constructing a wild-type and a mutant-type plasmid without enzyme activity and transfecting them into GC SGC7901 cells, we showed that only PRL-3 had enzyme activity to downregulate PTEN and cause PTEN phosphorylation. The results also showed that PRL-3 increased the expression levels of MMP-2/MMP-9 and promoted the migration and invasion of the SGC7901 cells. Knockdown of PRL-3 decreased the expression levels of MMP-2/MMP-9 significantly, which further inhibited the migration and invasion of the GC cells. PRL-3 also increased the expression ratio of p-Akt/Akt, which indicated that PRL-3 may mediate the PI3K/Akt pathway to promote GC metastasis. When we transfected the PTEN siRNA plasmid into the PRL-3 stable low expression GC cells, the expression of p-Akt, MMP-2 and MMP-9 was reversed. In conclusion, our results provide a bridge between PRL-3 and PTEN; PRL-3 decreased the expression of PTEN as well as increased the level of PTEN phosphorylation and inactivated it, consequently activating the PI3K/Akt signaling pathway, and upregulating MMP-2/MMP-9 expression to promote GC cell peritoneal metastasis. PMID:27572739

  5. Inhibition of PRL-3 gene expression in gastric cancer cell line SGC7901 via microRNA suppressed reduces peritoneal metastasis

    SciTech Connect

    Li Zhengrong; Zhan Wenhua . E-mail: wcywk@hotmail.com; Wang Zhao; Zhu Baohe; He Yulong; Peng Junsheng; Cai Shirong; Ma Jinping

    2006-09-15

    High expression of PRL-3, a protein tyrosine phosphatase, is proved to be associated with lymph node metastasis in gastric carcinoma from previous studies. In this paper, we examined the relationship between PRL-3 expression and peritoneal metastasis in gastric carcinoma. We applied the artificial miRNA (pCMV-PRL3miRNA), which is based on the murine miR-155 sequence, to efficiently silence the target gene expression of PRL-3 in SGC7901 gastric cancer cells at both mRNA and protein levels. Then we observed that, in vitro, pCMV-PRL3miRNA significantly depressed the SGC7901 cell invasion and migration independent of cellular proliferation. In vivo, PRL-3 knockdown effectively suppressed the growth of peritoneal metastases and improved the prognosis in nude mice. Therefore, we concluded that artificial miRNA can depress the expression of PRL-3, and that PRL-3 might be a potential therapeutic target for gastric cancer peritoneal metastasis.

  6. Leptin, GH, PRL, insulin and metabolic parameters throughout the dry period and lactation in dairy cows.

    PubMed

    Accorsi, P A; Govoni, N; Gaiani, R; Pezzi, C; Seren, E; Tamanini, C

    2005-06-01

    Leptin may play a role in the endocrine-metabolic processes that guarantee the physiological course of lactation in dairy cattle. This study was aimed at determining the changes in plasma concentrations of leptin and some of the main hormones and metabolites involved in the lactogenetic process in high-yielding dairy cows throughout lactation; we also wanted to assess whether leptin secretion is subjected to seasonal influences. Blood samples were collected from 23 Italian Friesian dairy cows from the end of a lactation to the ninth month of the subsequent one; in addition, blood was sampled from 47 dairy cows in different phases of lactation during February and July. Plasma concentrations of leptin, growth hormone (GH), insulin, prolactin (PRL), glucose, non-esterified fatty acids (NEFA) and urea were quantified by either validated radioimmunoassay (RIA) or enzymatic colorimetric methods. At the beginning of lactation, GH concentrations significantly increased, while a significant reduction occurred in leptin and insulin. This endocrine condition, such as the significant increase in NEFA plasma concentrations, is indicative of a marked lipid mobilization. In the more advanced stages of lactation, when both energy and protein balances become positive, leptin plasma concentrations increased, whereas GH and NEFA concentrations declined. During the summer months, a significant increase in leptin plasma concentrations, irrespective of the phase of lactation, was observed. Collectively, our findings suggest that, in dairy cows, leptin may represent a 'metabolic signal' of animal's status of fattening and nutritional level; in addition, leptin seems to be influenced by photoperiod and environmental temperature.

  7. Role of sortase-dependent pili of Bifidobacterium bifidum PRL2010 in modulating bacterium–host interactions

    PubMed Central

    Turroni, Francesca; Serafini, Fausta; Foroni, Elena; Duranti, Sabrina; O’Connell Motherway, Mary; Taverniti, Valentina; Mangifesta, Marta; Milani, Christian; Viappiani, Alice; Roversi, Tommaso; Sánchez, Borja; Santoni, Andrea; Gioiosa, Laura; Ferrarini, Alberto; Delledonne, Massimo; Margolles, Abelardo; Piazza, Laura; Palanza, Paola; Bolchi, Angelo; Guglielmetti, Simone; van Sinderen, Douwe; Ventura, Marco

    2013-01-01

    Bifidobacteria represent one of the dominant groups of microorganisms colonizing the human infant intestine. Commensal bacteria that interact with a eukaryotic host are believed to express adhesive molecules on their cell surface that bind to specific host cell receptors or soluble macromolecules. Whole-genome transcription profiling of Bifidobacterium bifidum PRL2010, a strain isolated from infant stool, revealed a small number of commonly expressed extracellular proteins, among which were genes that specify sortase-dependent pili. Expression of the coding sequences of these B. bifidum PRL2010 appendages in nonpiliated Lactococcus lactis enhanced adherence to human enterocytes through extracellular matrix protein and bacterial aggregation. Furthermore, such piliated L. lactis cells evoked a higher TNF-α response during murine colonization compared with their nonpiliated parent, suggesting that bifidobacterial sortase-dependent pili not only contribute to adherence but also display immunomodulatory activity. PMID:23776216

  8. A signal sequence is not required for protein export in prlA mutants of Escherichia coli.

    PubMed Central

    Derman, A I; Puziss, J W; Bassford, P J; Beckwith, J

    1993-01-01

    The prlA/secY gene, which codes for an integral membrane protein component of the Escherichia coli protein export machinery, is the locus of the strongest suppressors of signal sequence mutations. We demonstrate that two exported proteins of E.coli, maltose-binding protein and alkaline phosphatase, each lacking its entire signal sequence, are exported to the periplasm in several prlA mutants. The export efficiency can be substantial; in a strain carrying the prlA4 allele, 30% of signal-sequenceless alkaline phosphatase is exported to the periplasm. Other components of the E.coli export machinery, including SecA, are required for this export. SecB is required for the export of signal-sequenceless alkaline phosphatase even though the normal export of alkaline phosphatase does not require this chaperonin. Our findings indicate that signal sequences confer speed and efficiency upon the export process, but that they are not always essential for export. Entry into the export pathway may involve components that so overlap in function that the absence of a signal sequence can be compensated for, or there may exist one or more means of entry that do not require signal sequences at all. Images PMID:8458344

  9. Kefir fermented milk and kefiran promote growth of Bifidobacterium bifidum PRL2010 and modulate its gene expression.

    PubMed

    Serafini, Fausta; Turroni, Francesca; Ruas-Madiedo, Patricia; Lugli, Gabriele Andrea; Milani, Christian; Duranti, Sabrina; Zamboni, Nicole; Bottacini, Francesca; van Sinderen, Douwe; Margolles, Abelardo; Ventura, Marco

    2014-05-16

    Bifidobacteria constitute one of the dominant groups of microorganisms colonizing the human gut of infants. Their ability to utilize various host-derived glycans as well as dietary carbohydrates has received considerable scientific attention. However, very little is known about the role of fermented foods, such as kefir, or their constituent glycans, such as kefiran, as substrates for bifidobacterial growth and for the modulation of the expression of bifidobacterial host-effector molecules. Here, we show that Bifidobacterium bifidum PRL2010 exhibits high growth performance among the bifidobacterial strains tested when cultivated on kefir and/or kefiran polymer. Furthermore, a 16S rRNA metagenomic approach revealed that the microbiota of kefir is modified upon the addition of PRL2010 cells to the kefir matrix. Finally, our results show that kefir and kefiran are able to influence the transcriptome of B. bifidum PRL2010 causing increased transcription of genes involved in the metabolism of dietary glycans as well as genes that act as host-microbe effector molecules such as pili. Altogether, these data support the use of kefir as a valuable means for the delivery of effective microbial cells in probiotic therapy.

  10. PRL-3 engages the focal adhesion pathway in triple-negative breast cancer cells to alter actin structure and substrate adhesion properties critical for cell migration and invasion.

    PubMed

    Gari, Hamid H; DeGala, Gregory D; Ray, Rahul; Lucia, M Scott; Lambert, James R

    2016-10-01

    Triple-negative breast cancers (TNBCs) are among the most aggressive cancers characterized by a high propensity to invade, metastasize and relapse. We previously reported that the TNBC-specific inhibitor, AMPI-109, significantly impairs the ability of TNBC cells to migrate and invade by reducing levels of the metastasis-promoting phosphatase, PRL-3. Here, we examined the mechanisms by which AMPI-109 and loss of PRL-3 impede cell migration and invasion. AMPI-109 treatment or knock down of PRL-3 expression were associated with deactivation of Src and ERK signaling and concomitant downregulation of RhoA and Rac1/2/3 GTPase protein levels. These cellular changes led to rearranged filamentous actin networks necessary for cell migration and invasion. Conversely, overexpression of PRL-3 promoted TNBC cell invasion by upregulating matrix metalloproteinase 10, which resulted in increased TNBC cell adherence to, and degradation of, the major basement membrane component laminin. Our data demonstrate that PRL-3 engages the focal adhesion pathway in TNBC cells as a key mechanism for promoting TNBC cell migration and invasion. Collectively, these data suggest that blocking PRL-3 activity may be an effective method for reducing the metastatic potential of TNBC cells.

  11. Genome-wide functional genetic screen with the anticancer agent AMPI-109 identifies PRL-3 as an oncogenic driver in triple-negative breast cancers

    PubMed Central

    Gari, Hamid H.; Gearheart, Christy M.; Fosmire, Susan; DeGala, Gregory D.; Fan, Zeying; Torkko, Kathleen C.; Edgerton, Susan M.; Lucia, M. Scott; Ray, Rahul; Thor, Ann D.; Porter, Christopher C.; Lambert, James R.

    2016-01-01

    Triple-negative breast cancers (TNBC) are among the most aggressive and heterogeneous cancers with a high propensity to invade, metastasize and relapse. Here, we demonstrate that the anticancer compound, AMPI-109, is selectively efficacious in inhibiting proliferation and inducing apoptosis of multiple TNBC subtype cell lines as assessed by activation of pro-apoptotic caspases-3 and 7, PARP cleavage and nucleosomal DNA fragmentation. AMPI-109 had little to no effect on growth in the majority of non-TNBC cell lines examined. We therefore utilized AMPI-109 in a genome-wide shRNA screen in the TNBC cell line, BT-20, to investigate the utility of AMPI-109 as a tool in helping to identify molecular alterations unique to TNBC. Our screen identified the oncogenic phosphatase, PRL-3, as a potentially important driver of TNBC growth, migration and invasion. Through stable lentiviral knock downs and transfection with catalytically impaired PRL-3 in TNBC cells, loss of PRL-3 expression, or functionality, led to substantial growth inhibition. Moreover, AMPI-109 treatment, downregulation of PRL-3 expression or impairment of PRL-3 activity reduced TNBC cell migration and invasion. Histological evaluation of human breast cancers revealed PRL-3 was significantly, though not exclusively, associated with the TNBC subtype and correlated positively with regional and distant metastases, as well as 1 and 3 year relapse free survival. Collectively, our study is proof-of-concept that AMPI-109, a selectively active agent against TNBC cell lines, can be used as a molecular tool to uncover unique drivers of disease progression, such as PRL-3, which we show promotes oncogenic phenotypes in TNBC cells. PMID:26909599

  12. Loss of the oncogenic phosphatase PRL-3 promotes a TNF-R1 feedback loop that mediates triple-negative breast cancer growth.

    PubMed

    Gari, H H; DeGala, G D; Lucia, M S; Lambert, J R

    2016-01-01

    Stimulating tumor cell senescence and apoptosis are proven methods for therapeutically combating cancer. However, senescence and apoptosis are conventionally viewed as parallel, not sequential, processes. We have discovered that the metastasis-promoting phosphatase, PRL-3, is transcriptionally regulated by the NF-ĸB pathway in triple-negative breast cancer (TNBC) cells, and that PRL-3 knockdown elicits an autocrine tumor necrosis factor receptor 1 (TNF-R1) feedback loop that results in TNBC cell senescence followed by apoptosis. Knockdown of PRL-3 leads to rapid G1 cell cycle arrest and induction of a strong TNFα cytokine response that promotes a period of cellular senescence through TNF-R1-mediated activation of NF-ĸB. Senescent PRL-3 knockdown cells subsequently underwent apoptosis as a result of increased TNF-R1 signaling through the TNFα-associated extrinsic death pathway, shunting signaling away from the NF-ĸB cascade. These data suggest that TNF-R1 signaling dynamically re-programs after PRL-3 knockdown, from sustaining cell senescence through NF-ĸB to promoting apoptosis through TNF-R1 internalization and caspase-8 activation. The molecular mechanisms that determine the survival-death balance of TNF-R1 signaling are poorly understood, despite the fact that TNF-R1 has been extensively studied. Our results describe PRL-3 knockdown as a novel survival-death balance modifier of the TNF-R1 pathway, and show that senescent TNBC tumor cells can be sensitized to undergo apoptosis in a sequential manner. PMID:27526109

  13. Loss of the oncogenic phosphatase PRL-3 promotes a TNF-R1 feedback loop that mediates triple-negative breast cancer growth

    PubMed Central

    Gari, H H; DeGala, G D; Lucia, M S; Lambert, J R

    2016-01-01

    Stimulating tumor cell senescence and apoptosis are proven methods for therapeutically combating cancer. However, senescence and apoptosis are conventionally viewed as parallel, not sequential, processes. We have discovered that the metastasis-promoting phosphatase, PRL-3, is transcriptionally regulated by the NF-ĸB pathway in triple-negative breast cancer (TNBC) cells, and that PRL-3 knockdown elicits an autocrine tumor necrosis factor receptor 1 (TNF-R1) feedback loop that results in TNBC cell senescence followed by apoptosis. Knockdown of PRL-3 leads to rapid G1 cell cycle arrest and induction of a strong TNFα cytokine response that promotes a period of cellular senescence through TNF-R1-mediated activation of NF-ĸB. Senescent PRL-3 knockdown cells subsequently underwent apoptosis as a result of increased TNF-R1 signaling through the TNFα-associated extrinsic death pathway, shunting signaling away from the NF-ĸB cascade. These data suggest that TNF-R1 signaling dynamically re-programs after PRL-3 knockdown, from sustaining cell senescence through NF-ĸB to promoting apoptosis through TNF-R1 internalization and caspase-8 activation. The molecular mechanisms that determine the survival–death balance of TNF-R1 signaling are poorly understood, despite the fact that TNF-R1 has been extensively studied. Our results describe PRL-3 knockdown as a novel survival–death balance modifier of the TNF-R1 pathway, and show that senescent TNBC tumor cells can be sensitized to undergo apoptosis in a sequential manner. PMID:27526109

  14. Polymorphisms in the 5'-flanking regions of the GH, PRL, and Pit-1 genes with Muscovy duck egg production.

    PubMed

    Xu, Z Q; He, J; Ji, C L; Zhang, Y; Nie, Q H; Zhang, D X; Zhang, X Q

    2015-01-01

    Somatotropic axis-related genes contribute to reproduction of ducks. Five SNP in the 5'-flanking regions of the growth hormone (GH), prolactin (PRL), and pituitary-specific transcription factor (Pit-1) genes were identified and genotyped in a female population of Muscovy ducks. Association analysis of these SNP with Muscovy duck egg production traits was performed. Results showed that SNP C-515G of GH was significantly associated with egg number in ducks at age 59 wk (E59W; P = 0.0009) and egg number in ducks at age 300 d (E300D; P = 0.0022). Single nucleotide polymorphism C-441T of GH was significantly associated with E59W (P = 0.0014). Significant associations of SNP T-884C and T-335C of PRL with the age at first egg (A1D), E59W, and E300D were detected in this population (P < 0.0001). It was concluded that these 4 SNP might be useful markers to use with the aim of increasing Muscovy duck E59W. On the basis of genetic parameter estimation, the heritability of A1D, E300D, E59W, and molting time were 0.43 ± 0.04, 0.45 ± 0.04, 0.36 ± 0.04, and 0.04 ± 0.03, respectively. Strong positive genetic correlation was noted between E59W and E300D (correlation coefficient = 0.80), whereas a negative association was noted between E59W and A1D (correlation coefficient = -0.80). Therefore, the selection for improved A1D should also increase E59W.

  15. Bilateral and simultaneous venous sampling of inferior petrosal sinuses for ACTH and PRL determination: preoperative localization of ACTH-secreting microadenomas.

    PubMed

    Vignati, F; Berselli, M E; Scialfa, G; Boccardi, E; Loli, P

    1989-04-01

    We report our experience on venous sampling of the inferior petrosal sinuses for basal and CRH-stimulated ACTH and PRL gradients in 8 patients with surgically proven Cushing's disease who had normal preoperative neuroradiological studies. In 7 patients basal plasma ACTH concentrations in the inferior petrosal sinus ipsilateral to the tumor were higher than in the contralateral sinus; the gradients were enhanced by oCRH administration. In one out of two patients who had previously undergone unsuccessful pituitary microsurgery, neither basal nor oCRH-induced ACTH increases led to correct localization of the microadenoma within the pituitary. In 4 out of 7 patients basal serum PRL concentrations in the inferior petrosal sinus ipsilateral to the tumor were higher than in the contralateral; only two out of 4 showed an increase in PRL levels after oCRH injection. Our study confirms that simultaneous and bilateral venous sampling of inferior petrosal sinuses is a valuable means to identify the site of microadenomas in patients with Cushing's disease without neuroradiological evidence of the tumor. This procedure may give misleading results in patients previously operated on. Unilateral or predominant increases of PRL concentration during catheterization of the inferior petrosal sinuses, when present, always lateralize to the side of the corticotroph adenoma, providing a possible additional signal of the presence of the tumor.

  16. Breeding period-associated changes in semen quality, concentrations of LH, PRL, gonadal steroid and thyroid hormones in domestic goose ganders (Anser anser f. domesticus).

    PubMed

    Gumułka, Małgorzata; Rozenboim, Israel

    2015-03-01

    In flocks of geese fertility decreases in the second half of the breeding season. The reasons for this reduction in reproduction ability are still unclear. This study measured changes in semen quality variables throughout the period of intensive breeding in relation to hormonal concentrations associated with the sexual activity of ganders. Semen was collected (2×/week) from 2-year-old ganders in the period February-June. Standard ejaculation parameters and spermatozoa (spz) membrane integrity after E/N and SYBR-14/PI staining were evaluated. The DNA Fragmentation Index was measured by flow cytometry and sperm quality factors (SQF). The plasma levels of T, E2, P4, LH, PRL, THs in relation to semen parameters were evaluated. In ejaculate collected at the onset of the second half of breeding (April - spring period), a reduction in sperm concentration and % of liveE/N and liveSYBR-14+/PI- spz was shown. At this time, decrease in concentrations of LH and T and increase in PRL were found as well as moderate changes in THs were observed. However, in May a second peak in T and sperm production occurred. The DFI-% was higher in the middle part of breeding. Gonadal steroids concentration were not good prognostic marker of the reproductive potential of ganders. We suggest that a marked decline in LH and T in the spring period indicated the onset of endocrine changes mediated by PRL and THs resulting in progressive regression of testis functions. The lowest SQF in the spring/summer period coincided with the highest PRL suggesting an anti-spermatogenic action of PRL in ganders. PMID:25600146

  17. Breeding period-associated changes in semen quality, concentrations of LH, PRL, gonadal steroid and thyroid hormones in domestic goose ganders (Anser anser f. domesticus).

    PubMed

    Gumułka, Małgorzata; Rozenboim, Israel

    2015-03-01

    In flocks of geese fertility decreases in the second half of the breeding season. The reasons for this reduction in reproduction ability are still unclear. This study measured changes in semen quality variables throughout the period of intensive breeding in relation to hormonal concentrations associated with the sexual activity of ganders. Semen was collected (2×/week) from 2-year-old ganders in the period February-June. Standard ejaculation parameters and spermatozoa (spz) membrane integrity after E/N and SYBR-14/PI staining were evaluated. The DNA Fragmentation Index was measured by flow cytometry and sperm quality factors (SQF). The plasma levels of T, E2, P4, LH, PRL, THs in relation to semen parameters were evaluated. In ejaculate collected at the onset of the second half of breeding (April - spring period), a reduction in sperm concentration and % of liveE/N and liveSYBR-14+/PI- spz was shown. At this time, decrease in concentrations of LH and T and increase in PRL were found as well as moderate changes in THs were observed. However, in May a second peak in T and sperm production occurred. The DFI-% was higher in the middle part of breeding. Gonadal steroids concentration were not good prognostic marker of the reproductive potential of ganders. We suggest that a marked decline in LH and T in the spring period indicated the onset of endocrine changes mediated by PRL and THs resulting in progressive regression of testis functions. The lowest SQF in the spring/summer period coincided with the highest PRL suggesting an anti-spermatogenic action of PRL in ganders.

  18. Dynamic evaluation of growth hormone (GH) and prolactin (hPRL) secretion in active acromegaly with high and low GH output.

    PubMed

    Tolis, G; Kovacs, L; Friesen, H; Martin, J B

    1975-02-01

    Ten patients with active acromegaly were studied. In 9 plasma GH levels failed to suppress after glucose (OGTT), in 8 an increase in serum GH occurred after thyrotropin releasing hormone (TRH). After L-Dopa, 4 patients showed no change in serum GH, 3 exhibited a decrease and in 3 an increase in serum hGH occurred. With a combined insulin (ITT) and arginine (ATT) test, 2 patients exhibited an increase in hGH, and in 6 no change occurred. Fasting serum GH concentration was less than 11 ng/ml in 5 patients. Basal prolactin (hPRL) levels were normal in all patients including two with galactorrhea. L-Dopa suppressed and TRH stimulated hPRL secretion in all, but the responses which were seen were subnormal. Hydrocortisone infusion in two acromegalics did not affect the prolactin induced increase after TRH but blunted the GH increase after TRH.

  19. Targeted deletion of the metastasis-associated phosphatase Ptp4a3 (PRL-3) suppresses murine colon cancer.

    PubMed

    Zimmerman, Mark W; Homanics, Gregg E; Lazo, John S

    2013-01-01

    Ptp4a3 (commonly known as PRL-3) is an enigmatic member of the Ptp4a family of prenylated protein tyrosine phosphatases that are highly expressed in many human cancers. Despite strong correlations with tumor metastasis and poor patient prognosis, there is very limited understanding of this gene family's role in malignancy. Therefore, we created a gene-targeted murine knockout model for Ptp4a3, the most widely studied Ptp4a family member. Mice deficient for Ptp4a3 were grossly normal. Fewer homozygous-null males were observed at weaning, however, and they maintained a decreased body mass. Although Ptp4a3 is normally associated with late-stage cancer and metastasis, we observed increased Ptp4a3 expression in the colon of wildtype mice immediately following treatment with the carcinogen azoxymethane. To investigate the role of Ptp4a3 in malignancy, we used the most commonly studied murine colitis-associated colon cancer model. Wildtype mice treated with azoxymethane and dextran sodium sulfate developed approximately 7-10 tumors per mouse in the distal colon. The resulting tumor tissue had 4-fold more Ptp4a3 mRNA relative to normal colon epithelium and increased PTP4A3 protein. Ptp4a3-null mice developed 50% fewer colon tumors than wildtype mice after exposure to azoxymethane and dextran sodium sulfate. Tumors from the Ptp4a3-null mice had elevated levels of both IGF1Rβ and c-MYC compared to tumors replete with Ptp4a3, suggesting an enhanced cell signaling pathway engagement in the absence of the phosphatase. These results provide the first definitive evidence implicating Ptp4a3 in colon tumorigenesis and highlight the potential value of the phosphatase as a therapeutic target for early stage malignant disease.

  20. Area 3 Support Buildings (A3SB) H5-0992, H5-0996 PRL 218 Confirmatory Sampling Report

    NASA Technical Reports Server (NTRS)

    Mrdjenovich, Timothy

    2015-01-01

    The Area 3 Support Buildings site (A3SB) consists of two separate areas located on the north side of Beach Road in the northern portion of Kennedy Space Center, Florida (KSC), outside the secured perimeter of KSC. The A3SB areas are approximately 0.6 miles apart, and were developed as Shiffler's Grocery Store and Service Station (west site) and as a residence (east site) prior to acquisition by the National Aeronautics and Space Administration (NASA) in 1963. Both areas were used by the Bendix Company in support of NASA as chemical laboratories from 1963 through 1969. Both of the buildings were demolished by 1987. The west portion of the site was used by the US Fish & Wildlife Service (F&W) in support of the Merritt Island National Wildlife Refuge (MINWR) for parking at the entrance to the Hammock Trails from 1969 to the present. The east portion of the site was used for intermittent suspect materials staging in the early 1990s and is still used as an apiary location, but is otherwise no longer active. In support of the NASA HSWA permit requirements, this site was identified as Potential Release Location (PRL) 218 and a Solid Waste Management Unit (SWMU) Assessment (SA) was conducted in 2013. Confirmatory Sampling (CS) was recommended and approved by the KSC Remediation Team (KSCRT). Three locations of concern (LOCs) were identified and sampled at the site. The LOCs include two former chemical labs and a former suspect staging area. The CS was conducted in March of 2015 at three locations by means of Direct Push Technology (DPT) groundwater sampling and at one location for soil sampling. The samples were collected and analyzed in accordance with the approved CS Work Plan. There were no exceedances of criteria detected in any of the samples from the three LOCs. The results of this investigation indicate that past and/or present operations have not negatively impacted environmental media at the A3SB. Based upon no confirmed groundwater detections above GCTLs and no

  1. mRNA expression patterns for GH, PRL, SL, IGF-I and IGF-II during altered feeding status in rabbitfish, Siganus guttatus.

    PubMed

    Ayson, Felix G; de Jesus-Ayson, Evelyn Grace T; Takemura, Akihiro

    2007-01-15

    Feeding time is a major synchronizer of many physiological rhythms in many organisms. Alteration in the nutritional status, specifically fasting, also affects the secretion rhythms of growth hormone (GH) and insulin-like growth factor-I (IGF-I). In this study, we investigated whether the expression patterns for the mRNAs of GH, prolactin (PRL) and somatolactin (SL) in the pituitary gland, and insulin-like growth factor I and II (IGF-I and IGF-II) in the liver of juvenile rabbitfish (Siganus guttatus) follow a rhythm according to feeding time and whether these hormone rhythms changes with starvation. Hormone mRNA levels were determined by real time PCR. The daily expression pattern for the mRNAs of GH, PRL and SL was not altered whether food was given in the morning (10:00 h) or in the afternoon (15:00 h). The daily GH mRNA expression pattern, however, was affected when food was not available for 3 days. In contrast, the daily expression pattern for IGF-I mRNA reaches its peak at roughly 5-6h after feeding. This pattern, however, was not observed with IGF-II mRNA. During 15-day starvation, GH mRNA levels in starved fish were significantly higher than the control fish starting on the 9th day of starvation until day 15. The levels returned to normal after re-feeding. In contrast to GH, PRL mRNA levels in starved fish were significantly lower than the control group starting on the 6th day of starvation until 3 days after re-feeding. SL mRNA levels were not significantly different between the control and starved group at anytime during the experiment. Both IGF-I and IGF-II mRNA levels in starved group were significantly higher than the control fish on the 3rd and 6th day of starvation. mRNA levels of both IGF-I and II in the starved fish decreased starting on the 9th day of starvation. While IGF-I mRNA levels in the starved group continued to decrease as starvation progressed, IGF-II mRNA levels were not significantly different from the control during the rest of the

  2. P.R.L. Platelet Rich Lipotransfert: Our Experience and Current State of Art in the Combined Use of Fat and PRP

    PubMed Central

    Cervelli, V.; Bocchini, I.; Di Pasquali, C.; De Angelis, B.; Cervelli, G.; Curcio, C. B.; Orlandi, A.; Scioli, M. G.; Tati, E.; Delogu, P.; Gentile, Pietro

    2013-01-01

    The authors report their experience about the use of P.R.L. PLATELET RICH LIPOTRANSFERT method (platelet rich plasma mixed fat grafting) in 223 patients affected by soft tissue defects (ulcers, Romberg syndrome, Hemifacial atrophy, loss of substance, and signs of aging). This paper introduces the reader to PRP therapy and reviews the current literature on this emerging treatment modality, showing at the current clinical use of PRP in plastic and reconstructive surgery, with description of innovative methods and future prospects. This technique provides a promising alternative to surgery by promoting safe and natural healing. Here recent studies concerning the use of PRP in the treatment of chronic ulcers and soft tissue defect are reviewed. PMID:24191244

  3. Hypothyroidism advances mammary involution in lactating rats through inhibition of PRL signaling and induction of LIF/STAT3 mRNAs.

    PubMed

    Campo Verde Arboccó, Fiorella; Sasso, Corina V; Actis, Esteban A; Carón, Rubén W; Hapon, María Belén; Jahn, Graciela A

    2016-01-01

    Thyroid diseases have deleterious effects on lactation, litter growth and survival, and hinder the suckling-induced hormone release, leading in the case of hyperthyroidism, to premature mammary involution. To determine the effects of hypothyroidism (HypoT) on late lactation, we analyzed the effect of chronic 6-propyl-2-thiouracil (PTU)-induced HypoT on mammary histology and the expression of members of the JAK/STAT/SOCS signaling pathway, milk proteins, prolactin (PRLR), estrogen (ER), progesterone (PR) and thyroid hormone (TR) receptors, markers of involution (such as stat3, lif, bcl2, BAX and PARP) on lactation (L) day 21. HypoT mothers showed increased histological markers of involution compared with control rats, such as adipose/epithelial ratio, inactive alveoli, picnotic nuclei and numerous detached apoptotic cells within the alveolar lumina. We also found decreased PRLR, β-casein and α-lactoalbumin mRNAs, but increased SOCS1, SOCS3, STAT3 and LIF mRNAs, suggesting a decrease in PRL signaling and induction of involution markers. Furthermore, Caspase-3 and 8 and PARP labeled cells and the expression of structural proteins such as β-Actin, α-Tubulin and Lamin B were increased, indicating the activation of apoptotic pathways and tissue remodelation. HypoT also increased PRA (mRNA and protein) and erβ and decreased erα mRNAs, and increased strongly TRα1, TRβ1, PRA and ERα protein levels. These results show that lactating HypoT rats have premature mammary involution, most probably induced by the inhibition of prolactin signaling along with the activation of the LIF-STAT3 pathway.

  4. Daily expression patterns for mRNAs of GH, PRL, SL, IGF-I and IGF-II in juvenile rabbitfish, Siganus guttatus, during 24-h light and dark cycles.

    PubMed

    Ayson, Felix G; Takemura, Akihiro

    2006-12-01

    Most animals respond to changes in the external environment in a rhythmic fashion. In teleost fishes, daily rhythms are observed in plasma concentrations of some hormones but it is not clear whether these rhythms are exogenous or are entrained by predictable cues. We investigated whether the expression patterns for the mRNAs of growth hormone (GH), prolactin (PRL) and somatolactin (SL) in the pituitary gland, and insulin-like growth factor-I and II (IGF-I and IGF-II) in the liver, follow a daily rhythm when juvenile rabbitfish (Siganus guttatus) are reared under a normal 24-h light and dark cycle (LD), and when they are exposed to either continuous light (LL) or darkness (DD). Hormone mRNA levels were determined by real time PCR. Under LD conditions, GH mRNA expression in the pituitary was significantly lower during the light phase than during the dark phase suggesting a diurnal rhythm of expression. The rhythm disappeared when fish were exposed to LL or DD conditions. PRL mRNA expression pattern was irregular in all 3 conditions. Very low levels of SL mRNA were observed during the mid day under LD conditions. The expression pattern of SL mRNA became irregular under LL and DD conditions. No pattern could be observed in the expression profile of IGF-I and II mRNA in the liver during LD and LL conditions but a single peak in mRNA level was observed under DD conditions in both IGF-I and II. The results indicate that except for GH, the daily expression pattern for the mRNAs of the hormones examined do not seem to follow a rhythm according to light and dark cycles.

  5. Organization and partial sequence of a DNA region of the Rhizobium leguminosarum symbiotic plasmid pRL6JI containing the genes fixABC, nifA, nifB and a novel open reading frame.

    PubMed Central

    Grönger, P; Manian, S S; Reiländer, H; O'Connell, M; Priefer, U B; Pühler, A

    1987-01-01

    By hybridization and heteroduplex studies the fixABC and nifA genes of the Rhizobium leguminosarum symbiotic plasmid pRL6JI have been identified. DNA sequencing of the region containing nifA showed an open reading frame of 1557 bp encoding a protein of 56, 178 D. Based on sequence homology, this ORF was confirmed to correspond to the nifA gene. Comparison of three nifA proteins (Klebsiella pneumoniae, Rhizobium meliloti, Rhizobium leguminosarum) revealed only a weak relationship in their N-terminal regions, whereas the C-terminal parts exhibited strong homology. Sequence analysis also showed that the R. leguminosarum nifA gene is followed by nifB and preceded by fixC with an open reading frame inserted in between. This novel ORF of 294 bp was found to be highly conserved also in R. meliloti. No known promoter and termination signals could be defined on the sequenced R. leguminosarum fragment. Images PMID:3029674

  6. Price-Responsive Load (PRL) Program - Framing Paper No.1

    SciTech Connect

    Goldman, Charles A.

    2002-03-01

    By definition, effective and efficient competitive markets need a supply side and a demand side. One criticism of electric restructuring efforts in many states is that most of the attention has been focused on the supply side, in a market focused on the short term. In general, the demand side of the market has been under-addressed. The objective of the New England Demand Response Initiative (NEDRI) is to develop a comprehensive, coordinated set of demand response programs for the New England regional power markets. NEDRI aims to maximize the capability of demand response to compete in the wholesale market and to improve the economic efficiency and environmental profile of the electric sector. To those ends, NEDRI is focusing its efforts in four interrelated areas: (1) ISO-level reliability programs, (2) Market-based price-responsive load programs, (3) Demand response at retail through pricing, rate design, and advanced metering, and (4) End-use energy efficiency resources as demand response. The fourth area, energy efficiency, is the subject of this framing paper. Energy efficiency reduces the energy used by specific end-use devices and systems, typically without affecting the level of service and without loss of amenity. Energy savings and peak load reductions are achieved by substituting technically more advanced equipment, processes, or operational strategies to produce the same or an improved level of end-use service with less electricity. In contrast, load management programs lower peak demand during specific, limited time periods by either (1) influencing the timing of energy use by shifting load to another time period, or (2) reducing the level of energy use by curtailing or interrupting the load, typically with some loss of service or amenity.

  7. PRL at 50: A history of moving physics forward

    NASA Astrophysics Data System (ADS)

    Hebboul, Saad E.

    2008-03-01

    Fifty years ago, Editor Sam Goudsmit announced the introduction of a new journal, Physical Review Letters, which would collect the pre-existing ``Letters to the Editor'' in The Physical Review into a separate Review. According to his July 1958 editorial, the new journal would consider only ``Letters which really deserve rapid publication'' in order to ``maintain the high speed and high standards.'' Fifty years after its creation, Physical Review Letters has grown into a journal of choice for publishing important work, which includes many Nobel-Prize-winning discoveries, in all fields of physics. Today, the journal continues to attract a steady growth of worldwide submissions that have reached the level of over 10,000 submitted manuscripts per year. To gain insight into the evolution of the new journal from its beginning as an ``experiment'' to its current state as an established world leader among physics journals, I will present a brief historical perspective of key developments starting in 1893 when three physicists founded the parent physics journal, The Physical Review, at the physics department of Cornell University, Ithaca, New York. Other major events before the birth of Physical Review Letters in 1958 include the immediate introduction of ``Minor Contributions'' in 1893, the foundation of The American Physical Society in 1899 and its takeover of The Physical Review in 1913, and the publication of the first ``Letter to the Editor'' in 1929. Since 1958, Physical Review Letters experienced a steady growth of submissions as well as a few major format and procedural changes, which include the increase in Letter length from one printed page to four printed pages in the 1960s and the establishment of the editorial board for handling appeals in the 1970s. Despite early technical difficulties, the ``experiment'' was very successful at carrying physics into the twenty-first century.

  8. PRL advanced radial-velocity all-sky search (PARAS): an efficient fiber-fed spectrograph for planet searches

    NASA Astrophysics Data System (ADS)

    Chakraborty, Abhijit; Richardson, Eric Harvey; Mahadevan, Suvrath

    2008-07-01

    We present here the optical design of an efficient Fiber-fed, Prism Cross-dispersed, Echelle Spectrograph (Resolution ~70,000 @seeing limited ~2arcsecs conditions) which will operate in the wavelength region of 3700A to 8100A. It will be used for extra-solar planets searches down to the precision of 3m/s and as well as for follow-up observations for new transit discoveries. The spectrograph design is such that with a beam size of 100mm (4inch) it should suit the existing 1 to 2m class of telescopes available in India. The fiber-fed spectrograph will be installed with a 1.2m telescope, which is situated at Mt. Abu (5800feet), Rajasthan, India. We estimate the spectrograph to be >30% efficient from the slit to the CCD detector, and up to 15% efficient including sky, telescope, fiber-fed optics etc. We expect to reach the S/N ratio of 70 on a 10mag star for an integration time of 40mins. We aim to achieve 5m/s to 3m/s Radial Velocity accuracies on such a star using the simultaneous ThAr referencing method. Since thermal stability is absolutely necessary to achieve <5m/s RV accuracies, the whole spectrograph is planned to be kept inside a vibration free isolated tank under low vacuum (0.001 mbar) in a thermally isolated room at 28C +/- 0.01C. It should see the first light by the summer of 2009. We are guaranteed at least 120 nights per year for the planet search program, more nights are possible.

  9. Changes in biomarkers of the nitrooxidative stress response and Prolactin (PRL) signal transduction elements (STE) to E. coli infection (INFec) in the mammary gland (MG)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Key features of the MG response to INFec include (a) the cellular generation of reactive oxynitrogen molecules (Roxn) derived from nitric oxide (NO) and superoxide anion (SO) and (b) loss of responsiveness to lactogenic hormone signaling. Of significance to the MG is the damage done to mammary epit...

  10. Discovery of conventional prolactin from the holocephalan elephant fish, Callorhinchus milii.

    PubMed

    Yamaguchi, Yoko; Takagi, Wataru; Kuraku, Shigehiro; Moriyama, Shunsuke; Bell, Justin D; Seale, Andre P; Lerner, Darren T; Grau, E Gordon; Hyodo, Susumu

    2015-12-01

    The conventional prolactin (PRL), also known as PRL1, is an adenohypophysial hormone that critically regulates various physiological events in reproduction, metabolism, growth, osmoregulation, among others. PRL1 shares its evolutionary origin with PRL2, growth hormone (GH), somatolactin and placental lactogen, which together form the GH/PRL hormone family. Previously, several bioassays implied the existence of PRL1 in elasmobranch pituitaries. However, to date, all attempts to isolate PRL1 from chondrichthyans have been unsuccessful. Here, we cloned PRL1 from the pituitary of the holocephalan elephant fish, Callorhinchus milii, as the first report of chondrichthyan PRL1. The putative mature protein of elephant fish PRL1 (cmPRL1) consists of 198 amino acids, containing two conserved disulfide bonds. The orthologous relationship of cmPRL1 to known vertebrate PRL1s was confirmed by the analyses of molecular phylogeny and gene synteny. The cmPRL1 gene was similar to teleost PRL1 genes in gene synteny, but was distinct from amniote PRL1 genes, which most likely arose in an early amphibian by duplication of the ancestral PRL1 gene. The mRNA of cmPRL1 was predominantly expressed in the pituitary, but was considerably less abundant than has been previously reported for bony fish and tetrapod PRL1s; the copy number of cmPRL1 mRNA in the pituitary was less than 1% and 0.1% of that of GH and pro-opiomelanocortin mRNAs, respectively. The cells expressing cmPRL1 mRNA were sparsely distributed in the rostral pars distalis. Our findings provide a new insight into the studies on molecular and functional evolution of PRL1 in vertebrates. PMID:26320855

  11. Discovery of conventional prolactin from the holocephalan elephant fish, Callorhinchus milii.

    PubMed

    Yamaguchi, Yoko; Takagi, Wataru; Kuraku, Shigehiro; Moriyama, Shunsuke; Bell, Justin D; Seale, Andre P; Lerner, Darren T; Grau, E Gordon; Hyodo, Susumu

    2015-12-01

    The conventional prolactin (PRL), also known as PRL1, is an adenohypophysial hormone that critically regulates various physiological events in reproduction, metabolism, growth, osmoregulation, among others. PRL1 shares its evolutionary origin with PRL2, growth hormone (GH), somatolactin and placental lactogen, which together form the GH/PRL hormone family. Previously, several bioassays implied the existence of PRL1 in elasmobranch pituitaries. However, to date, all attempts to isolate PRL1 from chondrichthyans have been unsuccessful. Here, we cloned PRL1 from the pituitary of the holocephalan elephant fish, Callorhinchus milii, as the first report of chondrichthyan PRL1. The putative mature protein of elephant fish PRL1 (cmPRL1) consists of 198 amino acids, containing two conserved disulfide bonds. The orthologous relationship of cmPRL1 to known vertebrate PRL1s was confirmed by the analyses of molecular phylogeny and gene synteny. The cmPRL1 gene was similar to teleost PRL1 genes in gene synteny, but was distinct from amniote PRL1 genes, which most likely arose in an early amphibian by duplication of the ancestral PRL1 gene. The mRNA of cmPRL1 was predominantly expressed in the pituitary, but was considerably less abundant than has been previously reported for bony fish and tetrapod PRL1s; the copy number of cmPRL1 mRNA in the pituitary was less than 1% and 0.1% of that of GH and pro-opiomelanocortin mRNAs, respectively. The cells expressing cmPRL1 mRNA were sparsely distributed in the rostral pars distalis. Our findings provide a new insight into the studies on molecular and functional evolution of PRL1 in vertebrates.

  12. The prolactin gene is expressed in the hypothalamic-neurohypophyseal system and the protein is processed into a 14-kDa fragment with activity like 16-kDa prolactin.

    PubMed Central

    Clapp, C; Torner, L; Gutiérrez-Ospina, G; Alcántara, E; López-Gómez, F J; Nagano, M; Kelly, P A; Mejía, S; Morales, M A; Martínez de la Escalera, G

    1994-01-01

    The 23-kDa form of prolactin (PRL) has been proposed to function as both a mature hormone and a prohormone precursor for different uniquely bioactive forms of the molecule. We have shown that the 16-kDa N-terminal fragment of PRL (16K PRL) inhibits angiogenesis via a specific receptor. In addition, 16K PRL stimulates natriuresis and diuresis in the rat, and kidney membranes contain high-affinity specific binding sites for this PRL fragment. 16K PRL can be derived from an enzymatically cleaved form of PRL (cleaved PRL). With the use of a specific 16K PRL antiserum, we have localized a 14-kDa immunoreactive protein in the paraventricular and supraoptic nuclei of the hypothalamus and in the neurohypophysis. Reverse transcription-polymerase chain reaction of RNA from isolated paraventricular nuclei showed the expression of the full-length PRL mRNA. The neurohypophysis was found to contain the enzymes that produce cleaved PRL, small amounts of PRL, and cleaved PRL. Medium conditioned by neurohypophyseal cultures, enriched with the 14-kDa immunoreactive protein, has antiangiogenic effects that are blocked by the 16K PRL antiserum. These results are consistent with the expression of PRL in the hypothalamic-neurohypophyseal system, and the preferential processing of the protein into a 14-kDa fragment with biological and immunological properties of 16K PRL. Images PMID:7937959

  13. Differences in affinities between the homologous and the heterologous rabbit prolactin-receptor interaction with respect to proliferation and differentiation activities.

    PubMed

    Petridou, Barbara

    2015-03-01

    Interspecies differences in PRL-receptor binding and their relationship with bioactivity deserve investigation since cross-reactivity is relevant to the design of many experiments. We have previously shown that the lower affinity of rabbit prolactin (rbPRL) binding to its homologous receptor is due to its faster and more complete dissociation compared with that of ovine PRL (oPRL). In order to obtain sufficient amounts of rbPRL to study the functional consequences of its low affinity homologous interaction, rbPRL was expressed recombinantly in Escherichia coli (rec rbPRL) as insoluble inclusion bodies, refolded and purified to homogeneity, yielding electrophoretically pure, over 98% monomeric rec rbPRL. Proper renaturation of rec rbPRL was evidenced by comparison of its CD spectra, binding parameters and bioactivity with those determined for the rbPRL. The binding potency of rec rbPRL to its receptor, expressed either endogenously in the mammary gland or recombinantly in mammalian cells is one log unit lower than that to the receptor expressed recombinantly in insect cells. This difference is probably related to differences in cell-dependent receptor densities. The proliferation potency of rbPRL or rec rbPRL was one log unit lower than that of oPRL, consistent with its lower binding affinity, but the differentiation potencies of these PRLs were similar. Thus, the proliferation activity is sensitive to PRL-receptor affinity and dissociation kinetics, whereas the differentiation response is marginally modulated.

  14. The rhythmic secretion of mating-induced prolactin secretion is controlled by prolactin acting centrally.

    PubMed

    Helena, Cleyde V; McKee, De'Nise T; Bertram, Richard; Walker, Ameae M; Freeman, Marc E

    2009-07-01

    Artificial copulomimetic cervical stimulation (CS) induces an immediate release of oxytocin (OT) and prolactin (PRL) followed by a daily PRL rhythm characterized by nocturnal and diurnal surges. Although we have shown that the initial release of PRL is induced by the immediate release of OT, we tested whether the PRL that is released in response to CS is responsible for the initiation and maintenance of the subsequent PRL surges. Thus, we injected OVX rats centrally or peripherally with ovine PRL (oPRL) at 2200 h. Central oPRL induced PRL surges in OVX rats that were similar in size and timing to those of CS rats, whereas peripheral oPRL induced surges that were of smaller amplitude and delayed. We then infused a PRL antagonist (S179D, 0.1 ng/h) centrally into OVX and OVX-CS rats and measured the release of endogenous PRL and the activity of neuroendocrine dopaminergic neurons. Central infusion of S179D did not influence basal PRL secretion in OVX rats but prevented the expression of the CS-induced PRL surges and the accompanying noontime increase of CS-induced dopaminergic activity when continued for 3 d. However, central infusion of S179D only on the day of CS did not prevent the daily rhythm of PRL surges. These results demonstrate that PRL acts centrally to induce the PRL rhythm and that PRL in the brain is essential for the maintenance but not for the initiation of the CS-induced rhythmic PRL surges.

  15. The Role of Prolactin in Mammary Carcinoma

    PubMed Central

    CLEVENGER, CHARLES V.; FURTH, PRISCILLA A.; HANKINSON, SUSAN E.; SCHULER, LINDA A.

    2006-01-01

    The contribution of prolactin (PRL) to the pathogenesis and progression of human breast cancer at the cellular, transgenic, and epidemiological levels is increasingly appreciated. Acting at the endocrine and autocrine/paracrine levels, PRL functions to stimulate the growth and motility of human breast cancer cells. The actions of this ligand are mediated by at least six recognized PRL receptor isoforms found on, or secreted by, human breast epithelium. The PRL/PRL receptor complex associates with and activates several signaling networks that are shared with other members of the cytokine receptor superfamily. Coupled with the recently identified intranuclear function of PRL, these networks are integrated into the in vitro and in vivo actions induced by ligand. These findings indicate that antagonists of PRL/PRL receptor interaction or PRL receptor-associated signal transduction may be of considerable utility in the treatment of human breast cancer. PMID:12588805

  16. Prolactin receptor in regulation of neuronal excitability and channels.

    PubMed

    Patil, Mayur J; Henry, Michael A; Akopian, Armen N

    2014-01-01

    Prolactin (PRL) activates PRL receptor isoforms to exert regulation of specific neuronal circuitries, and to control numerous physiological and clinically-relevant functions including; maternal behavior, energy balance and food intake, stress and trauma responses, anxiety, neurogenesis, migraine and pain. PRL controls these critical functions by regulating receptor potential thresholds, neuronal excitability and/or neurotransmission efficiency. PRL also influences neuronal functions via activation of certain neurons, resulting in Ca(2+) influx and/or electrical firing with subsequent release of neurotransmitters. Although PRL was identified almost a century ago, very little specific information is known about how PRL regulates neuronal functions. Nevertheless, important initial steps have recently been made including the identification of PRL-induced transient signaling pathways in neurons and the modulation of neuronal transient receptor potential (TRP) and Ca(2+) -dependent K(+) channels by PRL. In this review, we summarize current knowledge and recent progress in understanding the regulation of neuronal excitability and channels by PRL.

  17. Hormonal regulation of prolactin receptors in male rat target tissues: the effect of hypothyroidism and adrenalectomy.

    PubMed

    Kharroubi, A T; Slaunwhite, W R

    1984-10-01

    The effects of hypothyroidism and adrenalectomy (ADX) on PRL receptors as well as the subcellular distribution of PRL-binding sites in adult male rat target tissues were investigated. In ventral prostate, kidney, and adrenal, PRL-binding activity was enriched in the 15,000 X g pellet (mitochondrial/Golgi fraction). The zona fasiculata/reticularis plus medulla of the adrenal had higher PRL-binding activity than the zona glomerulosa (plus capsule). Propylthiouracil-induced hypothyroidism significantly decreased PRL binding to kidney (65%) and testis (50%), and 16-h replacement with T4 restored PRL binding to control levels. T4 was, however, without effect on renal PRL binding in hypothyroid castrated rats, indicating that androgen may be required for this response. The increase in PRL binding to ventral prostate and adrenal due to hypothyroidism was not reversed within 16 h of T4 injection, whereas T3 injection decreased PRL binding to ventral prostate within 12 h. ADX increased PRL binding to rat testis (38%) and kidney (18%), and 5-day replacement with dexamethasone decreased PRL binding to levels lower than those in control rats. ADX had no effect, and dexamethasone treatment decreased (16-20%) PRL binding to ventral prostate and hCG binding to rat testis. The modulation of PRL receptors by hypothyroidism and ADX suggests that thyroid and adrenal hormones play a role in the regulation of PRL receptors. PMID:6090097

  18. Regulation of Transcription Factors and Repression of Sp1 by Prolactin Signaling Through the Short Isoform of Its Cognate Receptor

    PubMed Central

    Devi, Y. Sangeeta; Shehu, Aurora; Stocco, Carlos; Halperin, Julia; Le, Jamie; Seibold, Anita M.; Lahav, Michal; Binart, Nadine; Gibori, Geula

    2009-01-01

    Prolactin (PRL) affects the development and function of the reproductive system by binding to two types of receptors, which differ by the size of their intracellular domain in rodents. Whereas the signaling pathway through the long form of the receptor (PRL-RL) is well characterized, signaling through the short form (PRL-RS) remains obscure. In this investigation, we examined transcription factors regulated by PRL in the ovary and decidua of mice expressing only PRL-RS in a PRL receptor null background. These mice provide a powerful in vivo model to study the selective signaling mechanism of PRL through PRL-RS independent of PRL-RL. We also examined the regulation of transcription factors in ovarian and uterine cell lines stably transfected with PRL-RS or PRL-RL. We focused our investigation on transcription factors similarly regulated in both these tissues and clearly established that signaling through PRL-RS does not activate the JaK/Stat in vivo but leads to severe down-regulation of Sp1 expression, DNA binding activity, and nuclear localization, events that appear to involve the calmodulin-dependent protein kinase pathway. Our in vivo and in culture data demonstrate that the PRL-RS activates a signaling pathway distinct from that of the PRL-RL. PMID:19342455

  19. Autocrine Positive Feedback Regulation of Prolactin Release From Tilapia Prolactin Cells and Its Modulation by Extracellular Osmolality.

    PubMed

    Yamaguchi, Yoko; Moriyama, Shunsuke; Lerner, Darren T; Grau, E Gordon; Seale, Andre P

    2016-09-01

    Prolactin (PRL) is a vertebrate hormone with diverse actions in osmoregulation, metabolism, reproduction, and in growth and development. Osmoregulation is fundamental to maintaining the functional structure of the macromolecules that conduct the business of life. In teleost fish, PRL plays a critical role in osmoregulation in fresh water. Appropriately, PRL cells of the tilapia are directly osmosensitive, with PRL secretion increasing as extracellular osmolality falls. Using a model system that employs dispersed PRL cells from the euryhaline teleost fish, Oreochromis mossambicus, we investigated the autocrine regulation of PRL cell function. Unknown was whether these PRL cells might also be sensitive to autocrine feedback and whether possible autocrine regulation might interact with the well-established regulation by physiologically relevant changes in extracellular osmolality. In the cell-perfusion system, ovine PRL and two isoforms of tilapia PRL (tPRL), tPRL177 and tPRL188, stimulated the release of tPRLs from the dispersed PRL cells. These effects were significant within 5-10 minutes and lasted the entire course of exposure, ceasing within 5-10 minutes of removal of tested PRLs from the perifusion medium. The magnitude of response varied between tPRL177 and tPRL188 and was modulated by extracellular osmolality. On the other hand, the gene expression of tPRLs was mainly unchanged or suppressed by static incubations of PRL cells with added PRLs. By demonstrating the regulatory complexity driven by positive autocrine feedback and its interaction with osmotic stimuli, these findings expand upon the knowledge that pituitary PRL cells are regulated complexly through multiple factors and interactions. PMID:27379370

  20. The orphan nuclear receptor Nur77 regulates decidual prolactin expression in human endometrial stromal cells

    SciTech Connect

    Jiang, Yue; Hu, Yali; Zhao, Jing; Zhen, Xin; Yan, Guijun; Sun, Haixiang

    2011-01-14

    Research highlights: {yields} Decidually produced PRL plays a key role during pregnancy. {yields} Overexpression of Nur77 increased PRL mRNA expression and enhanced decidual PRL promoter activity. {yields} Knockdown of Nur77 decreased decidual PRL secretion induced by 8-Br-cAMP and MPA. {yields} Nur77 is a novel transcription factor that plays an active role in decidual prolactin expression. -- Abstract: Prolactin (PRL) is synthesized and released by several extrapituitary tissues, including decidualized stromal cells. Despite the important role of decidual PRL during pregnancy, little is understood about the factors involved in the proper regulation of decidual PRL expression. Here we present evidence that the transcription factor Nur77 plays an active role in decidual prolactin expression in human endometrial stromal cells (hESCs). Nur77 mRNA expression in hESCs was significantly increased after decidualization stimulated by 8-Br-cAMP and medroxyprogesterone acetate (MPA). Adenovirus-mediated overexpression of Nur77 in hESCs markedly increased PRL mRNA expression and enhanced decidual PRL promoter (dPRL/-332Luc) activity in a concentration-dependent manner. Furthermore, knockdown of Nur77 in hESCs significantly decreased decidual PRL promoter activation and substantially attenuated PRL mRNA expression and PRL secretion (P < 0.01) induced by 8-Br-cAMP and MPA. These results demonstrate that Nur77 is a novel transcription factor that contributes significantly to the regulation of prolactin gene expression in human endometrial stromal cells.

  1. Effects of age and reproductive experience on the distribution of prolactin and growth hormone secreting cells in the anterior pituitary of a passerine.

    PubMed

    Christensen, Debora; Vleck, Carol M

    2015-10-01

    Plasma prolactin (PRL) is released from lactotrophs in the anterior pituitary. As plasma PRL levels rise during incubation in domestic fowl, the number of lactotrophs (PRL-immunoreactive, PRL-IR cells) increases while the number of growth hormone secreting cells, somatotrophs (GH-IR cells), declines. We measured plasma PRL levels using radioimmunoassay (RIA) and examined the distribution of lactotrophs and somatotrophs in the anterior pituitary of breeding and nonbreeding zebra finches of known ages with and without prior breeding experience using fluorescent immunohistochemistry (IHC). Plasma PRL levels were higher in breeding than in nonbreeding birds, regardless of age, sex, or previous breeding history. PRL-IR cells were localized primarily, but not exclusively, to the cephalic aspect of the anterior pituitary (AP) and along the ventral margin. Birds with prior reproductive experience had more PRL-IR cells than birds with no prior reproductive experience and breeders had slightly higher PRL-IR cell counts than did nonbreeders, but there was no correlation between the number of PRL-IR cells and plasma PRL levels. GH-IR cells were concentrated in the caudal aspect of the AP with some cells in the cephalic lobe, but numbers did not differ between any of the groups studied. An increase in PRL-IR cells corresponded with an increase in GH-IR cells. An increase in lactotroph number with reproductive experience in zebra finches may facilitate future reproductive events by allowing for more robust PRL secretion and increased reproductive success.

  2. Human and murine prostate basal/stem cells are not direct targets of prolactin.

    PubMed

    Sackmann-Sala, Lucila; Angelergues, Antoine; Boutillon, Florence; d'Acremont, Bruno; Maidenberg, Marc; Oudard, Stéphane; Goffin, Vincent

    2015-09-01

    Local overexpression of prolactin (PRL) in the prostate of Pb-PRL transgenic mice induces benign prostate tumors exhibiting marked amplification of the epithelial basal/stem cell compartment. However, PRL-activated intracellular signaling seems to be restricted to luminal cells, suggesting that basal/stem cells may not be direct targets of PRL. Given their described role as prostate cancer-initiating cells, it is important to understand the mechanisms that regulate basal/stem cells. In this study, we evaluated whether PRL can act directly on these cells, by growing them as prostaspheres. For this, primary 3D prostasphere cultures were prepared from unfractionated cells isolated from freshly harvested human and mouse benign prostate tissues and subjected to PRL stimulation in vitro. None of the various concentrations of PRL tested showed any effects on the sizes or numbers of the prostaspheres generated. In addition, neither activation of canonical PRL-induced signaling pathways (Stat5, Stat3 or Erk1/2) nor increased expression of the proliferation marker Ki-67 were detected by immunostaining in PRL-stimulated prostaspheres. Consistent with the absence of response, PRL receptor mRNA levels were generally undetectable in mouse sphere cells. We conclude that human and mouse prostate basal/stem cells are not direct targets of PRL action. The observed amplification of basal/stem cells in Pb-PRL prostates might be due to paracrine mechanisms originating from PRL action on other cell compartments. Our current efforts are aimed at unraveling these mechanisms.

  3. Receptor-mediated mechanism for the transport of prolactin from blood to cerebrospinal fluid

    SciTech Connect

    Walsh, R.J.; Slaby, F.J.; Posner, B.I.

    1987-05-01

    Prolactin (PRL) interacts with areas of the central nervous system which reside behind the blood-brain barrier. While vascular PRL does not cross this barrier, it is readily accessible to the cerebrospinal fluid (CSF) from which it may gain access to the PRL-responsive areas of the brain. Studies were undertaken to characterize the mechanism responsible for the translocation of PRL from blood to CSF. Rats were given external jugular vein injections of (/sup 125/-I)iodo-PRL in the presence or absence of an excess of unlabeled ovine PRL (oPRL), human GH, bovine GH, or porcine insulin. CSF and choroid plexus were removed 60 min later. CSF samples were electrophoresed on sodium dodecyl sulfate-polyacrylamide slab gels and resultant autoradiographs were analyzed with quantitative microdensitometry. The data revealed that unlabeled lactogenic hormones, viz. oPRL and human GH, caused a statistically significant inhibition of (/sup 125/I)iodo-PRL transport from blood to CSF. In contrast, nonlactogenic hormones, viz bovine GH and insulin, had no effect on (/sup 125/I)iodo-PRL transport into the CSF. An identical pattern of competition was observed in the binding of hormone to the choroid plexus. Furthermore, vascular injections of (/sup 125/I)iodo-PRL administered with a range of concentrations of unlabeled oPRL revealed a dose-response inhibition in the transport of (/sup 125/I)iodo-PRL from blood to CSF. The study demonstrates that PRL enters the CSF by a specific, PRL receptor-mediated transport mechanism. The data is consistent with the hypothesis that the transport mechanism resides at the choroid plexus. The existence of this transport mechanism reflects the importance of the cerebroventricular system in PRL-brain interactions.

  4. Prolactin acts on the hypothalamic-pituitary axis to modulate follicle-stimulating hormone gene expression in the female brushtail possum (Trichosurus vulpecula).

    PubMed

    Crawford, J L; Mester, B; Thomson, B; Lawrence, S B; Eckery, D C

    2011-03-01

    Brushtail possums exhibit a distinct preovulatory pattern of prolactin (Prl) secretion suggesting that Prl is involved in normal reproductive function. In some mammals, Prl is essential for corpus luteum (CL) function and/or modulation of steroidal effects on hypothalamic-pituitary activity. The aim of this study was to test the effects of biologically active recombinant possum Prl (recPosPrl) on both pituitary gland and CL function in possums. To confirm biological activity, administration of recPosPrl-N2C1 (10 μg) resulted in an 18-fold stimulation (P<0.05) of progesterone (P(4)) production by possum granulosa cells in vitro. Based on these findings, minipumps containing either recPosPrl-N2C1 (n=10) or saline (n=8) were inserted into lactating female possums. The expression levels of pituitary-derived PRL, LHB, FSHB and GNRHR and CL-derived LHR mRNA were quantified. Following a resumption of reproductive activity, no differences in ovulation incidence or plasma Prl concentrations were observed. Plasma Prl levels were less variable (P<0.001) in Prl-treated possums, confirming a self-regulatory role for Prl in this species. There was a marked down-regulation (P<0.001) of FSHB mRNA at the mid-luteal stage in Prl-treated possums, whereas mean PRL, LHB, GNRHR and LHR mRNA expression levels were not different between experimental groups. Plasma P(4) concentrations were not different (P=0.05) in Prl-treated possums, although tended to be higher in the peri-ovulatory and early-luteal phase. We conclude in the brushtail possum that Prl is self-regulated via a short-feedback loop common to all mammals studied and is able to modulate FSHB expression probably at the level of the hypothalamus and/or pituitary gland.

  5. A Prolactin Family Paralog Regulates Placental Adaptations to a Physiological Stressor.

    PubMed

    Bu, Pengli; Alam, Sheikh M Khorshed; Dhakal, Pramod; Vivian, Jay L; Soares, Michael J

    2016-05-01

    The prolactin (PRL) family of hormones and cytokines participates in the regulation of optimal reproductive performance in the mouse and rat. Members of the PRL family are expressed in the anterior pituitary, uterus, and/or placenta. In the present study, we investigated the ontogeny of PRL family 7, subfamily b, member 1 (PRL7B1; also called PRL-like protein-N, PLP-N) expression in the developing mouse placenta and established a mouse model for investigating the biological function of PRL7B1. Transcripts for Prl7b1 were first detected on Gestation Day (d) 8.5. From gestation d8.5 through d14.5, Prl7b1 was expressed in trophoblast cells residing at the interface between maternal mesometrial decidua and the developing placenta. On gestation d17.5, the predominant cellular source of Prl7b1 mRNA was migratory trophoblast cells invading into the uterine mesometrial decidua. The Prl7b1 null mutant allele was generated via replacement of the endogenous Prl7b1 coding sequence with beta-galactosidase (LacZ) reporter and neomycin cassettes. The mutant Prl7b1 allele was successfully passed through the germline. Homozygous Prl7b1 mutant mice were viable and fertile. Under standard animal housing conditions, Prl7b1 had undetectable effects on placentation and pregnancy. Hypoxia exposure during pregnancy evoked adaptations in the organization of the wild-type placenta that were not observed in Prl7b1 null placentation sites. In summary, PRL7B1 is viewed as a part of a pathway regulating placental adaptations to physiological stressors.

  6. Prolactin regulates transcription of the ion uptake Na+/Cl- cotransporter (ncc) gene in zebrafish gill

    USGS Publications Warehouse

    Breves, Jason P.; Serizier, Sandy B.; Goffin, Vincent; McCormick, Stephen D.; Karlstrom, Rolf O.

    2013-01-01

    Prolactin (PRL) is a well-known regulator of ion and water transport within osmoregulatory tissues across vertebrate species, yet how PRL acts on some of its target tissues remains poorly understood. Using zebrafish as a model, we show that ionocytes in the gill directly respond to systemic PRL to regulate mechanisms of ion uptake. Ion-poor conditions led to increases in the expression of PRL receptor (prlra), Na+/Cl− cotransporter (ncc; slc12a10.2), Na+/H+ exchanger (nhe3b; slc9a3.2), and epithelial Ca2+ channel (ecac; trpv6) transcripts within the gill. Intraperitoneal injection of ovine PRL (oPRL) increased ncc and prlra transcripts, but did not affect nhe3b or ecac. Consistent with direct PRL action in the gill, addition of oPRL to cultured gill filaments stimulated ncc in a concentration-dependent manner, an effect blocked by a pure human PRL receptor antagonist (Δ1-9-G129R-hPRL). These results suggest that PRL signaling through PRL receptors in the gill regulates the expression of ncc, thereby linking this pituitary hormone with an effector of Cl− uptake in zebrafish for the first time.

  7. Prolactin regulates transcription of the ion uptake Na+/Cl− cotransporter (ncc) gene in zebrafish gill

    PubMed Central

    Breves, Jason P.; Serizier, Sandy B.; Goffin, Vincent; McCormick, Stephen D.; Karlstrom, Rolf O.

    2013-01-01

    Prolactin (PRL) is a well-known regulator of ion and water transport within osmoregulatory tissues across vertebrate species, yet how PRL acts on some of its target tissues remains poorly understood. Using zebrafish as a model, we show that ionocytes in the gill directly respond to systemic PRL to regulate mechanisms of ion uptake. Ion-poor conditions led to increases in the expression of PRL receptor (prlra), Na+/Cl− cotransporter (ncc; slc12a10.2), Na+/H+ exchanger (nhe3b; slc9a3.2), and epithelial Ca2+ channel (ecac; trpv6) transcripts within the gill. Intraperitoneal injection of ovine PRL (oPRL) increased ncc and prlra transcripts, but did not affect nhe3b or ecac. Consistent with direct PRL action in the gill, addition of oPRL to cultured gill filaments stimulated ncc in a concentration-dependent manner, an effect blocked by a pure human PRL receptor antagonist (Δ1-9-G129R-hPRL). These results suggest that PRL signaling through PRL receptors in the gill regulates the expression of ncc, thereby linking this pituitary hormone with an effector of Cl− uptake in zebrafish for the first time. PMID:23395804

  8. Role of Prolactin Receptors in Lymphangioleiomyomatosis

    PubMed Central

    Alkharusi, Amira; Lesma, Elena; Ancona, Silvia; Chiaramonte, Eloisa; Nyström, Thomas; Gorio, Alfredo; Norstedt, Gunnar

    2016-01-01

    Pulmonary lymphangioleiomyomatosis (LAM) is a rare lung disease caused by mutations in the tumor suppressor genes encoding Tuberous Sclerosis Complex (TSC) 1 and TSC2. The protein product of the TSC2 gene is a well-known suppressor of the mTOR pathway. Emerging evidence suggests that the pituitary hormone prolactin (Prl) has both endocrine and paracrine modes of action. Here, we have investigated components of the Prl system in models for LAM. In a TSC2 (+/-) mouse sarcoma cell line, down-regulation of TSC2 using siRNA resulted in increased levels of the Prl receptor. In human LAM cells, the Prl receptor is detectable by immunohistochemistry, and the expression of Prl in these cells stimulates STAT3 and Erk phosphorylation, as well as proliferation. A high affinity Prl receptor antagonist consisting of Prl with four amino acid substitutions reduced phosphorylation of STAT3 and Erk. Antagonist treatment further reduced the proliferative and invasive properties of LAM cells. In histological sections from LAM patients, Prl receptor immuno reactivity was observed. We conclude that the Prl receptor is expressed in LAM, and that loss of TSC2 increases Prl receptor levels. It is proposed that Prl exerts growth-stimulatory effects on LAM cells, and that antagonizing the Prl receptor can block such effects. PMID:26765535

  9. MATERNAL EXPOSURE TO ATRAZINE DURING LACTATION SUPPRESSES SUCKLING-INDUCED PROLACTIN RELEASE AND RESULTS IN PROSTATITIS IN THE ADULT OFFSPRING

    EPA Science Inventory

    The availability of prolactin (PRL) to the neonatal brain is known to affect the development of the tuberoinfundibular (TIDA) neurons and, as a consequence, lead to alterations in subsequent PRL regulation. Without early lactational exposure to PRL (derived from the dam's milk), ...

  10. Heat stress abatement during the dry period influences prolactin signaling in lymphocytes Heat stress abatement during the dry period influences prolactin signaling in lymphocytes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Heat stress perturbs PRL release and affects dairy cow lactational performance and immune cell function. We hypothesized that greater PRL concentration in plasma of heat-stressed cows would decrease expression of PRL-R mRNA and increase mRNA expression of suppressors of cytokine signaling (SOCS) in ...

  11. Relative prolactin-to-progesterone concentrations around farrowing influence colostrum yield in primiparous sows.

    PubMed

    Loisel, F; Farmer, C; van Hees, H; Quesnel, H

    2015-10-01

    In swine, colostrum production is induced by the drop of progesterone (P4) concentrations which leads to the prepartum peak of prolactin (PRL). PRL regulates mammary cell turnover and stimulates lacteal nutrient synthesis. P4 inhibits PRL secretion and downregulates the PRL receptor in the mammary gland. The aim of the present study was to determine if the relative prepartum concentrations of P4 and PRL (PRL/P4 ratio) influence sow colostrum production. The performance of 29 Landrace × Large White primiparous sows was analyzed. Colostrum yield was estimated during 24 h starting at the onset of parturition (T0) using litter weight gains. Colostrum was collected at T0 and 24 h later (T24). Repeated jugular blood samples were collected during the peripartum period, that is, from -72 to +24 h related to farrowing and were assayed for P4 and PRL. Sows were retrospectively categorized in 2 groups according to their PRL/P4 ratio 24 h before farrowing being either <2 (low PRL/P4, n = 16) or >3 (high PRL/P4, n = 13). During the peripartum period, the circulating concentrations of P4 were lower (P < 0.05) and those of PRL tended to be greater (P < 0.10) in high PRL/P4 compared with low PRL/P4 sows. Colostrum yield was greater in high PRL/P4 compared with low PRL/P4 sows (4.11 vs 3.48 kg [root mean square error = 0.69], P < 0.05). Colostrum composition (dry matter, energy, protein, lipid, and lactose contents) and IgG and IgA concentrations did not differ between the 2 groups of sows (P > 0.10). The Na/K ratio in colostrum 24 h after the onset of farrowing was lower in high PRL/P4 compared with low PRL/P4 sows (P < 0.05). Piglet mortality between birth and T24 averaged 10.0% in low PRL/P4 litters and 7.0% in high PRL/P4 litters (P = 0.29). In conclusion, a greater PRL/P4 ratio 24 h prepartum, characterized by lower P4 concentrations and a trend for greater PRL concentrations peripartum, led to increased colostrum yield in primiparous sows.

  12. Prolactin messenger ribonucleic acid levels, prolactin synthesis, and radioimmunoassayable prolactin during the estrous cycle in the Golden Syrian hamster

    SciTech Connect

    Massa, J.S. ); Blask, D.E. )

    1990-01-01

    The purpose of this study was to observe the molecular dynamics of pituitary prolactin (PRL) gene expression during the estrous cycle of the Golden Syrian hamster. PRL messenger ribonucleic acid (mRNA) levels, PRL synthesis were measured in the morning on each day of the cycle. We observed that all of these PRL indices declined or did not change from Day 2 to Day 3 of the cycle. From Day 3 to Day 4 however, PRL mRNA levels increased 33-38% and media {sup 3}H-PRL increased 32-42%, while there were no significant changes in pituitary {sup 3}H-PRL, or RIA-PRL in the media or pituitary. From Day 4 to Day 1 (estrus) there was reciprocal change in the levels of {sup 3}H-PRL in the pituitary vs. the media, with the former increasing 37-50% and the latter decreasing 25-32%. Pituitary RIA-PRL did also increased 45-64% from Day 4 to Day 1 while media RIA-PRL did not change. These data are consistent with the following hypothesis: On the morning of proestrus(Day 4) in the hamster, PRL mRNA levels are elevated compared to those on Day 3, signaling an increase in PRL synthesis. This newly synthesized PRL is shunted into a readily releasable pool on the morning of Day 4 (contributing to the afternoon surge of serum PRL), and into a preferentially stored pool by the morning of Day 1.

  13. Prolactin receptor attenuation induces zinc pool redistribution through ZnT2 and decreases invasion in MDA-MB-453 breast cancer cells

    SciTech Connect

    Bostanci, Zeynep; Alam, Samina; Soybel, David I.; Kelleher, Shannon L.

    2014-02-15

    Prolactin receptor (PRL-R) activation regulates cell differentiation, proliferation, cell survival and motility of breast cells. Prolactin (PRL) and PRL-R over-expression are strongly implicated in breast cancer, particularly contributing to tumor growth and invasion in the more aggressive estrogen-receptor negative (ER−) disease. PRL-R antagonists have been suggested as potential therapeutic agents; however, mechanisms through which PRL-R antagonists exert their actions are not well-understood. Zinc (Zn) is a regulatory factor for over 10% of the proteome, regulating critical cell processes such as proliferation, cell signaling, transcription, apoptosis and autophagy. PRL-R signaling regulates Zn metabolism in breast cells. Herein we determined effects of PRL-R attenuation on cellular Zn metabolism and cell function in a model of ER-, PRL-R over-expressing breast cancer cells (MDA-MB-453). PRL-R attenuation post-transcriptionally increased ZnT2 abundance and redistributed intracellular Zn pools into lysosomes and mitochondria. ZnT2-mediated lysosomal Zn sequestration was associated with reduced matrix metalloproteinase 2 (MMP-2) activity and decreased invasion. ZnT2-mediated Zn accumulation in mitochondria was associated with increased mitochondrial oxidation. Our results suggest that PRL-R antagonism in PRL-R over-expressing breast cancer cells may reduce invasion through the redistribution of intracellular Zn pools critical for cellular function. - Highlights: • PRL-R attenuation increased ZnT2 expression. • PRL-R attenuation increased lysosomal and mitochondrial Zn accumulation. • PRL-R attenuation decreased MMP-2 and invasion. • PRL-R antagonists may modulate lysosomal and mitochondrial Zn pools.

  14. Prolactin-derived vasoinhibins increase anxiety- and depression-related behaviors.

    PubMed

    Zamorano, Miriam; Ledesma-Colunga, Maria G; Adán, Norma; Vera-Massieu, Camila; Lemini, Maria; Méndez, Isabel; Moreno-Carranza, Bibiana; Neumann, Inga D; Thebault, Stéphanie; Martínez de la Escalera, Gonzalo; Torner, Luz; Clapp, Carmen

    2014-06-01

    The hormone prolactin (PRL) regulates neuroendocrine and emotional stress responses. It is found in the hypothalamus, where the protein is partially cleaved to vasoinhibins, a family of N-terminal antiangiogenic PRL fragments ranging from 14 to 18kDa molecular masses, with unknown effects on the stress response. Here, we show that the intracerebroventricular administration of a recombinant vasoinhibin, containing the first 123 amino acids of human PRL that correspond to a 14kDa PRL, exerts anxiogenic and depressive-like effects detected in the elevated plus-maze, the open field, and the forced swimming tests. To investigate whether stressor exposure affects the generation of vasoinhibins in the hypothalamus, the concentrations of PRL mRNA, PRL, and vasoinhibins were evaluated in hypothalamic extracts of virgin female rats immobilized for 30min at different time points after stress onset. The hypothalamic levels of PRL mRNA and protein were higher at 60min but declined at 360min to levels seen in non-stressed animals. The elevation of hypothalamic PRL did not correlate with the stress-induced increase in circulating PRL levels, nor was it modified by blocking adenohypophyseal PRL secretion with bromocriptine. A vasoinhibin having an electrophoretic migration rate corresponding to 17kDa was detected in the hypothalamus. Despite the elevation in hypothalamic PRL, the levels of this hypothalamic vasoinhibin were similar in stressed and non-stressed rats. Stress reduced the rate of cleavage of PRL to this vasoinhibin as shown by the incubation of recombinant PRL with hypothalamic extracts from stressed rats. These results suggest that vasoinhibins are potent anxiogenic and depressive factors and that stress increases PRL levels in the hypothalamus partly by reducing its conversion to vasoinhibins. The reciprocal interplay between PRL and vasoinhibins may represent an effective mechanism to regulate anxiety and depression. PMID:24767626

  15. N-glycoprofiling analysis in a simple glycoprotein model: a comparison between recombinant and pituitary glycosylated human prolactin.

    PubMed

    Capone, Marcos V N; Suzuki, Miriam F; Oliveira, João E; Damiani, Renata; Soares, Carlos R J; Bartolini, Paolo

    2015-05-20

    Human prolactin (hPRL) is a polypeptide hormone occurring in the non-glycosylated (NG-hPRL) and glycosylated (G-hPRL) forms, with MM of approximately 23 and 25kDa, respectively. It has a single, partially occupied N-glycosylation site located at Asn-31, which makes it a particularly simple and interesting model for glycosylation studies. The bioactivity of G-hPRL is lower than that of NG-hPRL (by ca. 4-fold) and its physiological function is not clear. However, carbohydrate moieties generally play important roles in the biosynthesis, secretion, biological activity, and plasma survival of glycohormones and can vary depending on the host cell. The main objective of this study was to determine the N-glycan structures present in native, pituitary G-hPRL and compare them with those present in the recombinant hormone. To obtain recombinant G-hPRL, genetically modified Chinese hamster ovary cells (CHO), adapted to growth in suspension, were treated with cycloheximide, thus increasing the glycosylation site occupancy from 5.5% to 38.3%, thereby facilitating G-hPRL purification. CHO cell-derived G-hPRL (CHO-G-hPRL) was compared to pituitary G-hPRL (pit-G-hPRL) especially with regard to N-glycoprofiling. Among the main differences found in the pituitary sample were an extremely low presence of sialylated (1.7%) and a high percentage of sulfated (74.0%) and of fucosylated (90.5%) glycans. A ∼6-fold lower in vitro bioactivity and a higher clearance rate in mice were also found for pit-G-hPRL versus CHO-G-hPRL. N-Glycan profiling proved to be a useful and accurate methodology also for MM and carbohydrate content determination for the two G-hPRL preparations, in good agreement with the values obtained directly via MALDI-TOF-MS.

  16. Prolactin177, prolactin188 and prolactin receptor 2 in the pituitary of the euryhaline tilapia, Oreochromis mossambicus, are differentially osmosensitive.

    PubMed

    Seale, Andre P; Moorman, Benjamin P; Stagg, Jacob J; Breves, Jason P; Lerner, Darren T; Grau, E Gordon

    2012-04-01

    Two forms of prolactin (Prl), prolactin 177 (Prl(177)) and prolactin 188 (Prl(188)), are produced in the rostral pars distalis (RPD) of the pituitary gland of euryhaline Mozambique tilapia, Oreochromis mossambicus. Consistent with their roles in fresh water (FW) osmoregulation, release of both Prls is rapidly stimulated by hyposmotic stimuli, both in vivo and in vitro. We examined the concurrent dynamics of Prl(177) and Prl(188) hormone release and mRNA expression from Prl cells in response to changes in environmental salinity in vivo and to changes in extracellular osmolality in vitro. In addition, mRNA levels of Prl receptors 1 and 2 (prlr1 and prlr2) and osmotic stress transcription factor 1 (ostf1) were measured. Following transfer from seawater (SW) to FW, plasma osmolality decreased, while plasma levels of Prl(177) and Prl(188) and RPD mRNA levels of prl(177) and prl(188) increased. The opposite pattern was observed when fish were transferred from FW to SW. Moreover, hyposmotically induced release of Prl(188) was greater in Prl cells isolated from FW-acclimated fish after 6 h of incubation, while the hyposmotically induced increase in prl(188) mRNA levels was only observed in SW-acclimated fish. In addition, prlr2 and ostf1 mRNA levels in Prl cells from both FW- and SW-acclimated fish increased in direct proportion to increases in extracellular osmolality both in vivo and in vitro. Taken together, these results indicate that the osmosensitivity of the tilapia RPD is modulated by environmental salinity with respect to hormone release and gene expression.

  17. Prolactin-derived vasoinhibins increase anxiety- and depression-related behaviors.

    PubMed

    Zamorano, Miriam; Ledesma-Colunga, Maria G; Adán, Norma; Vera-Massieu, Camila; Lemini, Maria; Méndez, Isabel; Moreno-Carranza, Bibiana; Neumann, Inga D; Thebault, Stéphanie; Martínez de la Escalera, Gonzalo; Torner, Luz; Clapp, Carmen

    2014-06-01

    The hormone prolactin (PRL) regulates neuroendocrine and emotional stress responses. It is found in the hypothalamus, where the protein is partially cleaved to vasoinhibins, a family of N-terminal antiangiogenic PRL fragments ranging from 14 to 18kDa molecular masses, with unknown effects on the stress response. Here, we show that the intracerebroventricular administration of a recombinant vasoinhibin, containing the first 123 amino acids of human PRL that correspond to a 14kDa PRL, exerts anxiogenic and depressive-like effects detected in the elevated plus-maze, the open field, and the forced swimming tests. To investigate whether stressor exposure affects the generation of vasoinhibins in the hypothalamus, the concentrations of PRL mRNA, PRL, and vasoinhibins were evaluated in hypothalamic extracts of virgin female rats immobilized for 30min at different time points after stress onset. The hypothalamic levels of PRL mRNA and protein were higher at 60min but declined at 360min to levels seen in non-stressed animals. The elevation of hypothalamic PRL did not correlate with the stress-induced increase in circulating PRL levels, nor was it modified by blocking adenohypophyseal PRL secretion with bromocriptine. A vasoinhibin having an electrophoretic migration rate corresponding to 17kDa was detected in the hypothalamus. Despite the elevation in hypothalamic PRL, the levels of this hypothalamic vasoinhibin were similar in stressed and non-stressed rats. Stress reduced the rate of cleavage of PRL to this vasoinhibin as shown by the incubation of recombinant PRL with hypothalamic extracts from stressed rats. These results suggest that vasoinhibins are potent anxiogenic and depressive factors and that stress increases PRL levels in the hypothalamus partly by reducing its conversion to vasoinhibins. The reciprocal interplay between PRL and vasoinhibins may represent an effective mechanism to regulate anxiety and depression.

  18. Inhibition of MAPK by Prolactin Signaling through the Short Form of Its Receptor in the Ovary and Decidua

    PubMed Central

    Devi, Y. Sangeeta; Seibold, Anita M.; Shehu, Aurora; Maizels, Evelyn; Halperin, Julia; Le, Jamie; Binart, Nadine; Bao, Lei; Gibori, Geula

    2011-01-01

    Prolactin (PRL) is essential for normal reproduction and signals through two types of receptors, the short (PRL-RS) and long (PRL-RL) form. We have previously shown that transgenic mice expressing only PRL-RS (PRLR−/−RS) display abnormal follicular development and premature ovarian failure. Here, we report that MAPK, essential for normal follicular development, is critically inhibited by PRL in reproductive tissues of PRLR−/−RS mice. Consequently, the phosphorylation of MAPK downstream targets are also markedly inhibited by PRL without affecting immediate upstream kinases, suggesting involvement of MAPK specific phosphatase(s) in this inhibition. Similar results are obtained in a PRL-responsive ovary-derived cell line (GG-CL) that expresses only PRL-RS. However, we found the expression/activation of several known MAPK phosphatases not to be affected by PRL, suggesting a role of unidentified phosphatase(s). We detected a 27-kDa protein that binds to the intracellular domain of PRL-RS and identified it as dual specific phosphatase DUPD1. PRL does not induce expression of DUDP1 but represses its phosphorylation on Thr-155. We also show a physical association of this phosphatase with ERK1/2 and p38 MAPK. Using an in vitro phosphatase assay and overexpression studies, we established that DUPD1 is a MAPK phosphatase. Dual specific phosphatase inhibitors as well as siRNA to DUPD1, completely prevent PRL-mediated MAPK inhibition in ovarian cells. Our results strongly suggest that deactivation of MAPK by PRL/PRL-RS contributes to the severe ovarian defect in PRLR−/−RS mice and demonstrate the novel association of PRL-RS with DUPD1 and a role for this phosphatase in MAPK deactivation. PMID:21199871

  19. Completely Humanizing Prolactin Rescues Infertility in Prolactin Knockout Mice and Leads to Human Prolactin Expression in Extrapituitary Mouse Tissues

    PubMed Central

    Christensen, Heather R.; Murawsky, Michael K.; Horseman, Nelson D.; Willson, Tara A.

    2013-01-01

    A variety of fundamental differences have evolved in the physiology of the human and rodent prolactin (PRL) systems. The PRL gene in humans and other primates contains an alternative promoter, 5.8 kbp upstream of the pituitary transcription start site, which drives expression of PRL in “extrapituitary” tissues, where PRL is believed to exert local, or paracrine, actions. Several of these extrapituitary PRL tissues serve a reproductive function (eg, mammary gland, decidua, prostate, etc), consistent with the hypothesis that local PRL production may be involved in, and required for, normal reproductive physiology in primates. Rodent research models have generated significant findings regarding the role of PRL in reproduction. Specifically, disruption (knockout) of either the PRL gene or its receptor causes profound female reproductive defects at several levels (ovaries, preimplantation endometrium, mammary glands). However, the rodent PRL gene differs significantly from the human, most notably lacking the alternative promoter. Understanding of the physiological regulation and function of extrapituitary PRL has been limited by the absence of a readily accessible experimental model, because the rodent PRL gene does not contain the alternative promoter. To overcome these limitations, we have generated mice that have been “humanized” with regard to the structural gene and tissue expression of PRL. Here, we present the characterization of these animals, demonstrating that the human PRL transgene is responsive to known physiological regulators both in vitro and in vivo. More importantly, the expression of the human PRL transgene is able to rescue the reproductive defects observed in mouse PRL knockout (mPRL−) females, validating their usefulness in studying the function or regulation of this hormone in a manner that is relevant to human physiology. PMID:24029242

  20. Protein tyrosine phosphatase of liver regeneration-1 is required for normal timing of cell cycle progression during liver regeneration.

    PubMed

    Jiao, Yang; Ye, Diana Z; Li, Zhaoyu; Teta-Bissett, Monica; Peng, Yong; Taub, Rebecca; Greenbaum, Linda E; Kaestner, Klaus H

    2015-01-15

    Protein tyrosine phosphatase of liver regeneration-1 (Prl-1) is an immediate-early gene that is significantly induced during liver regeneration. Several in vitro studies have suggested that Prl-1 is important for the regulation of cell cycle progression. To evaluate its function in liver regeneration, we ablated the Prl-1 gene specifically in mouse hepatocytes using the Cre-loxP system. Prl-1 mutant mice (Prl-1(loxP/loxP);AlfpCre) appeared normal and fertile. Liver size and metabolic function in Prl-1 mutants were comparable to controls, indicating that Prl-1 is dispensable for liver development, postnatal growth, and hepatocyte differentiation. Mutant mice demonstrated a delay in DNA synthesis after 70% partial hepatectomy, although ultimate liver mass restoration was not affected. At 40 h posthepatectomy, reduced protein levels of the cell cycle regulators cyclin E, cyclin A2, cyclin B1, and cyclin-dependent kinase 1 were observed in Prl-1 mutant liver. Investigation of the major signaling pathways involved in liver regeneration demonstrated that phosphorylation of protein kinase B (AKT) and signal transducer and activator of transcription (STAT) 3 were significantly reduced at 40 h posthepatectomy in Prl-1 mutants. Taken together, this study provides evidence that Prl-1 is required for proper timing of liver regeneration after partial hepatectomy. Prl-1 promotes G1/S progression via modulating expression of several cell cycle regulators through activation of the AKT and STAT3 signaling pathway.

  1. Effect of extracellular osmolality and ionic levels on pituitary prolactin release in euryhaline silver sea bream (Sparus sarba).

    PubMed

    Kwong, Anna K Y; Ng, Andus H Y; Leung, L Y; Man, Angel K Y; Woo, Norman Y S

    2009-01-01

    In many euryhaline fish, prolactin (PRL) plays a key role in freshwater adaptation. Consistent with this function, the present study showed a remarkable reduction in pituitary PRL content of silver sea bream abruptly transferred to low salinity (6ppt). This reduction in pituitary PRL content followed closely the temporal changes in serum osmolality and ion levels. Serum osmolality, Na(+) and Cl(-) levels of silver sea bream abruptly transferred to hyposmotic salinity (6ppt) were markedly reduced 2h after the transfer. The decline in pituitary PRL content lagged behind the serum changes implying that reduction in pituitary PRL content is a response to the drop in serum ion levels and osmotic pressure. Silver sea bream pituitary cells were dispersed and exposed to a medium with reduced ion levels and osmolality in vitro, and PRL released from pituitary cells was significantly elevated. In hyposmotic exposed anterior pituitary cells, cell volume exhibited a 20% increase when exposed to a medium with a 20% decrease in osmolality. The enlarged pituitary cells did not shrink until the surrounding hyposmotic medium was replaced, a phenomenon suggesting an osmosensing ability of silver sea bream PRL cells for PRL secretion in response to a change in extracellular osmotic pressure. The decrease in pituitary PRL content in vivo and stimulated pituitary PRL release in vitro under reduced osmolality together suggest hyposmotic exposure triggers PRL release from the pituitary. PMID:19027016

  2. Protein tyrosine phosphatase of liver regeneration-1 is required for normal timing of cell cycle progression during liver regeneration

    PubMed Central

    Jiao, Yang; Ye, Diana Z.; Li, Zhaoyu; Teta-Bissett, Monica; Peng, Yong; Taub, Rebecca; Greenbaum, Linda E.

    2014-01-01

    Protein tyrosine phosphatase of liver regeneration-1 (Prl-1) is an immediate-early gene that is significantly induced during liver regeneration. Several in vitro studies have suggested that Prl-1 is important for the regulation of cell cycle progression. To evaluate its function in liver regeneration, we ablated the Prl-1 gene specifically in mouse hepatocytes using the Cre-loxP system. Prl-1 mutant mice (Prl-1loxP/loxP;AlfpCre) appeared normal and fertile. Liver size and metabolic function in Prl-1 mutants were comparable to controls, indicating that Prl-1 is dispensable for liver development, postnatal growth, and hepatocyte differentiation. Mutant mice demonstrated a delay in DNA synthesis after 70% partial hepatectomy, although ultimate liver mass restoration was not affected. At 40 h posthepatectomy, reduced protein levels of the cell cycle regulators cyclin E, cyclin A2, cyclin B1, and cyclin-dependent kinase 1 were observed in Prl-1 mutant liver. Investigation of the major signaling pathways involved in liver regeneration demonstrated that phosphorylation of protein kinase B (AKT) and signal transducer and activator of transcription (STAT) 3 were significantly reduced at 40 h posthepatectomy in Prl-1 mutants. Taken together, this study provides evidence that Prl-1 is required for proper timing of liver regeneration after partial hepatectomy. Prl-1 promotes G1/S progression via modulating expression of several cell cycle regulators through activation of the AKT and STAT3 signaling pathway. PMID:25377314

  3. Tilapia prolactin: molecular cloning of two cDNAs and expression in Escherichia coli.

    PubMed

    Rentier-Delrue, F; Swennen, D; Prunet, P; Lion, M; Martial, J A

    1989-05-01

    We have isolated cDNA clones encoding tilapia prolactin (tiPRL) from a cDNA library prepared from tilapia (Oreochromis niloticus) anterior pituitary glands. A trout PRL cDNA fragment was used as hybridization probe to select the recombinant plasmids carrying the tiPRL coding sequence. Two types of PRL cDNA were isolated and their complete nucleotide sequence determined. The larger cDNA (tiPRL-I) codes for a polypeptide of 212 amino acids, including a putative signal sequence of 24 amino acids, and contains a 3' untranslated region of 787 bp. The second prolactin cDNA (tiPRL-II) encodes a polypeptide of 200 amino acids, including a presumptive signal peptide of 23 amino acids, and contains a noncoding region of 512 bp. tiPRL-I and tiPRL-II cDNA sequences are 81% similar, whereas the encoded proteins share 69% amino acid identity at optimal alignment. Mature tiPRL-I was efficiently expressed in Escherichia coli carrying a plasmid in which the tiPRL-I cDNA was under the control of the phi 10 promoter of T7 bacteriophage. The new recombinant protein representing about 45% of the total cellular proteins was found in inclusion bodies and cross-reacted with salmon PRL antiserum. PMID:2670495

  4. Prolactin 177, prolactin 188, and extracellular osmolality independently regulate the gene expression of ion transport effectors in gill of Mozambique tilapia.

    PubMed

    Inokuchi, Mayu; Breves, Jason P; Moriyama, Shunsuke; Watanabe, Soichi; Kaneko, Toyoji; Lerner, Darren T; Grau, E Gordon; Seale, Andre P

    2015-11-15

    This study characterized the local effects of extracellular osmolality and prolactin (PRL) on branchial ionoregulatory function of a euryhaline teleost, Mozambique tilapia (Oreochromis mossambicus). First, gill filaments were dissected from freshwater (FW)-acclimated tilapia and incubated in four different osmolalities, 280, 330, 380, and 450 mosmol/kg H2O. The mRNA expression of Na(+)/K(+)-ATPase α1a (NKA α1a) and Na(+)/Cl(-) cotransporter (NCC) showed higher expression with decreasing media osmolalities, while Na(+)/K(+)/2Cl(-) cotransporter 1a (NKCC1a) and PRL receptor 2 (PRLR2) mRNA levels were upregulated by increases in media osmolality. We then incubated gill filaments in media containing ovine PRL (oPRL) and native tilapia PRLs (tPRL177 and tPRL188). oPRL and the two native tPRLs showed concentration-dependent effects on NCC, NKAα1a, and PRLR1 expression; Na(+)/H(+) exchanger 3 (NHE3) expression was increased by 24 h of incubation with tPRLs. Immunohistochemical observation showed that oPRL and both tPRLs maintained a high density of NCC- and NKA-immunoreactive ionocytes in cultured filaments. Furthermore, we found that tPRL177 and tPRL188 differentially induce expression of these ion transporters, according to incubation time. Together, these results provide evidence that ionocytes of Mozambique tilapia may function as osmoreceptors, as well as directly respond to PRL to modulate branchial ionoregulatory functions.

  5. The role of the prolactin/vasoinhibin axis in rheumatoid arthritis: an integrative overview.

    PubMed

    Clapp, Carmen; Adán, Norma; Ledesma-Colunga, María G; Solís-Gutiérrez, Mariana; Triebel, Jakob; Martínez de la Escalera, Gonzalo

    2016-08-01

    Rheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disease destroying articular cartilage and bone. The female preponderance and the influence of reproductive states in RA have long linked this disease to sexually dimorphic, reproductive hormones such as prolactin (PRL). PRL has immune-enhancing properties and increases in the circulation of some patients with RA. However, PRL also suppresses the immune system, stimulates the formation and survival of joint tissues, acquires antiangiogenic properties upon its cleavage to vasoinhibins, and protects against joint destruction and inflammation in the adjuvant-induced model of RA. This review addresses risk factors for RA linked to PRL, the effects of PRL and vasoinhibins on joint tissues, blood vessels, and immune cells, and the clinical and experimental data associating PRL with RA. This information provides important insights into the pathophysiology of RA and highlights protective actions of the PRL/vasoinhibin axis that could lead to therapeutic benefits.

  6. The many faces of prolactin in breast cancer.

    PubMed

    Chen, Wen Y

    2015-01-01

    Prolactin (PRL) is a neuroendocrine polypeptide hormone primarily produced by the lactotrophs in the anterior pituitary gland of all vertebrates. The physiological role of PRL in mammary glands is relatively certain while its role in breast tumor has been a topic of debate for over 20 years. In this review, the author attempts to briefly summarize the data coming from his laboratory in the past years, focusing on G129R, a PRL receptor (PRLR) antagonist developed by introducing a single amino acid substitution mutation into human PRL (hPRL) at position 129, and a variety of G129R derivatives. The author has proposed two novel ideas for potential use of PRL, not anti-PRL agents, as an adjuvant agent for breast cancer, making it a hormone of many faces.

  7. Prolactin protects retinal pigment epithelium by inhibiting sirtuin 2-dependent cell death.

    PubMed

    Meléndez García, Rodrigo; Arredondo Zamarripa, David; Arnold, Edith; Ruiz-Herrera, Xarubet; Noguez Imm, Ramsés; Baeza Cruz, German; Adán, Norma; Binart, Nadine; Riesgo-Escovar, Juan; Goffin, Vincent; Ordaz, Benito; Peña-Ortega, Fernando; Martínez-Torres, Ataúlfo; Clapp, Carmen; Thebault, Stéphanie

    2016-05-01

    The identification of pathways necessary for retinal pigment epithelium (RPE) function is fundamental to uncover therapies for blindness. Prolactin (PRL) receptors are expressed in the retina, but nothing is known about the role of PRL in RPE. Using the adult RPE 19 (ARPE-19) human cell line and mouse RPE, we identified the presence of PRL receptors and demonstrated that PRL is necessary for RPE cell survival via anti-apoptotic and antioxidant actions. PRL promotes the antioxidant capacity of ARPE-19 cells by reducing glutathione. It also blocks the hydrogen peroxide-induced increase in deacetylase sirtuin 2 (SIRT2) expression, which inhibits the TRPM2-mediated intracellular Ca(2+) rise associated with reduced survival under oxidant conditions. RPE from PRL receptor-null (prlr(-/-)) mice showed increased levels of oxidative stress, Sirt2 expression and apoptosis, effects that were exacerbated in animals with advancing age. These observations identify PRL as a regulator of RPE homeostasis.

  8. Role of SRC family kinases in prolactin signaling.

    PubMed

    Martín-Pérez, Jorge; García-Martínez, José Manuel; Sánchez-Bailón, María Pilar; Mayoral-Varo, Víctor; Calcabrini, Annarica

    2015-01-01

    Prolactin (PRL) is a polypeptide hormone/cytokine mainly synthesized by the lactotrophic cells of the adenohypophysis. In addition to the best-known role in mammary gland development and the functional differentiation of its epithelium, PRL is involved in regulation of multiple physiological processes in higher organisms contributing to their homeostasis. PRL has been also associated with pathology, including breast cancer. Therefore, it is relevant to determine the molecular mechanisms by which PRL controls cellular functions. Here, we analyze the role of Src family kinases (SFKs) in the intracellular signaling pathways controlled by PRL in several model systems. The data show that SFKs are essential components in transmitting signals upon PRL receptor stimulation, as they control activation of Jak2/Stat5 and other routes that regulate PRL cellular responses.

  9. Tumour necrosis factor alpha, interferon gamma and substance P are novel modulators of extrapituitary prolactin expression in human skin.

    PubMed

    Langan, Ewan A; Vidali, Silvia; Pigat, Natascha; Funk, Wolfgang; Lisztes, Erika; Bíró, Tamás; Goffin, Vincent; Griffiths, Christopher E M; Paus, Ralf

    2013-01-01

    Human scalp skin and hair follicles (HFs) are extra-pituitary sources of prolactin (PRL). However, the intracutaneous regulation of PRL remains poorly understood. Therefore we investigated whether well-recognized regulators of pituitary PRL expression, which also impact on human skin physiology and pathology, regulate expression of PRL and its receptor (PRLR) in situ. This was studied in serum-free organ cultures of microdissected human scalp HFs and skin, i.e. excluding pituitary, neural and vascular inputs. Prolactin expression was confirmed at the gene and protein level in human truncal skin, where its expression significantly increased (p = 0.049) during organ culture. There was, however, no evidence of PRL secretion into the culture medium as measured by ELISA. PRL immunoreactivity (IR) in female human epidermis was decreased by substance P (p = 0.009), while neither the classical pituitary PRL inhibitor, dopamine, nor corticotropin-releasing hormone significantly modulated PRL IR in HFs or skin respectively. Interferon (IFN) γ increased PRL IR in the epithelium of human HFs (p = 0.044) while tumour necrosis factor (TNF) α decreased both PRL and PRLR IR. This study identifies substance P, TNFα and IFNγ as novel modulators of PRL and PRLR expression in human skin, and suggests that intracutaneous PRL expression is not under dopaminergic control. Given the importance of PRL in human hair growth regulation and its possible role in the pathogenesis of several common skin diseases, targeting intracutaneous PRL production via these newly identified regulatory pathways may point towards novel therapeutic options for inflammatory dermatoses. PMID:23626671

  10. Tumour necrosis factor alpha, interferon gamma and substance P are novel modulators of extrapituitary prolactin expression in human skin.

    PubMed

    Langan, Ewan A; Vidali, Silvia; Pigat, Natascha; Funk, Wolfgang; Lisztes, Erika; Bíró, Tamás; Goffin, Vincent; Griffiths, Christopher E M; Paus, Ralf

    2013-01-01

    Human scalp skin and hair follicles (HFs) are extra-pituitary sources of prolactin (PRL). However, the intracutaneous regulation of PRL remains poorly understood. Therefore we investigated whether well-recognized regulators of pituitary PRL expression, which also impact on human skin physiology and pathology, regulate expression of PRL and its receptor (PRLR) in situ. This was studied in serum-free organ cultures of microdissected human scalp HFs and skin, i.e. excluding pituitary, neural and vascular inputs. Prolactin expression was confirmed at the gene and protein level in human truncal skin, where its expression significantly increased (p = 0.049) during organ culture. There was, however, no evidence of PRL secretion into the culture medium as measured by ELISA. PRL immunoreactivity (IR) in female human epidermis was decreased by substance P (p = 0.009), while neither the classical pituitary PRL inhibitor, dopamine, nor corticotropin-releasing hormone significantly modulated PRL IR in HFs or skin respectively. Interferon (IFN) γ increased PRL IR in the epithelium of human HFs (p = 0.044) while tumour necrosis factor (TNF) α decreased both PRL and PRLR IR. This study identifies substance P, TNFα and IFNγ as novel modulators of PRL and PRLR expression in human skin, and suggests that intracutaneous PRL expression is not under dopaminergic control. Given the importance of PRL in human hair growth regulation and its possible role in the pathogenesis of several common skin diseases, targeting intracutaneous PRL production via these newly identified regulatory pathways may point towards novel therapeutic options for inflammatory dermatoses.

  11. Prolactin down-regulates CD4+CD25hiCD127low/- regulatory T cell function in humans.

    PubMed

    Legorreta-Haquet, M V; Chávez-Rueda, K; Montoya-Díaz, E; Arriaga-Pizano, L; Silva-García, R; Chávez-Sánchez, L; Moreno-Lafont, M; Zenteno-Galindo, E; Blanco-Favela, F

    2012-02-01

    Among its many functions, prolactin (PRL) participates in immune responses and promotes the activation, differentiation and proliferation of T cells. However, the mechanisms by which PRL regulates regulatory T (T(reg)) cells are still unknown. Our goal was to determine whether PRL plays a role in T(reg) function. We measured the expression of PRL and its receptor in T(reg) and effector T (T(eff)) cells from 15 healthy individuals. We also evaluated the functional activity of T(reg) cells by examining proliferation and cytokine secretion in cells activated with anti-CD3/CD28 in the presence or absence of PRL. We report that T(reg) cells constitutively expressed PRL receptor, whereas T(eff) cells required stimulation with anti-CD3/CD28 to induce PRL receptor expression. Expression of PRL was constitutive in both populations. We found that the addition of PRL inhibited the suppressor effect (proliferation) mediated by T(reg) cells in vitro, reducing suppression from 37.4 to 13% when PRL was added to co-cultures of T(reg) and T(eff) cells (P<0.05). Cultures treated with PRL favoured a Th1 cytokine profile, with increased production of TNF and IFNγ. We report for the first time that PRL receptor expression was constitutive in T(reg) cells but not in T(eff) cells, which require stimulation to induce PRL receptor expression. PRL inhibited the suppressive function of T(reg) cells, apparently through the induced secretion of Th1 cytokines.

  12. Cytokine-like effects of prolactin in human mononuclear and polymorphonuclear leukocytes.

    PubMed

    Dogusan, Z; Hooghe, R; Verdood, P; Hooghe-Peters, E L

    2001-11-01

    Some biochemical events following the binding of prolactin (PRL) to its receptor in normal human leukocytes were investigated. PRL enhanced JAK2 phosphorylation in peripheral blood mononuclear cells (PBMC) but not in granulocytes. PRL also induced phosphorylation of Stat-5 in PBMC and Stat-1 in granulocytes. Subsequent binding of Stat-5- and of Stat-1-like molecules to a GAS responsive element from the beta-casein promoter was detected by EMSA. p38 MAPK (but not p42/p44 MAPK) was activated by PRL in both leukocyte populations. PRL induced iNOS and CIS mRNA expression in granulocytes. Increased expression of IRF-1 and SOCS-2 was observed in granulocytes and of SOCS-3 and iNOS in PBMC. Similar effects were obtained with ovine and human PRL. Antiserum to PRL reduced iNOS and IRF-1 expression induced by PRL in granulocytes and reduced iNOS expression in PBMC. Also, pretreatment of granulocytes with a p38 MAPK inhibitor (SB 203580) prevented in part PRL-induced iNOS and IRF-1 expression. In PBMC, the p38 inhibitor decreased PRL-induced iNOS gene expression. These results indicate that PRL-induced gene regulation in leukocytes requires the activation of at least two different pathways: the Stat and the MAP kinase pathways. Moreover, although PRL activates Stat in both leukocyte types, signal transduction is different in granulocytes and in PBMC. Most importantly, PRL modulates the expression of genes crucial to leukocyte function. The present findings reinforce the concept that PRL has "cytokine-like" activity in human leukocytes.

  13. Biological significance of prolactin in gynecologic cancers.

    PubMed

    Levina, Vera V; Nolen, Brian; Su, YunYun; Godwin, Andrew K; Fishman, David; Liu, Jinsong; Mor, Gil; Maxwell, Larry G; Herberman, Ronald B; Szczepanski, Miroslaw J; Szajnik, Marta E; Gorelik, Elieser; Lokshin, Anna E

    2009-06-15

    There is increasing evidence that prolactin (PRL), a hormone/cytokine, plays a role in breast, prostate, and colorectal cancers via local production or accumulation. Elevated levels of serum PRL in ovarian and endometrial cancers have been reported, indicating a potential role for PRL in endometrial and ovarian carcinogenesis. In this study, we show that serum PRL levels are significantly elevated in women with a strong family history of ovarian cancer. We show dramatically increased expression of PRL receptor in ovarian and endometrial tumors as well as in endometrial hyperplasia, signifying the importance of PRL signaling in malignant and premalignant conditions. PRL mRNA was expressed in ovarian and endometrial tumors, indicating the presence of an autocrine loop. PRL potently induced proliferation in several ovarian and endometrial cancer cell lines. Binding of PRL to its receptor was followed by rapid phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, mitogen-activated protein kinase/ERK kinase 1, signal transducer and activator of transcription 3, CREB, ATF-2, and p53 and activation of 37 transcription factors in ovarian and endometrial carcinoma cells. PRL also activated Ras oncogene in these cells. When human immortalized normal ovarian epithelial cells were chronically exposed to PRL, a malignant transformation occurred manifested by the acquired ability of transformed cells to form clones, grow in soft agar, and form tumors in severe combined immunodeficient-beige mice. Transformation efficiency was diminished by a Ras inhibitor, providing proof that PRL-induced transformation uses the Ras pathway. In summary, we present findings that indicate an important role for PRL in ovarian and endometrial tumorigenesis. PRL may represent a risk factor for ovarian and endometrial cancers.

  14. In vivo inhibition followed by exogenous supplementation demonstrates galactopoietic effects of prolactin on mammary tissue and milk production in dairy cows.

    PubMed

    Lollivier, V; Lacasse, P; Angulo Arizala, J; Lamberton, P; Wiart, S; Portanguen, J; Bruckmaier, R; Boutinaud, M

    2015-12-01

    It has been previously shown that the long-term inhibition of milking-induced prolactin (PRL) release by quinagolide (QN), a dopamine agonist, reduces milk yield in dairy cows. To further demonstrate that PRL is galactopoietic in cows, we performed a short-term experiment that used PRL injections to restore the release of PRL at milking in QN-treated cows. Nine Holstein cows were assigned to treatments during three 5-d periods in a 3×3 Latin square design: 1) QN: twice-daily i.m. injections of 1mg of QN; 2) QN-PRL: twice-daily i.m. injections of 1mg of QN and twice-daily (at milking time) i.v. injections of PRL (2µg/kg body weight); and 3) control: twice-daily injections of the vehicles. Mammary epithelial cells (MEC) were purified from milk so that their viability could be assessed, and mammary biopsies were harvested for immunohistological analyses of cell proliferation using PCNA and STAT5 staining. In both milk-purified MEC and mammary tissue, the mRNA levels of milk proteins and BAX were determined using real-time reverse-transcription PCR. Daily QN injections reduced milking-induced PRL release. The area under the PRL curve was similar in the control and PRL injection treatments, but the shape was different. The QN treatment decreased milk, lactose, protein, and casein production. Injections of PRL did not restore milk yield but tended to increase milk protein yield. In mammary tissue, the percentage of STAT5-positive cells was reduced during QN but not during QN-PRL in comparison with the control treatment. The percentage of PCNA-positive cells was greater during QN-PRL injections than during the control or QN treatment and tended to be lower during QN than during the control treatment. In milk-purified MEC, κ-casein and α-lactalbumin mRNA levels were lower during QN than during the control treatment, but during QN-PRL, they were not different from the control treatment. In mammary tissue, the BAX mRNA level was lower during QN-PRL than during QN. The

  15. In vivo inhibition followed by exogenous supplementation demonstrates galactopoietic effects of prolactin on mammary tissue and milk production in dairy cows.

    PubMed

    Lollivier, V; Lacasse, P; Angulo Arizala, J; Lamberton, P; Wiart, S; Portanguen, J; Bruckmaier, R; Boutinaud, M

    2015-12-01

    It has been previously shown that the long-term inhibition of milking-induced prolactin (PRL) release by quinagolide (QN), a dopamine agonist, reduces milk yield in dairy cows. To further demonstrate that PRL is galactopoietic in cows, we performed a short-term experiment that used PRL injections to restore the release of PRL at milking in QN-treated cows. Nine Holstein cows were assigned to treatments during three 5-d periods in a 3×3 Latin square design: 1) QN: twice-daily i.m. injections of 1mg of QN; 2) QN-PRL: twice-daily i.m. injections of 1mg of QN and twice-daily (at milking time) i.v. injections of PRL (2µg/kg body weight); and 3) control: twice-daily injections of the vehicles. Mammary epithelial cells (MEC) were purified from milk so that their viability could be assessed, and mammary biopsies were harvested for immunohistological analyses of cell proliferation using PCNA and STAT5 staining. In both milk-purified MEC and mammary tissue, the mRNA levels of milk proteins and BAX were determined using real-time reverse-transcription PCR. Daily QN injections reduced milking-induced PRL release. The area under the PRL curve was similar in the control and PRL injection treatments, but the shape was different. The QN treatment decreased milk, lactose, protein, and casein production. Injections of PRL did not restore milk yield but tended to increase milk protein yield. In mammary tissue, the percentage of STAT5-positive cells was reduced during QN but not during QN-PRL in comparison with the control treatment. The percentage of PCNA-positive cells was greater during QN-PRL injections than during the control or QN treatment and tended to be lower during QN than during the control treatment. In milk-purified MEC, κ-casein and α-lactalbumin mRNA levels were lower during QN than during the control treatment, but during QN-PRL, they were not different from the control treatment. In mammary tissue, the BAX mRNA level was lower during QN-PRL than during QN. The

  16. Prolactin and Prolactin Receptor Expression in Rat, Small Intestine, Intraepithelial Lymphocytes During Neonatal Developmen

    PubMed Central

    Urtishak, Sandra L.; Mckenna, Elizabeth A.; Mastro, Andrea M.

    2001-01-01

    Intraepithelial lymphocytes (IEL) are specialized T cells found between the epithelial cells of the small intestine. Because of their location, IEL are the first lymphocytes to contact intestinal bacteria and food antigens. In the neonate, IEL may be the first cells of the immune system to interact with milk-borne hormones including prolactin (PRL). PRL, an endocrine hormone abundant in breast milk, interacts with cells through surface receptors. PRL has been shown to function as an immunoregulator and may affect the development of the newborn's immune system. To determine if PRL plays a role in IEL development, small intestine IEL from rats of various ages were examined for the presence of surface prolactin receptor (PRL-R) and several lymphoid markers by flow cytometry. Between birth and 96 days of age about 80% of IEL were found to express PRL-R. These same cells also expressed the mRNA for PRL. Additionally, all of the IEL subpopulations examined were found to express PRL-R. Analysis of the normal development of rat IEL revealed an age related increase in total IEL, CD4 positive cells as well as a peak in interleukin-2 receptor (IL-2R) expression at weaning. In summary, the results indicate that IEL express PRL and PRL-R. In addition, an activation marker, IL-2R, changes in expression during neonatal development. PMID:11785680

  17. Prolactin Levels Correlate with Abnormal B Cell Maturation in MRL and MRL/lpr Mouse Models of Systemic Lupus Erythematosus-Like Disease

    PubMed Central

    Legorreta-Haquet, Maria Victoria; Flores-Fernández, Rocio; Blanco-Favela, Francisco; Fuentes-Pananá, Ezequiel M; Chávez-Sánchez, Luis; Hernández-González, Rafael; Tesoro-Cruz, Emiliano; Arriaga-Pizano, Lourdes; Chávez-Rueda, Adriana Karina

    2013-01-01

    Prolactin (PRL) plays an important role in modulating the immune response. In B cells, PRL enhances antibody production, including antibodies with self-specificity. In this study, our aims were to determine the level of PRL receptor expression during bone-marrow B-cell development and to assess whether the presence of high PRL serum concentrations influences absolute numbers of developing populations and disease outcome in lupus-prone murine models. We observed that the PRL-receptor is expressed in early bone-marrow B-cell; the expression in lupus-prone mice, which had the highest level of expression in pro-B cells and immature cells, differed from that in wild-type mice. These expression levels did not significantly change in response to hyperprolactinemia; however, populations of pro-B and immature cells from lupus-prone strains showed a decrease in the absolute numbers of cells with high PRL-receptor expression in response to PRL. Because immature self-reactive B cells are constantly being eliminated, we assessed the expression of survival factor BIRC5, which is more highly expressed in both pro-B and immature B-cells in response to PRL and correlates with the onset of disease. These results identify an important role of PRL in the early stages of the B-cell maturation process: PRL may promote the survival of self-reactive clones. PMID:24454471

  18. Production and purification of biologically active recombinant tilapia (Oreochromis niloticus) prolactins.

    PubMed

    Swennen, D; Rentier-Delrue, F; Auperin, B; Prunet, P; Flik, G; Wendelaar Bonga, S E; Lion, M; Martial, J A

    1991-11-01

    Recombinant expression vectors carrying tilapia prolactin-I or -II (tiPRL-I or tiPRL-II) cDNA were constructed and the tiPRL-I and II proteins were produced in E. coli as inclusion bodies. These inclusion bodies were dissolved in 6 mol urea/l. Refolding of the proteins was followed by SDS-PAGE under non-reducing conditions so as to visualize the oxidized state of the molecules. Proteins tiPRL-I and tiPRL-II were purified by gel filtration and ion-exchange chromatography. The N-terminal sequence and bioactivities of both purified proteins were then analysed. Recombinant tiPRL-I and tiPRL-II induced a significant rise in plasma calcium levels as well as in mucocyte density in the abdominal skin epithelium. When tested on kidney membrane, both proteins exhibited potency in competing with 125I-labelled tiPRL-I for binding sites, but tiPRL-I seemed to be more potent than tiPRL-II in competing for these sites. The results obtained for the biological activities tested suggest that both recombinant prolactins were correctly refolded and had retained the full biological activity previously observed with the natural hormone preparations extracted from the animals. PMID:1744569

  19. Prolactin receptors in liver, kidney, and gill of the tilapia (Oreochromis mossambicus): Characterization and effect of salinity on specific binding of iodinated ovine prolactin

    SciTech Connect

    Dauder, S.; Young, G.; Hass, L.; Bern, H.A. )

    1990-03-01

    Specific binding of {sup 125}I-ovine prolactin (oPRL) to microsomal fractions from gill, kidney, and liver of adult tilapia was determined. Specific binding varied among tissues, the highest values being displayed by kidney membranes. In the liver, the binding of oPRL was not strongly displaced by tilapia prolactins (tPRL177 and tPRL188), although tPRL177 was six times more potent than tPRL188. On the other hand, in kidney and gill membranes, the two tPRLs were equipotent. Tilapia PRLs showed low potency in competing for oPRL-binding sites when pregnant rat liver membranes were utilized. Tilapia growth hormone (tGH) and human growth hormone (hGH) displaced {sup 125}I-oPRL from liver as well as did tPRL177 but were not recognized well by renal or branchial receptors. Two {sup 125}I-oPRL-binding sites were detected in every tissue tested. These binding sites are subject to physiological regulation since adaptation to seawater resulted in a significant decrease in specific binding.

  20. Serum prolactin concentrations are elevated after syncope.

    PubMed

    Oribe, E; Amini, R; Nissenbaum, E; Boal, B

    1996-07-01

    The distinction between syncope and epileptic seizures is a common clinical diagnostic problem. Elevated serum prolactin (PRL) concentrations are used to help differentiate epileptic from nonepileptic attacks such as pseudoseizures. Reports of PRL concentrations following syncope have been variable. To determine whether PRL rises after syncope, we measured serum PRL concentrations during a 45-minute passive 60-degree head-up tilt in 21 patients with a history of near-fainting or syncope. Head-up tilt triggered hypotension (mean arterial pressure 51 mm Hg, 95% CI = 45-57) with syncope in 11 patients. PRL concentrations were elevated ( > 19 ng/mL) and reached a maximum within the first 30 minutes after tilt-induced syncope in nine patients (PRL supine: 11 ng/mL, 95% CI = 7-15, vs. PRL after syncope: 52 ng/mL, 95% CI = 36-67; a greater than fourfold rise), while they remained unchanged in 10 patients who had a normal response to head-up tilt (PRL supine: 6 ng/mL, 95% CI = 5-8, vs. maximum PRL while upright: 8 ng/mL, 95% CI = 6-10). The findings indicate that elevated PRL concentrations are present after hypotensive syncope and are of little use in differentiating such syncope from epileptic seizures.

  1. Prolactin as an autocrine/paracrine factor in breast tissue.

    PubMed

    Clevenger, C V; Plank, T L

    1997-01-01

    The neuroendocrine hormone prolactin (PRL) stimulates breast growth and differentiation during puberty, pregnancy, and lactation. Despite extensive and convincing data indicating that PRL significantly contributes to the pathogenesis and progression of rodent mammary carcinoma, parallel observations for human breast cancer have not been concordant. In particular, the therapeutic alteration of somatolactogenic hormone levels has not consistently altered the course of human breast cancer. Recent data, however, suggest that extra-pituitary tissues are capable of elaborating PRL; indeed, the observation of sustained serum levels of PRL in post-hypophysectomy patients supports this hypothesis. Proof of an autocrine/paracrine loop for PRL within normal and malignant human breast tissues requires that the following three criteria be met: (1) PRL must be synthesized and secreted within mammary tissues; (2) the receptor for PRL (PRLR) must be present within these tissues; and, (3) proliferative responses to autocrine/paracrine PRL must be demonstrated. These criteria have now been fulfilled in several laboratories. With the demonstration of a PRL autocrine/paracrine loop in mammary glands, the basis for the ineffective treatment of human breast cancer by prior endocrine-based anti-somatolactogenic therapies is evident. These findings provide the precedent for novel therapeutic strategies aimed at interrupting the stimulation of breast cancer growth by PRL at both endocrine and autocrine/paracrine levels.

  2. Role of calcium in prolactin-stimulated c-myc gene expression and mitogenesis in Nb2 lymphoma cells

    SciTech Connect

    Murphy, P.R.; DiMattia, G.E.; Friesen, H.G.

    1988-06-01

    Receptor-activated transmembrane calcium flux has been implicated as a mediator of the actions of many growth factors and hormones. We examined the effects of PRL, calcium ionophores, and calcium antagonists on /sup 45/Ca2+ flux, c-myc gene expression, and DNA synthesis in the PRL-dependent rat Nb2 lymphoma cell line. PRL had no detectable effects on /sup 45/Ca2+ uptake or efflux, and the mitogenic effects of PRL could not be reproduced by the calcium ionophore A23187 alone or in combination with the tumor-promoting phorbol ester 12-O-tetra-decanoyl-phorbol-13 acetate (TPA). PRL, but not A23187 or TPA, stimulated c-myc gene expression in quiescent Nb2 cells. Exposure to PRL for brief periods (15 min to 4 h), followed by extensive washing, resulted in a time- and dose-dependent activation of DNA synthesis measured 16 h later. This activation was not blocked by addition of excess anti-PRL antiserum after the wash steps, indicating that the observed stimulation was not due to residual PRL. Despite the marked increase in DNA synthesis, removal of PRL after 4 h prevented mitosis, suggesting that PRL may be required throughout the cell cycle for Nb2 cell proliferation. Although continuous incubation with calcium antagonists resulted in a dose-dependent inhibition of PRL-stimulated DNA synthesis, activation of DNA synthesis by brief exposure to PRL was not inhibited by the presence of EGTA, calcium channel blockers (nifedipine, cobalt chloride), or calmodulin inhibitors (trifluoperazine, N-6-aminohexyl-5-chloronaphthalene sulfonamide). PRL-stimulated c-myc expression was attenuated, but not blocked, by the calcium channel antagonists. However, the putative intracellular calcium antagonist TMB-8 inhibited both c-myc expression and DNA synthesis in a dose-dependent manner (IC50 = 16 microM).

  3. Evidence for a Role of Prolactin in Mediating Effects of Photoperiod during the Dry Period

    PubMed Central

    Crawford, Heather M.; Morin, Dawn E.; Wall, Emma H.; McFadden, Thomas B.; Dahl, Geoffrey E.

    2015-01-01

    Photoperiod manipulation during the lactation cycle alters milk yield, with long days (LDPP) increasing yield in lactation and short days (SDPP) in the dry period improving subsequent yield. Circulating prolactin (PRL) is directly related to day length, with LDPP increasing and SDPP decreasing PRL, respectively. Two blocks of 24 multiparous Holstein cows were used during two consecutive years to test the hypothesis that the mammary response to SDPP is the result of decreased concentrations of PRL in the circulation relative to LDPP. Cows were randomly assigned to one of three treatment groups during the dry period: SDPP, LDPP, or SDPP+PRL. Cows were returned to ambient photoperiod at calving and milk yield and DMI recorded for 120 d and 42 d, respectively. Mammary biopsies were obtained to determine rates of [3H]-thymidine incorporation into DNA in vitro. Treatment of SDPP cows with PRL caused a rapid increase in systemic PRL that reached concentrations similar to cows under LDPP. The periparturient PRL surge was similar for LDPP and SDPP+PRL cows, but those groups had greater surge concentrations versus SDPP. Cows exposed to SDPP produced more milk than LDPP cows, and there was a trend for SDPP+PRL cows to produce more milk than LDPP cows. Milk production was inversely related to the periparturient PRL surge. There was a trend for a treatment effect on mammary cell proliferation with greater proliferation in mammary tissue of SDPP cows relative to LDPP or SDPP+PRL on day −20 relative to parturition. Replacement of PRL to cows on SDPP when dry resulted in milk yield intermediate to cows on SDPP or LDPP, supporting the concept of a link between dry period PRL and yield. PMID:26479387

  4. Prolactin and the skin: a dermatological perspective on an ancient pleiotropic peptide hormone.

    PubMed

    Foitzik, Kerstin; Langan, Ewan A; Paus, Ralf

    2009-05-01

    The polypeptide hormone prolactin (PRL) is best known as the pituitary modulator of lactation and reproduction. However, based on the almost ubiquitous distribution of PRL receptors (PRLR) and an ever-growing list of extrapituitary PRL-expressing tissues, a vast range of PRL actions "beyond the mammary horizon" has now been documented or claimed. For example, PRL modulates hair growth in domestic animals with seasonal hair growth changes ("PRL-pelage axis"). Given that the mammary gland is an epidermal derivative, it is not surprising that the pilosebaceous unit, another epidermal derivative, has also surfaced as a prominent, PRLR-expressing, nonclassical PRL target organ. Moreover, the fact that murine and human hair follicles even synthesize PRL strongly invites one to explore fully the dermatological dimensions of this multifunctional, cytokine-like neuroendocrine bioregulator, which remain insufficiently charted. After describing the relevant essentials of general PRL/PRLR biology, we summarize clinical observations that provide insights into how PRL may impact on the skin, and define important research frontiers and controversies in the quest to better characterize the complex role of PRL in human skin biology and pathology. Focusing on psoriasis, alopecia, and stress-related dermatoses, we then discuss the possible role of PRL/PRLR in cutaneous pathology, and identify potential therapeutic targets for the management of these skin disorders. We close by delineating major open questions at this emerging frontier of basic and clinical cutaneous neuroendocrinology, and argue that systematic exploration of the "PRL-skin connection" will fertilize the development of previously unreported neuroendocrinological strategies for managing selected skin disorders.

  5. SOEMPI: A Secure Open Enterprise Master Patient Index Software Toolkit for Private Record Linkage

    PubMed Central

    Toth, Csaba; Durham, Elizabeth; Kantarcioglu, Murat; Xue, Yuan; Malin, Bradley

    2014-01-01

    To mitigate bias in multi-institutional research studies, healthcare organizations need to integrate patient records. However, this process must be accomplished without disclosing the identities of the corresponding patients. Various private record linkage (PRL) techniques have been proposed, but there is a lack of translation into practice because no software suite supports the entire PRL lifecycle. This paper addresses this issue with the introduction of the Secure Open Enterprise Master Patient Index (SOEMPI). We show how SOEMPI covers the PRL lifecycle, illustrate the implementation of several PRL protocols, and provide a runtime analysis for the integration of two datasets consisting of 10,000 records. While the PRL process is slower than a non-secure setting, our analysis shows the majority of processes in a PRL protocol require several seconds or less and that SOEMPI completes the process in approximately two minutes, which is a practical amount of time for integration. PMID:25954421

  6. A role for growth hormone and prolactin in leukaemia and lymphoma?

    PubMed

    Hooghe, R; Merchav, S; Gaidano, G; Naessens, F; Matera, L

    1998-10-01

    Growth hormone (GH) and prolactin (PRL) quality as lymphohaemopoietic growth and differentiation factors, and so does insulin-like growth factor (IGF)-I, which mediates many of GH activities. Although there is only limited evidence that endocrine, paracrine or autocrine GH or PRL play a role in human leukaemia and lymphoma, the expression of these factors or their receptors may have diagnostic or therapeutic implications. Indeed, the participation of GH, PRL or IGF-I in the development or progression of certain haematological malignancies or to the antitumour immune response has been documented. Examples discussed in this review include a rat lymphoma in which the PRL receptor acts as an oncogene; the rat Nb2 lymphoma, which is dependent on PRL for growth; and experiments showing that PRL stimulates natural killer cell activity and the development of lymphokine-activated killer cells.

  7. Lungfish prolactin exhibits close tetrapod relationships.

    PubMed

    Noso, T; Nicoll, C S; Kawauchi, H

    1993-07-10

    This paper describes the isolation and the complete amino-acid sequence of prolactin (PRL) from the pituitary glands of African lungfish, Protoputerus aethiopicus. We purified the hormone from an alkaline extract of the pituitaries using a two-step chromatographic procedure by detecting specific immunoblot reactivity with rabbit antisera against salmon PRL. The lungfish PRL consists of 200 amino-acid residues. Sequence comparison revealed that the PRL shows 66% identities with amphibian, reptilian and bird PRLs, 57% with mammalian PRLs, and 38% with teleost (modern bony fish) PRLs. Moreover, the PRL contains three disulfide bonds homologous to those of tetrapod PRLs and differs from teleost PRLs which lack the amino-terminal disulfide bond. Thus, the structural features of lungfish PRL indicate a closer relationship to tetrapod PRLs than to teleost PRLs. All PRLs sequenced to date share 22 common amino acids, which may be important for the activities common to all PRLs. PMID:8329446

  8. The secretory pattern and source of immunoreactive prolactin in pregnant African (Loxodonta africana) and Asian (Elephas maximus) elephants.

    PubMed

    Yamamoto, Yuki; Yamamoto, Tatsuya; Yuto, Natsuki; Hildebrandt, Thomas B; Lueders, Imke; Wibbelt, Gudrun; Shiina, Osamu; Mouri, Yasushi; Sugimura, Keisuke; Sakamoto, Sayuri; Kaewmanee, Saroch; Nagaoka, Kentaro; Watanabe, Gen; Taya, Kazuyoshi

    2012-01-01

    The objective of the present study was to define the secretion of prolactin (PRL) in pregnant African and Asian elephants. Levels of immunoreactive (ir-) PRL in serum and placental homogenates were measured by a heterologous radioimmunoassay (RIA) based on an ovine and human RIA system, and the localization of ir-PRL in the placenta was detected by immunohistochemistry using anti-human PRL. Circulating ir-PRL clearly showed a biphasic pattern during pregnancy in African and Asian elephants. Serum levels of ir-PRL started to increase from the 4 - 6th month of gestation and reached the first peak level around the 11-14th month. A second peak of circulating ir-PRL levels was observed around the 18-20th month of gestation followed by an abrupt decline after parturition. In contrast, in a case of abortion of an African elephant, the second peak of ir-PRL was not observed, and the levels remained low for about four months until parturition. The weight of the fetus delivered at the 17th month of gestation was 23.5 kg, which was quite small compared with normal fetuses in previous reports. Ir-PRL was detected in placental homogenates, and immunolocalization was observed in trophoblasts in both the African and Asian elephants, indicating that the placenta is the source of ir-PRL during pregnancy in elephants. The present results clearly demonstrated that circulating ir-PRL shows a biphasic pattern during normal pregnancy and that the placenta appears to be an important source of circulating ir-PRL during pregnancy in both African and Asian elephants.

  9. Uncoupling clutch size, prolactin, and luteinizing hormone using experimental egg removal.

    PubMed

    Ryan, Calen P; Dawson, Alistair; Sharp, Peter J; Williams, Tony D

    2015-03-01

    Clutch size is a key avian fitness and life history trait. A physiological model for clutch size determination (CSD), involving an anti-gonadal effect of prolactin (PRL) via suppression of luteinizing hormone (LH), was proposed over 20 years ago, but has received scant experimental attention since. The few studies looking at a PRL-based mechanistic hypothesis for CSD have been equivocal, but recent experiments utilizing a pharmacological agent to manipulate PRL in the zebra finch (Taeniopygia guttata) found no support for a role of this hormone in clutch size determination. Here, we take a complementary approach by manipulating clutch size through egg removal, examining co-variation in PRL and LH between two breeding attempts, as well as through experimentally-extended laying. Clutch size increased for egg removal females, but not controls, but this was not correlated with changes in PRL or LH. There were also no differences in PRL between egg removal females and controls, nor did PRL levels during early, mid- or late-laying of supra-normal clutches predict clutch size. By uncoupling PRL, LH and clutch size in our study, several key predictions of the PRL-based mechanistic model for CSD were not supported. However, a positive correlation between PRL levels late in laying and days relative to the last egg (clutch completion) provides an alternative explanation for the equivocal results surrounding the conventional PRL-based physiological model for CSD. We suggest that females coordinate PRL-mediated incubation onset with clutch completion to minimize hatching asynchrony and sibling hierarchy, a behavior that is amplified in females laying larger clutches.

  10. Prolactin stimulates cell proliferation through a long form of prolactin receptor and K+ channel activation.

    PubMed Central

    Van Coppenolle, Fabien; Skryma, Roman; Ouadid-Ahidouch, Halima; Slomianny, Christian; Roudbaraki, Morad; Delcourt, Philippe; Dewailly, Etienne; Humez, Sandrine; Crépin, Alexandre; Gourdou, Isabelle; Djiane, Jean; Bonnal, Jean-Louis; Mauroy, Brigitte; Prevarskaya, Natalia

    2004-01-01

    PRL (prolactin) has been implicated in the proliferation and differentiation of numerous tissues, including the prostate gland. However, the PRL-R (PRL receptor) signal transduction pathway, leading to the stimulation of cell proliferation, remains unclear and has yet to be mapped. The present study was undertaken to develop a clear understanding of the mechanisms involved in this pathway and, in particular, to determine the role of K(+) channels. We used androgen-sensitive prostate cancer (LNCaP) cells whose proliferation is known to be stimulated by PRL. Reverse transcriptase PCR analysis showed that LNCaP cells express a long form of PRL-R, but do not produce its intermediate isoform. Patch-clamp techniques showed that the application of 5 nM PRL increased both the macroscopic K(+) current amplitude and the single K(+)-channel open probability. This single-channel activity increase was reduced by the tyrosine kinase inhibitors genistein, herbimycin A and lavandustine A, thereby indicating that tyrosine kinase phosphorylation is required in PRL-induced K(+) channel stimulation. PRL enhances p59( fyn ) phosphorylation by a factor of 2 after a 10 min application in culture. In addition, where an antip59( fyn ) antibody is present in the patch pipette, PRL no longer increases K(+) current amplitude. Furthermore, the PRL-stimulated proliferation is inhibited by the K(+) channel inhibitors alpha-dendrotoxin and tetraethylammonium. Thus, as K(+) channels are known to be involved in LNCaP cell proliferation, we suggest that K(+) channel modulation by PRL, via p59( fyn ) pathway, is the primary ionic event in PRL signal transduction, triggering cell proliferation. PMID:14565846

  11. Growth hormone- and prolactin-producing cells in the pituitary gland of striped bass (Morone saxatilis): immunocytochemical characterization at different life stages.

    PubMed

    Huang, L; Specker, J L

    1994-05-01

    The striped bass (Morone saxatilis) is a seasonally breeding, long-lived, anadromous fish of growing economic importance. To describe the apparent activities of growth hormone (GH)- and prolactin (PRL)-producing cells, pituitaries were collected from captive juveniles and from wild adult fish in late spring off the Rhode Island coast during their coastal migration and in the Hudson River during the spawning migration. GH and PRL were separated by reversed-phase HPLC of pituitary extracts from captive adults and characterized as having apparent molecular masses of 23 kDa (GH) and 26 kDa (PRL) by SDS-polyacrylamide gel electrophoresis. Antisera generated in rabbits against synthetic fragments of GH and PRL188 from tilapia were shown by Western blot analysis of reversed-phase HPLC-purified striped bass GH and PRL and of striped bass pituitary extract to be specific for the appropriate hormone and were used to localize GH and PRL cells. GH cells and PRL cells lie in the proximal pars distalis and the rostral pars distalis, respectively. Small clusters of GH- and PRL-immunoreactive cells were found at ectopic sites within the pituitary. There were many intensely labeled GH cells in the pituitaries of juvenile and adult striped bass, whereas the immunoreactivity of GH cells in the pituitaries of spawning fish decreased. PRL cells in juvenile fish kept in fresh water had big, round-nuclei, and were heavily labeled, indicating that they were active. PRL cells in adult fish from seawater were also intensely labeled, but had kidney-shaped nuclei, indicating inactivity. PRL cells in fish from the spawning ground had polymorphic nuclei, appearing as round, indented or kidney-shaped forms, and they were unevenly and lightly labeled, suggesting highly variable stages of activity. No difference was found between males and females. The apparent activities of GH- and PRL-producing cells differ among these life stages, suggesting changing roles for the hormones.

  12. Regulation of islet beta-cell pyruvate metabolism: interactions of prolactin, glucose, and dexamethasone.

    PubMed

    Arumugam, Ramamani; Horowitz, Eric; Noland, Robert C; Lu, Danhong; Fleenor, Donald; Freemark, Michael

    2010-07-01

    Prolactin (PRL) induces beta-cell proliferation and glucose-stimulated insulin secretion (GSIS) and counteracts the effects of glucocorticoids on insulin production. The mechanisms by which PRL up-regulates GSIS are unknown. We used rat islets and insulinoma (INS-1) cells to explore the interactions of PRL, glucose, and dexamethasone (DEX) in the regulation of beta-cell pyruvate carboxylase (PC), pyruvate dehydrogenase (PDH), and the pyruvate dehydrogenase kinases (PDKs), which catalyze the phosphorylation and inactivation of PDH. PRL increased GSIS by 37% (P < 0.001) in rat islets. Glucose at supraphysiological concentrations (11 mm) increased PC mRNA in islets; in contrast, PRL suppressed PC mRNA levels in islets and INS-1 cells, whereas DEX was without effect. Neither PRL nor DEX altered PC protein or activity levels. In INS-1 cells, PRL increased PDH activity 1.4- to 2-fold (P < 0.05-0.001) at glucose concentrations ranging from 2.5-11 mm. DEX reduced PDH activity; this effect was reversed by PRL. PDK1, -2, -3, and -4 mRNAs were detected in both islets and insulinoma cells, but the latter expressed trivial amounts of PDK4. PRL reduced PDK2 mRNA and protein levels in rat islets and INS-1 cells and PDK4 mRNA in islets; DEX increased PDK2 mRNA in islets and INS-1 cells; this effect was reversed by PRL. Our findings suggest that PRL induction of GSIS is mediated by increases in beta-cell PDH activity; this is facilitated by suppression of PDKs. PRL counteracts the effects of DEX on PDH and PDK expression, suggesting novel roles for the lactogens in the defense against diabetes. PMID:20484462

  13. Daily changes in plasma and amniotic fluid prolactin during the last third of pregnancy in the baboon.

    PubMed

    Nguyen, T; Diveky, L; Fedirko, B; Pak, S C; Parsons, M; Wilson, L

    1997-03-01

    Alterations in plasma and amniotic fluid prolactin (PRL) levels have not been previously described in the pregnant baboon. In addition, PRL increases dramatically in response to estrogens and thus might be a good marker for expression of estrogen's biologic action. Therefore, the purpose of this study was to characterize the changes in plasma and amniotic fluid PRL with advancing gestational age and assess whether there was a correlation between plasma estradiol and PRL levels. A tethered pregnant baboon model was utilized for these studies. Blood was collected from five animals every day at 0900-1000 h (AM value) and 1800 h (PM value) from 125 to 135 days of pregnancy until delivery. Amniotic fluid was collected every day in the morning. Samples were analyzed by RIA for PRL, estradiol, and progesterone. PRL did not change with advancing gestational age. However, PRL showed a significant diurnal variation, with the PM values significantly higher (p < 0.05) than the AM values. In contrast to findings for PRL, AM values for estradiol and progesterone were on average higher that PM values (p < 0.05). A significant correlation was observed between the log10 estradiol (AM+PM) and log10 PRL (AM) from the following day (r = 0.52; p < 0.05). Finally, amniotic fluid PRL was present in high concentrations (200-400 ng/ml) but did not vary with gestational age. In conclusion, PRL, estradiol, and progesterone show distinct diurnal variations during the last one-third of pregnancy in the baboon. In addition, plasma PRL is positively correlated with estradiol.

  14. Another player joins the complex field of sugar-regulated gene expression in plants

    SciTech Connect

    Gibson, Susan I.; Graham, Ian A.

    1999-04-01

    This article summarizes recent progress in understanding the molecular mechanisms by which soluble sugar levels affect plant development and gene expression. The article focuses on the role played by a newly identified protein, the PRL1 protein. The PRL1 protein has been found to interact with the SNF1 protein. Previously, SNF1 was shown to function in sugar-regulated gene expression in yeast. Mutations in the gene encoding PRL1 confer increased sensitivity to sugar and to several phytohormones.

  15. Prolactin levels in the western spotted skunk: changes during pre- and periimplantation and effects of melatonin and lesions to the anterior hypothalamus.

    PubMed

    Kaplan, J B; Berria, M; Mead, R A

    1991-06-01

    Prolactin (PRL) is the primary pituitary hormone responsible for initiating increased function of the corpus luteum and blastocyst implantation in the western spotted skunk. Therefore, we have designed experiments to validate a PRL RIA, characterize the preimplantation profile in PRL secretion, and determine the effects of exogenous melatonin and lesions to the anterior hypothalamic area (AHA) on PRL secretion in the skunk. These objectives were investigated with a heterologous RIA using canine PRL standards and antiserum. Displacement curves of skunk pituitary extract and serum were parallel to the canine PRL standard curve. Growth hormone-releasing hormone injection did not cause a significant change in plasma PRL levels as detected by the assay (p = 0.74). Injection of pimozide increased and bromocriptine decreased plasma PRL levels (p less than 0.05). A seasonal trend in plasma PRL levels was observed during the preimplantation period, with mean concentrations ranging from 5 ng/ml during the period of short day length in January to 17.1 ng/ml during the long day photoperiod in early May. The average date of blastocyst implantation in this study was 2 May (n = 16). Silastic capsules containing melatonin (n = 5) significantly delayed both the seasonal rise in plasma PRL levels and the time of implantation (p less than 0.05) compared to controls with empty capsules (n = 4). Lesions to the AHA (AHAx, n = 5) eliminated these effects of melatonin on both the rise in PRL and time of implantation. PRL levels were highly correlated with progesterone levels (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Lack of suppression of increased circulating prolactin by 2-hydroxyestrone.

    PubMed

    Kicovic, P M; Franchi, F; Luisi, M

    1982-01-01

    To study the effect of 2-hydroxyestrone (2-OHE1) on circulating prolactin (PRL) in a hyperprolactinaemic state, seven anovulatory women with hyperprolactinaemia were given a 2-OHE1 infusion at a rate of 80 microgram/h for 3 h following a control infusion. Plasma samples for PRL determination were obtained at 30-minute intervals for 6h. No changes in PRL levels were observed during the 2-OHE1 infusion as compared with the control period. It was concluded under conditions of the present experiment that 2-OHE1 does not suppress circulating PRL in hyperprolactinaemic anovulatory women.

  17. Serum prolactin levels in a uremic child: effects of bilateral nephrectomy and kidney transplantation.

    PubMed

    Rondeau, Geneviève; Merouani, Aïcha; Phan, Véronique; Deal, Cheri; Robitaille, Pierre

    2011-10-01

    Elevated levels of serum prolactin (PRL) are common and well described in patients with chronic renal failure. We report the case of a 4-year-old girl who also presented with premature thelarche and transient galactorrhea. Neither peritoneal dialysis nor hemodialysis reduced her extremely elevated levels of PRL, which fluctuated from time to time, probably reflecting variations in lactotroph secretion rate. Bilateral nephrectomy (BN) was eventually followed by a progressive and significant rise in PRL levels, suggesting that even uremic kidneys can eliminate PRL through tubular breakdown. Kidney transplantation was responsible for a very abrupt normalization of PRL serum levels, much faster than that observed for creatinine. This confirms animal studies suggesting that elimination of PRL occurs both through glomerular filtration and tubular breakdown. We hypothesized that the seemingly precocious puberty may have resulted from a combination of growth hormone therapy, elevated PRL and a rise in estrogens through the aromatization of adrenal androgens. This case illustrates the impact of dialysis, BN and kidney transplantation on PRL, providing new knowledge on renal PRL metabolism. PMID:25984175

  18. Studies on the regulatory effect of Peony-Glycyrrhiza Decoction on prolactin hyperactivity and underlying mechanism in hyperprolactinemia rat model.

    PubMed

    Wang, Di; Wang, Wei; Zhou, Yulin; Wang, Juan; Jia, Dongxu; Wong, Hei Kiu; Zhang, Zhang-Jin

    2015-10-01

    Clinical trials have demonstrated the beneficial effects of Peony-Glycyrrhiza Decoction (PGD) in alleviating antipsychotic-induced hyperprolactinemia (hyperPRL) in schizophrenic patients. In previous experiment, PGD suppressed prolactin (PRL) level in MMQ cells, involving modulating the expression of D2 receptor (DRD2) and dopamine transporter (DAT). In the present study, hyperPRL female rat model induced by dopamine blocker metoclopramide (MCP) was applied to further confirm the anti-hyperpPRL activity of PGD and underlying mechanism. In MCP-induced hyperPRL rats, the elevated serum PRL level was significantly suppressed by either PGD (2.5-10 g/kg) or bromocriptine (BMT) (0.6 mg/kg) administration for 14 days. However, in MCP-induced rats, only PGD restored the under-expressed serum progesterone (P) to control level. Both PGD and BMT administration restore the under-expression of DRD2, DAT and TH resulted from MCP in pituitary gland and hypothalamus. Compared to untreated group, hyperPRL animals had a marked reduction on DRD2 and DAT expression in the arcuate nucleus. PGD (10 g/kg) and BMT (0.6 mg/kg) treatment significant reversed the expression of DRD2 and DAT. Collectively, the anti-hyperPRL activity of PGD associates with the modulation of dopaminergic neuronal system and the restoration of serum progesterone level. Our finding supports PGD as an effective agent against hyperPRL.

  19. Treating prolactinoma can prevent autoimmune diseases.

    PubMed

    Watad, Abdulla; Versini, Mathilde; Jeandel, Pierre-Yves; Amital, Howard; Shoenfeld, Yehuda

    2015-04-01

    Prolactin (PRL) is a pleiotropic hormone; in addition to a wide variety of endocrine effects, PRL also exhibits immunostimulating effects. Therefore, there is increasing evidence linking PRL with a large number of systemic and organ specific autoimmune diseases. Herein, we report the case of an adolescent girl diagnosed with multiple sclerosis (MS) occurring in the context of untreated prolactinoma evolving since childhood. This raises the exciting question of the involvement of PRL in the pathogenesis of MS. It is likely that early treatment of hyperprolactinemia in this case would have significantly reduced the risk of developing MS or even prevented its occurrence.

  20. Actions of Prolactin in the Brain: From Physiological Adaptations to Stress and Neurogenesis to Psychopathology

    PubMed Central

    Torner, Luz

    2016-01-01

    Prolactin (PRL) is one of the most versatile hormones known. It is considered an adaptive hormone due to the key roles it plays in the modulation of the stress response and during pregnancy and lactation. Within the brain, PRL acts as a neuropeptide to promote physiological responses related to reproduction, stress adaptation, neurogenesis, and neuroprotection. The action of PRL on the nervous system contributes to the wide array of changes that occur in the female brain during pregnancy and result in the attenuation of the hypothalamic–pituitary–adrenal axis. Together, all these changes promote behavioral and physiological adaptations of the new mother to enable reproductive success. Brain adaptations driven by PRL are also important for the regulation of maternal emotionality and well-being. PRL also affects the male brain during the stress response, but its effects have been less studied. PRL regulates neurogenesis both in the subventricular zone and in the hippocampus. Therefore, alterations in the PRL system due to stress or exposure to substances that reduce neurogenesis or other conditions, could contribute to maladaptive responses and pathological behavioral outcomes. Here, we review the PRL system and the role it plays in the modulation of stress response and emotion regulation. We discuss the effects of PRL on neurogenesis and neuroprotection, the putative neuronal mechanisms underlying these effects, and their contribution to the onset of psychopathological states such as depression. PMID:27065946

  1. Possible modulation of N-methyl-D,L-aspartic acid induced prolactin release by testicular steroids in the adult male rhesus monkey

    SciTech Connect

    Arslan, M.; Rizvi, S.S.R.; Jahan, S.; Zaidi, P.; Shahab, M. )

    1991-01-01

    N-methyl-D,L-aspartic acid (NMA), an agonist of the neurotransmitter glutamate has been shown to acutely stimulate the release of prolactin (PRL) in intact rats and monkeys. To further investigate the role of neuroexcitatory amino acids in PRL secretion, the effects of NMA administration were examined on PRL release in long term orchidectomized adult rhesus monkeys, in both the absence and presence of testosterone. Intact and long term castrated adult male monkeys weighing between 8-13 kg, were implanted with a catheter via the saphenous vein for blood withdrawal and drug infusion. Blood samples were collected at 10 min intervals for 50 min before and 70 min after administration of the drug or vehicle. Plasma PRL concentrations were estimated using radioimmunoassay. Whereas a single iv injection of NMA induced a prompt discharge of PRL in intact monkeys, an identical dose had surprisingly no effect on PRL secretion in orchidectomized animals. On the other hand, plasma PRL increases in response to a challenge dose of thyrotropin releasing hormone were similar in magnitude in the two groups of monkeys. Testosterone replacement in orchidectomized animals by parenteral administration of testosterone enanthate reinitiated the PRL responsiveness to acute NMA stimulation. These results indicate that N-methyl-D-aspartic acid (NMDA) dependent drive to PRL release in the adult male rhesus monkey may be overtly influenced by the sex steroid milieu.

  2. Relationship between Prolactin Plasma Levels and White Matter Volume in Women with Multiple Sclerosis

    PubMed Central

    De Giglio, L.; Marinelli, F.; Prosperini, L.; Contessa, G. M.; Gurreri, F.; Piattella, M. C.; De Angelis, F.; Barletta, V. T.; Tomassini, V.; Pantano, P.; Pozzilli, C.

    2015-01-01

    Background. The role of prolactin (PRL) on tissue injury and repair mechanisms in multiple sclerosis (MS) remains unclear. The aim of this work was to investigate the relationship between PRL plasma levels and brain damage as measured by magnetic resonance imaging (MRI). Methods. We employed a chemiluminescence immunoassay for measuring plasma levels of PRL. We used a 1.5 T scanner to acquire images and Jim 4.0 and SIENAX software to analyse them. Results. We included 106 women with relapsing remitting (RR) MS and stable disease in the last two months. There was no difference in PRL plasma levels between patients with and without gadolinium enhancement on MRI. PRL plasma levels correlated with white matter volume (WMV) (rho = 0.284, p = 0.014) but not with grey matter volume (GMV). Moreover, PRL levels predicted changes in WMV (Beta: 984, p = 0.034). Conclusions. Our data of a positive association between PRL serum levels and WMV support the role of PRL in promoting myelin repair as documented in animal models of demyelination. The lack of an increase of PRL in the presence of gadolinium enhancement, contrasts with the view considering this hormone as an immune-stimulating and detrimental factor in the inflammatory process associated with MS. PMID:26236110

  3. New insights into the importance of prolactin in dairy ruminants.

    PubMed

    Lacasse, P; Ollier, S; Lollivier, V; Boutinaud, M

    2016-01-01

    In most mammals, prolactin (PRL) is essential for maintaining lactation, and the suppression of PRL inhibits lactation. However, the involvement of PRL in the control of ruminant lactation is less clear, because inconsistent effects on milk yield have been observed with the short-term suppression of PRL by bromocriptine. Therefore, several experiments have been conducted to assess the galactopoietic role of PRL. In an initial experiment, cows in early lactation received daily injections of the dopamine agonist quinagolide for 9 wk. Quinagolide reduced milking-induced PRL release and caused a faster decline in milk production. Quinagolide also reduced mammary epithelial cell activity, survival, and proliferation. In goats, cabergoline, another dopamine agonist, caused a 28% decrease in milk yield the day after injection. In another experiment, cows were injected for 5d with quinagolide, with quinagolide plus bovine PRL injected at milking time, or with vehicles only. Again, quinagolide reduced milk, protein, and lactose yields. Although PRL injections were not sufficient to restore milk yield, they tended to increase milk protein and lactose yields and increased the viability of mammary epithelial cells purified from milk. Recently, our team stimulated PRL secretion with daily injections of the dopamine antagonist domperidone for 5 wk. Milk production increased gradually and was greater in domperidone-treated cows during the last 4 wk of the treatment period. In most experiments where PRL secretion was manipulated, feed intake paralleled the changes of PRL concentration, supporting the idea that PRL increases feed intake to provide the nutrients necessary to support lactation in dairy ruminants. In late-lactation cows, quinagolide and cabergoline decreased milk production within the first day of treatment and induced more rapid changes in several markers of mammary gland involution after drying-off. In addition, quinagolide improved the resistance to intramammary

  4. Prolactin and growth hormone responses to hypoglycemia in patients with systemic sclerosis and psoriatic arthritis.

    PubMed

    Rovensky, Jozef; Raffayova, Helena; Imrich, Richard; Radikova, Zofia; Penesova, Adela; Macho, Ladislav; Lukac, Jozef; Matucci-Cerinic, Marco; Vigas, Milan

    2006-06-01

    This study compared prolactin (PRL) and growth hormone (GH) responses to hypoglycemia in premenopausal females with systemic sclerosis (SSc) and psoriatic arthritis (PsA) with those in matched healthy controls. No differences were found in glucose and GH responses to hypoglycemia in both groups of patients compared to controls. SSc patients had lower PRL response (P < 0.05) to hypoglycemia compared to controls. PRL response tended to be lower also in PsA patients, however the difference did not reach level of statistical significance (P = 0.11). The present study showed decreased PRL response to hypoglycemia in premenopausal females with SSc. PMID:16855141

  5. New insights into the importance of prolactin in dairy ruminants.

    PubMed

    Lacasse, P; Ollier, S; Lollivier, V; Boutinaud, M

    2016-01-01

    In most mammals, prolactin (PRL) is essential for maintaining lactation, and the suppression of PRL inhibits lactation. However, the involvement of PRL in the control of ruminant lactation is less clear, because inconsistent effects on milk yield have been observed with the short-term suppression of PRL by bromocriptine. Therefore, several experiments have been conducted to assess the galactopoietic role of PRL. In an initial experiment, cows in early lactation received daily injections of the dopamine agonist quinagolide for 9 wk. Quinagolide reduced milking-induced PRL release and caused a faster decline in milk production. Quinagolide also reduced mammary epithelial cell activity, survival, and proliferation. In goats, cabergoline, another dopamine agonist, caused a 28% decrease in milk yield the day after injection. In another experiment, cows were injected for 5d with quinagolide, with quinagolide plus bovine PRL injected at milking time, or with vehicles only. Again, quinagolide reduced milk, protein, and lactose yields. Although PRL injections were not sufficient to restore milk yield, they tended to increase milk protein and lactose yields and increased the viability of mammary epithelial cells purified from milk. Recently, our team stimulated PRL secretion with daily injections of the dopamine antagonist domperidone for 5 wk. Milk production increased gradually and was greater in domperidone-treated cows during the last 4 wk of the treatment period. In most experiments where PRL secretion was manipulated, feed intake paralleled the changes of PRL concentration, supporting the idea that PRL increases feed intake to provide the nutrients necessary to support lactation in dairy ruminants. In late-lactation cows, quinagolide and cabergoline decreased milk production within the first day of treatment and induced more rapid changes in several markers of mammary gland involution after drying-off. In addition, quinagolide improved the resistance to intramammary

  6. Identification of target genes for a prolactin family paralog in mouse decidua.

    PubMed

    Alam, S M Khorshed; Konno, Toshihiro; Soares, Michael J

    2015-06-01

    Prolactin family 8, subfamily a, member 2 (PRL8A2; also called decidual prolactin-related protein; dPRP) is a member of the expanded prolactin family. PRL8A2 is expressed in the uterine decidua and contributes to pregnancy-dependent adaptations to hypoxia. The purpose of this study was to identify gene targets for PRL8A2 action within the uteroplacental compartment. Affymetrix DNA microarray analysis was performed for RNA samples from WT and Prl8a2 null tissues. Validation of the DNA microarray was performed using quantitative RT-PCR. Nine genes were confirmed with decreased expression in Prl8a2 null tissues (e.g., Klk7, Rimklb, Arhgef6, Calm4, Sprr2h, Prl4a1, Ccl27, Lipg, and Htra3). These include potential decidual, endothelial and trophoblast cell targets positively regulated by PRL8A2. A significant upregulation of Derl3, Herpud1, Creld2, Hsp90b1, Ddit3 and Hspa5 was identified in Prl8a2 null tissues, reflecting an increased endoplasmic reticulum (ER) stress response. ER stress genes were prominently expressed in the uterine decidua. We propose that PRL8A2 is a mediator of progesterone-dependent modulation of intrauterine responses to physiological stressors.

  7. Actions of Prolactin in the Brain: From Physiological Adaptations to Stress and Neurogenesis to Psychopathology.

    PubMed

    Torner, Luz

    2016-01-01

    Prolactin (PRL) is one of the most versatile hormones known. It is considered an adaptive hormone due to the key roles it plays in the modulation of the stress response and during pregnancy and lactation. Within the brain, PRL acts as a neuropeptide to promote physiological responses related to reproduction, stress adaptation, neurogenesis, and neuroprotection. The action of PRL on the nervous system contributes to the wide array of changes that occur in the female brain during pregnancy and result in the attenuation of the hypothalamic-pituitary-adrenal axis. Together, all these changes promote behavioral and physiological adaptations of the new mother to enable reproductive success. Brain adaptations driven by PRL are also important for the regulation of maternal emotionality and well-being. PRL also affects the male brain during the stress response, but its effects have been less studied. PRL regulates neurogenesis both in the subventricular zone and in the hippocampus. Therefore, alterations in the PRL system due to stress or exposure to substances that reduce neurogenesis or other conditions, could contribute to maladaptive responses and pathological behavioral outcomes. Here, we review the PRL system and the role it plays in the modulation of stress response and emotion regulation. We discuss the effects of PRL on neurogenesis and neuroprotection, the putative neuronal mechanisms underlying these effects, and their contribution to the onset of psychopathological states such as depression.

  8. Identification of prolactin and growth hormone binding proteins in rabbit milk.

    PubMed Central

    Postel-Vinay, M C; Belair, L; Kayser, C; Kelly, P A; Djiane, J

    1991-01-01

    Two distinct soluble proteins that specifically bind 125I-labeled human growth hormone (GH) are identified in the supernatant of ultracentrifuged rabbit milk, using HPLC gel filtration. The higher molecular weight proteins is GH specific, whereas the other one is specific for prolactin (PRL). The PRL-binding protein has a very high affinity for the hormone, almost 10 times higher than the affinity of the mammary gland membrane receptor. The PRL-binding protein is immunoprecipitated by a monoclonal antibody against the PRL receptor; another monoclonal antibody, which inhibits the PRL binding to mammary gland membranes, is a poor competitor for the PRL binding to the milk protein. These findings suggest that the milk PRL-binding protein corresponds to the binding domain of the receptor, but also that the conformation of the receptor and of the binding protein might differ. The milk and the plasma GH-binding proteins have a similar binding affinity. In cross-linking experiments using 125I-labeled human GH, the Mr of the GH-binding protein and of the PRL-binding protein were estimated to be 51,000 and 33,000, respectively. The binding proteins identified in the present work are probably responsible for the transport of their specific ligands in the milk. It is also conceivable that they have a role in the effects of GH and PRL in the mammary gland and/or the intestine of the young. Images PMID:1862093

  9. Human growth hormone and prolactin secreting pituitary adenomas analyzed by in situ hybridization.

    PubMed

    Lloyd, R V; Cano, M; Chandler, W F; Barkan, A L; Horvath, E; Kovacs, K

    1989-03-01

    Acidophilic pituitary adenomas commonly produce growth hormone (GH) or prolactin (PRL), according to studies employing immunohistochemical and ultrastructural methods. To examine this question, in situ hybridization with oligonucleotide probes was done on routinely processed tissues received in the pathology laboratory to analyze for the presence of GH and PRL messenger RNA (mRNA) in 4 normal pituitaries, 10 prolactinomas, and 16 GH-secreting adenomas. Most acidophilic cells in normal pituitaries expressed either GH or PRL hormone and the respective mRNAs, but GH mRNA and PRL hormone were also detected in some of the same cells. Patients with a clinical diagnosis of prolactinoma had cells with only PRL mRNA in their tumors, while most (14 of 16) patients with a clinical diagnosis of acromegaly or gigantism had both GH and PRL mRNAs in their tumors. The GH adenomas varied in these studies. In situ hybridization was helpful in characterizing the adenoma from a patient with acromegaly who had immunoreactive PRL, but no immunoreactive GH in the resected tumor; in situ hybridization analysis revealed mRNAs for both GH and PRL in the same tumor cells. Our findings indicate that pituitary adenomas from patients with acromegaly commonly express PRL mRNA. It is concluded that in situ hybridization provides new information about the clinical biology and the histopathologic classification of pituitary adenomas. PMID:2466405

  10. Prolactin during pregnancy and lactation in the rabbit.

    PubMed

    McNeilly, A S; Friesen, H G

    1978-05-01

    By using a specific heterologous double-antibody RIA, changes in the blood levels of PRL during pregnancy, pseudopregnancy, and lactation have been investigated for the first time in the rabbit. Blood levels fluctuate during early and midpregnancy in a manner similar to that in pseudopregnancy. Levels decline in the third trimester of pregnancy and increase dramatically (3- to 25-fold) at or 1--2 days before delivery. Pituitary levels of PRL showed no significant alteration, and fetal serum and amniotic fluid levels of PRL remain low (less than 10 ng/ml) throughout pregnancy. No significant PRL-like, GH-like, or placental lactogen-like activity could be demonstrated either in serum or in extracts of placenta (n = 262) taken between days 10 and 31 of pregnancy. Postpartum blood levels of PRL were similar in lactating and postpartum nonlactating females. In lactating females, suckling evoked an immediate increase (15- to 25-fold) in circulating PRL levels. Handling the female or the iv injection of oxytocin during lactation did not cause PRL release. In contrast, manual test stimulation caused an immediate increase in blood levels of PRL and a response pattern very similar to that of natural suckling. These results suggest that PRL release during suckling occurs solely in response to the tactile stimulation of the teats.

  11. Inhibitory effect of prolactin on Toxoplasma proliferation in peripheral blood mononuclear cells from patients with hyperprolactinemia.

    PubMed

    Dzitko, K; Lawnicka, H; Gatkowska, J; Dziadek, B; Komorowski, J; Długońska, H

    2012-06-01

    Despite many years of studies on the mechanisms of immunological defence responses induced in host organisms by Toxoplasma, no satisfactory immunoprophylaxis or chemotherapy have yet been established for humans. Thus, alternative methods to prevent toxoplasmosis and to enhance the efficacy of currently used antitoxoplasmic drugs are under evaluation. In this work, we strove to determine the influence of human prolactin (endogenous present in serum--sPRL and recombinant--rhPRL) on the course of Toxoplasma infection of peripheral blood mononuclear cells (PBMC) originating from female hyperprolactinemia patients. This study revealed that exogenous rhPRL as well as autologous sPRL from inactivated sera significantly restricted intracellular growth of Toxoplasma in PBMC cultures. Moreover, analysis of IL-10 production by PBMC infected with Toxoplasma and cultured in the presence of sPRL showed a positive correlation between sPRL concentration and the level of IL-10. The obtained results could indicate the possible protective action of PRL in a host organism infected with Toxoplasma and suggest that a significant increase in the serum PRL level, during pregnancy for instance, might significantly limit the risk of Toxoplasma spreading and could play an important role in natural protection against toxoplasmosis. The mechanism of inhibitory effect of PRL needs further detailed study.

  12. Prolactin counteracts effects of short day lengths on pelage growth in the meadow vole, Microtus pennsylvanicus.

    PubMed

    Smale, L; Lee, T M; Nelson, R J; Zucker, I

    1990-02-01

    To test whether growth of the winter coat in short day lengths is contingent on suppression of plasma prolactin (Prl) levels, female meadow voles (Microtus pennsylvanicus) were kept in short day lengths for 12 weeks and were injected daily with saline or Prl; long-day animals were treated with either the dopamine agonist, bromocryptine (bromo), bromo plus Prl, or saline. Prl treatment prevented the growth of the winter coat normally observed after 12 weeks in short day lengths, but bromocryptine did not stimulate pelage growth in long-day voles. Pelage growth in short day lengths appears contingent upon decreased plasma prolactin levels. PMID:2179462

  13. Diethylstilbestrol increases the density of prolactin cells in male mouse pituitary by inducing proliferation of prolactin cells and transdifferentiation of gonadotropic cells.

    PubMed

    Shukuwa, Keiko; Izumi, Shin-Ichi; Hishikawa, Yoshitaka; Ejima, Kuniaki; Inoue, Satoshi; Muramatsu, Masami; Ouchi, Yasuyoshi; Kitaoka, Takashi; Koji, Takehiko

    2006-07-01

    Diethylstilbestrol (DES) has been implicated in mammalian abnormalities. We examined the effects of DES on follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) cells in the pituitaries of male mice treated with various doses of DES for 20 days. DES reduced the density of FSH and LH cells in a dose-dependent manner, but increased that of PRL cells. When the expression of estrogen receptor (ER) alpha and beta was assessed, an induction of ERbeta by DES was found predominantly in PRL cells. However, since these effects were abolished in ERalpha knockout mice, DES appears to act primarily through ERalpha. When the expression of Ki-67 and Pit-1 in PRL cells was examined at various time-points after DES treatment, some PRL cells became Ki-67 positive at 10-15 days, and Pit-1-positive cells were increased at 5-15 days. Furthermore, some FSH and LH cells became Pit-1 positive, and co-localized with PRL at 5-10 days. Our results indicate that DES increases PRL cells by inducing proliferation of PRL cells and transdifferentiation of FSH/LH cells to PRL cells. PMID:16468032

  14. Effect of chronic prolactin infusion on pituitary prolactin and hypothalamic proopiomelanocortin.

    PubMed

    Wardlaw, S L; Kim, J; Matera, C

    1997-02-01

    Although there is evidence that endogenous opioids, and in particular beta-endorphin (beta-EP), may mediate some of the suppressive effects of hyperprolactinemia on the hypothalamic-pituitary-gonadal (HPG) axis, there is controversy about the effects of prolactin (PRL) on beta-EP and its precursor, proopiomelanocortin (POMC), in the hypothalamus. In this study we have therefore examined the effects of chronic peripheral and intracerebroventricular (i.c.v.) infusion of ovine PRL on POMC gene expression and beta-EP levels in the medial basal hypothalamus (MBH) of castrated male and female rats. Endogenous pituitary and plasma PRL levels were determined by RIA with an antiserum to rat PRL which does not crossreact with oPRL. Suppression of endogenous rPRL levels was used as a confirmation of the biological effectiveness of the infused oPRL. POMC mRNA was measured in the MBH by solution hybridization assay. In the first experiment oPRL (5 microg/microl/h) or vehicle was infused for 2 weeks by osmotic minipump into the right lateral ventricle of ovariectomized rats. The mean plasma concentration of rPRL declined from 3.7+/-1.0 ng/ml in the controls to 1.4+/-0.13 ng/ml in the oPRL infused animals (P<0.05); pituitary rPRL content similarly decreased from 39.1+/-4.6 microg to 20.4+/-3.7 microg (P<0.02). There was no significant change in the concentration of POMC mRNA or beta-EP in the MBH of the oPRL treated animals. In the second experiment oPRL was infused for 1 week into the third ventricle of orchiectomized rats. Again despite a fall in endogenous PRL levels, there was no significant change in POMC or beta-EP in the MBH. In the third experiment oPRL was infused subcutaneously into orchiectomized rats for 2 weeks. Mean plasma oPRL levels were 150+/-7.3 ng/ml after 1 week and 58+/-7.5 ng/ml after 2 weeks. Pituitary rPRL content was again suppressed in the oPRL treated animals but no change in POMC or beta-EP was detected in the MBH. We conclude that oPRL can be infused

  15. The sensitivity of growth hormone and prolactin secretion to the somatostatin analogue SMS 201-995 in patients with prolactinomas and acromegaly.

    PubMed

    Lamberts, S W; Zweens, M; Klijn, J G; van Vroonhoven, C C; Stefanko, S Z; Del Pozo, E

    1986-08-01

    The somatostatin analogue SMS 201-995 has recently been shown to be effective in suppressing GH secretion in most acromegalic patients. In the present study it was investigated whether PRL release in prolactinoma and acromegalic patients might also be sensitive to SMS 201-995 and whether co-secretion of PRL in acromegaly plays a role in determining the sensitivity of GH secretion to SMS 201-995. The s.c. administration of 50 micrograms SMS 201-995 did not affect high plasma PRL levels in four microprolactinoma patients. Therapy of one of these patients for 3 d with 50 micrograms three times a day also did not affect PRL levels. The single administration of 50 micrograms SMS 201-995 in 22 acromegalic patients lowered plasma GH levels for 2-6 h to less than 5 micrograms/l in 14 patients and to less than 50% of control values in 16 patients. In 18 of these 22 patients the immunohistochemical picture of the pituitary tumour was known. Eleven patients had pure GH-containing tumours and in seven patients there were mixed GH/PRL-containing tumours. In two of these latter patients there was evidence for GH and PRL being secreted by the same tumour cells. The sensitivity of GH secretion to SMS 201-995 did not differ between the patients with pure GH or mixed GH/PRL-containing adenomas. Plasma PRL levels were not affected by SMS 201-995 in the patients with pure GH-secreting tumours, but were significantly suppressed in four of the seven patients with mixed GH/PRL containing tumours. Chronic treatment for 16 weeks of one patient with a mixed GH/PRL-containing tumour with SMS 201-995 (100 micrograms three times a day) resulted in normalization of both the increased GH and PRL levels. It is concluded that SMS 201-995 does not affect tumorous PRL secretion in patients with pure prolactinomas. In acromegalic patients with mixed GH/PRL-containing tumours PRL secretion in some patients is sensitive to SMS 201-995, making these patients good candidates for chronic treatment with

  16. Circulating breeding and pre-breeding prolactin and LH are not associated with clutch size in the zebra finch (Taeniopygia guttata).

    PubMed

    Ryan, Calen P; Dawson, Alistair; Sharp, Peter J; Meddle, Simone L; Williams, Tony D

    2014-06-01

    Clutch size is a fundamental predictor of avian fitness, widely-studied from evolutionary and ecological perspectives, but surprisingly little is known about the physiological mechanisms regulating clutch size variation. The only formal mechanistic hypothesis for avian clutch-size determination predicts an anti-gonadal effect of circulating prolactin (PRL) via the inhibition of luteinizing hormone (LH), and has become widely-accepted despite little experimental support. Here we investigated the relationship between pre-breeding and breeding plasma PRL and LH and clutch-size in captive-breeding female zebra finches (Taeniopygia guttata). Using a repeated-measures design, we followed individual females from pre-breeding, through multiple breeding attempts, and attempted to decrease PRL using the D2-receptor agonist, bromocriptine. Clutch size was independent of variation in pre-breeding PRL or LH, although pre-breeding LH was negatively correlated with the time between pairing and the onset of laying. Clutch size was independent of variation in plasma PRL on all days of egg-laying. Bromocriptine treatment had no effect on plasma PRL, but in this breeding attempt clutch size was also independent of plasma PRL. Finally, we found no evidence for an inverse relationship between plasma PRL and LH levels, as predicted if PRL had inhibitory effects via LH. Thus, our data fail to provide any support for the involvement of circulating PRL in clutch size determination. These findings suggest that alternative models for hormonal control of avian clutch size need to be considered, perhaps involving downstream regulation of plasma PRL at the level of the ovary, or other hormones that have not been considered to date.

  17. Non-classical effects of prolactin on the innate immune response of bovine mammary epithelial cells: Implications during Staphylococcus aureus internalization.

    PubMed

    Medina-Estrada, Ivan; Alva-Murillo, Nayeli; López-Meza, Joel E; Ochoa-Zarzosa, Alejandra

    2015-12-01

    Staphylococcus aureus has the ability to invade mammary epithelial cells (bMECs) causing mastitis. This event depends primarily on the α5β1 integrin in the host cell. In addition, bMECs are a target for the hormone prolactin (PRL), which can regulate β1 integrin-dependent actions related to differentiation and lactation. Previously, we demonstrated that bovine PRL (bPRL, 5 ng/ml) stimulates S. aureus internalization into bMECs. TLR2 is important during S. aureus infections, but its activation by PRL has not yet been established. The objective of this study was to determine the role of α5β1 integrin and TLR2 during S. aureus internalization into bMECs stimulated with bPRL. We demonstrated that the prolactin-stimulated internalization of S. aureus decreases in response to the blockage of α5β1 integrin (∼ 80%) and TLR2 (∼ 80%). bPRL increases the membrane abundance (MA) of α5β1 integrin (∼ 20%) and induces TLR2 MA (∼ 2-fold). S. aureus reduces the α5β1 integrin MA in bMECs treated with bPRL (∼ 75%) but induces TLR2 MA in bMECs (∼ 3-fold). Bacteria and bPRL did not modify TLR2 MA compared with the hormone alone. S. aureus induces the activation of the transcription factor AP-1, which was inhibited in bMECs treated with bPRL and infected. In general, bPRL induces both pro- and anti-inflammatory responses in bMECs, which are abated in response to bacterial challenge. Interestingly, the canonical Stat-5 transcription factor was not activated in the challenged bMECs and/or treated with bPRL. Taken together, these results support novel functions of prolactin as a modulator of the innate immune response that do not involve the classical prolactin pathway.

  18. Structure and Function of a New Class of Human Prolactin Antagonists

    PubMed Central

    DePalatis, Laura; Almgren, Colleen M.; Patmastan, Jypji; Troyer, Mark; Woodrich, Todd; Brooks, Charles L.

    2009-01-01

    Summary Δ41-52 hPRL (human prolactin with residues 41-52 removed) is a lead compound for a new class of hPRL antagonists. The deleted sequence contains residues that functionally couple sites 1 and 2, the two hormone surfaces that each bind receptors. Δ41-52 hPRL retains 0.03% agonist activity in FDC-1 cell bioassays, a 3,054-fold reduction in activity, and displays approximately 100-fold less agonist activity than G129R hPRL, an antagonist that reduces the binding of hPRL receptor at site 2 during the formation of the heterotrimeric hormone/receptor complex. Replacement of various numbers and types of residues into the gap created by the deletion of residues 41 through 52 created hPRLs with varying agonist activities, suggested that manipulation of the sequence connecting the C-terminal of helix 1 with the disulfide bond (cysteines 58 with 174) linking helices 1 and 4 modulates articulation of these helices and influences agonist activity. We have compared the antagonist activities of G129R and Δ41-52 hPRLs to induce apoptosis in Jurkat cells, a human lymphoid cell line displaying an autocrine/paracrine hPRL/receptor system. Δ41-52 hPRL induces apoptosis in a time and dose-dependent fashion. Under these same conditions G129R hPRL fails to induce apoptosis. We conclude Δ41-52 hPRL is a lead compound of a new class of hPRL antagonists capable at low concentrations of inducing apoptosis in human cells expressing an autocrine/paracrine hPRL/receptor system. PMID:19236917

  19. Poly(o-phenylenediamine)-carried nanogold particles as signal tags for sensitive electrochemical immunoassay of prolactin.

    PubMed

    Chen, Huafeng; Cui, Yuling; Zhang, Bing; Liu, Bingqian; Chen, Guonan; Tang, Dianping

    2012-05-30

    A novel class of redox-active molecular tags, poly(o-phenylenediamine)-carried nanogold particles (GPPDs), was first synthesized and functionalized with horseradish peroxidase-anti-prolactin conjugates (HRP-anti-PRL). Thereafter, a specific sandwich-type electrochemical immunoassay was designed for determination of prolactin (PRL) by using GPPD-labeled HRP-anti-PRL conjugates as molecular tags on anti-PRL antibody-modified glassy carbon electrode. Compared with pure gold nanoparticles and poly(o-phenylenediamine) microspheres, the as-prepared GPPDs increased the surface coverage of the nanostructures, and enhanced the immobilization amount of biomolecules. Several labeling protocols compromising GPPD-labeled HRP-anti-PRL, nanogold particles-labeled HRP-anti-PRL and poly(o-phenylenediamine) microspheres-labeled HRP-anti-PRL, were investigated for detection of PRL, and improved analytical features were obtained with the GPPD-based strategy. With the GPPD labeling method, dependence of the electrochemical signals on the incubation time and pH of the assay solution were also studied. The strong attachment of HRP-anti-PRL to the GPPDs resulted in a good repeatability and intermediate reproducibility down to 9.8%. The dynamic concentration range spanned from 0.5 to 180 ng mL(-1) PRL with a detection limit of 0.1 ng mL(-1) at the 3S(blank) level. No significant differences at the 95% confidence level were encountered in the analysis of 10 spiked blank cattle serum samples between the developed immunoassay and enzyme-linked immunosorbent assay method for determination of PRL.

  20. Prolactin-binding components in rabbit mammary gland: characterization by partial purification and affinity labeling

    SciTech Connect

    Katoh, M.; Djiane, J.; Kelly, P.A.

    1985-06-01

    The molecular characteristics of the PRL receptor isolated from rabbit mammary gland microsomes were investigated. Two approaches were employed: 1) affinity purification of PRL receptors and direct electrophoretic analysis, and 2) affinity cross-linking of microsomal receptors with (/sup 125/I)ovine PRL ((/sup 125/I)oPRL). PRL receptors were solubilized from mammary microsomes with 3-((3-cholamidopropyl)dimethylammonio)1-propane sulfonate and purified using an oPRL agarose affinity column. Sodium dodecylsulfate-polyacrylamide gel electrophoresis and silver staining of the gel revealed at least nine bands, including a 32,000 mol wt band which was most intensively labeled with /sup 125/I using the chloramine-T method. Covalent labeling of PRL receptors with (/sup 125/I)oPRL was performed using N-hydroxysuccinimidyl-4-azido benzoate, disuccinimidyl suberate, or ethylene glycol bis (succinimidyl succinate). A single band of 59,000 mol wt was produced by all three cross-linkers when sodium dodecylsulfate-polyacrylamide gel electrophoresis was performed under reducing conditions. Assuming 1:1 binding of hormone and binding subunit and by subtracting the mol wt of (/sup 125/I)oPRL, which was estimated from the migration distance on the gel, the mol wt of the binding subunit was calculated as 32,000. In the absence of dithiothreitol during electrophoresis, only one major hormone-receptor complex band was observed. The same mol wt binding components were also detected in microsomal fractions of rabbit kidney, ovary, and adrenal. A slightly higher mol wt binding subunit was observed in rat liver microsomes. Rabbit liver microsomes revealed five (/sup 125/I)oPRL-binding components, three of which were considered to be those of a GH receptor. Moreover, affinity labeling of detergent-solubilized and affinity purified mammary PRL receptors showed a similar major binding subunit.

  1. Chondroregulatory action of prolactin on proliferation and differentiation of mouse chondrogenic ATDC5 cells in 3-dimensional micromass cultures

    SciTech Connect

    Seriwatanachai, Dutmanee; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer Mouse chondrogenic ATDC5 cells expressed PRL receptor mRNAs and proteins. Black-Right-Pointing-Pointer Low PRL concentration (10 ng/mL) increased chondrocyte viability and differentiation. Black-Right-Pointing-Pointer Higher PRL concentrations ( Greater-Than-Or-Slanted-Equal-To 100 ng/mL) decreased viability and increased apoptosis. -- Abstract: A recent investigation in lactating rats has provided evidence that the lactogenic hormone prolactin (PRL) increases endochondral bone growth and bone elongation, presumably by accelerating apoptosis of hypertrophic chondrocytes in the growth plate and/or subsequent chondrogenic matrix mineralization. Herein, we demonstrated the direct chondroregulatory action of PRL on proliferation, differentiation and apoptosis of chondrocytes in 3-dimensional micromass culture of mouse chondrogenic ATDC5 cell line. The results showed that ATDC5 cells expressed PRL receptor (PRLR) transcripts, and responded typically to PRL by downregulating PRLR expression. Exposure to a low PRL concentration of 10 ng/mL, comparable to the normal levels in male and non-pregnant female rats, increased chondrocyte viability, differentiation, proteoglycan accumulation, and mRNA expression of several chondrogenic differentiation markers, such as Sox9, ALP and Hspg2. In contrast, high PRL concentrations of Greater-Than-Or-Slanted-Equal-To 100 ng/mL, comparable to the levels in pregnancy or lactation, decreased chondrocyte viability by inducing apoptosis, with no effect on chondrogenic marker expression. It could be concluded that chondrocytes directly but differentially responded to non-pregnant and pregnant/lactating levels of PRL, thus suggesting the stimulatory effect of PRL on chondrogenesis in young growing individuals, and supporting the hypothesis of hypertrophic chondrocyte apoptosis in the growth plate of lactating rats.

  2. Prolactin secretion after hypothalamic deafferentation in beef calves: response to haloperidol, alpha-methyl-rho-tyrosine, thyrotropin-releasing hormone and ovariectomy.

    PubMed

    Benoit, Allison M; Molina, Jose R; Lkhagvadorj, Sender; Anderson, Lloyd L

    2009-03-01

    In ruminant species photoperiod regulates prolactin (PRL) secretion. It is hypothesized that the inhibition of PRL secretion resides in dopaminergic neurons of the medial basal hypothalamus (MBH). To test this hypothesis, anterior (AHD), posterior (PHD) and complete (CHD) hypothalamic deafferentation and sham operation control (SOC) surgeries were carried out during May (long-day photoperiod) in beef heifer calves (6-8 mo old) to measure basal PRL secretion and PRL secretion as affected by intravenous secretagogues. On the day of surgery (day 0), PRL secretion reflected stress of anesthesia and surgery in all groups. Thyrotropin-releasing hormone (TRH), alpha-methyl-rho-tyrosine (alphaMrhoT), and haloperidol (HAL) was iv injected on days 11, 13 and 15, respectively. AHD, PHD, CHD, and SOC calves responded to TRH (100 microg) with an acute increase in PRL that peaked within 20 min. All heifers responded to alphaMrhoT (10 mg/kg BW) with an acute elevation in PRL within 10 min and remaining elevated for 3 h. HAL (0.1 mg/kg BW) induced an acute increase in PRL secretion in all groups, peaking within 15-30 min. Seven months later (December, short-day photoperiod) these heifers were ovariectomized. Basal plasma PRL levels were seasonally low, PRL secretion in AHD, PHD and CHD animals abruptly increased within 15 min to iv injection of 100 microg TRH to a greater amount than seen in SOC heifers. Although a biphasic effect on PRL secretion entrains under long-day and short-day photoperiods, hypothalamic deafferentation in cattle did not affect the pituitary gland's responsiveness to secretagogues.

  3. Rhythmic secretion of prolactin in rats: action of oxytocin coordinated by vasoactive intestinal polypeptide of suprachiasmatic nucleus origin.

    PubMed

    Egli, Marcel; Bertram, Richard; Sellix, Michael T; Freeman, Marc E

    2004-07-01

    Prolactin (PRL) is secreted from lactotrophs of the anterior pituitary gland of rats in a unique pattern in response to uterine cervical stimulation (CS) during mating. Surges of PRL secretion occur in response to relief from hypothalamic dopaminergic inhibition and stimulation by hypothalamic releasing neurohormones. In this study, we characterized the role of oxytocin (OT) in this system and the involvement of vasoactive intestinal polypeptide (VIP) from the suprachiasmatic nucleus (SCN) in controlling OT and PRL secretion of CS rats. The effect of OT on PRL secretion was demonstrated in cultured lactotrophs showing simultaneous enhanced secretion rate and increased intracellular Ca(2+). Neurosecretory OT cells of the hypothalamic paraventricular nucleus that express VIP receptors were identified by using immunocytochemical techniques in combination with the retrogradely transported neuronal tracer Fluoro-Gold (iv injected). OT measurements of serial blood samples obtained from ovariectomized (OVX) CS rats displayed a prominent increase at the time of the afternoon PRL peak. The injection of VIP antisense oligonucleotides into the SCN abolished the afternoon increase of OT and PRL in CS-OVX animals. These findings suggest that VIP from the SCN contributes to the regulation of OT and PRL secretion in CS rats. We propose that in CS rats the regulatory mechanism(s) for PRL secretion comprise coordinated action of neuroendocrine dopaminergic and OT cells, both governed by the daily rhythm of VIP-ergic output from the SCN. This hypothesis is illustrated with a mathematical model. PMID:15033917

  4. Experimental Modification of Rat Pituitary Prolactin Cell Function During and After Spaceflight

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.; Salada, T.; Avery, L.; Grindeland, R. E.

    1996-01-01

    Experimental modification of rat pituitary prolactin cell function during and after spaceflight. This study was done to evaluate the effects of microgravity on prolactin (PRL) cells of the male rat pituitary gland. We used the identical passive closed-vial cell culture system that was described for the culture of growth hormone cells (W C. Hymer, R. E. Grindeland, T. Salada, P. Nye, E. Grossman, and R Lane). After an 8-day spaceflight, all flight media (containing released PRL), as well as extracts (containing intracellular PRL), contained significantly lower amounts of immunoreactive PRL than their corresponding ground control samples. On the other hand, these same samples, when assessed for their biological activities by two different in vitro lymphocyte assays, yielded disparate results that may reflect posttranslational modifications to the hormone molecule. Other data showed that: (1) the apparent molecular weights of released PRL molecules were not altered by microgravity; but (2) the region from which the PRL cells came (dorsal or ventral) made a significant difference in the amount and activity of PRL released from the flight cells. Because there is much current interest in the role that PRL may play in the regulation of the immune system and because changes in both cellular and humoral immunity accompany spaceflight, this study could help define future microgravity research in this area.

  5. Involvement of hypothalamic dopamine in the regulation of prolactin secretion.

    PubMed

    Reymond, M J; Porter, J C

    1985-01-01

    The neuroendocrine control of prolactin (PRL) secretion is known to be a multifactorial process, but dopamine (DA) secreted by the tuberoinfundibular dopaminergic (TIDA) neurons of the hypothalamus is believed to exert a predominant inhibitory control on the secretion of PRL. The secretory activity of the TIDA neurons, including the rate of biosynthesis of DA and the rate of release of the neurohormone into hypophysial portal blood, can be readily evaluated in the rat. In most conditions in which an altered secretion of PRL has been documented, an altered secretory activity of the TIDA neurons has been found. When an acute reduction in the secretion of DA is observed, an increased secretion of PRL is associated, with an inverse relationship between DA and PRL concentrations in hypophysial portal and systemic blood, respectively. However, the secretion of PRL can be regulated by PRL itself through stimulation of the secretory activity of the TIDA neurons, and consequently hyperprolactinemia can be observed concomitantly with a sustained high secretion of DA, as seen after treatment with estrogen. The short loop feedback of PRL secretion seems to be impaired in the aging rat, since a sustained reduced hypothalamic secretion of DA is observed in spite of long-term hyperprolactinemia.

  6. Prolactin Serum Concentrations During Aripiprazole Treatment in Youth

    PubMed Central

    Calarge, Chadi A.; Safer, Alan M.

    2013-01-01

    Abstract Objective This study aimed to: document the extent of the reduction of serum prolactin (PRL) levels induced by aripiprazole (ARI) treatment in children and adolescents, compare this effect by age group, and shed light on this phenomenon. Methods PRL serum levels in unmedicated subjects were compared to those in subjects treated with aripiprazole to calculate the rate of subnormal PRL levels during aripiprazole treatment. Next, a literature search was performed to better understand the effects of dopaminergic drugs on PRL levels by age group. Results Sixty percent of those treated with aripiprazole exhibited subnormal PRL serum levels versus 8% of unmedicated subjects. The rate of PRL subnormality in response to aripiprazole was half as frequent in adolescents and was minimal in adults. The drug-induced reduction of PRL serum levels became more prominent with increasing doses of aripiprazole and with an increased treatment duration. Conclusions With the increasing use of aripiprazole in the United States population, it is important that future research be conducted to explore the potential sequelae of subnormal PRL serum levels in children and adolescents. PMID:23647135

  7. Dopamine–prolactin pathway potentially contributes to the schizophrenia and type 2 diabetes comorbidity

    PubMed Central

    Gragnoli, C; Reeves, G M; Reazer, J; Postolache, T T

    2016-01-01

    Schizophrenia (SCZ) and type 2 diabetes (T2D) are clinically associated, and common knowledge attributes this association to side effects of antipsychotic treatment. However, even drug-naive patients with SCZ are at increased risk for T2D. Dopamine dysfunction has a central role in SCZ. It is well-known that dopamine constitutively inhibits prolactin (PRL) secretion via the dopamine receptor 2 (DR2D). If dopamine is increased or if dopamine receptors hyperfunction, PRL may be reduced. During the first SCZ episode, low PRL levels are associated with worse symptoms. PRL is essential in human and social bonding, as well as it is implicated in glucose homeostasis. Dopamine dysfunction, beyond contributing to SCZ symptoms, may lead to altered appetite and T2D. To our knowledge, there are no studies of the genetics of the SCZ–T2D comorbidity focusing jointly on the dopamine and PRL pathway in the attempt to capture molecular heterogeneity correlated to possible disease manifestation heterogeneity. In this dopamine–PRL pathway-focused-hypothesis-driven review on the association of SCZ with T2D, we report a specific revision of what it is known about PRL and dopamine in relation to what we theorize is one of the missing links between the two disorders. We suggest that new studies are necessary to establish the genetic role of PRL and dopamine pathway in SCZ–T2D comorbidity. PMID:27093067

  8. Prolactin variations during risperidone therapy in a sample of drug-naive children and adolescents

    PubMed Central

    Matera, Emilia; Petruzzelli, Maria G.; Simone, Marta; Lamanna, Anna L.; Pastore, Adriana; Palmieri, Vincenzo O.; Margari, Francesco

    2015-01-01

    The aim of this prospective observational study was to investigate the variations of serum prolactin hormone (PRL) in a sample of 34 drug-naive patients (mean age 13 years) who started risperidone therapy assuming that several factors may favor the increase in serum PRL. Serum PRL and hyperprolactinemia clinical signs were examined at baseline (T0) and after almost 3 months of treatment (T1). We considered sex, pubertal status, risperidone dosage, psychiatric diagnosis, and any personal/family history of autoimmune diseases. The mean serum PRL value increased between T0 and T1 (P=0.004). The mean serum PRL was higher in females in the pubertal/postpubertal stage and for risperidone dosage up 1 mg/day. Hyperprolactinemia was found in 20% of patients at T0 and in 38% of patients at T1 (P=0.03). The mean serum PRL increase was greater in early-onset schizophrenia spectrum psychosis patients compared with no-early-onset schizophrenia spectrum psychosis patients (P=0.04). The increase in PRL was higher in patients with a personal and a family history of autoimmune diseases. This study suggests that the increase in serum PRL in patients treated with risperidone may be linked not only to the drug and its dosage but also to several risk factors such as sex, pubertal stage, psychiatric disease, and autoimmune disorders. PMID:25514607

  9. Heterogeneity of circulating prolactin in the bitch.

    PubMed

    Gobello, C; Colombani, M; Scaglia, H; De La Sota, R L; Goya, R G

    2001-01-01

    Different molecular forms of circulating prolactin (PRL) are known to occur in several species. As no such information was available in dogs, we assessed the molecular profile of circulating PRL in bitches. Pooled sera from covertly (CTRL) and overtly pseudopregnant (PSPT) diestrous bitches with high or low (> 10 or < 10 ng x mL(-1), respectively) serum PRL (measured by ELISA) were analyzed by Sephadex G-100 and Concanavalin A-Sepharose column chromatography. Four serum PRL fractions were identified and termed big-big, big (> 67 kDa), native (23 kDa) and fragmented (< 20) kDa) PRL. The percentages of these fractions were roughly similar in CTRL and PSPT animals, irrespective of their serum PRL levels (higher in PSPT than in CTRL bitches). A large proportion of glycosylated PRL (between 69 and 100%) was also detected in these sera. We conclude that in dogs, circulating PRL occurs in multiple molecular forms, whose relative abundance is comparable in covertly and overtly pseudopregnant bitches.

  10. Immunogold identification of prolactin cells of goats in anoestrus, pregnancy and milk production: ultrastructural variations.

    PubMed

    Sánchez, J; Bernabé, A; Navarro, J A; Gómez, M A; Gómez, J

    1992-01-01

    Prolactin (PRL) cells of the goat adenohypophysis have been identified by the IgG-gold procedure with anti-sheep PRL serum. The secretion of these cells show differences in size and labelling in the three reproductive stages under study. Cells containing PRL can be grouped into low secretory activity cells (PRL-I) and high secretory activity cells (PRL-II) regarding their ultrastructure and functional significance. PRL-I were the most frequent cells in animals at the anoestrus stage, presenting numerous secretory granules and scarce development of the rough endoplasmic reticulum (RER) and Golgi complex (GC). At anoestrus and pregnancy stages there are frequent granule fusions, and the hormonal content partially disappears, perhaps by digestion. PRL-II cells were the most numerous at the lactating stage, presenting a moderate number of secretory granules and well-developed GC and RER. Some PRL-II cells of lactating animals exhibiting scarce granules and numerous exocytosis suggesting a high secretory activity. In both anoestrus and pregnancy stages most granules range in diameter from 450 to 750 nm, in contrast to the lactating stage in which most granules range in diameter from 150 to 450 nm.

  11. Increased demand for steroid therapy in hyperprolactinemic patients with rheumatoid arthritis.

    PubMed

    Rovenský, J; Bakosová, J; Payer, J; Lukác, J; Raffayová, H; Vigas, M

    2001-01-01

    The role of increased plasma prolactin (PRL) in rheumatoid arthritis (RA) is not fully explained. The aim of this study was to compare the clinical features and the treatment administered in RA patients with normal and elevated plasma PRL concentrations. Forty-nine patients with rheumatoid arthritis and 16 healthy subjects were included in this study In healthy controls, PRL concentrations were 7.6 micro/l (median), in 34 patients plasma PRL was less than 20 micro/l (9.9 micro/l) and in 15 patients it was elevated, with a median of 26.7 micro/l. No differences in clinical features were found compared with normal or increased plasma PRL. The introduction of corticoid therapy produced a significant difference. Steroid therapy was administered to 93% of the patients with hyperprolactinemia, compared with 59% of those with normal PRL concentrations. Daily prednisone doses higher than 5 mg were administered to 43% of the patients with elevated PRL, compared with 25% of patients with normal prolactin concentrations. In conclusion, the clinical feature of patients with rheumatoid arthritis did not differ in subjects with elevated PRL concentrations and in those with normal concentrations. The difference between these two groups was in the higher demand for steroid therapy in patients with hyperprolactinemia. PMID:11771778

  12. Identification of Polymorphisms in the Enhancer Region of the Bovine Prolactin Gene and Association with Fertility in Beef Cows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives were to investigate the polymorphic nature of the enhancer region of the bovine prolactin (PRL) gene and determine the association of these polymorphisms with fertility in beef cows. Primers were designed to amplify a 500 base pair fragment 892 to 1392 bases upstream of the bovine PRL gen...

  13. Tissue-specific Regulation of Porcine Prolactin Receptor Expression by Estrogen, Progesterone and Prolactin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prolactin (PRL) acts through its receptor (PRLR) via both endocrine and local paracrine/autocrine pathways to regulate biological processes including reproduction and lactation. We analyzed the tissue and stage of gestation-specific regulation of PRL and PRLR expression in various tissues of pigs. ...

  14. EFFECT OF ATRAZINE ON IMPLANTATION AND EARLY PREGNANCY IN FOUR STRAINS OF RATS

    EPA Science Inventory

    Atrazine (ATR) is an herbicide that has been shown to have adverse reproductive effects including alterations in levels of pituitary hormones such as prolactin (prl) and luteinizing hormone (LH). Since prl's action to promote progesterone secretion is essential for the initiatio...

  15. Variation in the coding and 3’ untranslated regions of the porcine prolactin receptor short form modifies protein expression and function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The actions of prolactin (PRL) are mediated by both long (LF) and short isoforms (SF) of the PRL receptor (PRLR). Here, we report on a genetic and functional analysis of the porcine PRLR (pPRLR) SF. Three single nucleotide polymorphisms (SNPs) within exon 11 of the pPRLR-SF give rise to four amino a...

  16. The basal function of teleost prolactin as a key regulator on ion uptake identified with zebrafish knockout models

    PubMed Central

    Shu, Yuqin; Lou, Qiyong; Dai, Ziru; Dai, Xiangyan; He, Jiangyan; Hu, Wei; Yin, Zhan

    2016-01-01

    Prolactin (PRL) is an anterior pituitary hormone with a broad range of functions. Its ability to stimulate lactogenesis, maternal behavior, growth and development, osmoregulation, and epithelial ion transport has been reported in many vertebrates. In our present study, we have targeted the zebrafish prl locus via transcription activator-like effector nucleases (TALENs). Two independent targeted mutant lines with premature termination of the putative sequence of PRL peptides were generated. All prl-deficient zebrafish progeny died at 6–16 days post-fertilization stage (dpf) in egg water. However, the prl-deficient larvae thrived and survived through adulthood in brackish water (5175 mg/L ocean salts), without obvious defects in somatic growth or reproduction. When raised in egg water, the expression levels of certain key Na+/Cl− cotransporters in the gills and Na+/K+-ATPase subunits, Na+/H+ exchangers and Na+/Cl− transporters in the pronephros of prl-deficient larvae were down-regulated at 5 dpf, which caused Na+/K+/Cl− uptake defects in the mutant fish at 6 dpf. Our present results demonstrate that the primary function of zebrafish prl is osmoregulation via governing the uptake and homeostasis of Na+, K+ and Cl−. Our study provides valuable evidence to understand the mechanisms of PRL function better through both phylogenetic and physiological perspectives. PMID:26726070

  17. What Can We Learn from Rodents about Prolactin in Humans?

    PubMed Central

    Ben-Jonathan, Nira; LaPensee, Christopher R.; LaPensee, Elizabeth W.

    2008-01-01

    Prolactin (PRL) is a 23-kDa protein hormone that binds to a single-span membrane receptor, a member of the cytokine receptor superfamily, and exerts its action via several interacting signaling pathways. PRL is a multifunctional hormone that affects multiple reproductive and metabolic functions and is also involved in tumorigenicity. In addition to being a classical pituitary hormone, PRL in humans is produced by many tissues throughout the body where it acts as a cytokine. The objective of this review is to compare and contrast multiple aspects of PRL, from structure to regulation, and from physiology to pathology in rats, mice, and humans. At each juncture, questions are raised whether, or to what extent, data from rodents are relevant to PRL homeostasis in humans. Most current knowledge on PRL has been obtained from studies with rats and, more recently, from the use of transgenic mice. Although this information is indispensable for understanding PRL in human health and disease, there is sufficient disparity in the control of the production, distribution, and physiological functions of PRL among these species to warrant careful and judicial extrapolation to humans. PMID:18057139

  18. Prolactin signaling enhances colon cancer stemness by modulating Notch signaling in a Jak2-STAT3/ERK manner.

    PubMed

    Neradugomma, Naveen K; Subramaniam, Dharmalingam; Tawfik, Ossama W; Goffin, Vincent; Kumar, T Rajendra; Jensen, Roy A; Anant, Shrikant

    2014-04-01

    Prolactin (PRL) is a secretory cytokine produced by various tissues. Binding to the cognate PRL receptor (PRLR), it activates intracellular signaling via janus kinase (JAK), extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription (STAT) proteins. PRL regulates diverse activities under normal and abnormal conditions, including malignancies. Previous clinical data suggest serum PRL levels are elevated in colorectal cancer (CRC) patients. In this study, we first determined the expression of PRL and PRLR in colon cancer tissue and cell lines. Higher levels of PRLR expression were observed in the cancer cells and cell lines compared with normal colonic epithelial cells. Incubation of colon cancer cells with PRL-induced JAK2, STAT3 and ERK1/2 phosphorylation and increased expression of Jagged 1, which is a Notch-1 receptor ligand. Notch signaling regulates CRC stem cell population. We observed increased accumulation of the cleaved/active form of Notch-1 receptor (Notch intracellular domain) and increased expression of Notch responsive genes HEY1, HES1 and stem cell marker genes DCLK1, LGR5, ALDH1 and CD44. Finally, inhibiting PRL induced JAK2-STAT3 and JAK2-ERK1/2 using AG490 and PD98059, respectively, leads to complete abrogation of Notch signaling, suggesting a role for this pathway in regulating CRC stem cells. Together, our results demonstrate that cytokine signaling induced by PRL is active in colorectal cancers and may provide a novel target for therapeutic intervention.

  19. Src tyrosyl phosphorylates cortactin in response to prolactin.

    PubMed

    Hammer, Alan; Laghate, Sneha; Diakonova, Maria

    2015-08-01

    The hormone/cytokine prolactin (PRL) is implicated in breast cancer cell invasion and metastasis. PRL-induced pathways are mediated by two non-receptor tyrosine kinases, JAK2 and Src. We previously demonstrated that prolactin stimulates invasion of breast cancer cells TMX2-28 through JAK2 and its target serine/threonine kinase PAK1. We hypothesize herein that the actin-binding protein cortactin, a protein involved in invadopodia formation and cell invasion, is activated by PRL. We demonstrate that TMX2-28 cells are more invasive than T47D breast cancer cells in response to PRL. We determine that cortactin is tyrosyl phosphorylated in response to PRL in a time and dose-dependent manner in TMX2-28 cells, but not in T47D cells. Furthermore, we show that PRL mediates cortactin tyrosyl phosphorylation via Src, but not JAK2. Finally, we demonstrate that maximal PRL-mediated TMX2-28 cell invasion requires both Src and JAK2 kinase activity, while T47D cell invasion is JAK2- but not Src-dependent. Thus PRL may induce cell invasion via two pathways: through a JAK2/PAK1 mediated pathway that we have previously demonstrated, and Src-dependent activation and tyrosyl phosphorylation of cortactin.

  20. Prolactin anterior pituitary expression and circulating levels are reduced in obese and diabetic rats: role of TGF-β and TNF-α.

    PubMed

    Lemini, María; Ruiz-Herrera, Xarubet; Ledesma-Colunga, María G; Díaz-Lezama, Nundehui; De Los Ríos, Ericka A; López-Barrera, Fernando; Méndez, Isabel; Martínez de la Escalera, Gonzalo; Macotela, Yazmín; Clapp, Carmen

    2015-05-01

    The levels of the hormone prolactin (PRL) are reduced in the circulation of patients with Type 2 diabetes and in obese children, and lower systemic PRL levels correlate with an increased prevalence of diabetes and a higher risk of metabolic syndrome. The secretion of anterior pituitary (AP) PRL in metabolic diseases may be influenced by the interplay between transforming growth factor β (TGF-β) and tumor necrosis factor α (TNF-α), which inhibit and can stimulate AP PRL synthesis, respectively, and are known contributors to insulin resistance and metabolic complications. Here, we show that TGF-β and TNF-α antagonize the effect of each other on the expression and release of PRL by the GH4C1 lactotrope cell line. The levels of AP mRNA and circulating PRL decrease in high-fat diet-induced obese rats in parallel with increased and reduced AP levels of TGF-β and TNF-α mRNA, respectively. Likewise, AP expression and circulating levels of PRL are reduced in streptozotocin-induced diabetic rats and are associated with higher AP expression and protein levels of TGF-β and TNF-α. The opposing effects of the two cytokines on cultured AP cells, together with their altered expression in the AP of obese and diabetic rats suggest they are linked to the reduced PRL production and secretion characteristics of metabolic diseases.

  1. Biochemical evaluation of virtual screening methods reveals a cell-active inhibitor of the cancer-promoting phosphatases of regenerating liver.

    PubMed

    Hoeger, Birgit; Diether, Maren; Ballester, Pedro J; Köhn, Maja

    2014-12-17

    Computationally supported development of small molecule inhibitors has successfully been applied to protein tyrosine phosphatases in the past, revealing a number of cell-active compounds. Similar approaches have also been used to screen for small molecule inhibitors for the cancer-related phosphatases of regenerating liver (PRL) family. Still, selective and cell-active compounds are of limited availability. Since especially PRL-3 remains an attractive drug target due to its clear role in cancer metastasis, such compounds are highly demanded. In this study, we investigated various virtual screening approaches for their applicability to identify novel small molecule entities for PRL-3 as target. Biochemical evaluation of purchasable compounds revealed ligand-based approaches as well suited for this target, compared to docking-based techniques that did not perform well in this context. The best hit of this study, a 2-cyano-2-ene-ester and hence a novel chemotype targeting the PRLs, was further optimized by a structure-activity-relationship (SAR) study, leading to a low micromolar PRL inhibitor with acceptable selectivity over other protein tyrosine phosphatases. The compound is active in cells, as shown by its ability to specifically revert PRL-3 induced cell migration, and exhibits similar effects on PRL-1 and PRL-2. It is furthermore suitable for fluorescence microscopy applications, and it is commercially available. These features make it the only purchasable, cell-active and acceptably selective PRL inhibitor to date that can be used in various cellular applications.

  2. Dopamine-prolactin pathway potentially contributes to the schizophrenia and type 2 diabetes comorbidity.

    PubMed

    Gragnoli, C; Reeves, G M; Reazer, J; Postolache, T T

    2016-01-01

    Schizophrenia (SCZ) and type 2 diabetes (T2D) are clinically associated, and common knowledge attributes this association to side effects of antipsychotic treatment. However, even drug-naive patients with SCZ are at increased risk for T2D. Dopamine dysfunction has a central role in SCZ. It is well-known that dopamine constitutively inhibits prolactin (PRL) secretion via the dopamine receptor 2 (DR2D). If dopamine is increased or if dopamine receptors hyperfunction, PRL may be reduced. During the first SCZ episode, low PRL levels are associated with worse symptoms. PRL is essential in human and social bonding, as well as it is implicated in glucose homeostasis. Dopamine dysfunction, beyond contributing to SCZ symptoms, may lead to altered appetite and T2D. To our knowledge, there are no studies of the genetics of the SCZ-T2D comorbidity focusing jointly on the dopamine and PRL pathway in the attempt to capture molecular heterogeneity correlated to possible disease manifestation heterogeneity. In this dopamine-PRL pathway-focused-hypothesis-driven review on the association of SCZ with T2D, we report a specific revision of what it is known about PRL and dopamine in relation to what we theorize is one of the missing links between the two disorders. We suggest that new studies are necessary to establish the genetic role of PRL and dopamine pathway in SCZ-T2D comorbidity. PMID:27093067

  3. Rhythmic Secretion of Prolactin in Rats: Action of Oxytocin Coordinated by Vasoactive Intestinal Polypeptide of Suprachiasmatic Nucleus Origin

    PubMed Central

    Egli, Marcel; Bertram, Richard; Sellix, Michael T.; Freeman, Marc E.

    2007-01-01

    Prolactin (PRL) is secreted from lactotrophs of the anterior pituitary gland of rats in a unique pattern in response to uterine cervical stimulation (CS) during mating. Surges of PRL secretion occur in response to relief from hypothalamic dopaminergic (DA) inhibition and stimulation by hypothalamic releasing neurohormones. In this study we characterize the role of oxytocin (OT) in this system and the involvement of vasoactive intestinal polypeptide (VIP) from the suprachiasmatic nucleus (SCN) in controlling OT and PRL secretion of CS rats. The effect of OT on PRL secretion was demonstrated in cultured lactotrophs showing simultaneous enhanced secretion rate and increased intracellular Ca2+. Neurosecretory OT cells of the hypothalamic paraventricular nucleus which express VIP receptors were identified by using immunocytochemical techniques in combination with the retrogradely transported neuronal tracer Fluoro-Gold (i.v. injected). OT measurements of serial blood samples obtained from ovariectomized (OVX) CS rats displayed a prominent secretory peak at the time of the afternoon PRL peak. The injection of VIP antisense oligonucleotides into the SCN abolished the afternoon increase of OT and PRL in CS-OVX animals. These findings suggest that there is an involvement of VIP from the SCN contributing in the regulation of OT and PRL secretion in CS rats. We propose that in CS rats the regulatory mechanism(s) for PRL secretion comprise coordinated action of neuroendocrine DA and OT cells, both governed by the daily rhythm of VIPergic output from the SCN. This hypothesis is illustrated with a mathematical model. PMID:15033917

  4. Prolactin--a novel neuroendocrine regulator of human keratin expression in situ.

    PubMed

    Ramot, Yuval; Bíró, Tamás; Tiede, Stephan; Tóth, Balázs I; Langan, Ewan A; Sugawara, Koji; Foitzik, Kerstin; Ingber, Arieh; Goffin, Vincent; Langbein, Lutz; Paus, Ralf

    2010-06-01

    The controls of human keratin expression in situ remain to be fully elucidated. Here, we have investigated the effects of the neurohormone prolactin (PRL) on keratin expression in a physiologically and clinically relevant test system: organ-cultured normal human hair follicles (HFs). Not only do HFs express a wide range of keratins, but they are also a source and target of PRL. Microarray analysis revealed that PRL differentially regulated a defined subset of keratins and keratin-associated proteins. Quantitative immunohistomorphometry and quantitative PCR confirmed that PRL up-regulated expression of keratins K5 and K14 and the epithelial stem cell-associated keratins K15 and K19 in organ-cultured HFs and/or isolated HF keratinocytes. PRL also up-regulated K15 promoter activity and K15 protein expression in situ, whereas it inhibited K6 and K31 expression. These regulatory effects were reversed by a pure competitive PRL receptor antagonist. Antagonist alone also modulated keratin expression, suggesting that "tonic stimulation" by endogenous PRL is required for normal expression levels of selected keratins. Therefore, our study identifies PRL as a major, clinically relevant, novel neuroendocrine regulator of both human keratin expression and human epithelial stem cell biology in situ.

  5. Phosphatase of regenerating liver-3 inhibits invasiveness and proliferation in non-small cell lung cancer by regulating the epithelial-mesenchymal transition

    PubMed Central

    Lin, Sheng-Yi; Lee, Yue-Xun; Yu, Sung-Liang

    2016-01-01

    Phosphatase of regenerating liver-3 (PRL-3) has been reported to be associated with colon and gastric cancer metastasis. However, the role and function of PRL-3 in human non-small cell lung cancer cells is unknown. Our studies showed that the expression of PRL-3mRNA and protein are higher in less invasive human lung adenocarcinoma cells than in highly invasive cell lines. Ectopic expression of PRL-3 reduced cell capacity for anchorage-dependent growth, anchorage-independent growth, migration, and invasion in vitro, as well as tumorigenesis in vivo. Conversely, catalytic (C104S) and prenylation-site (C170S) mutants enhanced cell invasion. Microarray profiling of PRL-3 transfectants revealed the pathways potentially involving PRL-3, including the epithelial-mesenchymal transition (EMT), extracellular matrix remodeling, and the WNT signaling pathway. Furthermore, we demonstrated that increased PRL-3 reduced Slug and enhanced E-cadherin gene expression through the AKT/GSK3β/β-catenin pathway. In conclusion, our data suggest that PRL-3 might play a tumor suppressor role in lung cancer, distinct from other cancers, by inhibiting EMT-related pathways. PMID:26967563

  6. Mechanisms subserving the physiological nocturnal relative hypoprolactinemia of healthy older men: dual decline in prolactin secretory burst mass and basal release with preservation of pulse duration, frequency, and interpulse interval--a General Clinical Research Center study.

    PubMed

    Iranmanesh, A; Mulligan, T; Veldhuis, J D

    1999-03-01

    Increasing age is accompanied by decrements in randomly obtained, fasting, or frequently sampled serum PRL concentrations. The precise neuroendocrine mechanisms underlying such relative hypoprolactinemia in aging are incompletely understood. In the present study, we sampled blood at 2.5-min intervals overnight in 11 young (aged 21-34 yr) and 8 older (aged 62-72 yr) healthy men for subsequent chemiluminescence-based assay of serum PRL concentrations. The mean (+/- SEM) serum PRL concentration was significantly reduced at 4.3 +/- 0.78 microg/L in older men compared with 9.5 +/- 1.2 microg/L in young volunteers (P = 0.0049). PRL concentrations correlated with serum testosterone (r = 0.473; P = 0.041), dehydroepiandrosteroen sulfate (r = +0.455, P = 0.05), and insulin-like growth factor I (r = 0.494; P = 0.032) levels. Deconvolution analysis was used to evaluate combined pulsatile and basal modes of PRL secretion. In older men, discrete PRL secretory bursts were marked by a significantly (2.4-fold) attenuated mass of hormone secreted per burst (amount of PRL secreted per unit distribution volume), viz. 1.6 +/- 0.23 (older) vs. 3.9 +/- 0.57 microg/L (young; P < 0.01). In contrast, PRL secretory burst frequency, interpulse interval, and pulse duration were invariant of age. Concomitantly, basal PRL secretion was reduced by 2-fold in older subjects, namely to 0.00030 +/- 0.00027 (older) vs. 0.00065 +/- 0.0002 microg/L/min (young; P < 0.01). The amount of total PRL secretion that was pulsatile averaged 82 +/- 5.3% in young and 99 +/- 0.13% in older men (P = 0.012), indicating preferential loss of the basal mode of PRL release in aging. Assuming that basal PRL secretion mirrors functional pituitary lactotroph cell secretory mass, whereas pulsatile PRL release reflects effective (net) intermittent hypothalamic drive to responsive lactotroph cells, then our results suggest both an attrition in lactotroph cell mass and an impoverishment of net positive hypothalamic (agonistic

  7. Serotonin and acetylcholine affect the release of prolactin and growth hormone from pituitary glands of domestic fowl in vitro in the presence of hypothalamic tissue.

    PubMed

    Hall, T R; Harvey, S; Chadwick, A

    1984-04-01

    Anterior pituitary glands from broiler fowl were incubated alone or with hypothalamic tissue in medium containing either serotonin or serotoninergic drugs, acetylcholine or cholinergic drugs, and the release of prolactin (Prl) and growth hormone (GH) measured by homologous radioimmunoassays. The neurotransmitters and drugs affected the release of hormones from the pituitary gland only when hypothalamic tissue was also present. Serotonin and its agonist quipazine stimulated the release of Prl and inhibited release of GH in a concentration-related manner. The antagonist methysergide blocked the effects of serotonin and quipazine on Prl. Acetylcholine and its agonist pilocarpine also stimulated release of Prl and inhibited release of GH in a concentration-related manner. Atropine blocked these responses. The results show that serotonin and acetylcholine affect pituitary hormone secretion by acting on the hypothalamus. They may stimulate the secretion of a Prl releasing hormone and somatostatin. PMID:6144226

  8. Serotonin and acetylcholine affect the release of prolactin and growth hormone from pituitary glands of domestic fowl in vitro in the presence of hypothalamic tissue.

    PubMed

    Hall, T R; Harvey, S; Chadwick, A

    1984-04-01

    Anterior pituitary glands from broiler fowl were incubated alone or with hypothalamic tissue in medium containing either serotonin or serotoninergic drugs, acetylcholine or cholinergic drugs, and the release of prolactin (Prl) and growth hormone (GH) measured by homologous radioimmunoassays. The neurotransmitters and drugs affected the release of hormones from the pituitary gland only when hypothalamic tissue was also present. Serotonin and its agonist quipazine stimulated the release of Prl and inhibited release of GH in a concentration-related manner. The antagonist methysergide blocked the effects of serotonin and quipazine on Prl. Acetylcholine and its agonist pilocarpine also stimulated release of Prl and inhibited release of GH in a concentration-related manner. Atropine blocked these responses. The results show that serotonin and acetylcholine affect pituitary hormone secretion by acting on the hypothalamus. They may stimulate the secretion of a Prl releasing hormone and somatostatin.

  9. Understanding laser-induced ultrafast demagnetization in ferromagnets: First-principles and two-level model investigation

    NASA Astrophysics Data System (ADS)

    Zhang, G. P.; George, T. F.; Anderson, T.; Hübner, W.

    2007-03-01

    Ultrafast demagnetization in ferromagnets attracts lots of attention both experimentally [1] and theoretically [2]. However, up to now, there is no clear understanding whether the observed signal represents a magnetization, while the experimental results are very controversial. In this study, a two-level model is used to simulate the demagnetization process. All the transition matrix elements are computed using the Wien2K code and from bulk nickel. The pump and probe signals and the magnetization for this two level system are computed directly. This should provide insight into the laser-induced ultrafast demagnetization process. [1] E. Beaurepaire et al, PRL 76, 4250 (1996); B. Koopmans et al, PRL 85, 844 (2000); L. H. Andrade et al, PRL. 97, 127401 (2006). [2] G. P. Zhang and H"ubner, PRL 85, 3025 (2000); R. Gomez-Abal, O. Ney, K. Satitkovitchai, and W. H"ubner, PRL 92, 227402 (2004).

  10. Cyproheptadine-mediated inhibition of growth hormone and prolactin release from pituitary adenoma cells of acromegaly and gigantism in culture.

    PubMed

    Ishibashi, M; Fukushima, T; Yamaji, T

    1985-08-01

    The effect of cyproheptadine on growth hormone (GH) and prolactin (Prl) secretion from cultured pituitary adenoma cells of acromegaly and pituitary gigantism was studied. When varying doses of cyproheptadine ranging from 0.01 to 1 microM were added to the incubation media, GH secretion was consistently inhibited and a dose-response relationship was observed between the cyproheptadine concentrations and the amounts of GH released into the media. In pituitary adenomas which concurrently produced and secreted Prl, cyproheptadine likewise suppressed Prl release in a dose-related manner. This effect of cyproheptadine was not blocked by coincubation with serotonin. Similarly, coincubation with a dopaminergic antagonist, haloperidol, failed to reverse the inhibitory action produced by cyproheptadine. When coincubated with dopamine, cyproheptadine further inhibited GH and Prl secretion. These results suggest that cyproheptadine possesses a direct action on human somatotroph adenoma cells to inhibit GH and Prl secretion by an unknown mechanism that is different from serotonergic and dopaminergic systems. PMID:2994332

  11. Reading with multiple preferred retinal loci: implications for training a more efficient reading strategy.

    PubMed

    Déruaz, A; Whatham, A R; Mermoud, C; Safran, A B

    2002-12-01

    The reading strategies in individuals with central scotomas and more than one preferred retinal locus (PRL) were investigated using a scanning laser ophthalmoscope in order to understand the visual requirements that lead to the need to use more than one PRL during reading. It was found that: (1) PRL function can be deduced from variation in PRL usage for different size and length of isolated words; (2) each subject used two or more PRL to accomplish the functions of global viewing and discrimination, suggesting that these are two of the minimum requirements for reading; (3) reading strategies can change depending on the position of words in visual space; (4) line-changing strategies can revert to horizontal and vertical component movements. These findings have implications for improving reading performance through training in patients with central scotomas.

  12. Not only dopamine D2 receptors involved in Peony-Glycyrrhiza Decoction, an herbal preparation against antipsychotic-associated hyperprolactinemia.

    PubMed

    Wang, Di; Wong, Hei Kiu; Zhang, Li; McAlonan, Grainne M; Wang, Xiao-Min; Sze, Stephen Cho Wing; Feng, Yi-Bin; Zhang, Zhang-Jin

    2012-12-01

    Clinical studies have demonstrated the effectiveness of an herbal preparation called Peony-Glycyrrhiza Decoction (PGD) in alleviating antipsychotic-induced hyperprolactinemia (hyperPRL). In the present study, we further examined the pharmacological action of PGD on prolactin (PRL) secretion using in vitro and in vivo models, with specific attention to the role of dopaminergic mediators and other sex hormones. Treatment with PGD at 1-5mg/ml significantly suppressed PRL secretion and synthesis in MMQ cells, a model of hyperPRL derived from pituitary adenoma cells. The suppressive effects were completely abolished by pretreatment with 10μM haloperidol, a dopamine D(2) receptor antagonist. Consistent with a D(2)-action, PGD did not affect PRL in rat pituitary lactotropic tumor-derived GH3 cells that lack the D(2) receptor expression but significantly increased the expression of D(2) receptors and dopamine transporters (DAT) in PC12 cells. In a rat model of hyperPRL, produced by repeated injection of the dopamine blocker metoclopramide (MCP), chronic PGD (2.5-10g/kg daily) significantly reduced elevated serum PRL. The reduction in magnitude was similar to that elicited by bromocriptine (BMT), a dopamine D(2) receptor agonist currently used for treatment of hyperPRL. Neither PGD nor BMT altered serum estradiol, but PGD reversed decreased serum progesterone to control level, whereas BMT did not. These results indicate that the anti-hyperPRL effects of PGD are associated not only with D(2) receptor and DAT modulation, but also with a normalization of other sex hormone dysfunction. This experimental evidence supports clinical use of PGD as an effective treatment of antipsychotic-induced hyperPRL.

  13. The in vitro effect of prolactin on the growth, motility and expression of prolactin receptors in larvae of Toxocara canis.

    PubMed

    Chávez-Güitrón, L E; Morales-Montor, J; Muñoz-Guzmán, M A; Nava-Castro, K E; Ramírez-Álvarez, H; Moreno-Méndoza, N A; Hernández-Cervantes, R; Alba-Hurtado, F

    2016-07-15

    The in vitro effect of prolactin (PRL) on the growth and motility of Toxocara canis larvae was assessed. Additionally, the expression and location of prolactin receptors (PRL-Rs) were determined in the larvae. Larvae of T. canis were incubated with different concentrations of PRL for different periods of time. The stimulated larvae accelerated their enlargement and increased their motility. The mean percentage of PRL-R+ cells in non-stimulated larvae, measured by flow cytometry was 7.3±0.3%. Compared with non-stimulated larvae, the mean fluorescence intensity (p<0.05) increased in larvae incubated with 40ng/mL of PRL for 10 days. A 465-bp length fragment was amplified from larvae gDNA by PCR. The sequence of this fragment showed 99% similarity with the gene fragment that codes for the PRL-R of the domestic dog. A high concentration of PRL-Rs was immune-located in the posterior region of the larval intestine; therefore, the intestinal cells in this region were most likely the targets for this hormone. Based on these results, PRL-Rs were identified in T. canis larvae, and the in vitro stimulation with PRL increased the number of these receptors, accelerated the growth and modified the activity of larvae. All of the above suggest that T. canis larvae are evolutionarily adapted to recognize the PRL of their definitive host and furthermore might explain the reactivation of tissue-arrested larvae during the gestation of bitches, which does not occur in gestating females of other species.

  14. Prolactin involvement in the regulation of the hypothalamic-pituitary-ovarian axis during the early luteal phase of the porcine estrous cycle.

    PubMed

    Ciereszko, R; Opałka, M; Kamińska, B; Kamiński, T; Dusza, L

    2002-01-23

    Our previous in vivo and in vitro studies revealed that prolactin (PRL) affected luteal function during the first days of the porcine estrous cycle. Since the mechanism by which the luteotrophic action of PRL might be mediated was not elucidated, the goal of the present study is to investigate the effects of short term, in vivo administration of PRL on in vitro functions of hypothalamic explants, adenohypophyseal cells and luteal cells of sows. Injections of PRL or saline (performed every 2h) started shortly after the preovulatory LH surge and lasted for 2 or 3 days. Peripheral blood plasma for determination of LH, PRL and progesterone (P(4)) was sampled at 4h intervals. Ovaries, pituitaries and the stalk median eminence (SME) dissected after slaughter were used for in vitro studies. Luteal and adenohypophysial cells as well as hypothalamic tissue were incubated/cultured with different treatments. Medium and plasma levels of GnRH, LH and P(4) were quantified by radioimmunoassays (RIAs). Corpora lutea (CL) were used for LH/human chorionic gonadotrophin (hCG) receptor analysis. In vivo and in vitro treatment with PRL increased the in vitro GnRH release by hypothalamic explants (P<0.05). GnRH-stimulated LH production was enhanced in PRL-treated sows compared to that of control sows (P<0.05). PRL injections had no effect on plasma P(4) concentrations during the treatment period. However, luteal secretion of P(4) (P=0.06) and LH/hCG receptor concentration (P=0.079) tended to be higher in PRL-treated sows in comparison to those of controls. The results indicate that PRL may be involved in the regulation of the hypothalamic-pituitary-ovarian axis at the beginning of the luteal phase of the porcine estrous cycle.

  15. Expression of autocrine prolactin and the short isoform of prolactin receptor are associated with inflammatory response and apoptosis in monocytes stimulated with Mycobacterium bovis proteins.

    PubMed

    López-Rincón, Gonzalo; Mancilla, Raúl; Pereira-Suárez, Ana L; Martínez-Neri, Priscila A; Ochoa-Zarzosa, Alejandra; Muñoz-Valle, José Francisco; Estrada-Chávez, Ciro

    2015-06-01

    Increased levels of prolactin (PRL) have recently been associated with carcinogenesis and the exacerbation of autoimmune diseases, and might be involved in the progression of tuberculosis (TB). To investigate the relationship between PRL and prolactin receptor (PRLr) expression with inflammatory response and apoptosis in monocytes, we used THP-1 cells stimulated with antigens of the Mycobacterium bovis AN5 strain culture filtrate protein (CFP-M. bovis). Western blot (WB), real-time Polymerase chain reaction (PCR), and immunocytochemistry were performed to identify both PRL and PRLr molecules. PRL bioactivity and proinflammatory cytokine detection were assessed. The results showed that PRL and PRLr messenger RNA (mRNA) were synthesized in THP-1 monocytes induced with CFP-M. bovis at peaks of 176- and 404-fold, respectively. PRL forms of 60 and 80kDa and PRLr isoforms of 40, 50, and 65kDa were also identified as time-dependent, while 60-kDa PRL, as well as 40-, and 50-kDa PRLr, were found as soluble forms in culture media and later in the nucleus of THP-1 monocytes. PRL of 60kDa released by monocytes exhibited bioactivity in Nb2 cells, and both synthesized PRL and synthesized PRLr were related with nitrite and proinflammatory cytokine levels proapoptotic activity in CFP-M. bovis-induced monocytes. Our results suggest the overexpression of a full-autocrine loop of PRL and PRLr in monocytes that enhances the inflammatory response and apoptosis after priming with M. bovis antigens. PMID:25797370

  16. Prolactin mediates neuroprotection against excitotoxicity in primary cell cultures of hippocampal neurons via its receptor.

    PubMed

    Vergara-Castañeda, E; Grattan, D R; Pasantes-Morales, H; Pérez-Domínguez, M; Cabrera-Reyes, E A; Morales, T; Cerbón, M

    2016-04-01

    Recently it has been reported that prolactin (PRL) exerts a neuroprotective effect against excitotoxicity in hippocampus in the rat in vivo models. However, the exact mechanism by which PRL mediates this effect is not completely understood. The aim of our study was to assess whether prolactin exerts neuroprotection against excitotoxicity in an in vitro model using primary cell cultures of hippocampal neurons, and to determine whether this effect is mediated via the prolactin receptor (PRLR). Primary cell cultures of rat hippocampal neurons were used in all experiments, gene expression was evaluated by RT-qPCR, and protein expression was assessed by Western blot analysis and immunocytochemistry. Cell viability was assessed by using the MTT method. The results demonstrated that PRL treatment of neurons from primary cultures did not modify cell viability, but that it exerted a neuroprotective effect, with cells treated with PRL showing a significant increase of viability after glutamate (Glu)--induced excitotoxicity as compared with neurons treated with Glu alone. Cultured neurons expressed mRNA for both PRL and its receptor (PRLR), and both PRL and PRLR expression levels changed after the excitotoxic insult. Interestingly, the PRLR protein was detected as two main isoforms of 100 and 40 kDa as compared with that expressed in hypothalamic cells, which was present only as a 30 kDa variant. On the other hand, PRL was not detected in neuron cultures, either by western blot or by immunohistochemistry. Neuroprotection induced by PRL was significantly blocked by specific oligonucleotides against PRLR, thus suggesting that the PRL role is mediated by its receptor expressed in these neurons. The overall results indicated that PRL induces neuroprotection in neurons from primary cell cultures. PMID:26874070

  17. Expression of autocrine prolactin and the short isoform of prolactin receptor are associated with inflammatory response and apoptosis in monocytes stimulated with Mycobacterium bovis proteins.

    PubMed

    López-Rincón, Gonzalo; Mancilla, Raúl; Pereira-Suárez, Ana L; Martínez-Neri, Priscila A; Ochoa-Zarzosa, Alejandra; Muñoz-Valle, José Francisco; Estrada-Chávez, Ciro

    2015-06-01

    Increased levels of prolactin (PRL) have recently been associated with carcinogenesis and the exacerbation of autoimmune diseases, and might be involved in the progression of tuberculosis (TB). To investigate the relationship between PRL and prolactin receptor (PRLr) expression with inflammatory response and apoptosis in monocytes, we used THP-1 cells stimulated with antigens of the Mycobacterium bovis AN5 strain culture filtrate protein (CFP-M. bovis). Western blot (WB), real-time Polymerase chain reaction (PCR), and immunocytochemistry were performed to identify both PRL and PRLr molecules. PRL bioactivity and proinflammatory cytokine detection were assessed. The results showed that PRL and PRLr messenger RNA (mRNA) were synthesized in THP-1 monocytes induced with CFP-M. bovis at peaks of 176- and 404-fold, respectively. PRL forms of 60 and 80kDa and PRLr isoforms of 40, 50, and 65kDa were also identified as time-dependent, while 60-kDa PRL, as well as 40-, and 50-kDa PRLr, were found as soluble forms in culture media and later in the nucleus of THP-1 monocytes. PRL of 60kDa released by monocytes exhibited bioactivity in Nb2 cells, and both synthesized PRL and synthesized PRLr were related with nitrite and proinflammatory cytokine levels proapoptotic activity in CFP-M. bovis-induced monocytes. Our results suggest the overexpression of a full-autocrine loop of PRL and PRLr in monocytes that enhances the inflammatory response and apoptosis after priming with M. bovis antigens.

  18. Lipopolysaccharide induces the expression of an autocrine prolactin loop enhancing inflammatory response in monocytes

    PubMed Central

    2013-01-01

    Background Prolactin from pituitary gland helps maintain homeostasis but it is also released in immune cells where its function is not completely understood. Pleiotropic functions of prolactin (PRL) might be mediated by different isoforms of its receptor (PRLr). Methods The aim of this study was to investigate the relationship between the eventual synthesis of PRL and PRLr isoforms with the inflammatory response in monocytes. We used THP-1 and monocytes isolated from healthy subjects stimulated with lipopolysaccharide (LPS). Western blot, real time PCR and immunocytochemistry were performed to identify both molecules. The bioactivity of the PRL was assessed using a bioassay and ELISA to detect pro inflammatory cytokines. Results PRLr mRNA and PRL mRNA were synthesized in THP-1 monocytes activated with LPS with peaks of 300-fold and 130-fold, respectively. The long (100 kDa) and the intermediate (50 kDa) isoforms of PRLr and big PRL (60 kDa) were time-dependent upregulated for monocytes stimulated with LPS. This expression was confirmed in monocytes from healthy subjects. The PRLr intermediate isoform and the big PRL were found soluble in the culture media and later in the nucleus in THP-1 monocytes stimulated with LPS. Big PRL released by monocytes showed bioactivity in Nb2 Cells, and both PRL and PRLr, synthesized by monocytes were related with levels of nitrites and proinflammatory citokines. Conclusions Our results suggest the expression of a full-autocrine loop of PRL enhances the inflammatory response in activated monocytes. This response mediated by big PRL may contribute to the eradication of potential pathogens during innate immune response in monocytes but may also contribute to inflammatory disorders. PMID:23731754

  19. The in vitro effect of prolactin on the growth, motility and expression of prolactin receptors in larvae of Toxocara canis.

    PubMed

    Chávez-Güitrón, L E; Morales-Montor, J; Muñoz-Guzmán, M A; Nava-Castro, K E; Ramírez-Álvarez, H; Moreno-Méndoza, N A; Hernández-Cervantes, R; Alba-Hurtado, F

    2016-07-15

    The in vitro effect of prolactin (PRL) on the growth and motility of Toxocara canis larvae was assessed. Additionally, the expression and location of prolactin receptors (PRL-Rs) were determined in the larvae. Larvae of T. canis were incubated with different concentrations of PRL for different periods of time. The stimulated larvae accelerated their enlargement and increased their motility. The mean percentage of PRL-R+ cells in non-stimulated larvae, measured by flow cytometry was 7.3±0.3%. Compared with non-stimulated larvae, the mean fluorescence intensity (p<0.05) increased in larvae incubated with 40ng/mL of PRL for 10 days. A 465-bp length fragment was amplified from larvae gDNA by PCR. The sequence of this fragment showed 99% similarity with the gene fragment that codes for the PRL-R of the domestic dog. A high concentration of PRL-Rs was immune-located in the posterior region of the larval intestine; therefore, the intestinal cells in this region were most likely the targets for this hormone. Based on these results, PRL-Rs were identified in T. canis larvae, and the in vitro stimulation with PRL increased the number of these receptors, accelerated the growth and modified the activity of larvae. All of the above suggest that T. canis larvae are evolutionarily adapted to recognize the PRL of their definitive host and furthermore might explain the reactivation of tissue-arrested larvae during the gestation of bitches, which does not occur in gestating females of other species. PMID:27270387

  20. Prolactin mediates neuroprotection against excitotoxicity in primary cell cultures of hippocampal neurons via its receptor.

    PubMed

    Vergara-Castañeda, E; Grattan, D R; Pasantes-Morales, H; Pérez-Domínguez, M; Cabrera-Reyes, E A; Morales, T; Cerbón, M

    2016-04-01

    Recently it has been reported that prolactin (PRL) exerts a neuroprotective effect against excitotoxicity in hippocampus in the rat in vivo models. However, the exact mechanism by which PRL mediates this effect is not completely understood. The aim of our study was to assess whether prolactin exerts neuroprotection against excitotoxicity in an in vitro model using primary cell cultures of hippocampal neurons, and to determine whether this effect is mediated via the prolactin receptor (PRLR). Primary cell cultures of rat hippocampal neurons were used in all experiments, gene expression was evaluated by RT-qPCR, and protein expression was assessed by Western blot analysis and immunocytochemistry. Cell viability was assessed by using the MTT method. The results demonstrated that PRL treatment of neurons from primary cultures did not modify cell viability, but that it exerted a neuroprotective effect, with cells treated with PRL showing a significant increase of viability after glutamate (Glu)--induced excitotoxicity as compared with neurons treated with Glu alone. Cultured neurons expressed mRNA for both PRL and its receptor (PRLR), and both PRL and PRLR expression levels changed after the excitotoxic insult. Interestingly, the PRLR protein was detected as two main isoforms of 100 and 40 kDa as compared with that expressed in hypothalamic cells, which was present only as a 30 kDa variant. On the other hand, PRL was not detected in neuron cultures, either by western blot or by immunohistochemistry. Neuroprotection induced by PRL was significantly blocked by specific oligonucleotides against PRLR, thus suggesting that the PRL role is mediated by its receptor expressed in these neurons. The overall results indicated that PRL induces neuroprotection in neurons from primary cell cultures.

  1. Hormonal regulation of aquaporin 3: opposing actions of prolactin and cortisol in tilapia gill.

    PubMed

    Breves, Jason P; Inokuchi, Mayu; Yamaguchi, Yoko; Seale, Andre P; Hunt, Bethany L; Watanabe, Soichi; Lerner, Darren T; Kaneko, Toyoji; Grau, E Gordon

    2016-09-01

    Aquaporins (Aqps) are expressed within key osmoregulatory tissues where they mediate the movement of water and selected solutes across cell membranes. We leveraged the functional plasticity of Mozambique tilapia (Oreochromis mossambicus) gill epithelium to examine how Aqp3, an aquaglyceroporin, is regulated in response to osmoregulatory demands. Particular attention was paid to the actions of critical osmoregulatory hormones, namely, prolactin (Prl), growth hormone and cortisol. Branchial aqp3 mRNA levels were modulated following changes in environmental salinity, with enhanced aqp3 mRNA expression upon transfer from seawater to freshwater (FW). Accordingly, extensive Aqp3 immunoreactivity was localized to cell membranes of branchial epithelium in FW-acclimated animals. Upon transferring hypophysectomized tilapia to FW, we identified that a pituitary factor(s) is required for Aqp3 expression in FW. Replacement with ovine Prl (oPrl) was sufficient to stimulate Aqp3 expression in hypophysectomized animals held in FW, an effect blocked by coinjection with cortisol. Both oPrl and native tilapia Prls (tPrl177 and tPrl188) stimulated aqp3 in incubated gill filaments in a concentration-related manner. Consistent with in vivo responses, coincubation with cortisol blocked oPrl-stimulated aqp3 expression in vitro Our data indicate that Prl and cortisol act directly upon branchial epithelium to regulate Aqp3 in tilapia. Thus, within the context of the diverse actions of Prl on hydromineral balance in vertebrates, we define a new role for Prl as a regulator of Aqp expression. PMID:27402066

  2. Hypothalamic Prolactin Regulation of Luteinizing Hormone Secretion in the Female Rat.

    PubMed

    Grachev, Pasha; Li, Xiao Feng; Goffin, Vincent; O'Byrne, Kevin T

    2015-08-01

    Prolactin (PRL) levels increase in response to long-term antipsychotic treatment that disrupts reproductive function. Recent evidence suggests that activation of central PRL receptors (PRLR) inhibits LH secretion and in ovariectomized rats. However, the mechanisms involved, the mode of LH secretion affected and relevance to hyperprolactinemia remain unknown. We therefore investigated the contribution of central PRL/PRLR signaling to the control of estradiol-induced surges of LH and PRL and pulsatile LH secretion under basal and hyperprolactinemic conditions. First, by subjecting ovariectomized estradiol-primed rats intracerebroventricularly administered with PRL to frequent blood sampling, we demonstrated that acute activation of hypothalamic PRLR disrupts pulsatile LH secretion. Pretreatment (intracerebroventricularly) with the pure PRLR antagonist, Δ1-9-G129R-hPRL, or the γ-aminobutyric acid receptor type A antagonist, bicuculline, blocked this effect. Next, we revealed that sustained blockade of hypothalamic PRLR using Δ1-9-G129R-hPRL augmented the magnitude of LH surges induced by estradiol benzoate and progesterone treatment and suppressed the concomitant surges of PRL. Finally, we determined that acute antagonism of central PRLR is insufficient to normalize the duration of the LH pulse interval prolonged as a result of hyperprolactinemia induced by chronic exposure to the atypical antipsychotic sulpiride. These data serve as the first evidence to suggest that PRL signaling through hypothalamic PRLR inhibits pulsatile secretion of LH in a γ-aminobutyric acid receptor type A-dependent fashion and tonically restrains the magnitude of the LH surge. Furthermore, our results indicate that transient blockade of hypothalamic PRL/PRLR signaling is not an effective strategy for restoring LH pulsatility perturbed by chronic hyperprolactinemia.

  3. A liquid-phase two-site immunoradiometric assay for human prolactin.

    PubMed Central

    Hodgkinson, S C; Landon, J; Lowry, P J

    1984-01-01

    The development of a 'two-site' immunoradiometric assay for human prolactin (hPrl) is described. The assay is based on the addition of radio-iodinated sheep anti-hPrl immunoglobulin G (IgG) and rabbit anti-hPrl serum to standards and unknowns followed by 3 h incubation. The use of solid phase reagents was avoided in order to minimize non-specific effects and the time required for reactants to reach equilibrium. Instead, the separation of hPrl-bound and free labelled antibody is achieved by the addition of sheep anti-(rabbit IgG) serum which precipitates bound labelled antibody by complex formation with rabbit anti-hPrl antibodies which are also hPrl-bound. Varying the order of addition of specific antibodies had a pronounced effect on the 'operating range' and sensitivity of resultant assays. This was attributed to competition between labelled and unlabelled antibodies for binding sites on the hPrl molecule. The immunoradiometric assay employing 'simultaneous addition' of specific antibodies was compared to a 'simultaneous addition' hPrl radioimmunoassay developed using the same sheep antiserum as that used to prepare the radioiodinated sheep anti-hPrl IgG. This immunoradiometric assay is characterized by rapid equilibration of reactants, a wide 'operating range' (the precision of dose estimates was less than 10% over the range 8-10000 mU/l), and high sensitivity (2.6 mU/l, 13 pg). In contrast, the hPrl radioimmunoassay required an incubation of 18 h, demonstrated a much reduced 'operating range' (the precision of dose estimates was less than 10% only over the range 25-1500 mU/l) and reduced sensitivity (9.8 mU/l, 49 pg). PMID:6696724

  4. Prolactin variants in ram adenohypophyses vary with season

    NASA Technical Reports Server (NTRS)

    Stroud, C. M.; Deaver, D. R.; Peters, J. L.; Loeper, D. C.; Toth, B. E.; Derr, J. A.; Hymer, W. C.

    1992-01-01

    Secretion of PRL in sheep is affected by photoperiod being highest during the spring and summer, lowest in fall and winter. The objectives of this study were to determine if 1) the production of variant forms of PRL, and 2) immuno- and bioactivities of PRL (iPRL and bPRL) differ during times of the year selected to represent periods of low, transitional and high PRL secretion. Twelve mature rams were maintained on pasture and killed in October, December, and April (n = 4/month). Individual pituitary glands were dispersed, cells obtained, and fixed for immunocytochemical flow cytometry, extracted with 0.01 N NaHCO3 or cultured in serum-free, defined media. The Mr of PRL extracted from cells immediately following dispersion ranged from 14-140K, with significantly more bands greater than 40K being detected from rams sacrificed in December than from those killed in October and April (P less than 0.01). No bands of PRL greater than 25K were observed when samples were reduced with beta-mercaptoethanol prior to electrophoresis, indicating that the high Mr forms were disulfide-linked aggregates. Culture media from October and April contained variants of PRL that ranged from 22-40K but those greater than 25K were generally not observed from cells harvested during December. Extracts of cells after 24 h in culture contained fewer high Mr species during December than had been present in initial extracts from that month. In contrast, during April more high Mr intracellular forms were present after culture than had been detected prior to culture during that month. The percentage of lactotrophs averaged 50.0 +/- 2.5, 47.4 +/- 5.7, and 59.4 +/- 5.5 for October, December, and April, respectively. Initial lactotroph content (pg/lactotroph) of iPRL was higher (P = 0.06) in April (46.0 +/- 17.0) when compared to October and December (8.0 +/- 2.0 and 20.0 +/- 10.0, respectively). In contrast, the bPRL content of initial extracts was higher (P = 0.05) in December (267.0 +/- 68.0) than

  5. High expression of prolactin receptor is associated with cell survival in cervical cancer cells

    PubMed Central

    2013-01-01

    Background The altered expression of prolactin (PRL) and its receptor (PRLR) has been implicated in breast and other types of cancer. There are few studies that have focused on the analysis of PRL/PRLR in cervical cancer where the development of neoplastic lesions is influenced by the variation of the hormonal status. The aim of this study was to evaluate the expression of PRL/PRLR and the effect of PRL treatment on cell proliferation and apoptosis in cervical cancer cell lines. Results High expression of multiple PRLR forms and PRLvariants of 60–80 kDa were observed in cervical cancer cell lines compared with non-tumorigenic keratinocytes evaluated by Western blot, immunofluorecence and real time PCR. Treatment with PRL (200 ng/ml) increased cell proliferation in HeLa cells determined by the MTT assay at day 3 and after 1 day a protective effect against etoposide induced apoptosis in HeLa, SiHa and C-33A cervical cancer cell lines analyzed by the TUNEL assay. Conclusions Our data suggests that PRL/PRLR signaling could act as an important survival factor for cervical cancer. The use of an effective PRL antagonist may provide a better therapeutic intervention in cervical cancer. PMID:24148306

  6. Ultrastructural study of mixed growth hormone & prolactin secreting pituitary adenomas.

    PubMed

    Sarkar, C; Dinda, A K; Roy, S; Kochupillai, N; Kharbanda, K; Tandon, P N

    1992-08-01

    An ultrastructural study was done on 15 mixed growth hormone (GH) and prolactin (PRL)-secreting pituitary adenomas surgically removed from acromegalic patients with hyper-prolactinaemia, in order to see whether the 2 hormones were present in the same cell or in different cells. Double labelling immunogold technique was used for simultaneous ultrastructural localization of GH and PRL. It was found that each neoplastic cell in these 15 tumours (30 to 50 cells were studied in each case) contained 4 populations of granules viz., (i) granules positive for only GH; (ii) granules positive for only PRL; (iii) granules positive for both GH and PRL; and (iv) granules negative for both GH and PRL (unlabelled). Though the relative percentage of these 4 types of granules varied from cell to cell even within the same tumour, the major population (49.9 to 96%) was constituted by the mixed granules showing labelling for both GH and PRL. Almost all the cells examined from each tumour appeared to be mammosomatotrophs. Thus, the study indicated that mammosomatotroph adenomas are perhaps more common among mixed GH and PRL--secreting pituitary adenomas than previously believed. It could be important to recognize these tumours from the therapeutic point of view.

  7. Serum prolactin and dehydroepiandrosterone concentrations during the summer and winter hair growth cycles of mink (Mustela vison).

    PubMed

    Rose, J; Kennedy, M; Johnston, B; Foster, W

    1998-11-01

    We investigated the relationship between serum concentrations of prolactin (PRL) and dehydroepiandrosterone (DHEA) during initiation and development of summer and winter hair growth (anagen) cycles in mink. In the spring, haloperidol (HAL) increased PRL concentrations and induced summer anagen earlier than controls, whereas melatonin (MEL) inhibited PRL secretion and completely blocked summer anagen. In the fall, HAL increased PRL concentrations, inducing anagen at an earlier time than controls, although the resulting fur was abnormal being almost devoid of underhair fibers. Exogenous MEL during the fall reduced PRL concentrations, initiating winter anagen 4 weeks earlier than controls. Adrenalectomy (ADX) induced earlier onset of summer and winter anagen and neutralized the inhibitory effects of HAL in the fall and MEL in the spring. No change in serum DHEA concentrations was observed during the onset of summer or winter anagen in any group although MEL increased DHEA levels from 27 March through 5 June relative to HAL-treated mink. We conclude that changes in serum levels of DHEA and PRL are not requisite to onset of summer or winter anagen in mink. It is possible that metabolites of DHEA and/or PRL may still affect other aspects of the hair growth cycle. PMID:9972323

  8. S179D prolactin diminishes the effects of UV light on epidermal gamma delta T cells

    PubMed Central

    Guzmán, Esther A.; Langowski, John L.; De Guzman, Ariel; Konrad Muller, H.; Walker, Ameae M.; Owen, Laurie B.

    2008-01-01

    Epidermal gamma delta T cells (γδ T) and Langerhans cells (LC) are immune cells altered by exposure to ultraviolet radiation (UVB), a powerful stressor resulting in immune suppression. Prolactin (PRL) has been characterized as an immunomodulator, particularly during stress. In this study, we have asked whether separate administration of the two major forms of prolactin, unmodified and phosphorylated, to groups of 15 mice (3 experiments, each with 5 mice per treatment group) affected the number and morphology of these epidermal immune cells under control conditions, and following UV irradiation. Under control conditions, both PRLs reduced the number of γδ T, but a molecular mimic of phosphorylated PRL (S179D PRL) was more effective, resulting in a 30% reduction. In the irradiated group, however, S179D PRL was protective against a UV-induced reduction in γδ T number and change in morphology (halved the reduction and normalized the morphology). In addition, S179D PRL, but not unmodified (U-PRL), maintained a normal LC: γδ T ratio and sustained the dendritic morphology of LC after UV exposure. These findings suggest that S179D PRL may have an overall protective effect, countering UV-induced cellular alterations in the epidermis. PMID:17945411

  9. Prolactin Pro-Differentiation Pathway in Triple Negative Breast Cancer: Impact on Prognosis and Potential Therapy.

    PubMed

    López-Ozuna, Vanessa M; Hachim, Ibrahim Y; Hachim, Mahmood Y; Lebrun, Jean-Jacques; Ali, Suhad

    2016-01-01

    Triple negative breast cancer (TNBC) is a heterogeneous disease associated with poor clinical outcome and lack of targeted therapy. Here we show that prolactin (PRL) and its signaling pathway serve as a sub-classifier and predictor of pro-differentiation therapy in TNBC. Using immunohistochemistry and various gene expression in silica analyses we observed that prolactin receptor (PRLR) protein and mRNA levels are down regulated in TNBC cases. In addition, examining correlation of PRLR gene expression with metagenes of TNBC subtypes (580 cases), we found that PRLR gene expression sub-classifies TNBC patients into a new subgroup (TNBC-PRLR) characterized by epithelial-luminal differentiation. Importantly, gene expression of PRL signaling pathway components individually (PRL, PRLR, Jak2 and Stat5a), or as a gene signature is able to predict TNBC patients with significantly better survival outcomes. As PRL hormone is a druggable target we determined the biological role of PRL in TNBC biology. Significantly, restoration/activation of PRL pathway in TNBC cells representative of mesenchymal or TNBC-PRLR subgroups led to induction of epithelial phenotype and suppression of tumorigenesis. Altogether, these results offer potential new modalities for TNBC stratification and development of personalized therapy based on PRL pathway activation. PMID:27480353

  10. L-DOPA attenuates prolactin secretion in response to isolation stress in Holstein steers.

    PubMed

    Kasuya, Etsuko; Yayou, Ken-ichi; Sutoh, Madoka

    2013-07-01

    To clarify endocrine responses to psychological stressors in cattle, the effects of isolation from familiar peers on plasma prolactin (PRL) and cortisol (CORT) concentrations, and the effect of 3,4-dihydroxy-L-phenylalanine (L-DOPA), a precursor of dopamine (DA), on stress-induced PRL secretion were determined in Holstein steers. First, the potency of peripheral L-DOPA administration on attenuation of central DA levels was confirmed. Cerebrospinal fluid (CSF) collected from a chronic cannula in the third ventricle and plasma were sampled 1 h before and 3 h after intravenous injection of L-DOPA (100 mg/head). DA concentrations in CSF increased just after L-DOPA injection with subsequent decrease in PRL secretion. Injection of L-DOPA increased CORT secretion. Second, one experimental steer was isolated in its stall by removing its peers for 2 h with or without- pre-injection of L-DOPA. The concentration of PRL was elevated by isolation treatment, whereas the effect of isolation on CORT concentration could not be detected. The increase in PRL concentration after isolation was abolished by pre-injection of L-DOPA. These results suggest that PRL responds to isolation and that DA neurons in the central nervous system may regulate stress-induced PRL secretion in steers.

  11. On the Partially Reacted Boundary Layer in Rate Sticks

    NASA Astrophysics Data System (ADS)

    Partom, Yehuda

    2013-06-01

    Using our reactive flow model TDRR to simulate detonation in a rate stick, we observe that a partially reacted layer (PRL) is formed near the boundary. We are not aware that such a PRL has been observed in tests, and this is why we regarded it in the past as a numerical artifact. Assuming that such an artifact may be caused by the finite rise time of the detonation shock, we showed in how it can be eliminated by delaying the outward boundary motion for a length of time comparable with the shock rise time. Here we revisit the PRL problem. First we show that it is not a numerical artifact but a real phenomenon. We do this by repeating the reactive flow run with a finer resolution. By looking at the PRL structure, we see doubling the resolution affects the PRL only slightly. We then conjecture that the PRL formation has to do with the finite duration of the reaction process (or the finite extent of the reaction zone). By the time the boundary rarefaction reaches a cell near the boundary, it is only partially reacted, and its reaction is cut off. To strengthen our conjecture we also show how the PRL structure changes with the reaction duration.

  12. On the partially reacted boundary layer in rate sticks

    NASA Astrophysics Data System (ADS)

    Partom, Y.

    2014-05-01

    Using our temperature dependent reactive flow model (TDRR) to simulate detonation in a rate stick, we observe that a partially reacted layer (PRL) is formed near the boundary. We are not aware that such a PRL has been observed in tests, and this is why we regarded it in the past as a numerical artifact. Assuming that such an artefact may be caused by the finite rise time of the detonation shock, we showed in [1] how it can be eliminated by delaying the outward boundary motion for a length of time comparable with the shock rise time. Here we revisit the PRL problem. We first show that it is not a numerical artifact but a real phenomenon. We do this by repeating the reactive flow run with a finer mesh. By looking at the PRL structure, we see that doubling the resolution affects the PRL only slightly. We then conjecture that the PRL formation has to do with the finite duration of the reaction process (or the finite extent of the reaction zone). By the time the boundary rarefaction reaches a cell near the boundary, it may be only partially reacted, and its reaction may therefore be cut off. To establish our conjecture we show how the PRL structure changes with the reaction duration.

  13. Prolactin Rescues Immature B-Cells from Apoptosis Induced by B-Cell Receptor Cross-Linking

    PubMed Central

    Flores-Fernández, Rocio; Blanco-Favela, Francisco; Fuentes-Pananá, Ezequiel M.; Chávez-Sánchez, Luis; Gorocica-Rosete, Patricia; Pizaña-Venegas, Alberto; Chávez-Rueda, Adriana Karina

    2016-01-01

    Prolactin has an immunomodulatory effect and has been associated with B-cell-triggered autoimmune diseases, such as systemic lupus erythematosus (SLE). In mice that develop SLE, the PRL receptor is expressed in early bone marrow B-cells, and increased levels of PRL hasten disease manifestations, which are correlated with a reduction in the absolute number of immature B-cells. The aim of this work was to determine the effect of PRL in an in vitro system of B-cell tolerance using WEHI-231 cells and immature B-cells from lupus prone MRL/lpr mice. WEHI-231 cells express the long isoform of the PRL receptor, and PRL rescued the cells from cell death by decreasing the apoptosis induced by the cross-linking of the B-cell antigen receptor (BCR) as measured by Annexin V and active caspase-3. This decrease in apoptosis may have been due to the PRL and receptor interaction, which increased the relative expression of antiapoptotic Bcl-xL and decreased the relative expression of proapoptotic Bad. In immature B-cells from MRL/lpr mice, PRL increased the viability and decreased the apoptosis induced by the cross-linking of BCR, which may favor the maturation of self-reactive B-cells and contribute to the onset of disease. PMID:27314053

  14. Prolactin and growth hormone induce differential cytokine and chemokine profile in murine peritoneal macrophages in vitro: involvement of p-38 MAP kinase, STAT3 and NF-kappaB.

    PubMed

    Sodhi, Ajit; Tripathi, Anurag

    2008-02-01

    The role of immune-neuroendocrine interactions in the autoimmune diseases is well recognized. Autoimmune rheumatoid diseases in their active phase have been characterized by high levels of prolactin (PRL) as well as proinflammatory cytokines which suggest a co-relationship between them. In the present study, we have investigated the profile of cytokines secreted by macrophages on treatment with PRL and growth hormone (GH) in vitro. Significantly enhanced production of cytokines IL-1beta, IL-12p40 and IFN-gamma was observed on treatment of macrophages with PRL or GH. However, higher doses of PRL (1000 ng/ml) induced the production of anti-inflammatory cytokine IL-10, with significant abrogation in production of proinflammatory cytokines. It is further observed that PRL and GH induced the production of chemokines MIP-1alpha and RANTES. PRL but not GH selectively induced significantly enhanced production of MCP-1 and IP-10. It is further shown that p38 MAP kinase, STAT3 and NF-kappaB could play a differential regulatory role in PRL or GH induced production of cytokines by macrophages.

  15. Prolactin and autoimmunity.

    PubMed

    Shelly, Shahar; Boaz, Mona; Orbach, Hedi

    2012-05-01

    Sex hormones, especially estrogen and prolactin (PRL), have an important role in modulating the immune response. PRL is secreted from the pituitary gland as well as other organs and cells particularly lymphocytes. PRL has an immune stimulatory effect and promotes autoimmunity. PRL interferes specifically with B cell tolerance induction, enhances proliferative response to antigens and mitogens and increases the production of immune globulins, cytokines and autoantibodies. Hyperprolactinemia (HPRL) in women present with clinical manifestations of galactorrhea, primary or secondary amenorrhea, delayed menarche or a change in the menses either in the amount or in the regularity. Furthermore in the last 2 decades multi-organ and organ specific autoimmune diseases like systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjogren's syndrome (SS), Hashimoto's thyroiditis (HT), multiple sclerosis (MS), psoriasis, hepatitis C patients, Behçet's disease, peripartum cardiomyopathy (PPCM) and active celiac disease were discussed to be associated with HPRL. There is data showing correlation between PRL level and diseases activity in few diseases. Genetic factors may have a role in humans as in animal models. The PRL isoforms based on the differences in the amino acid sequence and size of the cytoplasmic domain have an important effect on the bioactivity on prolactin receptors (PRL-Rs).

  16. Expression of SOCS genes in normal and leukemic human leukocytes stimulated by prolactin, growth hormone and cytokines.

    PubMed

    Dogusan, Z; Hooghe-Peters, E L; Berus, D; Velkeniers, B; Hooghe, R

    2000-09-01

    To evaluate the possible role of the recently described family of suppressors of cytokine signaling (SOCS) factors in the human lympho-hemopoietic system, we have monitored SOCS factor expression, both constitutive and induced by either cytokines, prolactin (PRL) or growth hormone (GH), using polymerase chain reaction in normal and leukemic cells. CIS (cytokine-inducible SH2-containing protein), SOCS-2 and SOCS-3 were constitutively expressed in peripheral blood mononuclear leukocytes. SOCS-3 expression was enhanced by PRL or by IFN-gamma. In bone marrow cells and granulocytes, CIS expression was induced and SOCS-2 enhanced by IFN-gamma and by PRL. In tonsillar cells, CIS expression was increased and SOCS-2 was induced by IL-1beta, IL-6, PRL and GH. SOCS-3 expression was enhanced by IL-1beta. The expression of SOCS-7 was increased by IL-6, PRL and GH. In Raji B-lymphoma cells, the expression of SOCS-2 and SOCS-7 was enhanced by IL-1beta. In THP-1 myeloid leukemia cells pretreated with TPA (to induce receptors for IFN-gamma), IFN-gamma induced SOCS-2. Jurkat cells expressed more SOCS-2 when exposed to PRL. Original observations in this work include the first report on SOCS-7 induction by cytokines. Also our data shed new light on the possible involvement of PRL and GH in the cytokine network. These hormones could modulate the transduction of signals originating from receptors for various cytokines.

  17. A critical review finds styrene lacks direct endocrine disruptor activity.

    PubMed

    Gelbke, Heinz-Peter; Banton, Marcy; Leibold, Edgar; Pemberton, Mark; Samson, Susan Leanne

    2015-01-01

    The European Commission lists styrene (S) as an endocrine disruptor based primarily on reports of increased prolactin (PRL) levels in S-exposed workers. The US Environmental Protection Agency included S in its list of chemicals to be tested for endocrine activity. Therefore, the database of S for potential endocrine activity is assessed. In vitro and in vivo screening studies, as well as non-guideline and guideline investigations in experimental animals indicate that S is not associated with (anti)estrogenic, (anti)androgenic, or thyroid-modulating activity or with an endocrine activity that may be relevant for the environment. Studies in exposed workers have suggested elevated PRL levels that have been further examined in a series of human and animal investigations. While there is only one definitively known physiological function of PRL, namely stimulation of milk production, many normal stress situations may lead to elevations without any chemical exposure. Animal studies on various aspects of dopamine (DA), the PRL-regulating neurotransmitter, in the central nervous system did not give mechanistic explanations on how S may affect PRL levels. Overall, a neuroendocrine disruption of PRL regulation cannot be deduced from a large experimental database. The effects in workers could not consistently be reproduced in experimental animals and the findings in humans represented acute reversible effects clearly below clinical and pathological levels. Therefore, unspecific acute workplace-related stress is proposed as an alternative mode of action for elevated PRL levels in workers. PMID:26406562

  18. Antibodies for Growth Hormone and Prolactin Using Multiple Antigen Peptide Immunogens.

    PubMed

    González-Villaseñor; Chen

    1999-05-01

    : Antibodies elicited by novel synthetic peptide antigens derived from a highly conserved domain of the growth hormone (GH) and prolactin (PRL) of vertebrates were developed using the multiple antigen peptide approach. The sequence of the antigens is located near the carboxy-terminus in the D domain of the GH and PRL in a cluster of 11 and 10 conserved amino acids, respectively, within a sequence of 18 residues. The synthetic peptides were manually synthesized, purified by high-performance liquid chromatography, and the corresponding antibodies, elicited in rabbits, were cross-reacted with the GH and PRL of a variety of mammalian (human, bovine, ovine, pig, and equine) and nonmammalian (chicken, coho salmon, chum salmon, rainbow trout, catfish and striped bass) vertebrates. The cross-reactivity between the immunogen and its corresponding antigen was tested by immunobloting using either GH or PRL. The GH and PRL of the organisms tested cross-reacted specifically with the corresponding antibody. Chicken and fish GH and PRL showed stronger antibody cross-reactivity than that observed in mammalian sources. These results demonstrate the utility of peptide-derived polyclonal antibodies in the detection of native and recombinant GH and PRL of a variety of vertebrates.

  19. Prolactin Pro-Differentiation Pathway in Triple Negative Breast Cancer: Impact on Prognosis and Potential Therapy

    PubMed Central

    López-Ozuna, Vanessa M.; Hachim, Ibrahim Y.; Hachim, Mahmood Y.; Lebrun, Jean-Jacques; Ali, Suhad

    2016-01-01

    Triple negative breast cancer (TNBC) is a heterogeneous disease associated with poor clinical outcome and lack of targeted therapy. Here we show that prolactin (PRL) and its signaling pathway serve as a sub-classifier and predictor of pro-differentiation therapy in TNBC. Using immunohistochemistry and various gene expression in silica analyses we observed that prolactin receptor (PRLR) protein and mRNA levels are down regulated in TNBC cases. In addition, examining correlation of PRLR gene expression with metagenes of TNBC subtypes (580 cases), we found that PRLR gene expression sub-classifies TNBC patients into a new subgroup (TNBC-PRLR) characterized by epithelial-luminal differentiation. Importantly, gene expression of PRL signaling pathway components individually (PRL, PRLR, Jak2 and Stat5a), or as a gene signature is able to predict TNBC patients with significantly better survival outcomes. As PRL hormone is a druggable target we determined the biological role of PRL in TNBC biology. Significantly, restoration/activation of PRL pathway in TNBC cells representative of mesenchymal or TNBC-PRLR subgroups led to induction of epithelial phenotype and suppression of tumorigenesis. Altogether, these results offer potential new modalities for TNBC stratification and development of personalized therapy based on PRL pathway activation. PMID:27480353

  20. A mimic of phosphorylated prolactin induces apoptosis by activating AP-1 and upregulating p21/waf1 in human prostate cancer PC3 cells

    PubMed Central

    DU, LIANLIAN; WU, WEI

    2012-01-01

    A mimic of phosphorylated prolactin (S179D PRL) has been demonstrated to inhibit prostate cancer cell growth in vitro and in vivo; however, the mechanisms involved in this process remain unknown. In this study, we identified that a four-day treatment of S179D PRL (1 μg/ml) in human prostate PC3 cancer cells activated JNK, c-fos and c-jun, and led to apoptosis. We also demonstrated that p21/waf1 was upregulated in cells transfected with the human PRL receptor (S1b) following a four-day incubation with S179D PRL (1 μg/ml). Once the cells were cotransfected with S1b and either c-fos, c-jun or the c-fos/c-jun constructs for 24 h, S17D PRL activated JNK, c-fos and c-jun, and induced apoptosis in the c-fos/c-jun transfected cells. Additionally, S179D PRL upregulated p21 luciferase activity in the cells transfected with the S1b, activating protein-1 (AP-1) (7x) Luc or p21 Luc constructs. SP600125 (25 μM), a JNK blocker, inhibited the upregulation of AP-1 Luc and p21 Luc in the c-fos/c-jun transfected cells. These results demonstrate that S179D PRL activates JNK and AP-1, which leads to p21 upregulation and apoptosis in human prostate PC3 cancer cells. PMID:23162652

  1. Testosterone and prolactin in two songbirds that differ in paternal care: the Blue-headed Vireo and the Red-eyed Vireo.

    PubMed

    Van Roo, Brandi L; Ketterson, Ellen D; Sharp, Peter J

    2003-12-01

    We investigated the hypothesis that species differences in paternal care in birds may result from differences in concentrations of circulating testosterone (T) and prolactin (PRL). Concentrations of plasma T and PRL were compared in breeding Blue-headed Vireos (Vireo solitarius) and Red-eyed Vireos (Vireo olivaceus), passerine congeners with biparental and maternal incubation, respectively. In male Blue-headed Vireos, plasma T remained low from prenesting to fledgling stages; whereas in male Red-eyed Vireos, plasma T was highest during prenesting and progressively decreased during incubation, nestling, and fledgling stages. In male Blue-headed Vireos, plasma PRL was similar to that in female Blue-headed Vireos and was higher than in male Red-eyed Vireos at all breeding stages. Plasma PRL increased in male Red-eyed Vireos at the incubation stage and remained moderately elevated through the nestling and fledgling stages. In male Blue-headed Vireos, the combination of high PRL and low T during the prenesting stage may promote brood patch formation and nest building, and, at later stages, incubation and feeding of young. In male Red-eyed Vireos, high PRL and low T during incubation and nestling stages may facilitate the feeding of young, as seen in males of other species. Our observations support the hypothesis that differences in paternal care reflect differences in circulating T and PRL. PMID:14644638

  2. Prolactin stimulates the internalization of Staphylococcus aureus and modulates the expression of inflammatory response genes in bovine mammary epithelial cells.

    PubMed

    Gutiérrez-Barroso, Angelina; Anaya-López, José L; Lara-Zárate, Leticia; Loeza-Lara, Pedro D; López-Meza, Joel E; Ochoa-Zarzosa, Alejandra

    2008-01-15

    The incidence of mastitis in dairy cattle is highest at the drying off period and parturition, which are characterized by high levels of the lactogenic hormone prolactin (PRL). One of the most frequently isolated contagious pathogens causing mastitis is Staphylococcus aureus. However, the role of PRL on S. aureus infection in mammary epithelium has not been studied. In this work we evaluated the effect of bovine PRL (bPRL) on S. aureus internalization in a primary culture of bovine mammary epithelial cells (bMEC) and on the expression of cytokine and innate immune response genes. Our data show that 5ng/mL bPRL enhances approximately 3-fold the internalization of S. aureus (ATCC 27543) into bMEC. By RT-PCR analysis, we showed that bPRL is able to up-regulate the expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and inducible nitric oxide synthase (iNOS) mRNAs. However, bPRL together with S. aureus did not modify the expression of TNF-alpha and iNOS mRNAs, while it down-regulated the expression of beta-defensin and IL-1beta mRNAs, as well as nitric oxide production, suggesting that infection and bPRL together can inhibit elements of the host immune response. To our knowledge, this is the first report that shows a role of bPRL during the internalization of S. aureus into bMEC. PMID:17988748

  3. Progesterone receptor repression of prolactin/signal transducer and activator of transcription 5-mediated transcription of the beta-casein gene in mammary epithelial cells.

    PubMed

    Buser, Adam C; Gass-Handel, Elizabeth K; Wyszomierski, Shannon L; Doppler, Wolfgang; Leonhardt, Susan A; Schaack, Jerome; Rosen, Jeffrey M; Watkin, Harriet; Anderson, Steven M; Edwards, Dean P

    2007-01-01

    Prolactin (PRL) and glucocorticoids act synergistically to stimulate transcription of the beta-casein milk protein gene. Signal transducer and activator of transcription 5 (Stat5) mediates PRL-dependent trans-activation, and glucocorticoid potentiation occurs through cross talk between glucocorticoid receptor (GR) and Stat5 at the beta-casein promoter. In the mouse, progesterone withdrawal leads to terminal differentiation and secretory activation of the mammary gland at parturition, indicating progesterone's role in repressing milk protein gene expression during pregnancy. To investigate the mechanism of the inhibitory action of progesterone, experiments were performed with cell culture systems reconstituted to express progesterone receptor (PR), the PRL receptor/Stat5 signaling pathway, and GR, enabling evaluation of PR, GR, and Stat5 interactions at the beta-casein promoter. With COS-1, normal murine mammary gland, HC-11, and primary mammary epithelial cells, progestin-PR directly repressed the PRL receptor/Stat5a signaling pathway's mediation of PRL-induced beta-casein transcription. Progestin-PR also inhibited glucocorticoid-GR enhancement of PRL induced trans-activation of beta-casein. Inhibition depended on a functional PR DNA binding domain and specific PR-DNA interactions at the beta-casein promoter. Chromatin immunoprecipitation assays in HC-11 cells revealed recruitment of PR and Stat5a to the beta-casein promoter by progestin or PRL, respectively. Recruitment was disrupted by cotreatment with progestin and PRL, suggesting a mutual interference between activated PR and Stat5a. Without PRL, progestin-PR also recruited Stat5a to the beta-casein promoter, suggesting that recruitment of an unactivated form of Stat5a may contribute to inhibition of beta-casein by progesterone. These results define a negative cross talk between PR and Stat5a/GR that may contribute to the physiological role of progesterone to repress lactogenic hormone induction of the beta

  4. Integrating oculomotor and perceptual training to induce a pseudofovea: A model system for studying central vision loss

    PubMed Central

    Liu, Rong; Kwon, MiYoung

    2016-01-01

    People with a central scotoma often adopt an eccentric retinal location (Preferred Retinal Locus, PRL) for fixation. Here, we proposed a novel training paradigm as a model system to study the nature of the PRL formation and its impacts on visual function. The training paradigm was designed to effectively induce a PRL at any intended retinal location by integrating oculomotor control and pattern recognition. Using a gaze-contingent display, a simulated central scotoma was induced in eight normally sighted subjects. A subject's entire peripheral visual field was blurred, except for a small circular aperture with location randomly assigned to each subject (to the left, right, above, or below the scotoma). Under this viewing condition, subjects performed a demanding oculomotor and visual recognition task. Various visual functions were tested before and after training at both PRL and nonPRL locations. After 6–10 hr of the training, all subjects formed their PRL within the clear window. Both oculomotor control and visual recognition performance significantly improved. Moreover, there was considerable improvement at PRL location in high-level function, such as trigram letter-recognition, reading, and spatial attention, but not in low-level function, such as acuity and contrast sensitivity. Our results demonstrated that within a relatively short time, a PRL could be induced at any intended retinal location in normally-sighted subjects with a simulated scotoma. Our training paradigm might not only hold promise as a model system to study the dynamic nature of the PRL formation, but also serve as a rehabilitation regimen for individuals with central vision loss. PMID:27089065

  5. Effects of Hypergravity Exposure on Prolactin Levels in Pre-parturient , Parturient and Lactating Rat Dams

    NASA Technical Reports Server (NTRS)

    Baer. Lisa A.; Wade, Charles E.; Ronca, April E.; Sun, Sid (Technical Monitor)

    2001-01-01

    We analyzed the effects of 2.0-g, 1.75-g and 1.5-g hypergravity exposure on plasma concentrations of the lactotrophic hormone, prolactin (PRL), in female rats on pre-parturient (Gestation Day 20), parturient (Post-natal day 0) and lactating (P10) days. PRL levels have been found to be reduced in rat dams around the time of birth following exposure to gravitational loads varying from 2.16 to 3.14-g (Megory et. al., Aviation, Space and Environs 1129-1135, 1984). It has also been reported that at these high gravitational loads, neonatal mortality has been extremely high, suggesting a possible interaction between dam PRL concentration and neonatal outcome. We have previously reported no significant differences in PRL levels of parturient (PO) and lactating (P6 & P 15) dams when exposed to 1.5-g hypergravity, but did observe a slight elevation of PRL on PO and P 15, with a decrease on P6. In the present study, time-bred pregnant dams were exposed to either continuous 2.0-g, 1.75-g or 1.5-g centrifugation, beginning on Gestational day (G) 11 of the rats' 22-day pregnancy. We observed no significant differences in PRL concentrations between SC and any of the HG conditions. On G20 and PO, PRL concentrations of the 2.0-g and 1.5-g groups were slightly elevated as compared to SC. Similar to what we previously reported. PRL secretion was elevated in both HG and SC conditions on the day of birth relative to later during lactation, but on P10 it appeared to be reduced in HG relative to SC dams. These findings suggests that hypergravity slightly elevates plasma concentration of PRL in pre-parturient and lactating rat dams, with effects most pronounced during the periparturitional period and in a direction opposite to that observed following microgravity exposure.

  6. Antiapoptotic effects of erythropoietin in differentiated neuroblastoma SH-SY5Y cells require activation of both the STAT5 and AKT signaling pathways.

    PubMed

    Um, Moonkyoung; Lodish, Harvey F

    2006-03-01

    The hematopoietic cytokine erythropoietin (Epo) prevents neuronal death during ischemic events in the brain and in neurodegenerative diseases, presumably through its antiapoptotic effects. To explore the role of different signaling pathways in Epo-mediated antiapoptotic effects in differentiated human neuroblastoma SH-SY5Y cells, we employed a prolactin receptor (PrlR)/erythropoietin receptor (EpoR) chimera system, in which binding of prolactin (Prl) to the extracellular domain activates EpoR signaling in the cytosol. On induction of apoptosis by staurosporine, Prl supports survival of the SH-SY5Y cells expressing the wild-type PrlR/EpoR chimera. In these cells Prl treatment strongly activates the STAT5, AKT, and MAPK signaling pathways and induces weak activation of the p65 NF-kappaB factor. Selective mutation of the eight tyrosine residues of the EpoR cytoplasmic domain results in impaired or absent activation of either STAT5 (mutation of Tyr(343)) or AKT (mutation of Tyr(479)) or both (mutation of all eight tyrosine residues). Most interestingly, Prl treatment does not prevent apoptosis in cells expressing mutant PrlR/EpoR chimeras in which either the STAT5 or the AKT signaling pathways are not activated. In contrast, ERK 1/2 is fully activated by all mutant PrlR/EpoR chimeras, comparable with the level seen with the wild-type PrlR/EpoR chimera, implying that activation of the MAPK signaling pathway per se is not sufficient for antiapoptotic activity. Therefore, the antiapoptotic effects of Epo in neuronal cells require the combinatorial activation of multiple signaling pathways, including STAT5, AKT, and potentially MAPK as well, in a manner similar to that observed in hematopoietic cells.

  7. Osmoregulatory effects of hypophysectomy and homologous prolactin replacement in hybrid striped bass.

    PubMed

    Jackson, Leslie F; McCormick, Stephen D; Madsen, Steffen S; Swanson, Penny; Sullivan, Craig V

    2005-02-01

    The effects of ovine prolactin (oPRL) and striped bass prolactin (sbPRL; Morone saxatilis) on plasma osmolality, electrolyte balance, and gill Na(+),K(+)-ATPase activity were investigated in hypophysectomized (Hx), freshwater (FW)-acclimated, hybrid striped bass (M. saxatilisxMorone chrysops). They were kept in dilute (isoosmotic) seawater for about 10 days after surgery. Seven days after transfer to FW, Hx fish had lower plasma osmolality and lower levels of Na(+), Cl(-), and Ca(2+) than sham-operated and intact fish. Fish were injected four times with oPRL (1, 5, or 20 microg/g body mass), sbPRL (10 or 100 ng/g), or hormone vehicle (0.9% NaCl) at 48-h intervals (days 0, 2, 4, and 6) in FW and then sampled for blood plasma 24 h after the fourth injection (day 7). In Hx fish, oPRL (5 and 20 microg/g) and sbPRL (10 and 100 ng/g) were effective in maintaining plasma osmolality and levels of Na(+), Cl(-), and Ca(2+) above values seen in saline-injected controls. Hypophysectomy did not affect branchial Na(+),K(+)-ATPase activity, but enzyme activity was significantly reduced in Hx fish receiving oPRL (20 mug/g) or sbPRL (10 or 100 ng/g). These results indicate that PRL acts to maintain plasma osmotic and ionic balance in FW-adapted hybrid striped bass, and that this may involve downregulation of branchial Na(+),K(+)-ATPase activity.

  8. Prolactin administration during early postnatal life decreases hippocampal and olfactory bulb neurogenesis and results in depressive-like behavior in adulthood.

    PubMed

    Lajud, Naima; Gonzalez-Zapien, Rubén; Roque, Angélica; Tinajero, Eréndira; Valdez, Juan José; Clapp, Carmen; Torner, Luz

    2013-11-01

    Tight regulation of hormone and neurochemical milieu during developmental periods is critical for adequate physiological functions. For instance, activation of peptide systems during early life stress induces morphological changes in the brain resulting in depression and anxiety disorders. Prolactin (PRL) exerts different actions within the brain; it regulates neurogenesis and modulates neuroendocrine functions in the adult. However, PRL effects during early postnatal life are hardly known. Therefore, we examined whether neonatal administration of PRL influences cell survival in the hippocampal dentate gyrus (DG) and in the olfactory bulb (OB) and whether such influence results in behavioral consequences in adulthood. PRL-treated rat pups (13 mg/kg; PND1 to PND14), injected with BrdU at postnatal day 5 (PND5), showed a decrease in the density of DG BrdU/DCX and BrdU/NeuN-positive cells that survive at PND15. Similarly, PRL treatment decreased the density of BrdU+ cells in the OB compared with VEH. Fluorojade B analysis showed no significant changes in the amount of cell death in the DG between the groups. Postnatal PRL administration induced a passive coping strategy in the forced swimming test in male and female adult rats when compared with control and vehicle groups. Corticosterone endogenous levels at PND12 were not affected by PRL or VEH treatment. Altogether, these results suggest that opposed to its effects in the adult, postnatal PRL treatment affects neurogenesis and results in psychopathology later in life. High PRL levels, as observed in neonates under several pathological states, might contribute to detrimental effects on the developing brain.

  9. Plasma progesterone and prolactin concentrations in overtly pseudopregnant bitches: a clinical study.

    PubMed

    Tsutsui, T; Kirihara, N; Hori, T; Concannon, P W

    2007-03-15

    Plasma concentrations of progesterone (P(4)) and prolactin (PRL) were measured in 35 bitches presented at veterinary clinics for symptoms of overt pseudopregnancy (PSP) between 50 and 95 days after the onset of proestrus. Results were compared to those from samples collected from 35 control bitches at comparable stages of the ovarian cycle (expressed as days after the onset of observed signs of proestrus). In the PSP bitches at 71.4+/-1.6 (mean+/-S.E.M.) days of the cycle, P(4) (1.5+/-0.2ng/mL) was lower (P<0.01) and PRL (16.0+/-1.9ng/mL) was higher (P<0.01), compared to P(4) (2.7+/-0.4ng/mL) and PRL (2.9+/-0.6ng/mL) in control bitches at 70.6+/-1.5 days of the cycle. Low P(4) was not a prerequisite for elevated PRL. Although elevated (> or =10ng/mL) PRL (20.9+/-2.0ng/mL) occurred more often with low (<2ng/mL) P(4) (20 of 24 cases) it also occurred with P(4) above 3ng/mL in two affected bitches and in two control bitches. Whether the occurrence of relatively low PRL concentrations (<4ng/mL) in samples obtained from 4 of the 35 pseudopregnant bitches reflected variable and often elevated PRL secretion or increased sensitivity to PRL in the absence of elevated prolactin in those animals was not determined. We inferred that elevated plasma PRL was often involved in the etiology of overt PSP; furthermore, a premature decline in circulating P(4) concentrations may be a factor in some instances.

  10. Prolactin stimulates the L-type calcium channel-mediated transepithelial calcium transport in the duodenum of male rats.

    PubMed

    Dorkkam, Nitita; Wongdee, Kannikar; Suntornsaratoon, Panan; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

    2013-01-11

    Elevated plasma levels of prolactin (PRL) have been reported in several physiological and pathological conditions, such as lactation, prolactinoma, and dopaminergic antipsychotic drug uses. Although PRL is a calcium-regulating hormone that stimulates intestinal calcium absorption in lactating rats, whether PRL is capable of stimulating calcium absorption in male rats has been elusive. Herein, the transepithelial calcium transport and electrical characteristics were determined in ex vivo duodenal tissues of male rats by Ussing chamber technique. We found that PRL receptors were abundantly present in the basolateral membrane of the duodenal epithelial cells. PRL (200-800 ng/mL) markedly increased the active duodenal calcium transport in a dose-dependent fashion without effect on the transepithelial resistance. The PRL-enhanced active duodenal calcium transport was completely abolished by L-type calcium channel blocker (nifedipine) as well as inhibitors of the major basolateral calcium transporters, namely plasma membrane Ca(2+)-ATPase and Na(+)/Ca(2+) exchanger. Several intracellular mediators, such as JAK2, MEK, PI3K and Src kinase, were involved in the PRL-enhanced transcellular calcium transport. Moreover, PRL also stimulated the paracellular calcium transport in the duodenum of male rats in a PI3K-dependent manner. In conclusion, PRL appeared to be a calcium-regulating hormone in male rats by enhancing the L-type calcium channel-mediated transcellular and the paracellular passive duodenal calcium transport. This phenomenon could help restrict or alleviate negative calcium balance and osteoporosis that often accompany hyperprolactinemia in male patients. PMID:23206706

  11. Prolactin modulates cytokine production induced by culture filtrate proteins of M. bovis through different signaling mechanisms in THP1 cells.

    PubMed

    Martínez-Neri, Priscila A; López-Rincón, Gonzalo; Mancilla-Jiménez, Raúl; del Toro-Arreola, Susana; Muñoz-Valle, José Francisco; Fafutis-Morris, Mary; Bueno-Topete, Miriam Ruth; Estrada-Chávez, Ciro; Pereira-Suárez, Ana Laura

    2015-01-01

    The immunomodulatory functions of prolactin (PRL) are well recognized. Augmented PRL plasma levels were observed in patients with advanced tuberculosis (TB). Recently, we have reported that LPS and Mycobacterium bovis (M. bovis) induced differential expression of PRL receptor (PRLR) isoforms in THP-1 cells and bovine macrophages, respectively. The aim of this work was to determine whether PRL should be considered as a potential modulator of the signaling pathways and cytokine synthesis, induced by culture filtrate protein (CFP) from M. bovis in THP-1 monocytes. The THP-1 cells were stimulated with PRL (20ng/mL), M. bovis CFP (50μg/mL). PRLR as well as phosphorylated STAT3, STAT5, Akt1/2/3, ERK1/2 and p38 expression were evaluated by Western blot. IL1-β, TNF-α, IL-6, IL-12, IL-8, and IL-10 concentrations were measured by ELISA. Our results demonstrated that the expression pattern of PRLR short isoforms is induced by M. bovis CFP. M bovis CFP induced phosphorylation of Akt2, ERK1/2, p38, STAT3, and STAT5 pathways. In turn, PRL only activated the JAK2/STAT3-5 signaling pathway. However, when combined both stimuli, PRL significantly increased STAT3-5 phosphorylation and downregulated Akt2, ERK1/2, and p38 phosphorylation. As expected, M. bovis CFP induced substantial amounts of IL1-β, IL-6, TNF-α, IL-8, IL-12, and IL-10. However, the PRL costimulation considerably decreased IL1-β, TNF-α, and IL-12 secretion, and increased IL-10 production. This results suggest that up-regulation of IL-10 by PRL might be modulating the pro-inflammatory response against mycobacterial antigens through the MAPK pathway.

  12. Pregnancy Hyperglycemia in Prolactin Receptor Mutant, but Not Prolactin Mutant, Mice and Feeding-Responsive Regulation of Placental Lactogen Genes Implies Placental Control of Maternal Glucose Homeostasis1

    PubMed Central

    Rawn, Saara M.; Huang, Carol; Hughes, Martha; Shaykhutdinov, Rustem; Vogel, Hans J.; Cross, James C.

    2015-01-01

    Pregnancy is often viewed as a conflict between the fetus and mother over metabolic resources. Insulin resistance occurs in mothers during pregnancy but does not normally lead to diabetes because of an increase in the number of the mother's pancreatic beta cells. In mice, this increase is dependent on prolactin (Prl) receptor signaling but the source of the ligand has been unclear. Pituitary-derived Prl is produced during the first half of pregnancy in mice but the placenta produces Prl-like hormones from implantation to term. Twenty-two separate mouse genes encode the placenta Prl-related hormones, making it challenging to assess their roles in knockout models. However, because at least four of them are thought to signal through the Prl receptor, we analyzed Prlr mutant mice and compared their phenotypes with those of Prl mutants. We found that whereas Prlr mutants develop hyperglycemia during gestation, Prl mutants do not. Serum metabolome analysis showed that Prlr mutants showed other changes consistent with diabetes. Despite the metabolic changes, fetal growth was normal in Prlr mutants. Of the four placenta-specific, Prl-related hormones that have been shown to interact with the Prlr, their gene expression localizes to different endocrine cell types. The Prl3d1 gene is expressed by trophoblast giant cells both in the labyrinth layer, sitting on the arterial side where maternal blood is highest in oxygen and nutrients, and in the junctional zone as maternal blood leaves the placenta. Expression increases during the night, though the increase in the labyrinth is circadian whereas it occurs only after feeding in the junctional zone. These data suggest that the placenta has a sophisticated endocrine system that regulates maternal glucose metabolism during pregnancy. PMID:26269505

  13. Autocrine/paracrine roles of extrapituitary growth hormone and prolactin in health and disease: An overview.

    PubMed

    Harvey, Steve; Martínez-Moreno, Carlos G; Luna, Maricela; Arámburo, Carlos

    2015-09-01

    Growth hormone (GH) and prolactin (PRL) are both endocrines that are synthesized and released from the pituitary gland into systemic circulation. Both are therefore hormones and both have numerous physiological roles mediated through a myriad of target sites and both have pathophysiological consequences when present in excess or deficiency. GH or PRL gene expression is not, however, confined to the anterior pituitary gland and it occurs widely in many of their central and peripheral sites of action. This may reflect "leaky gene" phenomena and the fact that all cells have the potential to express every gene that is present in their genome. However, the presence of GH or PRL receptors in these extrapituitary sites of GH and PRL production suggests that they are autocrine or paracrine sites of GH and PRL action. These local actions often occur prior to the ontogeny of pituitary somatotrophs and lactotrophs and they may complement or differ from the roles of their pituitary counterparts. Many of these local actions are also of physiological significance, since they are impaired by a blockade of local GH or PRL production or by an antagonism of local GH or PRL action. These local actions may also be of pathophysiological significance, since autocrine or paracrine actions of GH and PRL are thought to be causally involved in a number of disease states, particularly in cancer. Autocrine GH for instance, is thought to be more oncogenic than pituitary GH and selective targeting of the autocrine moiety may provide a therapeutic approach to prevent tumor progression. In summary, GH and PRL are not just endocrine hormones, as they have autocrine and/or paracrine roles in health and disease.

  14. The role of prolactin in andrology: what is new?

    PubMed

    Rastrelli, Giulia; Corona, Giovanni; Maggi, Mario

    2015-09-01

    Prolactin (PRL) has been long deemed as a hormone involved only in female reproduction. However, PRL is a surprising hormone and, since its identification in the 1970s, its attributed functions have greatly increased. However, its specific role in male health is still widely unknown. Recently, low PRL has been associated with reduced ejaculate and seminal vesicle volume in infertile subjects. In addition, in men consulting for sexual dysfunction, hypoprolactinemia has been associated with erectile dysfunction and premature ejaculation, findings further confirmed in the general European population and infertile men. Several metabolic derangements, recapitulating metabolic syndrome, have also been associated with low PRL both in men with sexual dysfunction and from the general European population. In men with sexual dysfunction, followed-up for more than 4 years, low PRL was identified as an independent predictor of the incidence of major adverse cardiovascular events. Finally, an association with anxiety or depressive symptoms has been found in men with sexual dysfunction and from the general European population. While a direct role for impaired PRL function in the pathogenesis of these reproductive, sexual, metabolic and psychological disorders is conceivable, the possibility that low PRL is a mirror of an increased dopaminergic or a decreased serotonergic tone cannot be ruled-out. Hyperactivity of the dopaminergic system can explain only a few of the aforementioned findings, whereas a hypo-serotonergic tone fits well with the clinical features associated with low PRL, and there is significant evidence supporting the hypothesis that PRL could be a mirror of serotonin in the brain.

  15. Pregnancy Hyperglycemia in Prolactin Receptor Mutant, but Not Prolactin Mutant, Mice and Feeding-Responsive Regulation of Placental Lactogen Genes Implies Placental Control of Maternal Glucose Homeostasis.

    PubMed

    Rawn, Saara M; Huang, Carol; Hughes, Martha; Shaykhutdinov, Rustem; Vogel, Hans J; Cross, James C

    2015-09-01

    Pregnancy is often viewed as a conflict between the fetus and mother over metabolic resources. Insulin resistance occurs in mothers during pregnancy but does not normally lead to diabetes because of an increase in the number of the mother's pancreatic beta cells. In mice, this increase is dependent on prolactin (Prl) receptor signaling but the source of the ligand has been unclear. Pituitary-derived Prl is produced during the first half of pregnancy in mice but the placenta produces Prl-like hormones from implantation to term. Twenty-two separate mouse genes encode the placenta Prl-related hormones, making it challenging to assess their roles in knockout models. However, because at least four of them are thought to signal through the Prl receptor, we analyzed Prlr mutant mice and compared their phenotypes with those of Prl mutants. We found that whereas Prlr mutants develop hyperglycemia during gestation, Prl mutants do not. Serum metabolome analysis showed that Prlr mutants showed other changes consistent with diabetes. Despite the metabolic changes, fetal growth was normal in Prlr mutants. Of the four placenta-specific, Prl-related hormones that have been shown to interact with the Prlr, their gene expression localizes to different endocrine cell types. The Prl3d1 gene is expressed by trophoblast giant cells both in the labyrinth layer, sitting on the arterial side where maternal blood is highest in oxygen and nutrients, and in the junctional zone as maternal blood leaves the placenta. Expression increases during the night, though the increase in the labyrinth is circadian whereas it occurs only after feeding in the junctional zone. These data suggest that the placenta has a sophisticated endocrine system that regulates maternal glucose metabolism during pregnancy.

  16. Prolactin and hostility in hospitalised patients and healthy women: A systematic review and meta-analysis.

    PubMed

    Barry, J A; Moran, E; Thomas, M; Hardiman, P J

    2015-01-01

    The aim of this systematic review and meta-analysis was to assess any difference in the self-ratings of hostility in mentally healthy women with different levels of prolactin (PRL). Electronic databases (PubMed, MEDLINE, EMBASE and the Cochrane Library) were searched up to 2nd July 2012 for published literature comparing hostility levels in women with different levels of PRL. Keyword pairs ('prolactin' and 'aggression', 'prolactin' and 'hostil*', 'prolactin' and 'anger', and 'prolactin' and 'angry') were entered simultaneously. From 1065 resulting titles, and one unpublished study, 214 articles underwent full-text review by authors JB and EM. Studies were selected based on clinical relevance. Eight comparative studies consisting of 242 female patients with high PRL levels, 207 female patients with normal PRL levels and 127 healthy controls with normal PRL levels were included. Data were analysed using the inverse variance method with a random-effects model. Analysis revealed significantly higher hostility in patients with high PRL compared with that in healthy control women (Z = 1.94, p < 0.05; Hedges' g = 0.72; 95% confidence interval [CI]: -0.01-1.45), significantly higher hostility in patient controls compared with that in healthy controls (Z = 1.94, p < 0.05; Hedges' g = 0.47; 95% CI: 0.00-0.94) and non-significantly higher hostility levels in patients with high PRL compared with that in patients with normal PRL levels (Z = 1.45, p < 0.15; Hedges' g = 0.38; 95% CI: -0.13-0.89). In this meta-analysis, hostility appears to be accounted for partly by PRL levels and also partly by patient status, perhaps due to the stress of being a patient. Methodological considerations and implications for patient care are discussed.

  17. Induction of multidrug resistance transporter ABCG2 by prolactin in human breast cancer cells.

    PubMed

    Wu, Alex Man Lai; Dalvi, Pooja; Lu, Xiaoli; Yang, Mingdong; Riddick, David S; Matthews, Jason; Clevenger, Charles V; Ross, Douglas D; Harper, Patricia A; Ito, Shinya

    2013-02-01

    The multidrug transporter, breast cancer resistance protein, ABCG2, is up-regulated in certain chemoresistant cancer cells and in the mammary gland during lactation. We investigated the role of the lactogenic hormone prolactin (PRL) in the regulation of ABCG2. PRL dose-dependently induced ABCG2 expression in T-47D human breast cancer cells. This induction was significantly reduced by short-interfering RNA-mediated knockdown of Janus kinase 2 (JAK2). Knockdown or pharmacologic inhibition of the down-stream signal transducer and activator of transcription-5 (STAT5) also blunted the induction of ABCG2 by PRL, suggesting a role for the JAK2/STAT5 pathway in PRL-induced ABCG2 expression. Corroborating these findings, we observed PRL-stimulated STAT5 recruitment to a region containing a putative γ-interferon activation sequence (GAS) element at -434 base pairs upstream of the ABCG2 transcription start site. Introduction of a single mutation to the -434 GAS element significantly attenuated PRL-stimulated activity of a luciferase reporter driven by the ABCG2 gene promoter and 5'-flanking region containing the -434 GAS motif. In addition, this GAS element showed strong copy number dependency in its response to PRL treatment. Interestingly, inhibitors against the mitogen-activated protein kinase and phosphoinositide-3-kinase signaling pathways significantly decreased the induction of ABCG2 by PRL without altering STAT5 recruitment to the GAS element. We conclude that the JAK2/STAT5 pathway is required but not sufficient for the induction of ABCG2 by PRL.

  18. Suppression of Serum Prolactin Levels after Sports Concussion with Prompt Resolution Upon Independent Clinical Assessment To Permit Return-to-Play.

    PubMed

    La Fountaine, Michael F; Toda, Michita; Testa, Anthony; Bauman, William A

    2016-05-01

    A significant outflow of neurotransmitters and metabolites with associated enhanced cortical excitation occurs after concussive head trauma. Cellular changes in the acute post-injury period cannot be observed directly in humans, and as such, require indirect evidence from systems sufficiently sensitive to central neuronal cellular excitation. Dopamine is a neurotransmitter with numerous targets in the central and peripheral nervous system. Changes to central dopaminergic tone result in reciprocal responses to the level of serum prolactin (PRL). Thus, a concussion may lead to abnormal dopaminergic tone, resulting in dynamic perturbations in the serum PRL concentration. To determine the effect of concussion on serum PRL concentrations, venipuncture was performed in the morning in four male intercollegiate athletes (age, 20 ± 1 years; height, 71 ± 5 inches; weight, 174 ± 21 pounds) within 48 h of concussion and again at 7 and 14 days post-injury. Serum PRL concentrations for each visit were categorized by quartile within the normal range. In all athletes, serum PRL concentrations increased from the lower quartiles in samples obtained closer to the time of injury to the higher quartiles at 14 days post-injury. These serum PRL changes accompanied the resolution of symptoms and the clinical decision to permit return-to-play. It may be postulated that transient augmentation of central dopaminergic tone resulted in inhibition of PRL secretion early after concussion and that disinhibition of PRL release occurred when central dopaminergic tone subsequently returned to baseline levels. This novel observation provides evidence for dopaminergic dysfunction after concussion that may be tracked by determination of serum PRL levels.

  19. Integrating oculomotor and perceptual training to induce a pseudofovea: A model system for studying central vision loss.

    PubMed

    Liu, Rong; Kwon, MiYoung

    2016-01-01

    People with a central scotoma often adopt an eccentric retinal location (Preferred Retinal Locus, PRL) for fixation. Here, we proposed a novel training paradigm as a model system to study the nature of the PRL formation and its impacts on visual function. The training paradigm was designed to effectively induce a PRL at any intended retinal location by integrating oculomotor control and pattern recognition. Using a gaze-contingent display, a simulated central scotoma was induced in eight normally sighted subjects. A subject's entire peripheral visual field was blurred, except for a small circular aperture with location randomly assigned to each subject (to the left, right, above, or below the scotoma). Under this viewing condition, subjects performed a demanding oculomotor and visual recognition task. Various visual functions were tested before and after training at both PRL and nonPRL locations. After 6-10 hr of the training, all subjects formed their PRL within the clear window. Both oculomotor control and visual recognition performance significantly improved. Moreover, there was considerable improvement at PRL location in high-level function, such as trigram letter-recognition, reading, and spatial attention, but not in low-level function, such as acuity and contrast sensitivity. Our results demonstrated that within a relatively short time, a PRL could be induced at any intended retinal location in normally-sighted subjects with a simulated scotoma. Our training paradigm might not only hold promise as a model system to study the dynamic nature of the PRL formation, but also serve as a rehabilitation regimen for individuals with central vision loss. PMID:27089065

  20. Physico-chemical and immunological characteristics of pituitary prolactin from water buffaloes (Bubalus bubalis).

    PubMed

    Chadha, N; Kohli, R; Kumari, G L; Muralidhar, K

    1991-06-26

    Prolactin (PRL) was purified from freshly frozen pituitary glands of water buffaloes (Bubalus bubalis) by a combination of existing procedures of Ellis and Jiang and Wilhelmi involving serial extraction of different pituitary proteins. The partially purified preparation was further fractionated on DEAE-Sephadex followed by Sephadex G-100 chromatography. This was finally purified on HPLC. This preparation was found to be homogeneous by SDS-PAGE and HPLC and had a single N-terminus amino acid (Threonine). The molecular size was estimated to be 24K +/- 0.5 by SDS-PAGE and approximately 25K by GPC-HPLC. The buffalo PRL gave a dose dependent inhibition curve in a rat liver based radio receptor assay with a potency of 30-35 I.U./mg and also in a partial homologous RIA using 125I-buffalo PRL and rabbit anti-oPRL serum giving a potency of 30 I.U./mg. Metabolic labelling studies using 35SO4(2-) with buffalo pituitary minces showed the incorporation of radioactive sulfate into immunoprecipitable PRL-like material. Physico-chemical characterization of the site of the linkage between sulfate and PRL revealed the presence of Tyr-O-SO4 in bu-PRL. A high affinity monoclonal antibody (MAB) with Ka of 10(10) L/M, belonging to IgG1 isotype, and capable of cross reacting with ovine and bovine PRL was generated. This MAB was conformation specific as reduced and carboxymethylated PRL did not react with it. A homologous RIA system using this MAB has been standardised.

  1. Physical randomness sources for loophole-free Bell tests

    NASA Astrophysics Data System (ADS)

    Mitchell, Morgan W.

    2016-05-01

    We describe the strategy and physics used to select unpredictable measurement settings in the loophole-free Bell tests reported in [Hensen et al. Nature 2015, Giustina et al. PRL 2015, and Shalm et al. PRL 2015]. We demonstrate direct measurements of laser phase diffusion, a process driven by spontaneous emission, rigorous bounds on the effect of other, less-trusted contributions, and exponential predictability reduction by randomness extraction. As required for the cited experiments, we show the six-sigma bound for the predictability of the basis choices is below 0.001%. C. Abellan et al. PRL 2015.

  2. Primary Renal Lymphoma Mimicking a Subcapsular Hematoma: A Case Report

    PubMed Central

    Dedekam, Erik; Graham, Jess; Strenge, Karen; Mosier, Andrew D.

    2013-01-01

    Primary renal lymphoma (PRL) is a rare entity with a history of controversy regarding its existence. Lymphomatous involvement of the kidney is more commonly seen secondarily to spread from an adjacent lymphomatous mass, rather than arising primarily from the kidney. PRL can mimic other renal lesions such as renal cell carcinoma, renal abscess, and metastasis; therefore, an early diagnosis is crucial to guide treatment and properly assess prognosis. We present a rare case of a 77 year-old male who presented with hematuria and PRL mimicking a subcapsular hematoma. PMID:24421949

  3. Primary renal lymphoma mimicking a subcapsular hematoma: a case report.

    PubMed

    Dedekam, Erik; Graham, Jess; Strenge, Karen; Mosier, Andrew D

    2013-08-01

    Primary renal lymphoma (PRL) is a rare entity with a history of controversy regarding its existence. Lymphomatous involvement of the kidney is more commonly seen secondarily to spread from an adjacent lymphomatous mass, rather than arising primarily from the kidney. PRL can mimic other renal lesions such as renal cell carcinoma, renal abscess, and metastasis; therefore, an early diagnosis is crucial to guide treatment and properly assess prognosis. We present a rare case of a 77 year-old male who presented with hematuria and PRL mimicking a subcapsular hematoma. PMID:24421949

  4. Prolactin decrease and shift to a normal-like isoform profile during treatment with quinagolide in a patient affected by an invasive prolactinoma.

    PubMed

    Guido, R; Valenti, S; Foppiani, L; De Martini, D; Cossu, M; Giusti, M

    1997-05-01

    Prolactin (PRL) circulates as multiple molecular weight variants: glycosylated phosphorylated, deamidated and sulphated forms. The profiles of the forms, as determined by isoelectrofocusing (IEF), differ in physiological and pathological conditions. The case of a 72-year-old woman affected by an invasive prolactinoma is described. The patient had undergone surgical treatment followed by radiotherapy at the age of 71 years. Bromocriptine therapy followed (up to 10 mg/die), but the PRL levels were still extremely high (over 13,000 micrograms/l as determined by IRMA, after dilution). We therefore treated the patient with quinagolide, at increasing dosages, from 150 micrograms/die on day 0 to 600 micrograms/die on day 220. This treatment progressively lowered PRL to 23.2 micrograms/l. In addition to a decrease in PRL levels, a progressive change in the IEF profile was also noted. Indeed, on day 0, the PRL isoforms were very acidic and during treatment they progressively shifted toward a more basic range. For purpose of comparison PRL profiles were also determined in 8 women with pathological hyperprolactinaemia (group A, aged 16-50 years, PRL levels: 25.1-170.4 micrograms/l), in 6 normal women (group B, aged 25-29 years, PRL levels: 3.4-7.9 micrograms/l) and in 5 normal women during a TRH test (group C, aged 17-52 years, PRL levels: 2.7-10.3 micrograms/l). The profiles observed in group A had a single major peak at isoelectric point (pI) 6.5, while the group B and C profiles were more heterogeneous displaying multiple minor peaks, the majority of the molecules being in a more basic range (pI 6.9 for group B and pI 7.5 for group C). During treatment, the profiles of our subject at first resembled those of group A; subsequently, when the PRL levels had normalised, the profile resembled those noted in group B. Altered (immature?, more glycosilated?, less bioactive?) PRL molecules could be secreted by the tumour. These data show that quinagolide successfully reduced PRL

  5. Transition to zero resistance in an irradiated 2DEG

    NASA Astrophysics Data System (ADS)

    Alicea, J.; Balents, L.; Fisher, M. P. A.; Paramekanti, A.; Radzihovsky, L.

    2004-03-01

    Recent experiments have demonstrated that high mobility 2D electron systems driven with microwaves exhibit an oscillatory longitudinal resistance that vanishes for certain magnetic field strengths [1]. While theoretical calculations [2] predict a negative longitudinal resistivity, Andreev et al. (PRL 91, 056803 (2003)) showed that this renders the system unstable towards an inhomogeneous zero resistance state. We explore analytically and numerically the properties of the transition to this inhomogeneous state. [1] M. A. Zudov et al., PRL 90, 046807 (2003); R. G. Mani et al., Nature 420, 646 (2002) [2] Ryzhii, Sov. Phys. Solid State 11, 2078 (1970); Durst et al., PRL 91, 086803 (2003)

  6. The effect of prolactin on the Dunning R3327H rat prostatic adenocarcinoma.

    PubMed

    Kharroubi, A; Slaunwhite, W R

    The Dunning R3327 rat prostatic adenocarcinoma contains specific binding sites for iodo-oPRL (ovine prolactin) in the membrane fraction (100,000 X g pellet). These are normally present at a low level, but immunization with oPRL produces a dramatic increase in tumor binding in either sex (females bear an implant of testosterone propionate pellet). Under these experimental conditions, the ventral prostate of rats bearing the tumors have no detectable PRL receptors. 5 alpha-Reductase activity, on the other hand, is lower in the tumors than in the normal prostates. Immunization also decreased somewhat the rate of growth of the tumors. PMID:6323127

  7. Rainbow trout prolactin cDNA cloning in Escherichia coli.

    PubMed

    Mercier, L; Rentier-Delrue, F; Swennen, D; Lion, M; Le Goff, P; Prunet, P; Martial, J A

    1989-03-01

    We describe the isolation and characterization of a cDNA for trout prolactin (tPrl). An extensive analysis of tPrl recombinant clones by restriction analysis and sequencing revealed the presence of only one form of tPrl mRNA. The deduced protein sequence consists of 210 amino acids, including a signal peptide of 23 amino acids. The amino acid sequence of the mature protein is compared among teleosts and mammals, showing two domains of strong similarity that may be involved in biological activity. PMID:2647439

  8. Direct effects of catecholamines, thyrotropin-releasing hormone, and somatostatin on growth hormone and prolactin secretion from adenomatous and nonadenomatous human pituitary cells in culture.

    PubMed Central

    Ishibashi, M; Yamaji, T

    1984-01-01

    To determine the mechanism and the site of action of catecholamines as well as hormones including thyrotropin-releasing hormone (TRH)1 and somatostatin on pituitary hormone release in patients with acromegaly and in normal subjects, the effects of these substances on growth hormone (GH) and prolactin (PRL) secretion from adenomatous and nonadenomatous human pituitary cells in culture were examined. When dopamine (0.01-0.1 microM) or bromocriptine (0.01-0.1 microM) was added to the culture media, a significant inhibition of GH and PRL secretion from adenoma cells from acromegalic patients was observed. This inhibition was blocked by D2 receptor blockade with metoclopramide or sulpiride, but not by D1 receptor blockade. Similarly, dopamine suppressed GH and PRL release by nonadenomatous pituitary cells in a dose-dependent manner, which was again blocked by D2 receptor blockade. The minimum effective concentration of dopamine required for a significant inhibition of PRL secretion (0.01 microM) was lower than that for GH release (0.1 microM). Norepinephrine, likewise, caused a suppression of PRL secretion from adenomatous and nonadenomatous pituitary cells. This effect was blocked by sulpiride, phentolamine, however, was ineffective. When TRH was added to the media, both GH and PRL secretion were enhanced in adenoma cells, while only the stimulation of PRL release was observed in nonadenomatous pituitary cells. Coincubation of TRH and dopamine resulted in variable effects on GH and PRL secretion. Somatostatin consistently lowered GH and PRL secretion in both adenomatous and nonadenomatous pituitary cells and completely blocked the TRH-induced stimulation of GH and PRL secretion from adenoma cells. Opioid peptides (1 microM) failed to affect hormone release. These results suggest that no qualitative difference in GH and PRL responses to dopaminergic agonists or to somatostatin exists between adenoma cells of acromegalic patients and normal pituitary cells, and that the

  9. Maternal exposure to atrazine during lactation suppresses suckling-induced prolactin release and results in prostatitis in the adult offspring.

    PubMed

    Stoker, T E; Robinette, C L; Cooper, R L

    1999-11-01

    The availability of prolactin (PRL) to the neonatal brain is known to affect the development of the tuberoinfundibular (TIDA) neurons and, as a consequence, lead to alterations in subsequent PRL regulation. Without early lactational exposure to PRL (derived from the dam's milk), TIDA neuronal growth is impaired and elevated PRL levels are present in the prepubertal male. These observations, combined with the finding that alterations in PRL secretion (i.e., hyperprolactinemia) in the adult male rat have been implicated in the development of prostatitis, led us to hypothesize that early lactational exposure to agents that suppress suckling-induced PRL release would lead to a disruption in TIDA development, altered PRL regulation, and subsequent prostatitis in the male offspring. To test this hypothesis, suckling-induced PRL release was measured in Wistar dams treated twice daily with the herbicide atrazine (ATR, by gavage, on PND 1-4 at 0, 6.25, 12.5, 25, and 50 mg/kg body weight), or twice daily with the dopamine receptor agonist bromocriptine (BROM, sc, at 0.052, 0.104, 0.208, and 0.417 mg/kg); BROM is known to suppress PRL release. Similarly, atrazine has also been reported to suppress PRL in adult females. Serum PRL was measured on PND 3 using a serial sampling technique and indwelling cardiac catheters. A significant rise in serum PRL release was noted in all control females within 10 min of the initiation of suckling. Fifty-mg/kg ATR inhibited suckling-induced PRL release in all females, whereas 25 and 12.5 mg/kg ATR inhibited this measure in some dams and had no discernible effect in others. The 6.25 mg/kg dose of ATR was without effect. BROM, used here as a positive control, also inhibited suckling-induced PRL release at doses of 0.104 to 0.417 mg/kg, with no effect at 0.052 mg/kg. To examine the effect of postnatal ATR and BROM on the incidence and severity of inflammation (INF) of the lateral prostate of the offspring, adult males were examined at 90 and

  10. Correlation and comparison of Nb/sub 2/ lymphoma cell bioassay with radioimmunoassay for human prolactin

    SciTech Connect

    Subramanian, M.G.; Spirtos, N.J.; Moghissi, K.S.; Magyar, D.M.; Hayes, M.F.; Gala, R.R.

    1984-12-01

    Serum samples from groups of men and women with normal and elevated prolactin (PRL) levels were assayed by radioimmunoassay (RIA) and by Nb/sub 2/ lymphoma cell bioassay (BA) for the presence of PRL. Because the Nb/sub 2/ lymphoma cells respond to both PRL and growth hormone, BA for PRL activity was carried out before and after neutralization of growth hormone in the serum samples. There were excellent correlations between RIA and BA both in euprolactinemic and hyperprolactinemic subjects. On an absolute basis, RIA and BA values were similar in the euprolactinemic group (6.6 +/- 0.8 versus 6.2 +/- 1.0), whereas in the hyperprolactinemic group, RIA values were significantly higher than the BA results. The two assay systems also appeared to correlate better in women who were hyperprolactinemic, with obvious menstrual cycle disturbances, than in hyperprolactinemic women without menstrual cycle disturbances.

  11. Concomitant Cushing's Disease and Marked Hyperprolactinemia: Response to a Dopamine Receptor Agonist.

    PubMed

    Shiraishi, Jun; Koyama, Hidenori; Shirakawa, Manabu; Ishikura, Reiichi; Okazaki, Hirokazu; Kurajoh, Masafumi; Shoji, Takuhito; Moriwaki, Yuji; Yamamoto, Tetsuya; Namba, Mitsuyoshi

    2016-01-01

    A 38-year-old woman was admitted to our hospital because of amenorrhea, multiple bone fractures, and a Cushingoid appearance. Endocrinological investigations revealed that she had co-existing Cushing's disease and prolactinoma, with a serum level of prolactin (PRL) at 1,480 ng/mL, corticotropin (ACTH) at 81.3 pg/mL, and cortisol at 16.6 μg/dL. Due to the lack of indication for transsphenoidal surgery, cabergoline monotherapy was initiated. A 6-month course of treatment resulted in only subtle amelioration of hypercortisolism, while hyperprolactinemia was dramatically improved. In 5 cases of bihormonal (ACTH/PRL) pituitary macroadenoma reported in the English literature, 2 were initially treated with dopaminergic agonists with substantial effectiveness for both PRL and ACTH. We herein report an extremely rare case of bihormonal macroadenoma in which only PRL was responsive to treatment. PMID:27086808

  12. Effects of dopamine receptor stimulation on opiate-induced modifications of pituitary-gonadal function.

    PubMed

    Vescovi, P P; Pezzarossa, A; Ceresini, G; Rastelli, G; Valenti, G; Gerra, G

    1985-01-01

    We evaluated the effects of the dopaminergic drug bromocriptine (Br) on prolactin (PRL), luteinizing hormone (LH) and testosterone (Te) levels in a homogeneous group of opiate addicts in a methadone maintenance program (20 mg twice daily). Basal blood levels of PRL, LH and Te were determined in 15 adult male drug addicts, before 30 and 60 days after Br administration (7.5 mg/day) was started. 15 healthy volunteers served as controls for the evaluation of basal values of the hormones. Before treatment PRL values were high, while LH and Te levels were lower than normal. 30 days later, PRL lowered significantly while LH and Te increased significantly. 60 days later, the blood hormone values were still significantly different from pretreatment values, and close to the normal range. This observation shows that Br, probably through an increase of dopaminergic tone, may counteract some effects of opiates on the hypothalamic-pituitary-gonadal axis.

  13. Learning and Memory Improvement through Chemistry: Dream or Reality in the Offing?

    ERIC Educational Resources Information Center

    Hansl, Nikolaus R.; Hansl, Adele B.

    1979-01-01

    Reports on PRL-8-53, an experimental drug that will boost the chemical system in the brain called the cholinergic system and thereby improve one's ability to retrieve information from a preexisting information pool. (Author/IRT)

  14. The role of the interaction of the vinculin proline-rich linker region with vinexin α in sensing the stiffness of the extracellular matrix.

    PubMed

    Yamashita, Hiroshi; Ichikawa, Takafumi; Matsuyama, Daisuke; Kimura, Yasuhisa; Ueda, Kazumitsu; Craig, Susan W; Harada, Ichiro; Kioka, Noriyuki

    2014-05-01

    Although extracellular matrix (ECM) stiffness is an important aspect of the extracellular microenvironment and is known to direct the lineage specification of stem cells and affect cancer progression, the molecular mechanisms that sense ECM stiffness have not yet been elucidated. In this study, we show that the proline-rich linker (PRL) region of vinculin and the PRL-region-binding protein vinexin are involved in sensing the stiffness of ECM substrates. A rigid substrate increases the level of cytoskeleton-associated vinculin, and the fraction of vinculin stably localizing at focal adhesions (FAs) is larger on rigid ECM than on soft ECM. Mutations in the PRL region or the depletion of vinexin expression impair these responses to ECM stiffness. Furthermore, vinexin depletion impairs the stiffness-dependent regulation of cell migration. These results suggest that the interaction of the PRL region of vinculin with vinexin α plays a crucial role in sensing ECM stiffness and in mechanotransduction.

  15. Changes in the nuclear uptake and retention of /sup 3/H-estrogen in gonadotrophs and lactotrophs as a function of age

    SciTech Connect

    Nogami, H.; Yoshimura, F.; Herbert, D.C.; Aufdemorte, T.B.; Gates, G.A.; Holt, G.R.; Sheridan, P.J.

    1985-07-01

    A quantitative autoradiographic immunocytochemical study was performed in which the nuclear uptake and retention of /sup 3/H-estradiol (/sup 3/H-E2) by luteinizing hormone (LH) and prolactin (PRL) cells was examined in 19-21-year-old baboons. /sup 3/H-E2 concentrating cells were found in all of the three lobes of the pituitary in varying percentages. Approximately 80% of PRL cells and nearly 100% of LH cells were labeled. A count of the number of silver grains over nuclei revealed a marked variation of the accumulation of /sup 3/H-E2 by LH cells and to a lesser extent in PRL cells. These results suggest functional heterogeneity among LH and PRL cells. The present results are discussed in relation to the physiological state of old animals.

  16. Receptor domains involved in signal transduction of prolactin and growth hormone

    SciTech Connect

    Kelly, P.A.; Edery, M.; Finidori, J.

    1994-12-31

    Prolactin (PRL) and growth hormone (GH) receptors are members of a superfamily that include receptors for a number of cytokines. GH and its receptor form an unusual homodimer consisting of one molecule of GH and two molecules of receptor. A similar homodimer of the PRL receptor is probably required for biological effects to be seen. Using specific assays to measure the functional activity of PRL and GH receptors, a 25 amino acid juxtamembrane region has been identified as essential but not sufficient for normal action. More detailed studies have limited the region to eight amino acids, rich in prolines, that is highly conserved in many members of the receptor superfamily. Finally, GH and PRL have been shown to induce the rapid tyrosine phosphorylation of an associated kinase, Janus kinase 2, and of the receptor itself. 28 refs., 1 fig.

  17. 16-kDa prolactin and bromocriptine in postpartum cardiomyopathy.

    PubMed

    Hilfiker-Kleiner, Denise; Struman, Ingrid; Hoch, Melanie; Podewski, Edith; Sliwa, Karen

    2012-09-01

    Peripartum cardiomyopathy (PPCM) is a potentially life-threatening heart disease emerging toward the end of pregnancy or in the first postpartal months in previously healthy women. Recent data suggest a central role of unbalanced peri-/postpartum oxidative stress that triggers the proteolytic cleavage of the nursing hormone prolactin (PRL) into a potent antiangiogenic, proapoptotic, and proinflammatory 16-kDa PRL fragment. This notion is supported by the observation that inhibition of PRL secretion by bromocriptine, a dopamine D2-receptor agonist, prevented the onset of disease in an animal model of PPCM and by first clinical experiences where bromocriptine seem to exert positive effects with respect to prevention or treatment of PPCM patients. Here, we highlight the current state of knowledge on diagnosis of PPCM, provide insights into the biology and pathophysiology of 16-kDa PRL and bromocriptine, and outline potential consequences for the clinical management and treatment options for PPCM patients.

  18. Pituitary adenoma in Carney complex: an immunohistochemical, ultrastructural, and immunoelectron microscopic study.

    PubMed

    Kurtkaya-Yapicier, O; Scheithauer, B W; Carney, J A; Kovacs, K; Horvath, E; Stratakis, C A; Vidal, S; Vella, A; Young, W F; Atkinson, J L D; Lloyd, R V; Kontogeorgos, G

    2002-01-01

    First described in 1985, Carney complex is a rare, heritable disorder featuring abnormal skin pigmentation, cardiac and cutaneous myxoma, melanotic schwannoma of psammomatous type, and endocrine abnormalities, including pituitary adenomas. Patients with the latter present with elevated growth hormone (GH) levels and acromegaly or gigantism. Prolactin (PRL) elevation may also be seen. The authors have investigated 2 resected pituitary adenomas from patients with Carney complex. One, a 19-year-old female acromegalic with elevated GH, IgF-1, and PRL levels, had a mammosomatotroph adenoma immunoreactive for GH and PRL. Ultrastructurally, GH and PRL were present in the same secretory granules. The second patient, a 27-year-old acromegalic, had a sparsely granulated GH cell adenoma that by immuno-electron microscopy revealed GH immunoreactivity only. The lack of morphologic similarity between the 2 adenomas indicatesthat pituitary tumors in patients with Carney complex may not exhibit the same phenotype. PMID:12537759

  19. Prolactin-stimulated ornithine decarboxylase induction in rat hepatocytes: Coupling to diacylglycerol generation and protein kinase C

    SciTech Connect

    Buckley, A.R.; Buckley, D.J. )

    1991-01-01

    The trophic effects of prolactin (PRL) in rat liver have been linked to activation of protein kinase C (PKC). Since alterations in PKC activity imply its activation by 1,2-diacylglycerol (DAG), we tested whether PRL treatment stimulated DAG generation coupled to induction of a growth response in primary hepatocytes. Addition of PRL to hepatocyte cultures significantly increased ({sup 3}H)-glycerol incorporation into DAG within 5 minutes which was followed by a loss of cytosolic PKC activity by 10 minutes. Prolactin also significantly enhanced radiolabel incorporation into triacylglycerol and phospholipids within 10 minutes and induced ODC activity at 6 hours. Therefore, prolactin-stimulated alterations in PKC activity are preceded by enhanced DAG generation. Moreover, these events appear to be coupled to PRL-stimulated entry of hepatocytes into cell cycle.

  20. S179D Prolactin

    PubMed Central

    Walker, Ameae M.

    2007-01-01

    The aims of this review are threefold: First, to collate what is known about the production and activities of phosphorylated prolactin (PRL), the latter largely, but not exclusively, as illustrated through the use of the molecular mimic, S179D PRL; second, to apply this and related knowledge to produce an updated model of prolactin-receptor interactions that may apply to other members of this cytokine super-family; and third, to promote a shift in the current paradigm for the development of clinically important growth antagonists. This third aim explains the title since, based on results with S179D PRL, it is proposed that agents which signal to antagonistic ends may be better therapeutics than pure antagonists - hence antagonistic agony. Since S179D PRL is not a pure antagonist, we have proposed the term selective prolactin receptor modulator (SPeRM) for this and like molecules. PMID:17669587

  1. Blood pressure, plasma and pituitary prolactin levels and their responses to bromocriptine in the segregating F2 generation of the SHR/WKY hybrid.

    PubMed

    Tan, B K; Hutchinson, J S

    1988-01-01

    Our previous study in the spontaneously hypertensive rat (SHR) and its normotensive control, the Wistar-Kyoto (WKY), had shown differences in plasma and pituitary prolactin (PRL) levels as well as in their responses to bromocriptine (BRC), a centrally acting dopaminergic agonist. The results provided evidence for a central dopaminergic deficiency in the SHR and suggested a possible genetic linkage between blood pressure (BP) and PRL and their responses to BRC in the SHR. To investigate this possibility further, we have repeated the experiment, using the same protocol, in the segregating F2 generation of the SHR/WKY hybrid which was classified according to BP into low, intermediate and high BP groups. The results from this study show that the differences between BP and PRL and their responses to BRC are similarly present in the three groups of the F2 generation. They provide further evidence that suggests a genetic linkage between BP and PRL in the SHR.

  2. Bulls grazing Kentucky 31 tall fescue exhibit impaired growth, semen quality, and decreased semen freezing potential

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Serum prolactin (PRL) and testosterone concentrations, body weight, body composition, semen quality, and semen freezing potential for bulls grazing the toxic tall fescue (Lolium arundinaceum [Schreb.] Darbysh. ¼ Schedonorous arundinaceum [Schreb.] Dumort.) cultivar Kentucky 31 (E+) compared with a n...

  3. Role of abnormal anterior pituitary hormones-growth hormone and prolactin in active systemic lupus erythematosus

    PubMed Central

    Zhu, Xiaohua; Xu, Jinhua; Li, Shujuan; Huang, Wen; Li, Feng

    2015-01-01

    Background: The role of anterior pituitary hormones in systemic lupus erythematosus (SLE) remains controversial. Aims and Objectives: We determined the expression levels of human growth hormone (GH), prolactin (PRL), and their receptors in subjects presenting with SLE, and modulation of disease severity. Materials and methods: Forty-seven subjects and ten healthy controls were assessed for possible association between SLE disease activity and levels of serum PRL, GH and thyrotropin-releasing hormone (TRH). In peripheral blood mononuclear cells (PBMC), specific binding and mRNA expression of receptors for GH (GHR), and PRL (PRLR) were determined by receptor-ligand binding assay (RLBA) and RT-PCR. PBMC of recruited subjects were treated with hPRL and rhGH to assess IgG production and antibodies against dsDNA. Results: In active SLE subjects we found elevated PRL and GH levels. Study subject PBMCs displayed augmented GHR and PRLR protein and mRNA expression. Study subjects also showed a positive correlation in serum PRL levels and specific antibodies against dsDNA, SLE disease activity index (SLEDAI), and proteinuria. However, a negative correlation was found between serum PRL levels and complement component C3. We found a positive correlation between specific binding rates of PRLR and GHR and both SLE activity and dsDNA antibody titers. Enhanced IgG and anti-dsDNA secretion was observed in cultured PBMC stimulated by PRL or GH with/without PHA, PWM, IL-2 or IL-10. In active SLE, a close association was found between augmented PRL and GH levels, expression and specific binding activities of PRLR and GHR, and changes in the specific titer of anti-dsDNA. Conclusion: Anterior pituitary hormones play an important role in the pathogenesis of SLE. High levels of growth hormone (GH) and prolactin (PRL) play a role in pathogenesis of SLE, which is correlated with SLE disease activity and antibodies against dsDNA. The mechanism of GH and PRL in SLE was complicated and should

  4. [A review of the effects of prolactin hormone and cytokine on the development and pathogenesis of autoimmune diseases].

    PubMed

    Fojtíková, M; Cerná, M; Pavelka, K

    2010-05-01

    Prolactin (PRL) is not only a pituitary hormone with important role in the reproduction but it also acts as a cytokine involved in the immune response. Prolactin is produced by many immune system cells that express the prolactin receptor (PRL-R). PRL is then able to affect local microenvironment of the immune system organs and contribute to maturation as well as functioning of the immune system cells. The role of PRL in the immune reactions is stimulating; its presence significantly increases the ability of the immune cells to proliferate and produce cytokines such as TNF-alpha, IFN-gamma, IL-12, IL-1 beta. This effect results from activation of a number of intracellular pathways (Jak2/STAT, Ras/Raf/MAPK etc.) and activation of the genes linked to apoptosis and proliferation (Bcl-XL, Bcl-2, pim, XIAP) or transcription factors (IRF-1). Interestingly, PRL itself is unable to initiate an immune reaction; it is more a factor maintaining balance within immune reactions, contra-regulatory to glucocorticoids, which effect is manifested under critical circumstances of physical or psychological stress. Intensified immunosuppression during stress, combined with a lack of prolactin, has surprisingly been identified during experiments on mice and is also found in human medicine. On the other hand, increased prolactin serum levels were described in several systemic as well as organ-specific autoimmune diseases. PRL levels elevation in these diseases might result from several factors: an increased release of prolactin from the anterior pituitary due to inflammatory cytokines or reduced production of suppressive dopamine, or, alternatively, an increased production of prolactin in immune system cells. In some of these diseases, such as celiac disease and systemic lupus erythematosus (SLE), the PRL level correlates with the disease activity. This supports the hypothesis that PRL oversupply shifts the balance in the immune response towards higher activity of the immune system cells

  5. Hypothyroidism may account for reduced prolactin secretion in lactating rats bearing paraventricular area lesions.

    PubMed

    de Greef, W J; Rondeel, J M; van der Vaart, P D; van der Schoot, P; Lamberts, S W; Visser, T J

    1989-08-01

    Lesions in the paraventricular area (PVA) of lactating rats have been found to inhibit PRL release. We have examined whether this reduced PRL release is due to hypothyroidism resulting from destruction of the PVA. Rats were made hypothyroid by thyroidectomy on day 15 of pregnancy or by methimazole treatment from the day of parturition. Electrolytic lesions were placed bilaterally in the PVA on day 15 of pregnancy. The following variables were studied: weight gain of the pups, nursing behavior, thyroid status, and release of PRL. The treatments did not affect the time the mothers spent with the pups but reduced the daily weight gain of the pups. Rats with PVA lesions had reduced PRL and TSH levels during lactation compared with controls. Suckling-induced PRL release after 6 h of separation of mothers and pups was less in PVA-lesioned rats than in controls, but T4-treatment did overcome this blunted response in rats with lesions. Levels of T3 and T4 in PVA-lesioned rats were lower than those in controls. In rats made hypothyroid by thyroidectomy or treatment with methimazole, PRL levels were lower and TSH levels higher than those in euthyroid mothers on days 8, 15, and 22 of lactation. Suckling after 6 h of separation of pups and mothers raised PRL levels both in control and methimazole-treated rats, but in the latter animals the response was blunted. It is suggested that the reduced PRL release in lactating rats with PVA lesions could be due to hypothyroidism resulting from these lesions.

  6. Evidence for a second receptor binding site on human prolactin.

    PubMed

    Goffin, V; Struman, I; Mainfroid, V; Kinet, S; Martial, J A

    1994-12-23

    The existence of a second receptor binding site on human prolactin (hPRL) was investigated by site-directed mutagenesis. First, 12 residues of helices 1 and 3 were mutated to alanine. Since none of the resulting mutants exhibit reduced bioactivity in the Nb2 cell proliferation bioassay, the mutated residues do not appear to be functionally necessary. Next, small residues surrounding the helix 1-helix 3 interface were replaced with Arg and/or Trp, the aim being to sterically hinder the second binding site. Several of these mutants exhibit only weak agonistic properties, supporting our hypothesis that the channel between helices 1 and 3 is involved in a second receptor binding site. We then analyzed the antagonistic and self-antagonistic properties of native hPRL and of several hPRLs analogs altered at binding site 1 or 2. Even at high concentrations (approximately 10 microM), no self-inhibition was observed with native hPRL; site 2 hPRL mutants self-antagonized while site 1 mutants did not. From these data, we propose a model of hPRL-PRL receptor interaction which slightly differs from that proposed earlier for the homologous human growth hormone (hGH) (Fuh, G., Cunningham, B. C., Fukunaga, R., Nagata, S., and Goeddel, D. V., and Well, J. A. (1992) Science 256, 1677-1680). Like hGH, hPRL would bind sequentially to two receptor molecules, first through site 1, then through site 2, but we would expect the two sites of hPRL to display, unlike the two binding sites of hGH, about the same binding affinity, thus preventing self-antagonism at high concentrations. PMID:7798264

  7. Prolactin is a major inhibitor of hepatic Leptin A synthesis and secretion: studies utilizing a homologous Leptin A ELISA in the tilapia.

    PubMed

    Douros, Jonathan D; Baltzegar, David A; Breves, Jason P; Lerner, Darren T; Seale, Andre P; Gordon Grau, E; Borski, Russell J

    2014-10-01

    The present study identifies regulatory interactions between leptin A (LepA) and the pituitary hormone prolactin (PRL). In order to measure tilapia (Oreochromis mossambicus) LepA, an enzyme-linked immunosorbent assay (ELISA) utilizing a rabbit polyclonal antibody specific to tilapia LepA was first developed. The antibody shows strong cross reactivity to recombinant tilapia LepA (rtLepA), and a corresponding 16kDa protein in both tilapia and striped bass plasma, but not to recombinant human leptin (rhLep). The assay has a linear detection range of 0.25-1000nM, with intra- and interassay variability of 9% and 16%, respectively. Plasma LepA levels measured in tilapia ranged from 0.8 to 3.9nM, similar to that found for other vertebrates. Hypophysectomy (Hx) increased circulating LepA and lepa mRNA levels in the liver, the dominant source of hormone production. Adminstration of ovine PRL (oPRL, 5μg/g BW) to Hx fish restored circulating LepA and hepatic lepa mRNA levels to those of control fish. Additionally, oPRL reduced lepa mRNA levels in a dose-dependent fashion in cultured hepatocytes following an 18h incubation. Previous work in our lab indicates that rhLep stimulates PRL release in vitro from tilapia pituitaries. Here, both rtLepA and rhLep (0.5μg/g BW) increased mRNA expression of tilapia prolactin mRNAs (prl1, prl2) in the pituitary in vivo. These results demonstrate that LepA enhances pituitary prolactin synthesis and release, while PRL in turn inhibits hepatic leptin secretion and synthesis in teleosts. We postulate this regulatory interaction may be necessary for mobilizing energy reserves during acute hyperosmotic adaptation. PMID:24662392

  8. Role of growth hormone and prolactin in the control of reproduction: what are we learning from transgenic and knock-out animals?

    PubMed

    Bartke, A

    1999-09-01

    Growth hormone (GH), insulin-like growth factor (IGF-I), and prolactin (PRL) can influence various aspects of reproductive functions in both females and males. However, the physiological role of PRL and the GH-IGF-I axis in the control of reproduction has been difficult to define, and the recent availability of knock-out (KO) animals allows re-examination of this issue. PRL-receptor (R)-KO and PRL-KO females are sterile because of luteal failure. In addition, these mice have severe deficits in the development of oocytes and early embryos. However, male fertility is not affected in the PRL-KO and in most of the PRL-R-KO animals. IGF-KO animals have an infantile reproductive system and are sterile. GH-R-KO mice can reproduce, but their breeding performance is reduced, particularly in females. These data indicate that IGF-I signaling is required for normal reproductive development and confirm the requirement for PRL for fertility in the female mouse. GH resistance leads to quantitative deficits in reproductive development and functions, but does not preclude fertility in either sex. We suspect that PRL and the GH-IGF-I axis provide partially overlapping (redundant) regulatory inputs to the hypothalamic-pituitary-gonadal axis, and consequently, targeted disruption of either signaling pathway has relatively mild consequences on many functions related to reproduction. Overexpression of heterologous or homologous GH in transgenic animals can lead to severe reproductive deficits, including female sterility in some of the lines. Studies in GH transgenics should allow the identification of mechanisms that mediate the effects of chronic overexposure to GH on reproduction.

  9. Liposomal formulations of prilocaine: effect of complexation with hydroxypropyl-ß-cyclodextrin on drug anesthetic efficacy.

    PubMed

    Bragagni, Marco; Maestrelli, Francesca; Mennini, Natascia; Ghelardini, Carla; Mura, Paola

    2010-12-01

    A combined strategy, based on cyclodextrin complexation and loading in liposomes, has been investigated to develop a new delivery system with improved therapeutic activity of the local anesthetic, prilocaine (PRL). In order to evaluate the actual effectiveness and advantages of this approach compared to the traditional drug-in-liposome one, four different liposomal formulations were prepared: (1) liposomes loaded with PRL base as complex with hydroxypropyl-β-cyclodextrin (HP CD) in the aqueous phase; (2) liposomes loaded with PRL hydrochloride in the aqueous phase; (3) liposomes loaded with PRL base in the lipophilic phase; and (4) "double-loaded" liposomes, containing free PRL base in the membrane bilayer and its HP CD complex in the aqueous compartment. All batches were characterized for particle size, charge, deformability, and entrapment efficiency from using, respectively, light scattering, extrusion, and dialysis techniques, while the anesthetic effect was evaluated in vivo on Guinea pigs, according to the test of dorsal muscle contraction. All drug liposomal dispersions showed enhanced analgesic duration with respect to the corresponding aqueous solutions, but significant differences were observed between the different formulations. In particular, cyclodextrin complexation not only allowed an efficient encapsulation of PRL base in the aqueous vesicle core, but also increased the anesthetic effect duration and reduced the initial lag time, in comparison with the corresponding formulations containing, respectively, free PRL in the lipophilic phase or PRL hydrochloride in the aqueous vesicle core. The technique of double loading was the most effective, giving rise to the shortest onset time and longest duration of anesthetic effect.

  10. PAK1 translocates into nucleus in response to prolactin but not to estrogen.

    PubMed

    Oladimeji, Peter; Diakonova, Maria

    2016-04-22

    Tyrosyl phosphorylation of the p21-activated serine-threonine kinase 1 (PAK1) has an essential role in regulating PAK1 functions in breast cancer cells. We previously demonstrated that PAK1 serves as a common node for estrogen (E2)- and prolactin (PRL)-dependent pathways. We hypothesize herein that intracellular localization of PAK1 is affected by PRL and E2 treatments differently. We demonstrate by immunocytochemical analysis that PAK1 nuclear translocation is ligand-dependent: only PRL but not E2 stimulated PAK1 nuclear translocation. Tyrosyl phosphorylation of PAK1 is essential for this nuclear translocation because phospho-tyrosyl-deficient PAK1 Y3F mutant is retained in the cytoplasm in response to PRL. We confirmed these data by Western blot analysis of subcellular fractions. In 30 min of PRL treatment, only 48% of pTyr-PAK1 is retained in the cytoplasm of PAK1 WT clone while 52% re-distributes into the nucleus and pTyr-PAK1 shuttles back to the cytoplasm by 60 min of PRL treatment. In contrast, PAK1 Y3F is retained in the cytoplasm. E2 treatment causes nuclear translocation of neither PAK1 WT nor PAK1 Y3F. Finally, we show by an in vitro kinase assay that PRL but not E2 stimulates PAK1 kinase activity in the nuclear fraction. Thus, PAK1 nuclear translocation is ligand-dependent: PRL activates PAK1 and induces translocation of activated pTyr-PAK1 into nucleus while E2 activates pTyr-PAK1 only in the cytoplasm.

  11. Monte Carlo and Molecular Dynamics in the Multicanonical Ensemble: Connections between Wang-Landau Sampling and Metadynamics

    NASA Astrophysics Data System (ADS)

    Vogel, Thomas; Perez, Danny; Junghans, Christoph

    2014-03-01

    We show direct formal relationships between the Wang-Landau iteration [PRL 86, 2050 (2001)], metadynamics [PNAS 99, 12562 (2002)] and statistical temperature molecular dynamics [PRL 97, 050601 (2006)], the major Monte Carlo and molecular dynamics work horses for sampling from a generalized, multicanonical ensemble. We aim at helping to consolidate the developments in the different areas by indicating how methodological advancements can be transferred in a straightforward way, avoiding the parallel, largely independent, developments tracks observed in the past.

  12. Immunological properties of prolactin and studies on a gonadotropin binding inhibitor

    SciTech Connect

    Chang, Y.S.

    1985-01-01

    The physiological role of prolactin in horses has not yet been well defined. With the availability of highly purified ePRL for inducing antibody formation in rabbits and for radiolabeling with Na/sup 125/I, a very sensitive (0.4-0.6 ng/ml) and highly specific homologous RIA for ePRL was developed. A heterologous RIA using /sup 125/I-labeled ovine PRL and anti-ePRL antiserum was also developed and compared to the homologous RIA for ePRL. Of the two systems, it is concluded that this homologous RIA system is more suitable and more reliable for measuring prolactin concentration in horse serum samples. Until now, biochemical information on PRL has not been available for reptilian species. Sea turtle (Chelonia mydas) prolactin was purified from pituitary extracts by selective precipitation, DEAE-cellulose chromatography and gel filtration. Similar to other species of PRL, sea turtle PRL is a 22,000-24,000 daltons protein and contains a high content of glutamic acid, aspartic acid, serine and leucine, the N-terminal amino acid residue. Gonadotropin (FSH) binding inhibitor was partially purified from sheep testes by ammonium sulfate fractionation and ion exchange chromatography. The FSH-BI (molecular weight: 50,000 daltons, estimated by gel filtration) contains a protein moiety necessary for binding inhibitory activity. The inhibition of the binding of /sup 125/I-labeled ovine FSH to its receptor by the FSH-BI is not competitive. Both in vivo and in vitro biological studies of FSH-BI preparations in rats indicated various effects on FSH and LH activities at the gonadal level. These findings suggest a physiological role for FSH-BI in the regulation of reproduction.

  13. No Long-Lived Coherent Oscillations in Proteins at Room Temperature

    NASA Astrophysics Data System (ADS)

    Austin, Robert; White, Michael

    2007-03-01

    A recent PRL (PRL 95, 253601 (2005)) suggested that proteins could have very narrow holes (Hz wide) burnt into their electronic spectra at 300K, and suggested that ``snail-paced'' light group velocity light could result. We will show that the authors mistook conformational diffusion phase shifts for narrow lines and show that there are no narrow long-lived holes in a protein spectra at 300 K nor is there any snail-paced light.

  14. Simultaneous radioimmunoassay for luteinizing hormone and prolactin

    SciTech Connect

    Steele, M.K.; Deschepper, C.F.

    1985-05-01

    A combined radioimmunoassay (RIA) for the measurement of the anterior pituitary proteins luteinizing hormone (LH) and prolactin (PRL) is described and compared with individual RIAs for these hormones. The standard curves and the sample values for LH and PRL were identical when determined in a combined or in an individual RIA. This technique may prove useful to a number of laboratories where it is desirable to determine levels of more than one hormone in limited sample volumes.

  15. High prevalence of radiological vertebral fractures in women with prolactin-secreting pituitary adenomas.

    PubMed

    Mazziotti, Gherardo; Mancini, Tatiana; Mormando, Marilda; De Menis, Ernesto; Bianchi, Antonio; Doga, Mauro; Porcelli, Teresa; Vescovi, Pier Paolo; De Marinis, Laura; Giustina, Andrea

    2011-12-01

    Hyperprolactinemia may cause bone loss but data on fractures are scanty. The aim of this study was to evaluate the prevalence of vertebral fractures in women with prolactin (PRL)-secreting adenoma. In this cross-sectional study, 78 women (median age 45.5 years, range: 20-81) with PRL-secreting pituitary adenoma (66 with microadenoma and 12 with macroadenoma) and 156 control subjects, with normal PRL values and with comparable age to patients with hyperprolactinemia, were evaluated for vertebral fractures by a morphometric approach and for bone mineral density (BMD) by a dual-energy X-ray absorptiometry at lumbar spine. Vertebral fractures were shown in 25 patients with PRL-secreting adenoma (32.6%) and in 20 controls (12.8%, P < 0.001). Fractured patients were significantly older (P < 0.001) and had lower BMD T-score (P < 0.001), longer duration of disease (P < 0.001), higher serum PRL (P = 0.004) and lower serum IGF-I (P < 0.001) values as compared to patients who did not fracture. The prevalence of vertebral fractures was significantly (P < 0.001) higher in post-menopausal women with PRL-secreting adenoma as compared to pre-menopausal patients. Fractures occurred more frequently (P = 0.01) in patients with untreated hyperprolactinemia versus patients treated with cabergoline. Logistic regression analysis demonstrated that duration of disease maintained a significant correlation with vertebral fractures (odds ratio 1.16, C.I. 95% 1.02-1.33) even after correction for age, menopausal status, treatment with cabergoline, BMD, serum IGF-I and serum PRL values. Hyperprolactinemia is associated with high prevalence of radiological vertebral fractures in women with PRL-secreting adenoma.

  16. Ovariectomy during the luteal phase influences secretion of prolactin, growth hormone, and insulin-like growth factor-I in the bitch.

    PubMed

    Lee, W M; Kooistra, H S; Mol, J A; Dieleman, S J; Schaefers-Okkens, A C

    2006-07-15

    A decline in circulating progesterone concentration plays an important role in the ethiopathogenesis of pseudopregnancy in the bitch. Because growth hormone (GH) and prolactin (PRL) are essential for normal mammogenesis and the secretion of these hormones is influenced by changes in the circulating progesterone concentration, the purpose of this study was to investigate the effects of mid-luteal phase ovariectomy on the 6-h pulsatile plasma profiles of GH and PRL and the basal plasma concentrations of GH, PRL, and insulin-like growth factor-I (IGF-I) in six beagle bitches. Ovariectomy was followed by only mild or covert signs of pseudopregnancy. The sharp decrease of the plasma progesterone concentration was accompanied by decreased basal plasma concentrations of GH and IGF-I and a rise in basal plasma PRL concentration. GH and PRL were secreted in a pulsatile fashion both prior to and after ovariectomy. The mean basal plasma GH concentration was significantly higher before ovariectomy than on days 1 and 7 after ovariectomy. The mean area under the curve above the zero level (AUC(0)) for GH was significantly higher before than at 7 days after ovariectomy. The mean area under the curve above basal level (AUC(b)) and the frequency of GH pulses at 7 days after ovariectomy were significantly higher than before and 1 day after ovariectomy. Both the mean basal plasma PRL concentration and the mean AUC(0) for PRL increased after ovariectomy. In conclusion, ovariectomy of bitches in the mid-luteal phase stops progesterone-induced GH release from the mammary gland, as evidenced by the lowering of basal plasma GH levels, the recurrence of GH pulsatility, and the lowering of circulating IGF-I levels. The sudden lowering of plasma progesterone concentration is probably a primary cause of a prolonged increase in PRL secretion. These observations underscore the importance of similar, albeit less abrupt, hormonal changes in the cyclical physiological alterations in the mammary

  17. PAK1 translocates into nucleus in response to prolactin but not to estrogen.

    PubMed

    Oladimeji, Peter; Diakonova, Maria

    2016-04-22

    Tyrosyl phosphorylation of the p21-activated serine-threonine kinase 1 (PAK1) has an essential role in regulating PAK1 functions in breast cancer cells. We previously demonstrated that PAK1 serves as a common node for estrogen (E2)- and prolactin (PRL)-dependent pathways. We hypothesize herein that intracellular localization of PAK1 is affected by PRL and E2 treatments differently. We demonstrate by immunocytochemical analysis that PAK1 nuclear translocation is ligand-dependent: only PRL but not E2 stimulated PAK1 nuclear translocation. Tyrosyl phosphorylation of PAK1 is essential for this nuclear translocation because phospho-tyrosyl-deficient PAK1 Y3F mutant is retained in the cytoplasm in response to PRL. We confirmed these data by Western blot analysis of subcellular fractions. In 30 min of PRL treatment, only 48% of pTyr-PAK1 is retained in the cytoplasm of PAK1 WT clone while 52% re-distributes into the nucleus and pTyr-PAK1 shuttles back to the cytoplasm by 60 min of PRL treatment. In contrast, PAK1 Y3F is retained in the cytoplasm. E2 treatment causes nuclear translocation of neither PAK1 WT nor PAK1 Y3F. Finally, we show by an in vitro kinase assay that PRL but not E2 stimulates PAK1 kinase activity in the nuclear fraction. Thus, PAK1 nuclear translocation is ligand-dependent: PRL activates PAK1 and induces translocation of activated pTyr-PAK1 into nucleus while E2 activates pTyr-PAK1 only in the cytoplasm. PMID:27003261

  18. Prolactin/Stat5 and androgen R1881 coactivate carboxypeptidase-D gene in breast cancer cells.

    PubMed

    Koirala, Samir; Thomas, Lynn N; Too, Catherine K L

    2014-03-01

    Plasma membrane-bound carboxypeptidase-D (CPD) cleaves C-terminal arginine from extracellular substrates. In the cell, arginine is converted to nitric oxide (NO). We have reported that up-regulation of CPD mRNA/protein levels by 17β-estradiol and prolactin (PRL) in breast cancer cells, and by testosterone in prostate cancer cells, increased NO production and cell survival. The CPD promoter contains a consensus γ-interferon-activated sequence (GAS) and 3 putative androgen response elements (ARE.1, ARE.2, ARE.3) that could potentially bind PRL-activated transcription factor Stat5 (signal transducer and activator of transcription 5) and the liganded androgen receptor (AR), respectively. This study showed that synthetic androgen R1881 and PRL elevated CPD mRNA/protein levels in human MCF-7 and T47D breast cancer cells in a time-/dose-dependent manner. PRL/R1881-elevated CPD expression was blocked by actinomycin-D, and a CPD promoter construct containing these GAS and AREs was stimulated by PRL or R1881, indicating transcriptional regulation by both hormones. Luciferase reporter assays showed that GAS and the adjacent ARE.1 only were active. Mutation of GAS in the ΔGAS-CPD construct (ARE.1 intact) abolished CPD promoter activity in response to PRL and, surprisingly, to R1881 as well. ΔGAS-CPD promoter activity was restored by PRL+R1881 in combination, and enhanced by ectopic Stat5, but abolished by Stat5 gene knockdown. Chromatin immunoprecipitation analysis confirmed binding of activated Stat5 and liganded AR to GAS and ARE.1, respectively. Activated Stat5 also induced binding of unliganded AR to ARE.1, and liganded AR induced binding of unactivated Stat5 to GAS. In summary, PRL and R1881, acting through Stat5 and AR, act cooperatively to stimulate CPD gene transcription in breast cancer cells. PMID:24433040

  19. Human growth hormone and human prolactin function as autocrine/paracrine promoters of progression of hepatocellular carcinoma

    PubMed Central

    Yuan, Yan; Pandey, Vijay; Wu, Zhengsheng; Lu, Xuefei; Zhang, Weijie; Chen, Yijun; Wu, Mingming; Zhang, Min; Li, Gaopeng; Tan, Sheng; Qian, Pengxu; Perry, Jo K.; Lobie, Peter E.; Zhu, Tao

    2016-01-01

    The death rates of hepatocellular carcinoma (HCC) are extremely high due to the paucity of therapeutic options. Animal models and anecdotal clinical evidence indicate a potential role of hGH and hPRL in HCC. However, the prognostic relevance and the functional role of tumor expression of these hormones in human HCC are not defined. Herein, we analyzed the mRNA and protein expression of hGH and hPRL in histopathological samples of non-neoplastic liver and HCC by in situ hybridization, PCR and immunohistochemistry techniques. Increased mRNA and protein expression of both hormones was observed in HCC compared with non-neoplastic liver tissues. hGH expression was significantly associated with tumor size and tumor grade. No significant association was observed between the expression of hPRL and any histopathological features. Amplification of both hGH and hPRL genes in HCC was observed when compared to non-neoplastic tissue. Expression of both hGH and hPRL was associated with worse relapse-free and overall survival in HCC patients. In vitro and in vivo functional assays performed with HCC cell lines demonstrated that autocrine expression of hGH or hPRL in HCC cells increased STAT3 activation, oncogenicity and tumor growth while functional antagonism with hGH-G120R significantly reduced these parameters. Hence, tumor expression of hGH/hPRL is associated with a worse survival outcome for patients with HCC and hGH/hPRL function as autocrine/paracrine promoters of HCC progression. PMID:27102295

  20. A dopamine receptor d2-type agonist attenuates the ability of stress to alter sleep in mice.

    PubMed

    Jefferson, F; Ehlen, J C; Williams, N S; Montemarano, J J; Paul, K N

    2014-11-01

    Although sleep disruptions that accompany stress reduce quality of life and deteriorate health, the mechanisms through which stress alters sleep remain obscure. Psychological stress can alter sleep in a variety of ways, but it has been shown to be particularly influential on rapid eye movement (REM) sleep. Prolactin (PRL), a sexually dimorphic, stress-sensitive hormone whose basal levels are higher in females, has somnogenic effects on REM sleep. In the current study, we examined the relationship between PRL secretion and REM sleep after restraint stress to determine whether: 1) the ability of stress to increase REM sleep is PRL-dependent, and 2) fluctuating PRL levels underlie sex differences in sleep responses to stress. Because dopamine D2 receptors in the pituitary gland are the primary regulator of PRL secretion, D2 receptor agonist, 1-[(6-allylergolin-8β-yl)-carbonyl]-1-[3-(dimethylamino) propyl]-3-ethylurea (cabergoline), was used to attenuate PRL levels in mice before 1 hour of restraint stress. Mice were implanted with electroencephalographic/electromyographic recording electrodes and received an ip injection of either 0.3-mg/kg cabergoline or vehicle before a control procedure of 1 hour of sleep deprivation by gentle handling during the light phase. Six days after the control procedure, mice received cabergoline or vehicle 15 minutes before 1 hour of restraint stress. Cabergoline blocked the ability of restraint stress to increase REM sleep amount in males but did not alter REM sleep amount after stress in females even though it reduced basal REM sleep amount in female controls. These data provide evidence that the ability for restraint stress to increase REM sleep is dependent on PRL and that sex differences in REM sleep amount may be driven by PRL.

  1. Effect of confinement stress on circulating levels of growth hormone and two prolactins in freshwater-adapted tilapia (Oreochromis niloticus).

    PubMed

    Auperin, B; Baroiller, J F; Ricordel, M J; Fostier, A; Prunet, P

    1997-10-01

    The aim of the present study was to assess a potential link between confinement stress and prolactin (PRL), the hormone responsible for adaptation to a hypoosmotic environment in freshwater-adapted tilapia (Oreochromis niloticus). The effect of stress on plasma levels of the two tilapia PRL forms, tiPRLI (or tiPRL188) and tiPRLII (or tiPRL177), was examined along with the effects on plasma levels of cortisol and growth hormone (GH). In a preliminary study, various sampling protocols (immediate sampling; sampling one by one; anesthesia at 0.5, 1, 2 ml/liter phenoxyethanol) were tested for their ability to modify basal plasma PRL and cortisol. In fish sampled within 1 min of capture (immediate sampling), no changes in the plasma levels of these hormones were observed, whereas when fish were sampled one at a time, PRL levels did not change but cortisol levels were modified. The immediate sampling protocol was used to study the effects of 1 hr confinement stress, which induced a large increase in plasma cortisol levels as well as increases tiPRLI and tiPRLII levels with kinetics similar to those of cortisol. In contrast, plasma tiGH levels significantly decreased after 1 hr confinement. When this stress situation was removed, plasma cortisol and tiPRL levels decreased and plasma GH levels increased. Two and one-half hours later, values were not significantly different from those measured in control fish. In tilapia exposed to 24 hr confinement stress, similar changes in hormone levels were observed. However, after 24 hr confinement, only cortisol levels were significantly different from those measured in control fish. None of these stress conditions significantly changed plasma chloride levels. Together, these results indicate that both PRL and GH have important roles in the adaptive response of freshwater-adapted tilapia to confinement stress.

  2. Prolactin/Stat5 and androgen R1881 coactivate carboxypeptidase-D gene in breast cancer cells.

    PubMed

    Koirala, Samir; Thomas, Lynn N; Too, Catherine K L

    2014-03-01

    Plasma membrane-bound carboxypeptidase-D (CPD) cleaves C-terminal arginine from extracellular substrates. In the cell, arginine is converted to nitric oxide (NO). We have reported that up-regulation of CPD mRNA/protein levels by 17β-estradiol and prolactin (PRL) in breast cancer cells, and by testosterone in prostate cancer cells, increased NO production and cell survival. The CPD promoter contains a consensus γ-interferon-activated sequence (GAS) and 3 putative androgen response elements (ARE.1, ARE.2, ARE.3) that could potentially bind PRL-activated transcription factor Stat5 (signal transducer and activator of transcription 5) and the liganded androgen receptor (AR), respectively. This study showed that synthetic androgen R1881 and PRL elevated CPD mRNA/protein levels in human MCF-7 and T47D breast cancer cells in a time-/dose-dependent manner. PRL/R1881-elevated CPD expression was blocked by actinomycin-D, and a CPD promoter construct containing these GAS and AREs was stimulated by PRL or R1881, indicating transcriptional regulation by both hormones. Luciferase reporter assays showed that GAS and the adjacent ARE.1 only were active. Mutation of GAS in the ΔGAS-CPD construct (ARE.1 intact) abolished CPD promoter activity in response to PRL and, surprisingly, to R1881 as well. ΔGAS-CPD promoter activity was restored by PRL+R1881 in combination, and enhanced by ectopic Stat5, but abolished by Stat5 gene knockdown. Chromatin immunoprecipitation analysis confirmed binding of activated Stat5 and liganded AR to GAS and ARE.1, respectively. Activated Stat5 also induced binding of unliganded AR to ARE.1, and liganded AR induced binding of unactivated Stat5 to GAS. In summary, PRL and R1881, acting through Stat5 and AR, act cooperatively to stimulate CPD gene transcription in breast cancer cells.

  3. ErbB receptor-driven prolactinomas respond to targeted lapatinib treatment in female transgenic mice.

    PubMed

    Liu, Xiaohai; Kano, Maya; Araki, Takako; Cooper, Odelia; Fukuoka, Hidenori; Tone, Yukiko; Tone, Masahide; Melmed, Shlomo

    2015-01-01

    As ErbB receptors are expressed in prolactinomas and exhibit downstream effects on prolactin (PRL) production and cell proliferation, we generated transgenic mice using a PRL enhancer/promoter expression system to restrict lactotroph-specific expression of human epidermal growth factor receptor (EGFR) or human EGFR2 (HER2). EGFR or HER2 transgenic mice developed prolactinomas between 13 and 15 months, and confocal immunofluorescence and Western blot analysis confirmed lactotroph-restricted PRL and EGFR or HER2 coexpression. Circulating PRL levels in EGFR and HER2 transgenic mice were increased 5- and 3.8-fold, respectively. Inhibiting EGFR or HER2 signaling with oral lapatinib (100 mg/kg), a dual tyrosine kinase inhibitor for both EGFR and HER2, suppressed circulating PRL by 72% and attenuated tumor PRL expression by 80% and also attenuated downstream tumor EGFR/HER2 signaling. This model demonstrates the role of ErbB receptors underlying prolactinoma tumorigenesis and the feasibility of targeting these receptors for translation to treatment of refractory prolactinomas.

  4. The Glenn A. Fry Award Lecture 2012: Plasticity of the visual system following central vision loss.

    PubMed

    Chung, Susana T L

    2013-06-01

    Following the onset of central vision loss, most patients develop an eccentric retinal location outside the affected macular region, the preferred retinal locus (PRL), as their new reference for visual tasks. The first goal of this article is to present behavioral evidence showing the presence of experience-dependent plasticity in people with central vision loss. The evidence includes the presence of oculomotor re-referencing of fixational saccades to the PRL; the characteristics of the shape of the crowding zone (spatial region within which the presence of other objects affects the recognition of a target) at the PRL are more "foveal-like" instead of resembling those of the normal periphery; and the change in the shape of the crowding zone at a para-PRL location that includes a component referenced to the PRL. These findings suggest that there is a shift in the referencing locus of the oculomotor and the sensory visual system from the fovea to the PRL for people with central vision loss, implying that the visual system for these individuals is still plastic and can be modified through experiences. The second goal of the article is to demonstrate the feasibility of applying perceptual learning, which capitalizes on the presence of plasticity, as a tool to improve functional vision for people with central vision loss. Our finding that visual function could improve with perceptual learning presents an exciting possibility for the development of an alternative rehabilitative strategy for people with central vision loss.

  5. Protective Effect of Prolactin against Methylmercury-Induced Mutagenicity and Cytotoxicity on Human Lymphocytes

    PubMed Central

    Silva-Pereira, Liz Carmem; da Rocha, Carlos Alberto Machado; Cunha, Luiz Raimundo Campos da Silva e; da Costa, Edmar Tavares; Guimarães, Ana Paula Araújo; Pontes, Thais Brilhante; Diniz, Domingos Luiz Wanderley Picanço; Leal, Mariana Ferreira; Moreira-Nunes, Caroline Aquino; Burbano, Rommel Rodríguez

    2014-01-01

    Mercury exhibits cytotoxic and mutagenic properties as a result of its effect on tubulin. This toxicity mechanism is related to the production of free radicals that can cause DNA damage. Methylmercury (MeHg) is one of the most toxic of the mercury compounds. It accumulates in the aquatic food chain, eventually reaching the human diet. Several studies have demonstrated that prolactin (PRL) may be differently affected by inorganic and organic mercury based on interference with various neurotransmitters involved in the regulation of PRL secretion. This study evaluated the cytoprotective effect of PRL on human lymphocytes exposed to MeHg in vitro, including observation of the kinetics of HL-60 cells (an acute myeloid leukemia lineage) treated with MeHg and PRL at different concentrations, with both treatments with the individual compounds and combined treatments. All treatments with MeHg produced a significant increase in the frequency of chromatid gaps, however, no significant difference was observed in the chromosomal breaks with any treatment. A dose-dependent increase in the mitotic index was observed for treatments with PRL, which also acts as a co-mitogenic factor, regulating proliferation by modulating the expression of genes that are essential for cell cycle progression and cytoskeleton organization. These properties contribute to the protective action of PRL against the cytotoxic and mutagenic effects of MeHg. PMID:25247425

  6. Induction of mammary gland development in estrogen receptor-alpha knockout mice.

    PubMed

    Bocchinfuso, W P; Lindzey, J K; Hewitt, S C; Clark, J A; Myers, P H; Cooper, R; Korach, K S

    2000-08-01

    Mammary glands from the estrogen receptor-a knockout (alphaERKO) mouse do not undergo ductal morphogenesis or alveolar development. Disrupted ERalpha signaling may result in reduced estrogen-responsive gene products in the mammary gland or reduced mammotropic hormones that contribute to the alphaERKO mammary phenotype. We report that circulating PRL is reduced in the female alphaERKO mouse. Implantation of an age-matched, heterozygous ERalpha pituitary isograft under the renal capsule of 25-day-old or 12-week-old alphaERKO mice increased circulating PRL and progesterone levels, and induced mammary gland development. Grafted alphaERKO mice also possessed hypertrophied corpora lutea demonstrating that PRL is luteotropic in the alphaERKO ovary. By contrast, ovariectomy at the time of pituitary grafting prevented mammary gland development in alphaERKO mice despite elevated PRL levels. Hormone replacement using pellet implants demonstrated that pharmacological doses of estradiol induced limited mammary ductal elongation, and estradiol in combination with progesterone stimulated lobuloalveolar development. PRL alone or in combination with progesterone or estradiol did not induce alphaERKO mammary growth. Estradiol and progesterone are required for the structural development of the alphaERKO mammary gland, and PRL contributes to this development by inducing ovarian progesterone levels. Therefore, the manifestation of the alphaERKO mammary phenotype appears due to the lack of direct estrogen action at the mammary gland and an indirect contributory role of estrogen signaling at the hypothalamic/pituitary axis.

  7. Further evidence that big,big prolactin is preferentially secreted in women with hyperprolactinemia and normal ovarian function.

    PubMed

    Larrea, F; Villanueva, C; Carmen Cravioto, M; Escorza, A; del Real, O

    1985-07-01

    The heterogeneity of human serum prolactin (PRL) in 12 women with hyperprolactinemia and different derangements of the hypothalamic-pituitary-ovarian axis was studied. The patients were subdivided into three groups: four women with hyperprolactinemia and normal ovarian function (group I), four women with hyperprolactinemia associated with sporadic endometrial bleedings and a positive progestin test (group II), and four women with amenorrhea and a negative progestin test (group III). Gel filtration chromatography of serum samples from patients in group I revealed in three of them that most (80%) of their immunoreactive PRL eluted as big,big PRL (Mr greater than 100,000); whereas the rest of the patients, including those from groups II and III, exhibited a distribution pattern similar to that obtained in normal menstruating women. All PRL species had similar affinities for the antibody, as disclosed by the slopes generated in dose-response curves. These results indicate that ovarian function in hyperprolactinemia might be dependent upon PRL heterogeneity and suggest that big,big PRL may have, under in vivo conditions, a low degree of biologic activity.

  8. Overexpression of Protein Kinase Mζ in the Prelimbic Cortex Enhances the Formation of Long-Term Fear Memory.

    PubMed

    Xue, Yan-Xue; Zhu, Zhen-Zhen; Han, Hai-Bin; Liu, Jian-Feng; Meng, Shi-Qiu; Chen, Chen; Yang, Jian-Li; Wu, Ping; Lu, Lin

    2015-08-01

    Neuroplasticity in the prefrontal cortex (PFC) after fear conditioning has been suggested to regulate the formation and expression of fear memory. Protein kinase Mζ (PKMζ), an isoform of protein kinase C with persistent activity, is involved in the formation and maintenance of memory. However, less is known about the role of PKMζ in the PFC in the formation of fear memory. We investigated whether the overexpression of PKMζ enhances the formation of auditory fear memory in rats. We found that microinfusion of lentiviral vector-expressing PKMζ into the prelimbic cortex (PrL) selectively enhanced the expression of PKMζ without influencing the expression of other isoforms of PKC. The overexpression of PKMζ in the PrL enhanced the formation of long-term fear memory without affecting short-term fear memory, whereas the overexpression of PKMζ in the infralimbic cortex had no effect on either short-term or long-term fear memory. The overexpression of PKMζ in the PrL had no effect on anxiety-like behavior or locomotor activity. We also found that PKMζ overexpression potentiated the fear conditioning-induced increase in the membrane levels of glutamate subunit 2 of AMPA receptors in the PrL. These results demonstrate that the overexpression of PKMζ in the PrL but not infralimbic cortex selectively enhanced the formation of long-term fear memory, and PKMζ in the PrL may be involved in the formation of fear memory.

  9. Rat lymphoma cell bioassay for prolactin: observations on its use and comparison with radioimmunoassay

    SciTech Connect

    Dawson, D.M.; Sensui, N.; Haisenleder, D.H.; Gala, R.R.

    1982-12-27

    The rat Nb/sub 2/ node lymphoma cell bioassay (BA) for prolactin (PRL) was validated for use in our laboratories. During the course of this validation we observed that rat prolactin (NIAMDD-RP-1) stimulated cell division by as much as 16.5 fold over the range of 0.04 to 40.0 ng/ml at the end of 72 hours of incubation. We also observed a dose related increase in the size of the lymphoma cells. Prolactin concentrations in rat plasma, serum, anterior pituitary (AP) homogenates and milk were measured by both radioimmunoassay (RIA) and BA. In individual BA's there was parallelism between samples and standard; but when several dilutions of the same plasma and pituitary homogenates were assayed repeatedly, higher PRL levels were consistently observed for the more concentrated samples. At low or moderate levels of plasma PRL there was excellent agreement between RIA and BA; however, at high levels plasma PRL bioactivity exceeded radioimmunoactivity by a small, but significant, amount. A comparison of pituitary PRL concentrations measured by RIA and BA were in good agreement when homogenization was done at pH 10.6. However, when homogenization was done at pH 7.6, slightly but significantly more PRL was extracted when assayed by BA than when assayed by RIA.

  10. Ultrafiltration – an alternative method to polyethylene glycol precipitation for macroprolactin detection

    PubMed Central

    Beda-Maluga, Karolina; Pisarek, Hanna; Romanowska, Irena; Komorowski, Jan; Świętosławski, Jacek

    2015-01-01

    Introduction The aim of the study was to evaluate two methods of macroprolactin (MaPRL) detection – precipitation with polyethylene glycol (PEG) and ultrafiltration and to compare these techniques with “gold standard” – gel filtration chromatography (GFC). Material and methods The study was conducted on 245 patients – 45 with organic and 200 with functional hyperprolactinaemia. In all the subjects MaPRL was detected by precipitation with PEG and ultrafiltration. Additionally, gel filtration chromatography was performed in some of the serum samples. Results Macroprolactinaemia was detected in 27 patients – 8 with prolactinoma and 19 with functional hyperprolactinaemia. Assessing positive and negative results for MaPRL, we observed high diagnostic agreement (95.9%) and positive correlation (r = 0.506, p < 0.001) between the methods. The results of precipitation and ultrafiltration positive for MaPRL were concordant in 63%. The dominance of MaPRL detected with precipitation and/or ultrafiltration was confirmed by GFC in 76% of cases (all patients with functional hyperprolactinaemia). Among 6 examined patients with prolactinoma, GFC showed four false-positive results – 1 case of precipitation and 3 cases of ultrafiltration. Conclusions Efficacy of MaPRL detection with precipitation and ultrafiltration is comparable especially in cases of functional hyperprolactinaemia. In patients with prolactinoma, precipitation seems to be a more efficient separation method. PMID:26528343

  11. Intestinal mucosal changes and upregulated calcium transporter and FGF-23 expression during lactation: Contribution of lactogenic hormone prolactin.

    PubMed

    Wongdee, Kannikar; Teerapornpuntakit, Jarinthorn; Sripong, Chanakarn; Longkunan, Asma; Chankamngoen, Wasutorn; Keadsai, Chutiya; Kraidith, Kamonshanok; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

    2016-01-15

    As the principal lactogenic hormone, prolactin (PRL) not only induces lactogenesis but also enhances intestinal calcium absorption to supply calcium for milk production. How the intestinal epithelium res-ponses to PRL is poorly understood, but it is hypothesized to increase mucosal absorptive surface area and calcium transporter expression. Herein, lactating rats were found to have greater duodenal, jejunal and ileal villous heights as well as cecal crypt depths than age-matched nulliparous rats. Morphometric analyses in the duodenum and cecum showed that their mucosal adaptations were diminished by bromocriptine, an inhibitor of pituitary PRL release. PRL also upregulated calcium transporter expression (e.g., TRPV6 and PMCA1b) in the duodenum of lactating rats. Since excessive calcium absorption could be detrimental to lactating rats, local negative regulator of calcium absorption, e.g., fibroblast growth factor (FGF)-23, should be increased. Immunohistochemistry confirmed the upregulation of FGF-23 protein expression in the duodenal and cecal mucosae of lactating rats, consistent with the enhanced FGF-23 mRNA expression in Caco-2 cells. Bromocriptine abolished this lactation-induced FGF-23 expression. Additionally, FGF-23 could negate PRL-stimulated calcium transport across Caco-2 monolayer. In conclusion, PRL was responsible for the lactation-induced mucosal adaptations, which were associated with compensatory increase in FGF-23 expression probably to prevent calcium hyperabsorption.

  12. Hypothyroidism increases prolactin secretion and decreases the intromission threshold for induction of pseudopregnancy in adult female rats.

    PubMed

    Tohei, A; Taya, K; Watanabe, G; Voogt, J L

    In order to understand the mechanism by which thyroid hormones alter prolactin (PRL) secretion, we investigated the role of tuberoinfundibular dopamine (TIDA) neurons and pituitary and hypothalamus vasoactive intestinal peptide (VIP) in thiouracil- (0. 03% in drinking water for 16 days) induced-hypothyroid adult female rats. The intromission threshold for induction of pseudopregnancy also was examined to evaluate the PRL response to coital stimulation in hypothyroid rats. Hypothyroidism in adult female rats did not affect TIDA neuronal activity as measured by tyrosine hydroxylase activity (DOPA accumulation 30 min after administration of m-hydroxybenzylhydrazine dihydrochloride, 100 mg/kg, i.p.) in the stalk-median eminence compared with that in euthyroid rats, whereas pituitary concentration of VIP was dramatically increased. Plasma concentration of PRL was higher at 1100 h of proestrus and estrus in hypothyroid rats as compared with that of euthyroid rats. The proportion of female rats exhibiting pseudopregnancy was higher in hypothyroid animals (100%) receiving seven intromissions than in euthyroid animals (43%). Administration of L-thyroxine in hypothyroid rats decreased the proportion of pseudopregnancy (40%) to the level of euthyroid animals. These results indicate that the increased level of pituitary VIP probably affects PRL secretion in a paracrine or autocrine manner and account for the hyperprolactinemia induced in hypothyroid female rats. No role for TIDA neurons in PRL elevation can be ascribed. A decrease in the intromission threshold for induction of pseudopregnancy might be due to increased levels of PRL in hypothyroid female rats.

  13. Inhibition of prolactin with bromocriptine for 28days increases blood-brain barrier permeability in the rat.

    PubMed

    Rosas-Hernandez, H; Ramirez, M; Ramirez-Lee, M A; Ali, S F; Gonzalez, C

    2015-08-20

    The blood-brain barrier (BBB) is necessary for the proper function of the brain. Its maintenance is regulated by endogenous factors. Recent evidences suggest prolactin (PRL) regulates the BBB properties in vitro, nevertheless no evidence of these effects have been reported in vivo. The aim of this study was to evaluate the role of PRL in the maintenance of the BBB in the rat. Male Wistar rats were treated with Bromocriptine (Bromo) to inhibit PRL production for 28days in the absence or presence of lipopolysaccharide (LPS). BBB permeability was evaluated through the Evans Blue dye and fluorescein-dextran extravasation as well as through edema formation. The expression of claudin-5, occludin, glial fibrillary acidic protein (GFAP) and the PRL receptor (PRLR) was evaluated through western blot. Bromo reduced the physiological levels of PRL at 28days. At the same time, Bromo increased BBB permeability and edema formation associated with a decrement in claudin-5 and occludin and potentiated the increase in BBB permeability induced by LPS. However, no neuroinflammation was detected, since the expression of GFAP was unchanged, as well as the expression of the PRLR. These data provide the first evidence that inhibition of PRL with Bromo affects the maintenance of the BBB through modulating the expression of tight junction proteins in vivo.

  14. Endocrine responses after d-fenfluramine and ipsapirone challenge: further support for Cloninger's tridimensional model of personality.

    PubMed

    Hennig, J; Toll, C; Schonlau, P; Rohrmann, S; Netter, P

    2000-01-01

    The tridemensional model of personality introduced by Cloninger relates aspects of novelty seeking to the dopaminergic, harm avoidance (HA) to the serotonergic, and reward dependence to the noradrenergic neurotransmitter system. Using a neuroendocrine challenge paradigm, this study investigates whether subjects characterized by blunted cortisol (CORT) responses after ipsapirone (IPS) relate to different subfactors of HA from those characterized by blunted prolactin (PRL) responses after treatment with d-fenfluramine (D-FEN). Moreover, subjects blunted in both responses should differ in scale values of subfactors of HA from those with only one or no blunted reactions. In the first part of the experiment, 16 healthy male volunteers were treated with 15 mg D-FEN. The second part of the study (about 1 year later) consists of a challenge with the partial 5-hydroxytryptamine-1a (5-HT(1a)) agonist IPS (10 mg) in the same subjects. The results indicate that blunted PRL responses are accompanied by high values in HA, while the main effect of IPS responsivity did not relate significantly to this dimension. With respect to the subscales of HA, subjects blunted in both responses (PRL-/C-) exhibit significantly higher levels in fatigability and asthenia when compared to all other groups (PRL-/C+, PRL+/C-,PRL+/C+). The data demonstrate that combined challenge tests may shed more light on the biological basis of personality and that HA and most clearly fatigability and asthenia relate to the 5-HT system.

  15. Isolation of Sparus auratus prolactin gene and activity of the cis-acting regulatory elements.

    PubMed

    Astola, Antonio; Ortiz, Manuela; Calduch-Giner, Josep A; Pérez-Sánchez, Jaume; Valdivia, Manuel M

    2003-10-15

    A sea bream prolactin (sbPRL) gene was isolated using a prolactin cDNA fragment, generated by PCR as a probe. The gene analyzed comprises 3.5 kb of DNA containing five exons as described previously for other fish PRL genes. Analysis of 1.0 kb of the proximal promoter sequence reveals a consensus TATAA box, up to seven (A/T)3NCAT consensus motifs for binding of the pituitary-specific factor Pit-1 and putative CREB and GATA binding sites. CHO culture cells co-transfected with a sbPRL promoter sequence and a sea bream Pit-1 cDNA expression plasmid showed expression of a linked luciferase reporter gene. Transient expression experiments with 5'-delection mutants reveals at least three regulatory regions on the sbPRL gene, two with a stimulatory effect on transcription and one with apparent inhibitory effect. From a comparative point of view, this study of PRL gene in Sparus auratus, correlates well with those previously published on tilapia and rainbow trout. The molecular data reported will be useful for comparative analysis of gene regulation in the GH/PRL gene family in teleosts.

  16. The m-chlorophenylpiperazine test in cluster headache: a study on central serotoninergic activity.

    PubMed

    Leone, M; Attanasio, A; Croci, D; Libro, G; Grazzi, L; D'Amico, D; Nespolo, A; Bussone, G

    1997-10-01

    The central serotoninergic agonist m-chlorophenylpiperazine (m-CPP) stimulates several 5HT receptor subtypes. It induces the release of both cortisol and prolactin (PRL). In this study we investigated central serotoninergic responsiveness in cluster headache by monitoring cortisol and PRL responses to m-CPP administration. Twenty-three patients with episodic cluster headache and 17 sex-matched and age-matched healthy subjects were studied. The cluster headache patients were tested during a cluster period, and none were receiving prophylaxis. A single oral dose of m-CPP, 0.5 mg/kg, was given at time 0. Blood samples were drawn at -30, 0, 30, 60, 90, 120, 150 and 180 min. PRL and cortisol levels were assayed in the samples. PRL and cortisol delta maxima (delta maximum = maximum response - baseline level at time 0/baseline level at time 0) were evaluated in each patient and mean values compared. Serum levels of m-CPP were detected by HPLC and correlated to hormonal responses. Reduced cortisol (p < 0.02) and increased PRL (p < 0.05) delta maxima were observed in cluster headache patients. Increased basal cortisol plasma levels (p < 0.05) and reduced basal PRL plasma levels (p = 0.06) also characterized cluster headache patients. This is the first study evaluating central serotoninergic responsiveness to m-CPP in cluster headache and these data suggest impaired central serotoninergic function in this pathology. PMID:9350388

  17. Paradoxical effects of oxytocin and vasopressin on basal prolactin secretion and the estrogen-induced prolactin surge

    SciTech Connect

    Mai, Leemin ); Pan, Jenntser )

    1990-01-01

    The roles of oxytocin (OT) and vasopressin (AVP) on both basal and estrogen-induced prolactin (PRL) secretion were examined. Adult female Sprague-Dawley rats that were ovariectomized for 3 weeks and received estrogen treatment for 1 week were used. Intravenous administration of hormones and serial blood sampling were accomplished through indwelling intraatrial catheters which were implanted two days before. Plasma PRL levels were measured by radioimmunoassay. Oxytocin at a dose of 20 {mu}g/rat stimulated a moderate PRL release in the morning and lower doses were without effect. Vasopressin was most effective at a dose of 5 {mu}g/rat in stimulating PRL release, while consecutive injections of higher doses were less effective. In contrast, TRH, ranging from 1 to 8 {mu}g/rat, induced a dose-dependent increases in PRL secretion. Using the effective dosages determined from the morning studies, repeated injections of either OT, AVP or their specific antagonists MPOMeOVT were given hourly between 1300 to 1800h and blood samples were obtained hourly from 1100 to 1900h. It was found that either OT or AVP significantly reduced the afternoon PRL surge, while their antagonists were not as effective.

  18. Protective effect of prolactin against methylmercury-induced mutagenicity and cytotoxicity on human lymphocytes.

    PubMed

    Silva-Pereira, Liz Carmem; da Rocha, Carlos Alberto Machado; Cunha, Luiz Raimundo Campos da Silva E; da Costa, Edmar Tavares; Guimarães, Ana Paula Araújo; Pontes, Thais Brilhante; Diniz, Domingos Luiz Wanderley Picanço; Leal, Mariana Ferreira; Moreira-Nunes, Caroline Aquino; Burbano, Rommel Rodríguez

    2014-09-01

    Mercury exhibits cytotoxic and mutagenic properties as a result of its effect on tubulin. This toxicity mechanism is related to the production of free radicals that can cause DNA damage. Methylmercury (MeHg) is one of the most toxic of the mercury compounds. It accumulates in the aquatic food chain, eventually reaching the human diet. Several studies have demonstrated that prolactin (PRL) may be differently affected by inorganic and organic mercury based on interference with various neurotransmitters involved in the regulation of PRL secretion. This study evaluated the cytoprotective effect of PRL on human lymphocytes exposed to MeHg in vitro, including observation of the kinetics of HL-60 cells (an acute myeloid leukemia lineage) treated with MeHg and PRL at different concentrations, with both treatments with the individual compounds and combined treatments. All treatments with MeHg produced a significant increase in the frequency of chromatid gaps, however, no significant difference was observed in the chromosomal breaks with any treatment. A dose-dependent increase in the mitotic index was observed for treatments with PRL, which also acts as a co-mitogenic factor, regulating proliferation by modulating the expression of genes that are essential for cell cycle progression and cytoskeleton organization. These properties contribute to the protective action of PRL against the cytotoxic and mutagenic effects of MeHg. PMID:25247425

  19. Prolactin mediates effects of chronic psychological stress on induction of fibrofatty cells in the heart.

    PubMed

    Song, Jiangping; Wang, Mangyuan; Chen, Xiao; Liu, Li; Chen, Liang; Song, Zhizhao; Teng, Xiao; Xing, Yong; Chen, Kai; Zhao, Kun; Hou, Jianfeng; Yang, Pingchang

    2016-01-01

    Cardiocyte apoptosis plays an important role in the pathogenesis of heart diseases. The mechanism is unclear. It is reported that prolactin (PRL) is involved in cardiac disorders. This study aims to investigate the role of PRL in mediating the psychological stress-induced fibrofatty cell differentiation in the heart. In this study, BALB/c mice were treated with a 30-day restraint stress. The heart tissue was processed by paraffin embedding and hematoxylin and eosin. The expression of Sca1 in NIH3T3 cells was assessed by cell culture, flow cytometry and Western blotting. The results showed that chronic stress induced fibrofatty cells in the mouse heart and high serum PRL levels. The induction of fibrofatty cell was mimicked by administration with recombinant PRL. The stress also induced the expression of Sca1 in the mouse heart. Exposure of NIH3T3 cells (a fibroblast cell line) to PRL in the culture enhanced the expression of stem cell antigen-1 (Sca1), phosphorylation of signal transducer and activator of transcription 3 (STAT3) and expression of adipocyte-related protein molecules, including adiponectin, fatty acid binding protein (aP2), peroxisome proliferator activated receptor-g (PPARg) and CCAAT/enhancer binding protein (C/EBP)α, in the cells. We conclude that psychological stress-derived PRL induces fibroblasts to differentiate into fibrofatty cells in the heart. PMID:27158356

  20. Binding proteins for growth hormone and prolactin in rabbit kidney cytosol

    SciTech Connect

    Herington, A.C.; Stevenson, J.L.; Ymer, S.I. )

    1988-09-01

    Two soluble, receptor-like binding proteins with apparent somatotrophic (growth hormone (GH)) and lactogenic (prolactin (PRL)) specificities, respectively, and that are present in rabbit kidney cytosol have now been examined in more detail using specific GH receptor and PRL receptor monoclonal antibodies (MAb). Gel chromatography of {sup 125}I-labeled human GH ({sup 125}I-hGH) kidney cytosol complexes in the absence of these MAbs revealed two specifically bound regions of radioactivity at molecular weights (MW) of {approximately}120,000 and {approximately}60,000, which are similar in size to complexes formed by the native GH receptor of rabbit liver cytosol and the PRL receptor of mammary gland. Co-incubation with GH-receptor MAb inhibited {sup 125}I-hGH binding only to the higher MW (120,000) species, whereas the PRL-receptor MAb inhibited only the lower MW (60,000) species, thus establishing definitively the hormonal specificities of the two binding proteins. The presence of both GH- and PRL-specific binding subunits in cytosol was confirmed using covalent cross-linking techniques. No GH binding protein was detected in kidney membranes. The presence of naturally soluble, receptor-like binding proteins for GH and PRL in kidney cytosol preparations raises the possibility of their playing a role in the intracellular regulation of kidney function and/or metabolism.

  1. The m-chlorophenylpiperazine test in cluster headache: a study on central serotoninergic activity.

    PubMed

    Leone, M; Attanasio, A; Croci, D; Libro, G; Grazzi, L; D'Amico, D; Nespolo, A; Bussone, G

    1997-10-01

    The central serotoninergic agonist m-chlorophenylpiperazine (m-CPP) stimulates several 5HT receptor subtypes. It induces the release of both cortisol and prolactin (PRL). In this study we investigated central serotoninergic responsiveness in cluster headache by monitoring cortisol and PRL responses to m-CPP administration. Twenty-three patients with episodic cluster headache and 17 sex-matched and age-matched healthy subjects were studied. The cluster headache patients were tested during a cluster period, and none were receiving prophylaxis. A single oral dose of m-CPP, 0.5 mg/kg, was given at time 0. Blood samples were drawn at -30, 0, 30, 60, 90, 120, 150 and 180 min. PRL and cortisol levels were assayed in the samples. PRL and cortisol delta maxima (delta maximum = maximum response - baseline level at time 0/baseline level at time 0) were evaluated in each patient and mean values compared. Serum levels of m-CPP were detected by HPLC and correlated to hormonal responses. Reduced cortisol (p < 0.02) and increased PRL (p < 0.05) delta maxima were observed in cluster headache patients. Increased basal cortisol plasma levels (p < 0.05) and reduced basal PRL plasma levels (p = 0.06) also characterized cluster headache patients. This is the first study evaluating central serotoninergic responsiveness to m-CPP in cluster headache and these data suggest impaired central serotoninergic function in this pathology.

  2. Tyrosyl Phosphorylated Serine-Threonine Kinase PAK1 is a Novel Regulator of Prolactin-Dependent Breast Cancer Cell Motility and Invasion

    PubMed Central

    Hammer, Alan

    2015-01-01

    Despite efforts to discover the cellular pathways regulating breast cancer metastasis, little is known as to how prolactin (PRL) cooperates with extracellular environment and cytoskeletal proteins to regulate breast cancer cell motility and invasion. We implicated serine-threonine kinase p21-activated kinase 1 (PAK1) as a novel target for PRL-activated Janus-kinase 2 (JAK2). JAK2-dependent PAK1 tyrosyl phosphorylation plays a critical role in regulation of both PAK1 kinase activity and scaffolding properties of PAK1. Tyrosyl phosphorylated PAK1 facilitates PRL-dependent motility via at least two mechanisms: formation of paxillin/GIT1/βPIX/pTyr-PAK1 complexes resulting in increased adhesion turnover and phosphorylation of actin-binding protein filamin A. Increased adhesion turnover is the basis for cell migration and phosphorylated filamin A stimulates the kinase activity of PAK1 and increases actin-regulating activity to facilitate cell motility. Tyrosyl phosphorylated PAK1 also stimulates invasion of breast cancer cells in response to PRL and three-dimensional (3D) collagen IV via transcription and secretion of MMP-1 and MMP-3 in a MAPK-dependent manner. These data illustrate the complex interaction between PRL and the cell microenvironment in breast cancer cells and suggest a pivotal role for PRL/PAK1 signaling in breast cancer metastasis. PMID:25472536

  3. The progesterone and estrogen modify the uterine prolactin and prolactin receptor expression of hyperprolactinemic mice.

    PubMed

    do Amaral, Vinícius Cestari; Carvalho, Kátia Candido; Maciel, Gustavo Arantes Rosa; Simoncini, Tommaso; da Silva, Priscilla Ludovico; Marcondes, Rodrigo Rodrigues; Soares, José Maria; Baracat, Edmund Chada

    2015-02-01

    The aim of this study was to evaluate the effects of metoclopramide-induced hyperprolactinemia on the prolactin (PRL) and PRL receptor's expression in the uterus of mice. For this purpose, 49 Swiss mice were divided into the following groups: GrSS (non-ovariectomized mice given vehicle); GrMET (non-ovariectomized mice treated with metoclopramide); OvSS (ovariectomized mice given vehicle); OvMET (ovariectomized mice treated with metoclopramide); OvMET+17βE (ovariectomized mice treated with metoclopramide and 17β estradiol); OvMET+MP (ovariectomized mice treated with metoclopramide and micronized progesterone); OvMET+17βE+MP (ovariectomized mice treated with metoclopramide and a solution of 17β estradiol and micronized progesterone). Immunohistochemical analyzes were evaluated semi-quantitatively. Our results showed that GrMET, OvMET+MP, and OvMET+17βE+MP presented strong PRL expression. OvMET and OvMET+17βE presented mild reaction, while GrSS and OvSS presented weak reaction. Concerning PRL receptor, OvMET+MP and OvMET+17βE+MP showed strong reaction; GrMET, OvSS, and OvMET+17βE showed mild reaction; and GrSS and OvMET showed weak reaction. These findings suggest that progesterone alone or in combination with estrogen may increase the expression of uterine PRL and PRL receptor.

  4. Prolactin mediates effects of chronic psychological stress on induction of fibrofatty cells in the heart.

    PubMed

    Song, Jiangping; Wang, Mangyuan; Chen, Xiao; Liu, Li; Chen, Liang; Song, Zhizhao; Teng, Xiao; Xing, Yong; Chen, Kai; Zhao, Kun; Hou, Jianfeng; Yang, Pingchang

    2016-01-01

    Cardiocyte apoptosis plays an important role in the pathogenesis of heart diseases. The mechanism is unclear. It is reported that prolactin (PRL) is involved in cardiac disorders. This study aims to investigate the role of PRL in mediating the psychological stress-induced fibrofatty cell differentiation in the heart. In this study, BALB/c mice were treated with a 30-day restraint stress. The heart tissue was processed by paraffin embedding and hematoxylin and eosin. The expression of Sca1 in NIH3T3 cells was assessed by cell culture, flow cytometry and Western blotting. The results showed that chronic stress induced fibrofatty cells in the mouse heart and high serum PRL levels. The induction of fibrofatty cell was mimicked by administration with recombinant PRL. The stress also induced the expression of Sca1 in the mouse heart. Exposure of NIH3T3 cells (a fibroblast cell line) to PRL in the culture enhanced the expression of stem cell antigen-1 (Sca1), phosphorylation of signal transducer and activator of transcription 3 (STAT3) and expression of adipocyte-related protein molecules, including adiponectin, fatty acid binding protein (aP2), peroxisome proliferator activated receptor-g (PPARg) and CCAAT/enhancer binding protein (C/EBP)α, in the cells. We conclude that psychological stress-derived PRL induces fibroblasts to differentiate into fibrofatty cells in the heart.

  5. Tyrosyl Phosphorylated PAK1 Regulates Breast Cancer Cell Motility in Response to Prolactin through Filamin A

    PubMed Central

    Hammer, Alan; Rider, Leah; Oladimeji, Peter; Cook, Leslie; Li, Quanwen; Mattingly, Raymond R.

    2013-01-01

    The p21-activated serine-threonine kinase (PAK1) is activated by small GTPase-dependent and -independent mechanisms and regulates cell motility. Both PAK1 and the hormone prolactin (PRL) have been implicated in breast cancer by numerous studies. We have previously shown that the PRL-activated tyrosine kinase JAK2 (Janus tyrosine kinase 2) phosphorylates PAK1 in vivo and identified tyrosines (Tyr) 153, 201, and 285 in the PAK1 molecule as sites of JAK2 tyrosyl phosphorylation. Here, we have used human breast cancer T47D cells stably overexpressing PAK1 wild type or PAK1 Y3F mutant in which Tyr(s) 153, 201, and 285 were mutated to phenylalanines to demonstrate that phosphorylation of these three tyrosines are required for maximal PRL-dependent ruffling. In addition, phosphorylation of these three tyrosines is required for increased migration of T47D cells in response to PRL as assessed by two independent motility assays. Finally, we show that PAK1 phosphorylates serine (Ser) 2152 of the actin-binding protein filamin A to a greater extent when PAK1 is tyrosyl phosphorylated by JAK2. Down-regulation of PAK1 or filamin A abolishes the effect of PRL on cell migration. Thus, our data presented here bring some insight into the mechanism of PRL-stimulated motility of breast cancer cells. PMID:23340249

  6. Prolactin promotes cartilage survival and attenuates inflammation in inflammatory arthritis.

    PubMed

    Adán, Norma; Guzmán-Morales, Jessica; Ledesma-Colunga, Maria G; Perales-Canales, Sonia I; Quintanar-Stéphano, Andrés; López-Barrera, Fernando; Méndez, Isabel; Moreno-Carranza, Bibiana; Triebel, Jakob; Binart, Nadine; Martínez de la Escalera, Gonzalo; Thebault, Stéphanie; Clapp, Carmen

    2013-09-01

    Chondrocytes are the only cells in cartilage, and their death by apoptosis contributes to cartilage loss in inflammatory joint diseases, such as rheumatoid arthritis (RA). A putative therapeutic intervention for RA is the inhibition of apoptosis-mediated cartilage degradation. The hormone prolactin (PRL) frequently increases in the circulation of patients with RA, but the role of hyperprolactinemia in disease activity is unclear. Here, we demonstrate that PRL inhibits the apoptosis of cultured chondrocytes in response to a mixture of proinflammatory cytokines (TNF-α, IL-1β, and IFN-γ) by preventing the induction of p53 and decreasing the BAX/BCL-2 ratio through a NO-independent, JAK2/STAT3-dependent pathway. Local treatment with PRL or increasing PRL circulating levels also prevented chondrocyte apoptosis evoked by injecting cytokines into the knee joints of rats, whereas the proapoptotic effect of cytokines was enhanced in PRL receptor-null (Prlr(-/-)) mice. Moreover, eliciting hyperprolactinemia in rats before or after inducing the adjuvant model of inflammatory arthritis reduced chondrocyte apoptosis, proinflammatory cytokine expression, pannus formation, bone erosion, joint swelling, and pain. These results reveal the protective effect of PRL against inflammation-induced chondrocyte apoptosis and the therapeutic potential of hyperprolactinemia to reduce permanent joint damage and inflammation in RA.

  7. Immunoregulation of autocrine prolactin: suppressing the expression of costimulatory molecules and cytokines in T lymphocytes by prolactin receptor knockdown.

    PubMed

    Xu, Dongming; Lin, Ling; Lin, Xiahong; Huang, Ziyang; Lei, Zhenmin

    2010-01-01

    Ample evidence indicates that prolactin (PRL) secreted from the pituitary gland plays an important role in a variety of human immune responses. However, the immunoregulation of autocrine PRL in T lymphocytes is not fully understood. To evaluate the role of autocrine PRL in T lymphocyte activation, PRL receptor (PRLR) in Jurkat cells was silenced by lentivirus-mediated stable expression of PRLR shRNAi. Knockdown of PRLR resulted in a considerable reduction of phytohemagglutinin (PHA)-induced T cell proliferation. Moreover, the synthesis and secretion of CD137, CD154, IL-2 and IL-4 were significantly decreased, while the production of CD28, IFN-gamma and IL-10 was not affected in PHA-primed PRLR-deficient cells. These results demonstrate the importance of autocrine regulation of the PRL signaling in T lymphocyte growth and activation, and support a mechanism by which autocrine PRL participates in the immunoregulation through selectively influencing the expression of certain critical costimulatory molecules and cytokines.

  8. Relationships between pathological diagnosis and clinical parameters in acromegaly.

    PubMed

    Trouillas, J; Sassolas, G; Guigard, M P; Fonlupt, P; Ansaneli-Naves, L; Perrin, G

    1996-08-01

    From our series of 185 somatotropic adenomas with acromegaly, we found that sparsely granulated adenomas were more frequent (56%) than densely granulated ones. Immunocytochemistry detected growth hormone (GH) plurihormonal adenomas in 68% of patients. GH-alpha-subunit (alpha SU) and GH-alpha SU-prolactin (PRL) were more frequent (38%) than GH monohormonal adenomas (32%). The colocalization of GH and alpha SU in the same cell was obvious in many tumors. In contrast, colocalization of GH and PRL was demonstrated in only 25% of GH-PRL adenomas. The relationships between age, sex, tumor size, GH and PRL plasma levels, granularity, and percentage of GH-, alpha SU-, and PRL-immunoreactive cells were established in 105 acromegalic patients by three statistical methods, mainly by a principal component analysis. Correlations were found between the percentage of alpha SU- and GH-immunoreactive cells, and between densely granulated character and the percentage of GH-immunoreactive cells. Tumor size was not correlated with alpha SU, but was positively correlated with PRL plasma levels. Patients' age and percentage of GH-immunoreactive cells were inversely related to tumor size. Plurisecretion and sparsely granulated aspect are not related to age and tumor size. PMID:8769382

  9. Study of the change of prolactin and progesterone during dopaminergic agonist treatments in pseudopregnant bitches.

    PubMed

    Gobello, C; de la Sota, R L; Goya, R G

    2001-05-31

    In order to clarify the role of prolactin (PRL) and progesterone (P(4)) in the pathophysiology of canine pseudopregnancy (PSP) we designed an experiment, where we induced an abrupt pharmacological blockade of PRL secretion with dopaminergic agonists (DA) or placebo (PL). Thirty overtly pseudopregnant (PSPT) bitches were randomly allocated to three groups of 10 animals each: PL, bromocriptine (BR), and cabergoline (CA), which were treated with PL, 7.5microg/kg BR and 5microg/kg CA, respectively. On days 1, 7 and 14 (day 0: beginning of the treatment) all the animals were classified into grades of intensity of PSP clinical signs, considering serum or milk secretion and enlargement of the mammary glands. Presence or absence of treatment side effects were recorded and blood samples for PRL and P(4) determinations collected. Serum PRL and P(4) concentrations (ng/ml) of all the animals on day 1 were (least squares means [LSM]+/-S.E.M.) 17.70+/-2.05 and 1.13+/-0.13, respectively. During the experiment, serum PRL and P(4) concentrations decreased (day effect, P<0.05). During the experiment, serum PRL concentrations were lower in the DA treated group (BR and CA) compared with PL group (P<0.05). After a week of treatment, the percentage change of PRL was -62.52 versus 102.16+/-46.20 (P<0.01) for the treated (BR and CA) and PL groups, respectively. Conversely, no significant differences were found in the percent change in PRL between the BR and the CA groups nor in P(4) percentage change among all groups for the same week. Significant differences in the achievement of complete remission between treated and PL groups were found on days 7 (40 versus 0%, P<0.05) and 14 (90 versus 0%, P<0.01). No significant correlation between PRL and P(4) was found on day 1 in any of the animals. However, a significant correlation for the same hormones was found on days 7 and 14 for the DA treated groups (r=0.46, P<0.01). While in the PL group, PRL concentrations and intensity of clinical signs

  10. The dopamine antagonist domperidone increases prolactin concentration and enhances milk production in dairy cows.

    PubMed

    Lacasse, P; Ollier, S

    2015-11-01

    In previous studies, our team showed that the inhibition of prolactin (PRL) secretion by the dopamine agonist quinagolide reduces milk production in dairy cows. The objective of this study was to determine the effects of administration of a dopamine antagonist on basal and milking-induced PRL concentrations in blood and on milk production during positive energy balance and feed restriction in dairy cows. Eighteen mid-lactation Holstein cows received daily s.c. injections of either domperidone (300 mg, DOMP, n=9) or the vehicle, canola oil (CTL, n=9), for 5 wk. During wk 5, all cows were fed at 65% of their dry matter intake in the previous week. Blood and milk samples were collected before (for blood) and during (for milk) the a.m. milking thrice weekly from d -9 to 41 (8d after the last injection). In addition, blood samples were collected during the a.m. milking on d -1 (before the first injection), and on d 1, 28, and 34. Basal PRL concentration was similar in both groups before the start of the treatments. Domperidone injections caused a gradual increase in basal PRL concentration. Feed restriction reduced basal PRL concentration in both the CTL and DOMP cows, but PRL concentration remained higher in the DOMP cows. Prolactin concentration remained elevated in the DOMP cows 7d after the last injection. The milk concentration of PRL increased during the DOMP treatment, but the increase was smaller than that observed in serum. In the CTL cows, the milking-induced PRL release above the premilking concentration was similar on d -1, 1, and 28 but was reduced during feed restriction. In the DOMP cows, the milking-induced PRL release was similar on d -1 and 1 but was reduced on d 28 and 34. Milk production was similar for both groups before the treatments started but was greater in the DOMP cows during the treatment period, at 2.9 ± 0.6 and 2.4 ± 0.6 kg/d greater during wk 3 and 4 of treatment, respectively. Milk production declined in both groups during feed

  11. The extrapituitary prolactin promoter polymorphism is associated with rheumatoid arthritis and anti-CCP antibodies in Mexican population.

    PubMed

    Reyes-Castillo, Zyanya; Pereira-Suárez, Ana Laura; Palafox-Sanchez, Claudia Azucena; Rangel-Villalobos, Héctor; Estrada-Chávez, Ciro; Oregón-Romero, Edith; Angel-Chávez, Luis Ignacio; Muñoz-Barrios, Salvador; Bueno-Topete, Miriam Ruth; Muñoz-Valle, José Francisco

    2013-08-01

    Prolactin (PRL) is a hormone-cytokine that has been involved in autoimmunity due to its immunoregulatory and lymphoproliferative effects. It is produced by various extrapituitary sites including immune cells, under control of a superdistal promoter that contains a single nucleotide polymorphism -1149 G/T previously associated with rheumatoid arthritis (RA) susceptibility in European population. The aim of this study was to investigate the association of the extrapituitary PRL -1149 G/T promoter polymorphism with clinical parameters, clinical activity and disability indices in RA patients from Western Mexico and to analyze the PRL mRNA expression according to the PRL -1149 G/T promoter polymorphism in total leucocytes from RA patients and controls. We conducted a case-control study that included 258 RA patients and 333 control subjects (CS). The DNA samples were genotyped using the PCR-RFLP method and the PRL mRNA expression was determined by quantitative real time PCR. PRL serum levels and antibodies to cyclic citrullinated peptides (anti-CCP) were measured with ELISA. We found significant differences in the genotype (p=0.022) and allelic (p=0.046) distribution of the polymorphism between RA patients and control subjects. According to the dominant genetic model, there is an association between the T allele (GT+TT genotypes) and decreased RA susceptibility in comparison to the G allele carriers (GG genotype) (OR 0.64, 95% CI 0.45-0.92; p=0.011). The T allele carriers (GT+TT genotypes) had lower titers of anti-CCP antibodies in comparison to the G allele carriers (GG genotype) (median, 66 U/mL vs. 125 U/mL; p=0.03). Furthermore, the GG homozygotes had higher PRL mRNA expression in comparison to the GT heterozygotes, and this latter with respect to the TT homozygotes, in both groups (RA: 1>0.72>0.19; CS: 1>0.54>0.28). However, PRL serum levels were similar in both groups. Our results suggest that the PRL -1149 T allele is a genetic marker for decreased RA

  12. Effect of iodination on human growth hormone and prolactin: characterized by bioassay, radioimmunoassay, radioreceptor assay, and electrophoresis

    SciTech Connect

    Hughes, J.P.; Tanaka, T.; Gout, P.W.; Beer, C.T.; Noble, R.L.; Friesen, H.G.

    1982-09-01

    Human GH (hGH) and PRL (hPRL) were iodinated using lactoperoxidase. The iodinated hormones were characterized by RIA, radioreceptor assay (RRA), and bioassay (BA) using the Nb2 Node lymphoma cell line. The proportion of tracer that could bind to rat liver membranes or rabbit antibodies was determined, and the distribution of iodinated hormones was examined using polyacrylamide gel electrophoresis. Excess antibody was capable of precipitating 87.9% of the radioactivity associated with the hGH tracer and 86.0% of the hPRL tracer. The maximal specific binding to a liver membrane preparation averaged 67.3% of the (/sup 125/I)iodo-hGH radioactivity and 48.8% of the (/sup 125/I)iodo-hPRL radioactivity. The respective BA and RRA activity estimates for (/sup 125/)iodo-hGH averaged 90% and 114% of the activity measured by the RIA. For (/sup 125/I)iodo-hPRL, the values were 75% by BA and 68% by RRA. The bioactivity profiles of iodinated hGH and hPRL shifted anodally on polyacrylamide gel electrophoresis in comparison to the bioactivity distribution of the respective uniodinated hormones. Iodine incorporation rather than oxidation appeared to be responsible for the shift. After electrophoresis, all eluates which contained significant radioactivity were active in the BA and RIA. Furthermore, specific activities calculated from the bioactive hormone and radioactivity in each electrophoretic segment agreed well with the average specific activity estimated from the amount of iodine incorporated into the protein peak upon gel filtration. These data suggest that hGH and hPRL to a major degree retain biological integrity after iodination.

  13. Effect of iodination on human growth hormone and prolactin: characterized by bioassay, radioimmunoassay, radioreceptor assay, and electrophoresis

    SciTech Connect

    Hughes, J.P.; Tanaka, T.; Gout, P.W.; Beer, C.T.; Noble, R.L.; Friesen, H.G.

    1982-09-01

    Human GH (hGH) and PRL (hPRL) were iodinated using lactoperoxidase. The iodinated hormones were characterized by RIA, radioreceptor assay (RRA), and bioassay (BA) using the Nb2 Node lymphoma cell line. The proportion of tracer that could bind to rat liver membranes or rabbit antibodies was determined, and the distribution of iodinated hormones was examined using polyacrylamide gel electrophoresis. Excess antibody was capable of precipitating 87.9% of the radioactivity associated with the hGH tracer and 86.0% of the hPRL tracer. The maximal specific binding to a liver membrane preparation averaged 67.3% of the (/sup 125/I)iodo-hGH radioactivity and 48.8% of the (/sup 125/I)iodo-hPRL radioactivity. The respective BA and RRA activity estimates for (/sup 125/I)iodo-hGH averaged 90% and 114% of the activity measured by the RIA. For (/sup 125/I)iodo-hPRL, the values were 75% by BA and 68% by RRA. The bioactivity profiles of iodinated hGH and hPRL shifted anodally on polyacrylamide gel electrophoresis in comparison to the bioactivity distribution of the respective uniodinated hormones. Iodine incorporation rather than oxidation appeared to be responsible for the shift. After electrophoresis, all eluates which contained significant radioactivity were active in the BA and RIA. Furthermore, specific activities calculated from the bioactive hormone and radioactivity in each electrophoretic segment agreed well with the average specific activity estimated from the amount of iodine incorporated into the protein peak upon gel filtration. These data suggest that hGH and hPRL to a major degree retain biological integrity after iodination.

  14. Estradiol and its membrane-impermeable conjugate estradiol-BSA inhibit tamoxifen-stimulated prolactin secretion in incubated rat pituitaries.

    PubMed

    Aguilar, R; Bellido, C; Garrido-Gracia, J C; Alonso, R; Sánchez-Criado, J E

    2006-04-01

    In the absence of estrogen (E), the selective E receptor modulator tamoxifen (TX) has two agonist effects in the rat pituitary: induction of progesterone receptor (PR)-dependent GnRH self-priming in the gonadotrope, and stimulation of prolactin (PRL) secretion in the lactotrope. TX-induced gonadotropin (GnRH) self-priming is absent when 10(-8) M estradiol-17beta (E2) is added to the incubation medium of pituitaries from TX-treated rats. The present experiments investigated whether PR-independent PRL release into the incubation medium of pituitaries from TX-treated ovariectomized (OVX) rats was affected by E2, and the effect of different ER ligands (ICI182780, TX, estradiol-17alpha, E2 -BSA) on TX-stimulated PRL secretion. Moreover, the effect of E2 on TRH-stimulated PRL secretion in pituitaries collected from estradiol benzoate- and TX-treated OVX rats was studied. It was found that: i) incubation with E2 supressed the PRL releasing effect of injected TX; ii) whereas coincubation with the pure anti-E type II ICI182780 antagonized the inhibitory effect of E2, coincubation with the anti-E type I TX did not; iii) estradiol-17alpha lacked inhibitory action, whereas a dose-dependent inhibitory effect of both E2 and E2 -BSA was noticed; and iv) TRH stimulatory effect on PRL release in pituitaries from TX-treated rats was blocked by addition of E2 to the medium. Taken together, these data argue in favor of the presence of specific membrane recognition sites for E in the lactotrope involved in steroid-specific E2 inhibition of TX-stimulated PRL secretion.

  15. Regulation by the extracellular matrix (ECM) of prolactin-induced alpha s1-casein gene expression in rabbit primary mammary cells: role of STAT5, C/EBP, and chromatin structure.

    PubMed

    Jolivet, Geneviève; Pantano, Thaïs; Houdebine, Louis Marie

    2005-05-15

    The aim of the present study was to understand how the extracellular matrix (ECM) regulates at the gene level the prolactin (Prl)-induced signal transducer and activator of transcription 5 (STAT5)-dependent expression of the alpha s1-casein gene in mammary epithelial cells. CCAAT enhancer binding proteins (C/EBPs) are assumed regulators of beta-casein gene expression. Rabbit primary mammary cells express alpha s1-casein gene when cultured on collagen and not on plastic. Similar C/EBPbeta, C/EBPdelta, STAT5, and Prl-activated STAT5 were found under all culture conditions. Thus the ECM does not act through C/EBPs or STAT5. This was confirmed by transfections of rabbit primary mammary cells by a construct sensitive to ovine prolactin (oPrl) and ECM (6i TK luc) encompassing STAT5 and C/EBP binding sites. The mutation of C/EBPs binding sites showed that these sites were not mandatory for Prl-induced expression of the construct. Interestingly, chromatin immunoprecipitation by the anti-acetylhistone H4 antibody (ChIP) showed that the ECM (and not Prl) maintained a high amount of histone H4 acetylation upstream of the alpha s1-casein gene especially at the level of a distal Prl- and ECM-sensitive enhancer. Alpha6 integrin (a membrane receptor of laminin, the principal active component of the mammary ECM) was found at the surface of cells cultured on collagen but not on plastic. In cells cultured on collagen in the presence of anti-alpha6 integrin antibody, Prl-induced transcription of the endogenous alpha s1-casein gene was significantly reduced, without modifying C/EBPs and STAT5. Besides, histone H4 acetylation was reduced. Thus, we propose that the ECM regulates rabbit alpha s1-casein protein expression by local modification of chromatin structure, independently of STAT5 and C/EBPs.

  16. Two Wrongs Can Make a Right: Dimers of Prolactin and Growth Hormone Receptor Antagonists Behave as Agonists

    PubMed Central

    Langenheim, John F.; Tan, Dunyong; Walker, Ameae M.; Chen, Wen Y.

    2006-01-01

    Prolactin (PRL) and GH have two distinct binding sites (site 1 with high affinity; site 2 with low affinity) that each interact with a PRL receptor (PRLR) to form a functional receptor dimer that activates signal transduction. The G129R mutation in PRL and the G120R mutation in GH disrupt the structural integrity of site 2 such that the ligands retain the ability to bind to the first receptor with high affinity, but act as receptor antagonists. In this study, we examined the ability of monomeric and dimeric forms of these ligands, human (h) PRL and hGH, and their antagonists (hPRL-G129R and hGH-G120R) to 1) bind to PRLRs; 2) induce conformational changes in PRLRs; 3) activate signaling pathways associated with the PRLR; and 4) mediate cell proliferation in vitro. In contrast to monomeric hPRL-G129R, homodimeric hPRL-G129R induced PRLR dimerization; activated Janus family of tyrosine kinases 2/signal transducer and activator of transcription 5, Ras/Raf/MAPK kinase/Erk, and phosphatidylinositol 3-kinase/Akt signaling; and stimulated Nb2 cell proliferation. Similarly, homodimeric hGH-G120R was able to mediate signaling via the PRLR and to stimulate Nb2 cell proliferation. These experiments demonstrate that a ligand must have two functional binding sites, but that these may be site 1 plus site 2 or two site 1’s, to elicit receptor-mediated signal transduction. The size of the ligand plays less of a role in receptor activation, suggesting that the extracellular portion of the PRLR (and possibly the GH receptor) is rather flexible and can accommodate larger ligands. These findings may have implications for designing multifunctional therapeutics that target this class of cytokine receptors. PMID:16269515

  17. Prolactin increases the synthesis of 7alpha-hydroxypregnenolone, a key factor for induction of locomotor activity, in breeding male Newts.

    PubMed

    Haraguchi, Shogo; Koyama, Teppei; Hasunuma, Itaru; Vaudry, Hubert; Tsutsui, Kazuyoshi

    2010-05-01

    We recently found that the Japanese red-bellied newt, Cynops pyrrhogaster, actively produces 7alpha-hydroxypregnenolone, a previously undescribed amphibian neurosteroid. 7alpha-Hydroxypregnenolone stimulates locomotor activity of male newts. Locomotor activity of male newts increases during the breeding period as in other wild animals, but the molecular mechanism for such a change in locomotor activity is poorly understood. Here we show that the adenohypophyseal hormone prolactin (PRL) stimulates 7alpha-hydroxypregnenolone synthesis in the brain, thus increasing locomotor activity of breeding male newts. In this study, cytochrome P450(7alpha) (CYP7B), a steroidogenic enzyme catalyzing the formation of 7alpha-hydroxypregnenolone, was first identified to analyze seasonal changes in 7alpha-hydroxypregnenolone synthesis. Only males exhibited marked seasonal changes in 7alpha-hydroxypregnenolone synthesis and CYP7B expression in the brain, with a maximum level in the spring breeding period when locomotor activity of males increases. Subsequently we identified PRL as a key component of the mechanism regulating 7alpha-hydroxypregnenolone synthesis. Hypophysectomy decreased 7alpha-hydroxypregnenolone synthesis in the male brain, whereas administration of PRL but not gonadotropins to hypophysectomized males caused a dose-dependent increase in 7alpha-hydroxypregnenolone synthesis. To analyze the mode of PRL action, CYP7B and the receptor for PRL were localized in the male brain. PRL receptor was expressed in the neurons expressing CYP7B in the magnocellular preoptic nucleus. Thus, PRL appears to act directly on neurosteroidogenic magnocellular preoptic nucleus neurons to regulate 7alpha-hydroxypregnenolone synthesis, thus inducing seasonal locomotor changes in male newts. This is the first report describing the regulation of neurosteroidogenesis in the brain by an adenohypophyseal hormone in any vertebrate.

  18. Role of prolactin in regulating the onset of winter fur growth in mink (Mustela vison): A reconsideration.

    PubMed

    Johnston, B; Rose, J

    1999-09-01

    The objectives of this study were to determine: (1) if the onset of winter hair growth (anagen) in mink could be delayed or inhibited by elevating endogenous PRL concentrations; (2) if bilaterally adrenalectomy (ADX)-induced winter anagen occurs concomitantly with a reduction in serum PRL concentrations, and (3) if exogenous dehydroepiandrosterone (DHEA), an adrenal steroid or Delta(5)-DIOL (a peripherally produced metabolite of DHEA), would delay or inhibit the onset of winter anagen. During early July, while in the resting (telogen) stage of the hair growth cycle, mink were treated with slow release implants containing haloperidol (HAL, a dopaminergic antagonist), melatonin (MEL), deoxycorticosterone (DOC), DHEA and Delta(5)-DIOL. In addition, mink were ADX'd and supplemented with DOC and DHEA. MEL reduced PRL levels to basal levels and induced winter anagen 7 weeks earlier than controls. Surprisingly, HAL initiated winter anagen 7 weeks earlier than controls (P < 0.05), although serum PRL levels were not different between the two groups. Mink that were ADX'd or ADX + DHEA-treated exhibited winter anagen 6 weeks earlier than controls (P < 0.05), but serum PRL concentrations were not different between the three groups. The administration of DHEA or Delta(5)-DIOL to mink with intact adrenals had no effect on the time of onset of winter anagen or serum PRL levels. Our findings suggest that a reduction in circulating PRL levels is not essential for onset of winter anagen in the mink and that the apparent inhibitory effects of the adrenal glands on initiation of winter anagen is not mediated through DHEA or its metabolite Delta(5)-DIOL. J. Exp. Zool. 284:437-444, 1999. PMID:10451421

  19. LPXRFamide peptide stimulates growth hormone and prolactin gene expression during the spawning period in the grass puffer, a semi-lunar synchronized spawner.

    PubMed

    Shahjahan, Md; Doi, Hiroyuki; Ando, Hironori

    2016-02-01

    Gonadotropin-inhibitory hormone (GnIH) plays as a multifunctional neurohormone that controls reproduction in birds and mammals. LPXRFamide (LPXRFa) peptide, the fish ortholog of GnIH, has been shown to regulate the secretion of not only gonadotropin (GTH) but also growth hormone (GH) and prolactin (PRL), which are potentially important for gonadal function. To investigate the role of LPXRFa peptide on reproduction of the grass puffer, which spawns in semilunar cycles, we examined changes in the levels of gh and prl expression over the several months during the reproductive cycle, and the effects of goldfish LPXRFa peptide-1 (gfLPXRFa-1) on their expression were examined using primary pituitary cultures. The expression levels of both gh and prl showed significant changes during the reproductive cycle in both sexes with one peak in the spawning and pre-spawning periods for gh and prl, respectively. Particularly, gh showed substantial increase in expression in the spawning and post-spawning periods, indicative of its essentiality in the advanced stage of reproduction. gfLPXRFa-1 stimulated the expression of both gh and prl but there was a marked difference in response between them: gfLPXRFa-1 stimulated gh expression at a relatively low dose but little effect was observed on prl. Combined with the previous results of daily and circadian oscillations of lpxrfa expression, the present results suggest that LPXRFa peptide is important in the control of the cyclic reproduction by serving as a multifunctional hypophysiotropic factor that regulates the expression of gh and prl as well as GTH subunit genes.

  20. Long-term follow-up of 'cured' prolactinoma patients after successful adenomectomy.

    PubMed

    Ciccarelli, E; Ghigo, E; Miola, C; Gandini, G; Muller, E E; Camanni, F

    1990-05-01

    The long-term follow-up (greater than or equal to 4 years) of clinical, hormonal and radiological aspects in 22 'cured' prolactinoma patients after adenomectomy was studied. Dynamic secretion of PRL and TSH was also evaluated, in order to identify the persistence of any underlying abnormality of hypothalamic pituitary control and to predict relapses. A relapse into hyperprolactinaemia was shown in 36% of patients 5-90 months (mean 46) after surgery. This was accompanied by reappearance of clinical symptoms but not by the radiological demonstration of the adenoma in any patients. A significant PRL rise after domperidone, a dopaminergic antagonist drug, was shown in cured patients after surgery (mean +/- SEM peak, 2977 +/- 645 mU/l) but this was markedly lower than that observed in control subjects (5732 +/- 440 mU/l). In fact, normal PRL increments were shown in only 6/16 (37%) patients. TSH hyper-responsiveness to domperidone normalized in only 46% of patients. Similar PRL responses to those obtained with domperidone were shown when a TRH test was given. A relapse into hyperprolactinaemia was observed in six of ten (60%) non-responders to domperidone and in four of seven (57%) non-responders to TRH, whereas six normal responders to domperidone and TRH had not relapsed at that time. Plasma PRL levels during pregnancy showed increments lower than those observed in normal pregnant women only in domperidone and TRH non-responder patients. These results indicate that a relapse into hyperprolactinaemia and a blunted PRL rise during pregnancy were present only in patients with persistently reduced PRL response to dynamic tests.

  1. Role of Estrogen Response Element in the Human Prolactin Gene: Transcriptional Response and Timing

    PubMed Central

    McNamara, Anne V.; Adamson, Antony D.; Dunham, Lee S. S.; Semprini, Sabrina; Spiller, David G.; McNeilly, Alan S.; Mullins, John J.

    2016-01-01

    The use of bacterial artificial chromosome (BAC) reporter constructs in molecular physiology enables the inclusion of large sections of flanking DNA, likely to contain regulatory elements and enhancers regions that contribute to the transcriptional output of a gene. Using BAC recombineering, we have manipulated a 160-kb human prolactin luciferase (hPRL-Luc) BAC construct and mutated the previously defined proximal estrogen response element (ERE) located −1189 bp relative to the transcription start site, to assess its involvement in the estrogen responsiveness of the entire hPRL locus. We found that GH3 cell lines stably expressing Luc under control of the ERE-mutated hPRL promoter (ERE-Mut) displayed a dramatically reduced transcriptional response to 17β-estradiol (E2) treatment compared with cells expressing Luc from the wild-type (WT) ERE hPRL-Luc promoter (ERE-WT). The −1189 ERE controls not only the response to E2 treatment but also the acute transcriptional response to TNFα, which was abolished in ERE-Mut cells. ERE-WT cells displayed a biphasic transcriptional response after TNFα treatment, the acute phase of which was blocked after treatment with the estrogen receptor antagonist 4-hydroxy-tamoxifen. Unexpectedly, we show the oscillatory characteristics of hPRL promoter activity in individual living cells were unaffected by disruption of this crucial response element, real-time bioluminescence imaging showed that transcription cycles were maintained, with similar cycle lengths, in ERE-WT and ERE-Mut cells. These data suggest the −1189 ERE is the dominant response element involved in the hPRL transcriptional response to both E2 and TNFα and, crucially, that cycles of hPRL promoter activity are independent of estrogen receptor binding. PMID:26691151

  2. Prolactin-Stimulated Activation of ERK1/2 Mitogen-Activated Protein Kinases is Controlled by PI3-Kinase/Rac/PAK Signaling Pathway in Breast Cancer Cells

    PubMed Central

    Aksamitiene, Edita; Achanta, Sirisha; Kolch, Walter; Kholodenko, Boris N.; Hoek, Jan B.; Kiyatkin, Anatoly

    2011-01-01

    There is strong evidence that deregulation of prolactin (PRL) signaling contributes to pathogenesis and chemoresistance of breast cancer. Therefore, understanding cross-talk between distinct signal transduction pathways triggered by activation of the prolactin receptor (PRL-R), is essential for elucidating the pathogenesis of metastatic breast cancer. In this study, we applied a sequential inhibitory analysis of various signaling intermediates to examine the hierarchy of protein interactions within the PRL signaling network and to evaluate the relative contributions of multiple signaling branches downstream of PRL-R to the activation of the extracellular signal-regulated kinases ERK1 and ERK2 in T47D and MCF-7 human breast cancer cells. Quantitative measurements of the phosphorylation/activation patterns of proteins showed that PRL simultaneously activated Src family kinases (SFKs) and the JAK/STAT, phosphoinositide-3 (PI3)-kinase/Akt and MAPK signaling pathways. The specific blockade or siRNA-mediated suppression of SFK/FAK, JAK2/STAT5, PI3-kinase/PDK1/Akt, Rac/PAK or Ras regulatory circuits revealed that (1) the PI3-kinase/Akt pathway is required for activation of the MAPK/ERK signaling cascade upon PRL stimulation; (2) PI3-kinase-mediated activation of the c-Raf-MEK1/2-ERK1/2 cascade occurs independent of signaling dowstream of STATs, Akt and PKC, but requires JAK2, SFKs and FAK activities; (3) activated PRL-R mainly utilizes the PI3-kinase-dependent Rac/PAK pathway rather than the canonical Shc/Grb2/SOS/Ras route to initiate and sustain ERK1/2 signaling. By interconnecting diverse signaling pathways PLR may enhance proliferation, survival, migration and invasiveness of breast cancer cells. PMID:21726627

  3. Estradiol and its membrane-impermeable conjugate estradiol-BSA inhibit tamoxifen-stimulated prolactin secretion in incubated rat pituitaries.

    PubMed

    Aguilar, R; Bellido, C; Garrido-Gracia, J C; Alonso, R; Sánchez-Criado, J E

    2006-04-01

    In the absence of estrogen (E), the selective E receptor modulator tamoxifen (TX) has two agonist effects in the rat pituitary: induction of progesterone receptor (PR)-dependent GnRH self-priming in the gonadotrope, and stimulation of prolactin (PRL) secretion in the lactotrope. TX-induced gonadotropin (GnRH) self-priming is absent when 10(-8) M estradiol-17beta (E2) is added to the incubation medium of pituitaries from TX-treated rats. The present experiments investigated whether PR-independent PRL release into the incubation medium of pituitaries from TX-treated ovariectomized (OVX) rats was affected by E2, and the effect of different ER ligands (ICI182780, TX, estradiol-17alpha, E2 -BSA) on TX-stimulated PRL secretion. Moreover, the effect of E2 on TRH-stimulated PRL secretion in pituitaries collected from estradiol benzoate- and TX-treated OVX rats was studied. It was found that: i) incubation with E2 supressed the PRL releasing effect of injected TX; ii) whereas coincubation with the pure anti-E type II ICI182780 antagonized the inhibitory effect of E2, coincubation with the anti-E type I TX did not; iii) estradiol-17alpha lacked inhibitory action, whereas a dose-dependent inhibitory effect of both E2 and E2 -BSA was noticed; and iv) TRH stimulatory effect on PRL release in pituitaries from TX-treated rats was blocked by addition of E2 to the medium. Taken together, these data argue in favor of the presence of specific membrane recognition sites for E in the lactotrope involved in steroid-specific E2 inhibition of TX-stimulated PRL secretion. PMID:16595727

  4. [Prolactin as an immunomodulatory factor in psoriatic arthritis].

    PubMed

    Kokot, Izabela; Pawlik-Sobecka, Lilla; Płaczkowska, Sylwia; Piwowar, Agnieszka

    2013-12-11

    Prolactin (PRL) is a hormone synthesized and secreted by lactotroph cells in the anterior pituitary gland. There is also extrapituitary hormone secretion by many cells, including cells of the immune system. In physiological conditions PRL is responsible for lactogenesis and other processes associated with it. PRL plays a significant role during the immune response as a cytokine, affecting proliferation and differentiation of many immune system cells. The biological effect of the hormone depends on binding with the specific prolactin receptor PRL-R, and activation of the transcription factors of targeted genes. For T lymphocyte stimulated PRL, that factor is mainly the interferon regulatory factor (IRF-1), which gives the possibility of adjusting the prolactin immune response. Literature data indicate that hyperprolactinemia (HPRL) is one of the important factors in the pathogenesis and course of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis and Sjogren's syndrome. HPRL is diagnosed in nearly one-third of these patients. However, only a few data indicate the role of prolactin in psoriatic arthritis (PsA), whose etiology and disease progression are not fully elucidated, and the diagnosis is very difficult. Currently there is indicated a pronounced connection between the course of HPRL and activity of PsA. It seems also to be interesting that, regardless of the PRL levels in serum of patients with PsA, administration of bromocriptine--drug-lowering hormone--improves joint and skin symptoms, which indicates a decrease in disease activity, and is a promising way of alternative therapy for psoriatic arthritis. However, the effect of PRL on the pathogenesis and the severity of psoriatic arthritis has not yet been fully understood and further research will provide a possibility to assess the prognostic and diagnostic significance of prolactin in patients with PsA.

  5. Prolactin as an Adjunct for Type 1 Diabetes Immunotherapy.

    PubMed

    Hyslop, Colin M; Tsai, Sue; Shrivastava, Vipul; Santamaria, Pere; Huang, Carol

    2016-01-01

    Type 1 diabetes is caused by autoimmune destruction of β-cells. Although immunotherapy can restore self-tolerance thereby halting continued immune-mediated β-cell loss, residual β-cell mass and function is often insufficient for normoglycemia. Using a growth factor to boost β-cell mass can potentially overcome this barrier and prolactin (PRL) may fill this role. Previous studies have shown that PRL can stimulate β-cell proliferation and up-regulate insulin synthesis and secretion while reducing lymphocytic infiltration of islets, suggesting that it may restore normoglycemia through complementary mechanisms. Here, we test the hypothesis that PRL can improve the efficacy of an immune modulator, the anticluster of differentiation 3 monoclonal antibody (aCD3), in inducing diabetes remission by up-regulating β-cell mass and function. Diabetic nonobese diabetic (NOD) mice were treated with a 5-day course of aCD3 with or without a concurrent 3-week course of PRL. We found that a higher proportion of diabetic mice treated with the aCD3 and PRL combined therapy achieved diabetes reversal than those treated with aCD3 alone. The aCD3 and PRL combined group had a higher β-cell proliferation rate, an increased β-cell fraction, larger islets, higher pancreatic insulin content, and greater glucose-stimulated insulin release. Lineage-tracing analysis found minimal contribution of β-cell neogenesis to the formation of new β-cells. Although we did not detect a significant difference in the number or proliferative capacity of T cells, we observed a higher proportion of insulitis-free islets in the aCD3 and PRL group. These results suggest that combining a growth factor with an immunotherapy may be an effective treatment paradigm for autoimmune diabetes.

  6. Milk prolactin response and quarter milk yield after experimental infection with coagulase-negative staphylococci in dairy heifers.

    PubMed

    Piccart, K; Piepers, S; Verbeke, J; de Sousa, N M; Beckers, J F; De Vliegher, S

    2015-07-01

    Coagulase-negative staphylococci (CNS) are the most common bacteria involved in subclinical mastitis in dairy cows. Remarkably, CNS-infected dairy heifers produce more milk than uninfected heifers. Because the lactation hormone prolactin (PRL) is also involved in mammary gland immunity, we investigated the milk PRL response and the mammary quarter milk yield following experimental CNS challenge. Eight healthy Holstein-Friesian heifers in mid-lactation were experimentally infected using a split-udder design with 3 different CNS strains: one Staphylococcus fleurettii (from sawdust bedding) and 2 Staphylococcus chromogenes strains (one isolate from a teat apex, the other isolate from a chronic intramammary infection). Three mammary quarters per heifer were simultaneously inoculated with 1.0×10(6) cfu, whereas the remaining mammary quarter was infused with sterile phosphate-buffered saline, serving as a control. An existing radioimmunoassay was modified, validated, and used to measure PRL frozen-thawed milk at various time points until 78h after challenge. The mean milk PRL level tended to be higher in the CNS-challenged mammary quarters compared with the control mammary quarters (7.56 and 6.85ng/mL, respectively). The increase in PRL over time was significantly greater in the CNS-challenged mammary quarters than in the control mammary quarters. However, no difference was found in the PRL response when comparing each individual CNS strain with the control mammary quarters. The mean mammary quarter milk yield tended to be lower in the CNS-infected mammary quarters than in the control mammary quarters (1.73 and 1.98kg per milking, respectively). The greatest milk loss occurred in the mammary quarters challenged with the intramammary strain of S. chromogenes. Future observational studies are needed to elucidate the relation between PRL, the milk yield, and the inflammatory condition, or infection status, of the mammary gland. PMID:25981074

  7. Calcitriol stimulates prolactin expression in non-activated human peripheral blood mononuclear cells: breaking paradigms.

    PubMed

    Díaz, Lorenza; Martínez-Reza, Isela; García-Becerra, Rocío; González, Leticia; Larrea, Fernando; Méndez, Isabel

    2011-08-01

    Calcitriol, the hormonal form of vitamin D(3), exerts immunomodulatory effects through the vitamin D(3) receptor (VDR) and increases prolactin (PRL) expression in the pituitary and decidua. Nevertheless, the effects of calcitriol upon lymphocyte PRL have not been evaluated. Therefore, we investigated calcitriol effects upon PRL in resting and phytohemagglutinin-activated human peripheral blood mononuclear cells (PBMNC) and Jurkat T lymphoma cells. Immunoblots showed constitutive expression of the 50-kDa VDR species in activated PBMNC and Jurkat cells, while a 75-kDa species was recognized in both resting and activated-PBMNC. Only in resting PBMNC calcitriol significantly stimulated PRL expression in a dose-dependent manner. The positive control CYP24A1, a highly VDR-responsive gene, was stimulated by calcitriol, effect that was stronger in resting than in activated-PBMNC (P<0.05), and without effect in Jurkat cells. Calcitriol upregulation of PRL and CYP24A1 was significantly inhibited by the VDR antagonist TEI-9647. EMSA showed that resting PBMNC contain a protein that binds to DR3-type VDRE. Cell activation reduced basal CYP24A1 while induced CYP27B1, VDR and pregnane X receptor (PXR) expression. In summary, calcitriol stimulated PRL and CYP24A1 gene expression in quiescent lymphocytes through a VDR-mediated mechanism. Our results suggest that the 75-kDa VDR species could be participating in calcitriol-mediated effects, and that activation induces factors such as PXR that restrain VDR transcriptional processes. This study supports the presence of a functional VDR in quiescent lymphocytes, providing evidence to reevaluate the VDR paradigm that assumes that lymphocytes respond to calcitriol only after activation. Altogether, our results offer new insights into the mechanisms whereby PRL is regulated in immune cells.

  8. Prolactin promotes normal liver growth, survival, and regeneration in rodents: effects on hepatic IL-6, suppressor of cytokine signaling-3, and angiogenesis.

    PubMed

    Moreno-Carranza, Bibiana; Goya-Arce, Maite; Vega, Claudia; Adán, Norma; Triebel, Jakob; López-Barrera, Fernando; Quintanar-Stéphano, Andrés; Binart, Nadine; Martínez de la Escalera, Gonzalo; Clapp, Carmen

    2013-10-01

    Prolactin (PRL) is a potent liver mitogen and proangiogenic hormone. Here, we used hyperprolactinemic rats and PRL receptor-null mice (PRLR(-/-)) to study the effect of PRL on liver growth and angiogenesis before and after partial hepatectomy (PH). Liver-to-body weight ratio (LBW), hepatocyte and sinusoidal endothelial cell (SEC) proliferation, and hepatic expression of VEGF were measured before and after PH in hyperprolactinemic rats, generated by placing two anterior pituitary glands (AP) under the kidney capsule. Also, LBW and hepatic expression of IL-6, as well as suppressor of cytokine signaling-3 (SOCS-3), were evaluated in wild-type and PRLR(-/-) mice before and after PH. Hyperprolactinemia increased the LBW, the proliferation of hepatocytes and SECs, and VEGF hepatic expression. Also, liver regeneration was increased in AP-grafted rats and was accompanied by elevated hepatocyte and SEC proliferation, and VEGF expression compared with nongrafted controls. Lowering circulating PRL levels with CB-154, an inhibitor of AP PRL secretion, prevented AP-induced stimulation of liver growth. Relative to wild-type animals, PRLR(-/-) mice had smaller livers, and soon after PH, they displayed an approximately twofold increased mortality and elevated and reduced hepatic IL-6 and SOCS-3 expression, respectively. However, liver regeneration was improved in surviving PRLR(-/-) mice. PRL stimulates normal liver growth, promotes survival, and regulates liver regeneration by mechanisms that may include hepatic downregulation of IL-6 and upregulation of SOCS-3, increased hepatocyte proliferation, and angiogenesis. PRL contributes to physiological liver growth and has potential clinical utility for ensuring survival and regulating liver mass in diseases, injuries, or surgery of the liver.

  9. Prolactin prevents hepatocellular carcinoma by restricting innate immune activation of c-Myc in mice.

    PubMed

    Hartwell, Hadley J; Petrosky, Keiko Y; Fox, James G; Horseman, Nelson D; Rogers, Arlin B

    2014-08-01

    Women are more resistant to hepatocellular carcinoma (HCC) than men despite equal exposure to major risk factors, such as hepatitis B or C virus infection. Female resistance is hormone-dependent, as evidenced by the sharp increase in HCC incidence in postmenopausal women who do not take hormone replacement therapy. In rodent models sex-dimorphic HCC phenotypes are pituitary-dependent, suggesting that sex hormones act via the gonadal-hypophyseal axis. We found that the estrogen-responsive pituitary hormone prolactin (PRL), signaling through hepatocyte-predominant short-form prolactin receptors (PRLR-S), constrained TNF receptor-associated factor (TRAF)-dependent innate immune responses invoked by IL-1β, TNF-α, and LPS/Toll-like receptor 4 (TLR4), but not TRIF-dependent poly(I:C)/TLR3. PRL ubiquitinated and accelerated poststimulatory decay of a "trafasome" comprised of IRAK1, TRAF6, and MAP3K proteins, abrogating downstream activation of c-Myc-interacting pathways, including PI3K/AKT, mTORC1, p38 MAPK, and NF-κB. Consistent with this finding, we documented exaggerated male liver responses to immune stimuli in mice and humans. Tumor promotion through, but regulation above, the level of c-Myc was demonstrated by sex-independent HCC eruption in Alb-Myc transgenic mice. PRL deficiency accelerated liver carcinogenesis in Prl(-/-) mice of both sexes. Conversely, pharmacologic PRL mobilization using the dopamine D2 receptor antagonist domperidone prevented HCC in tumor-prone C3H/HeN males. Viewed together, our results demonstrate that PRL constrains tumor-promoting liver inflammation by inhibiting MAP3K-dependent activation of c-Myc at the level of the trafasome. PRL-targeted therapy may hold promise for reducing the burden of liver cancer in high-risk men and women.

  10. Epidermal growth factor and Ras regulate gene expression in GH4 pituitary cells by separate, antagonistic signal transduction pathways.

    PubMed Central

    Pickett, C A; Gutierrez-Hartmann, A

    1995-01-01

    We have previously demonstrated that epidermal growth factor (EGF) produces activation of the rat prolactin (rPRL) promoter in GH4 neuroendocrine cells via a Ras-independent mechanism. This Ras independence of the EGF response appears to be cell rather than promoter specific. Oncogenic Ras also produces activation of the rPRL promoter when transfected into GH4 cells and requires the sequential activation of Raf kinase, mitogen-activated protein (MAP) kinase, and c-Ets-1/GHF-1 to mediate this response. In these studies, we have investigated the interaction between EGF and Ras in stimulating rPRL promoter activity and the role of Raf and MAP kinases in mediating the EGF response. We have also examined the role of several transcription factors and used various promoter mutants of the rPRL gene in order to better define the trans- and cis-acting components of the EGF response. EGF treatment of GH4 cells inhibits activation of the rPRL promoter produced by transfection of V12Ras from 24- to 4-fold in an EGF dose-dependent manner. This antagonistic effect of EGF and Ras is mutual in that transfection of V12Ras also blocks EGF-induced activation of the rPRL promoter in a Ras dose-dependent manner, from 5.5- to 1.6-fold. Transfection of a plasmid encoding the dominant-negative Raf C4 blocks Ras-induced activation by 66% but fails to inhibit EGF-mediated activation of the rPRL promoter. Similarly, transfection of a construct encoding an inhibitory form of MAP kinase decreases the Ras response by 50% but does not inhibit the EGF response. Previous studies have demonstrated that c-Ets-1 is necessary and that GHF-1 acts synergistically with c-Ets-1 in the Ras response of the rPRL promoter. In contrast, overexpression of neither c-Ets-1 nor GHF-1 enhanced EGF-mediated activation of the rPRL promoter, and dominant-negative forms of these transcription factors failed to inhibit the EGF response. Using 5' deletion and site-specific mutations, we have mapped the EGF response to two

  11. Role of prolactin in the regulation of sensitivity of the hypothalamic-pituitary system to steroid feedback.

    PubMed

    Bartke, A; Matt, K S; Steger, R W; Clayton, R N; Chandrashekar, V; Smith, M S

    1987-01-01

    During sexual maturation, pituitary gonadotropins stimulate the gonads to produce increasing amounts of biologically active steroids and yet gonadotropin release does not become suppressed until concentrations of sex hormones, LH and FSH, in peripheral circulation stabilizes at a higher adult level. There is a substantial amount of evidence that in many mammals, this transition from prepubertal to adult level of activity of the pituitary-gonadal axis is associated with a reduction in the sensitivity of the hypothalamic-adenohypophyseal system to negative feedback of gonadal steroids. In the female, these changes are accompanied by the appearance of positive estrogen feedback on gonadotropin release. In seasonal breeders, annual transitions between the periods of gonadal activity and quiescence are associated with corresponding shifts in the sensitivity to steroid feedback. Peripheral levels of pituitary prolactin (PRL) typically increase during sexual maturation and exhibit large seasonal fluctuations in response to changes in photoperiod and ambient temperature. We propose that PRL is one of the factors which regulate the sensitivity of gonadotropin release to gonadal steroid feedback. In hyperprolactinemic women, responsiveness to negative estrogen feedback increases, while LH response to positive estrogen feedback is reduced or absent. In hyperprolactinemic men, both LH and testosterone levels are reduced, implying increased sensitivity of LH release to negative testosterone feedback. In the male rat, both physiological amounts of PRL and experimentally-induced hyperprolactinemia increase the ability of exogenous testosterone to suppress LH and FSH release. Different regulatory mechanisms appear to operate in the seasonally breeding male golden hamster, in which short photoperiod causes concomitant suppression of PRL, LH, FSH and testosterone release. In this species, pharmacologic suppression of PRL release leads to increased responsiveness of plasma

  12. Exercise thermoregulation and hyperprolactinaemia.

    PubMed

    Low, David; Cable, Tim; Purvis, Alison

    The anterior pituitary hormone prolactin (PRL), measured in the peripheral blood circulation, reflects alterations in central brain 5-hydroxytryptamine (serotonin) and dopaminergic activity and is used as a marker of 'central fatigue' during active heat exposure. Significant correlations have consistently been found between PRL and core temperature (T(CORE)) during prolonged exercise. There has been no investigation into the relationship between PRL and other key thermoregulatory variables during exercise, such as weighted mean skin (T(SK)) and mean body temperature (T(B)), heat storage (HS), thermal gradient (T(GRAD)), heart rate (HR) and skin blood flow (cutaneous vascular conductance, CVC). Therefore, the aim of this study was to ascertain if a significant relationship exists between PRL and these thermoregulatory variables during prolonged exercise. Nine active male subjects conducted three trials of approximately 60% VO(2peak) at 70-80 rpm for 45 min on a semi-recumbent cycle ergometer at three different ambient temperatures [6 degrees C (Cold), 18 degrees C (Neutral) and 30 degrees C (Hot)] to elicit varying levels of thermoregulatory stress during exercise. Significant differences existed in T(SK), T(B), HS, T(GRAD) and CVC across the environmental conditions (p < 0.001). Core temperature (T(CORE)), HR and PRL were significantly elevated only in Hot (p < 0.05). Moderate correlations were found for T(CORE), T(SK), T(B), HS, T(GRAD), HR and CVC with post-exercise PRL (rho = 0.358-0.749). The end-of-exercise <38.0 degrees C T(CORE) responses were not (rho = -0.129, p > 0.05) but the >38.0 degrees C T(CORE) responses were (rho = 0.845, p < 0.001) significantly related to their corresponding PRL responses. The significant relationships between PRL release and T(SK), T(B), HS, T(GRAD), HR and CVC have extended previous research on T(CORE) and PRL release and indicate an association between these thermoregulatory variables, as well as T(CORE), and serotonergic

  13. 17β-Estradiol modulates the prolactin secretion induced by TRH through membrane estrogen receptors via PI3K/Akt in female rat anterior pituitary cell culture.

    PubMed

    Sosa, Liliana d V; Gutiérrez, Silvina; Petiti, Juan P; Palmeri, Claudia M; Mascanfroni, Iván D; Soaje, Marta; De Paul, Ana L; Torres, Alicia I

    2012-05-01

    Considering that estradiol is a major modulator of prolactin (PRL) secretion, the aim of the present study was to analyze the role of membrane estradiol receptor-α (mERα) in the regulatory effect of this hormone on the PRL secretion induced by thyrotropin-releasing hormone (TRH) by focusing on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway activation. Anterior pituitary cell cultures from female rats were treated with 17β-estradiol (E(2), 10 nM) and its membrane-impermeable conjugated estradiol (E(2)-BSA, 10 nM) alone or coincubated with TRH (10 nM) for 30 min, with PRL levels being determined by RIA. Although E(2), E(2)-BSA, TRH, and E(2)/TRH differentially increased the PRL secretion, the highest levels were achieved with E(2)-BSA/TRH. ICI-182,780 did not modify the TRH-induced PRL release but significantly inhibited the PRL secretion promoted by E(2) or E(2)-BSA alone or in coincubation with TRH. The PI3K inhibitors LY-294002 and wortmannin partially inhibited the PRL release induced by E(2)-BSA, TRH, and E(2)/TRH and totally inhibited the PRL levels stimulated by E(2)-BSA/TRH, suggesting that the mER mediated the cooperative effect of E(2) on TRH-induced PRL release through the PI3K pathway. Also, the involvement of this kinase was supported by the translocation of its regulatory subunit p85α from the cytoplasm to the plasma membrane in the lactotroph cells treated with E(2)-BSA and TRH alone or in coincubation. A significant increase of phosphorylated Akt was induced by E(2)-BSA/TRH. Finally, the changes of ERα expression in the plasmalemma of pituitary cells were examined by confocal microscopy and flow cytometry, which revealed that the mobilization of intracellular ERα to the plasma membrane of lactotroph cells was only induced by E(2). These finding showed that E(2) may act as a modulator of the secretory response of lactotrophs induced by TRH through mER, with the contribution by PI3K/Akt pathway activation providing a new

  14. Profiles of mRNA expression for prolactin, growth hormone, and somatolactin in Japanese eels, Anguilla japonica: The effect of salinity, silvering and seasonal change.

    PubMed

    Sudo, Ryusuke; Suetake, Hiroaki; Suzuki, Yuzuru; Aoyama, Jun; Tsukamoto, Katsumi

    2013-01-01

    For understanding the functions of the growth hormone (GH)/prolactin (PRL)/somatolactin (SL) family of hormones, we examined pituitary mRNA expression of these hormones in anguillid eels in relation to salinity difference, silvering, and seasonal change. Female Japanese eels (Anguilla japonica) were collected in the brackish Hamana Lake and its freshwater rivers from July to December. To clarify the effect of salinity, the habitat use history of the eels were determined using otolith microchemistry. Expression levels of mRNA of each hormone were determined using real time PCR. Although GH and PRL have been known to be osmoregulatory hormones, there were no consistent differences in expression levels of these hormones between different salinity habitats. In contrast, SL mRNA expression was higher in eels from freshwater rivers than from the brackish lake. GH mRNA expression clearly decreased during silvering, whereas PRL and SL mRNA expression did not change. We also showed that PRL mRNA and SL mRNA decreased in the brackish lake and PRL mRNA increased in freshwater rivers from autumn to early winter. These findings provide basic knowledge for a further understanding of the role of these hormones. PMID:23047050

  15. A Common Phenotype Polymorphism in Mammalian Brains Defined by Concomitant Production of Prolactin and Growth Hormone

    PubMed Central

    Daude, Nathalie; Lee, Inyoul; Kim, Taek-Kyun; Janus, Christopher; Glaves, John Paul; Gapeshina, Hristina; Yang, Jing; Sykes, Brian D.; Carlson, George A.; Hood, Leroy E.; Westaway, David

    2016-01-01

    Pituitary Prolactin (PRL) and Growth Hormone (GH) are separately controlled and sub-serve different purposes. Surprisingly, we demonstrate that extra-pituitary expression in the adult mammalian central nervous system (CNS) is coordinated at mRNA and protein levels. However this was not a uniform effect within populations, such that wide inter-individual variation was superimposed on coordinate PRL/GH expression. Up to 44% of individuals in healthy cohorts of mice and rats showed protein levels above the norm and coordinated expression of PRL and GH transcripts above baseline occurred in the amygdala, frontal lobe and hippocampus of 10% of human subjects. High levels of PRL and GH present in post mortem tissue were often presaged by altered responses in fear conditioning and stress induced hyperthermia behavioral tests. Our data define a common phenotype polymorphism in healthy mammalian brains, and, given the pleiotropic effects known for circulating PRL and GH, further consequences of coordinated CNS over-expression may await discovery. PMID:26894278

  16. Role of luteinizing hormone in luteotropic complex of pregnant hamster

    SciTech Connect

    Tamura, H.; Greenwald, G.S.

    1987-04-01

    Hamsters were hypophysectomized on day 4 of pregnancy and injected subcutaneously on days 4-7 with various combinations of 200 ..mu..g prolactin (Prl), 10 ..mu..g follicle-stimulating hormone (FSH), and 20 ..mu..g luteinizing hormone (LH) in polyvinylpyrrolidone (PVP) to decrease its rate of absorption or in saline. End points for luteal function on day 8 were maintenance of pregnancy, serum progesterone (P/sub 4/), luteal weight, and luteal binding for human chorionic gonadotropin, FSH, and Prl. After hypophysectomy, a drastic decline occurred in all parameters including an 89% decrease in luteal weight. Injection of Prl did not maintain pregnancy nor serum P/sub 4/ but partially maintained luteal weight and human chorionic gonadotropin binding sites per corpus luteum. The minimal luteotropic complex of Prl and FSH was effective in maintaining pregnancy and significantly increased serum P/sub 4/ and Prl and FSH receptors but not to control levels. Thus, the luteotropic activity of LH was only demonstrable when it was injected in a long-acting form; when delivered as a bolus, LH (saline) was luteolytic. P/sub 4/ and estradiol were measured by radioimmunoassay. Radioiodinated gonadotropins were prepared. The percentage of tracer reacting with an excess of receptor were 51% of /sup 125/I-FSH and 45.9% of /sup 125/I-hCG using whole homogenates of hamster ovaries.

  17. The role of germline AIP, MEN1, PRKAR1A, CDKN1B and CDKN2C mutations in causing pituitary adenomas in a large cohort of children, adolescents, and patients with genetic syndromes.

    PubMed

    Stratakis, C A; Tichomirowa, M A; Boikos, S; Azevedo, M F; Lodish, M; Martari, M; Verma, S; Daly, A F; Raygada, M; Keil, M F; Papademetriou, J; Drori-Herishanu, L; Horvath, A; Tsang, K M; Nesterova, M; Franklin, S; Vanbellinghen, J-F; Bours, V; Salvatori, R; Beckers, A

    2010-11-01

    The prevalence of germline mutations in MEN1, AIP, PRKAR1A, CDKN1B and CDKN2CI is unknown among pediatric patients with pituitary adenomas (PA). In this study, we screened children with PA for mutations in these genes; somatic GNAS mutations were also studied in a limited number of growth hormone (GH) or prolactin (PRL)-secreting PA. We studied 74 and 6 patients with either isolated Cushing disease (CD) or GH- or PRL-secreting PA, respectively. We also screened four pediatric patients with CD, and four with GH/PRL-secreting tumors who had some syndromic features. There was one AIP mutation (p.Lys103Arg) among 74 CD patients. Two MEN1 mutations that occurred in patients with recurrent or difficult-to-treat disease were found among patients with CD. There was one MEN1 and three AIP mutations (p.Gln307ProfsX104, p.Pro114fsX, p.Lys241X) among pediatric patients with isolated GH- or PRL-secreting PA and one additional MEN1 mutation in a patient with positive family history. There were no mutations in the PRKAR1A, CDKN1B, CDKN2C or GNAS genes. Thus, germline AIP or MEN1 gene mutations are frequent among pediatric patients with GH- or PRL-secreting PA but are significantly rarer in pediatric CD; PRKAR1A mutations are not present in PA outside of Carney complex. PMID:20507346

  18. Changes in LH and prolactin levels in diabetic male rats and the role of the opiate system in the control of their secretion.

    PubMed

    Yogev, L; Gottriech, A; Timan, B; Homonnai, Z T; Paz, G F

    1985-09-16

    Diabetic male rat has low serum levels of luteinizing hormone (LH) and testosterone (T), which are accompanied by atrophy of the testes and accessory glands. The present study investigated changes in the serum levels of LH, prolactin (PRL) and glucose, following diabetes induction by streptozotocin. In addition, involvement of the opiate system in the control of LH and PRL secretion was evaluated. There was no difference in PRL levels between diabetic and control animals, except at 8 hours after streptozotocin injection. In contrast, the diabetic animals had consistently lower levels of LH, starting on the second day of diabetes. Blockade of the opiate system by naltrexone caused a sharp increase of LH levels in normoglycemic rats, while only a gradual decrease was observed in hyperglycemic animals. PRL secretion was inhibited by naltrexone, both in diabetic and control groups. It is concluded that, unlike normoglycemic rats, inhibition of LH secretion in diabetes is not under the control of the opiate system, probably as a result of T deficiency. In contrast, PRL secretion in diabetic rats, as in the control group, is under the influence of endogenous opiates. PMID:4033351

  19. Evolutionary aspects of growth hormones and prolactins and their receptors

    SciTech Connect

    Tarpey, J.F.

    1986-01-01

    The interactions of GH's, PRL's and PL's with receptors for GH and PRL were examined from a comparative and evolutionary viewpoint. The binding of /sup 125/I-bGH to membrane preparations from liver of representatives of the major classes of non-mammalian vertebrates was also studied. Only hepatic membranes from sturgeon and Gillichthys had significant bGH binding and were further characterized and compared with male rabbit liver membranes in terms of time, temperature, pH, and membrane concentration to optimize binding conditions. The binding of several members of the GH, PRL, PL family of hormones to GH receptors from liver of sturgeon, Gillichthys, rabbit, mouse and rat was investigated. in terms of hormonal specificity, the mammalian receptors and the sturgeon binding sites were similar, while Gillichthys receptors had a different pattern of hormonal specificity. The binding of /sup 125/I-oPRL to renal membranes of the turtle, Pseudemys scripta elegans, was characterized and compared to PRL binding sites of kidney membranes of the bullfrog, Rana catesbeiana, and the tiger salamander, Ambystoma tigrinum.

  20. Incompatibility of FRC `Self--Colliding Beams' with Classical Large Orbit Theory and Experiment

    NASA Astrophysics Data System (ADS)

    Maglich, Bogdan

    2012-03-01

    Rosenbluth^1: ``One key physics issue is the behavior of very large gyro radius systems, for which the usual thermal physics is inadequate.''- Rostoker^2 posited (1) 0.42 KeV d^+ FRC can achieve confinement^ τ =30 s observed^3 in self-colliding orbits (SCO) of 725 KeV d^+,^ stabilized by magnet focusing^4 and electrons^5 ; (2) FRC result ^6τ=2 x10-3 s is ``record long lived plasma state for advanced, aneutronic fuels ''; (3) non-intersecting collision-less orbits produce nuclear reactions. (i) Bz(r) of FRC is defocusing, field index n>0. From single particle orbit theory^7,8 destructive instability must occur with τ^ <= 10-3 s. (ii) τ cannot be scaled up by ion energy increase. (iii) Luminosity in SCO^3: L˜10^31s-1 cm-2; in co-revolving FRC orbits: L=0 unless 2 species in same orbit, which requires v2/v1= z1m1/z2m2 and Nτ ˜ 10^17 by Lawson^ 9-11. See http://www.aneutronicfusion.org 1. NIM271, p.1 (88); 2. PRL 70, 1818 (93); 3.PRL 54, 796 (1985); 4.PRL 29, 1590 (72); 5.PRL 70, 299 (93); 6.PRL 105, 045003-1,(10); 7.Part. Acc.1, (70); 8. AIP CP 311, 292 (93); 9. J.App.Phys.46, 2915 (75); 10. NIM A346 322 (93); 11.NIM 144, 65 (77)

  1. Site-specific methylation of the rat prolactin and growth hormone promoters correlates with gene expression.

    PubMed Central

    Ngô, V; Gourdji, D; Laverrière, J N

    1996-01-01

    The methylation patterns of the rat prolactin (rPRL) (positions -440 to -20) and growth hormone (rGH) (positions -360 to -110) promoters were analyzed by bisulfite genomic sequencing. Two normal tissues, the anterior pituitary and the liver, and three rat pituitary GH3 cell lines that differ considerably in their abilities to express both genes were tested. High levels of rPRL gene expression were correlated with hypomethylation of the CpG dinucleotides located at positions -277 and -97, near or within positive cis-acting regulatory elements. For the nine CpG sites analyzed in the rGH promoter, an overall hypomethylation-expression coupling was also observed for the anterior pituitary, the liver, and two of the cell lines. The effect of DNA methylation was tested by measuring the transient expression of the chloramphenicol acetyltransferase reporter gene driven by a regionally methylated rPRL promoter. CpG methylation resulted in a decrease in the activity of the rPRL promoter which was proportional to the number of modified CpG sites. The extent of the inhibition was also found to be dependent on the position of methylated sites. Taken together, these data suggest that site-specific methylation may modulate the action of transcription factors that dictate the tissue-specific expression of the rPRL and rGH genes in vivo. PMID:8668139

  2. Hepatic prolactin binding is rapidly altered by endotoxin in lactating mice

    SciTech Connect

    Carr, J.K.; Keefer, L.M.; Cohen, J.C.

    1987-09-21

    Endotoxin or lipopolysaccharide (LPS), a component of the outer membrane of gram-negative bacteria, produces profound physiologic changes in most mammals. The effects of LPS on ovine prolactin (oPRL) binding by hepatic membranes of lactating mice is explored in this report. Specific /sup 125/I-oPRL binding by liver membranes from LPS-responder C3HfB/HeN mice increased two-fold within fifteen minutes of the injection of LPS, while no change was observed in the non-responder C3H/HeJ mice. Specific /sup 125/I-insulin binding did not change. Scatchard analysis of equilibrium binding of oPRL to C3HfB/HeN liver membranes indicated that within fifteen minutes of LPS injection, a receptor of differing binding affinity appears and then disappears by one hour post-injection. The authors propose that these rapid alterations in the specific binding of oPRL by liver membranes from LPS-injected, lactating C3HfB/HeN mice are due to the transient creation or unmasking of a novel class of PRL receptor. 32 references, 6 figures.

  3. Adaptive changes in the transcription factor HoxA-11 are essential for the evolution of pregnancy in mammals.

    PubMed

    Lynch, Vincent J; Tanzer, Andrea; Wang, Yajun; Leung, Frederick C; Gellersen, Birgit; Emera, Deena; Wagner, Gunter P

    2008-09-30

    Evolutionary change in gene regulation can result from changes in cis-regulatory elements, leading to differences in the temporal and spatial expression of genes or in the coding region of transcription factors leading to novel functions or both. Although there is a growing body of evidence supporting the importance of cis-regulatory evolution, examples of protein-mediated evolution of novel developmental pathways have not been demonstrated. Here, we investigate the evolution of prolactin (PRL) expression in endometrial cells, which is essential for placentation/pregnancy in eutherian mammals and is a direct regulatory target of the transcription factor HoxA-11. Here, we show that (i) endometrial PRL expression is a derived feature of placental mammals, (ii) the PRL regulatory gene HoxA-11 experienced a period of strong positive selection in the stem-lineage of eutherian mammals, and (iii) only HoxA-11 proteins from placental mammals, including the reconstructed ancestral eutherian gene, are able to up-regulate PRL from the promoter used in endometrial cells. In contrast, HoxA-11 from the reconstructed therian ancestor, opossum, platypus, and chicken are unable to up-regulate PRL expression. These results demonstrate that the evolution of novel gene expression domains is not only mediated by the evolution of cis-regulatory elements but can also require evolutionary changes of transcription factor proteins themselves. PMID:18809929

  4. Short prolactin profile for monitoring treatment in BH4 deficiency.

    PubMed

    Porta, Francesco; Ponzone, Alberto; Spada, Marco

    2015-05-01

    Tetrahydrobiopterin (BH4) deficiency causes hyperphenylalaninemia and impaired synthesis of serotonin and dopamine, leading to brain degeneration and early death if left untreated. Replacement therapy with neurotransmitters precursors is the cornerstone of treatment, relying on 5-hydroxytryptophan and L-dopa administration. Effective restoration of dopaminergic activity is thickened, like in Parkinson's disease, by the pulsatile pharmacokinetic profile of L-dopa. Monitoring of L-dopa therapy in BH4 deficiency is generally based upon clinical observation and periodical measurement of homovanillic acid (HVA) concentration in the cerebrospinal fluid (CSF). According to the finding that dopamine is the natural inhibitor of prolactin (PRL) incretion, we introduced the use of peripheral PRL measurement as an index of dopaminergic homeostasis, so avoiding the need of repeated lumbar punctures in patients with BH4 deficiency. As a single PRL evaluation can be misleading, due to the dependency of PRL fluctuations on L-dopa administration schedule, here we show that a short PRL profile is suitable for monitoring these patients. Together with the assessment of patients' clinical symptoms, this standardized tool will ensure an objective non-invasive reference to the management of dopaminergic replacement therapy in BH4 deficiency, even in patients treated with dopamine agonists.

  5. Hormonal profile and reproductive performance in lactation deficient (OFA hr/hr) and normal (Sprague-Dawley) female rats.

    PubMed

    Valdez, Susana R; Penissi, Alicia B; Deis, Ricardo P; Jahn, Graciela A

    2007-04-01

    Lactation deficiency may have important consequences on infant health, particularly in populations of low socioeconomic status. The OFA hr/hr (OFA) strain of rats, derived from Sprague-Dawley (SD) rats, has deficient lactation and is a good model of lactation failure. We examined the reproductive performance and hormonal profiles in OFA and SD strains to determine the cause(s) of the lactation failure of the OFA strain. We measured hormonal (PRL, GH, gonadotropins, oxytocin, and progesterone) levels by RIA in cycling, pregnant, and lactating rats and in response to suckling. Dopaminergic metabolism was assessed by determination of mediobasal hypothalamic dopamine and dihydroxyphenylacetic acid (DOPAC) concentrations by HPLC and tyrosine hydroxylase expression by immunocytochemistry and western blot. OFA rats have normal fertility but 50% of the litters die of malnutrition on early lactation; only 6% of the mothers show normal lactation. The OFA rats showed lower circulating PRL during lactation, increased hypothalamic dopamine and DOPAC, and impaired milk ejection with decreased PRL and oxytocin response to suckling. Before parturition, PRL release and lactogenesis were normal, but dopaminergic metabolism was altered, suggesting activation of the dopaminergic system in OFA but not in SD rats. The number of arcuate and periventricular neurons expressing tyrosine hydroxylase was higher in SD rats, but hypothalamic expression of TH was higher in OFA rats at the end of pregnancy and early lactation. These results suggest that the OFA rats have impaired PRL release linked with an augmented dopaminergic tone which could be partially responsible for the lactational failure.

  6. Immunocytochemical light- and electron-microscopic studies of growth hormone, prolactin and somatomammotroph cells in female goat.

    PubMed

    Vásquez, F; Gómez, M A; Serrano, J; Bernabé, A

    2002-01-01

    We have studied the structural and ultrastructural changes that occur in growth hormone (GH), prolactin (PRL) and somatomammotroph (SMT) cells of female goats of the Murciano-Granadina breed during different physiological stages: prepuberty, anestrus, pregnancy and lactation. Serial sections were stained with double immunolabeling, alkaline phosphatase and avidin-biotin complex for light microscopy, and immunogold labeling was used for electron microscopy. These techniques allowed the identification of GH, PRL and SMT cells, which were evenly distributed throughout the whole pars distalis. PRL cells were the most frequent. Both PRL and GH cells showed morphological changes that may be related to a given physiological stage. These changes include the number of cells and the number and size of the secretory granules. SMT cells were clearly identified by having two types of monohormonal secretory granule showing single labeling, in spite of their similar ultrastructural characteristics to the other adenohypophysary cells. They are found in low percentages (0.6%). We postulate that cell aggregates which look like SMT syncytia may be artifacts caused by interdigitation of PRL and GH cells, and that cells which are normally taken to be SMT cells are not an interconversion stage between monohormonal cells.

  7. A Common Phenotype Polymorphism in Mammalian Brains Defined by Concomitant Production of Prolactin and Growth Hormone.

    PubMed

    Daude, Nathalie; Lee, Inyoul; Kim, Taek-Kyun; Janus, Christopher; Glaves, John Paul; Gapeshina, Hristina; Yang, Jing; Sykes, Brian D; Carlson, George A; Hood, Leroy E; Westaway, David

    2016-01-01

    Pituitary Prolactin (PRL) and Growth Hormone (GH) are separately controlled and sub-serve different purposes. Surprisingly, we demonstrate that extra-pituitary expression in the adult mammalian central nervous system (CNS) is coordinated at mRNA and protein levels. However this was not a uniform effect within populations, such that wide inter-individual variation was superimposed on coordinate PRL/GH expression. Up to 44% of individuals in healthy cohorts of mice and rats showed protein levels above the norm and coordinated expression of PRL and GH transcripts above baseline occurred in the amygdala, frontal lobe and hippocampus of 10% of human subjects. High levels of PRL and GH present in post mortem tissue were often presaged by altered responses in fear conditioning and stress induced hyperthermia behavioral tests. Our data define a common phenotype polymorphism in healthy mammalian brains, and, given the pleiotropic effects known for circulating PRL and GH, further consequences of coordinated CNS over-expression may await discovery.

  8. Plasma cortisol and prolactin secretion rhythms in cattle under varying external environments and management techniques.

    PubMed

    Ogino, Mizuna; Matsuura, Akihiro; Yamazaki, Atusi; Irimajiri, Mami; Suzuki, Yoshihiro; Kushibiki, Shiro; Singu, Hroyuki; Kasuya, Etsuko; Hasegawa, Yoshihisa; Hodate, Koichi

    2014-01-01

    The secretion rhythms of plasma cortisol (CORT) and prolactin (PRL), hormones related to stress responsiveness and biological rhythm and controlled by light and temperature, were investigated under varying external environments and different management techniques. Serial blood samples were collected from female cattle reared in free-stall and freely fed (FF) conditions (n = 4) or in tie-stall and restricted feeding (RF) conditions (hay and concentrate twice daily, n = 4). Plasma CORT and PRL concentrations, eating behavior, and environmental parameters were analyzed. Cyclic patterns for each parameter were examined using spectral analysis, and correlations between CORT, PRL and other parameters were investigated using cross-spectral analysis. Under FF conditions, CORT secretion was not related to the lighting intensity and eating behavior. However, under RF conditions, the CORT secretion rhythm showed a distinct correlation with lighting intensity and eating behavior. Under FF conditions, the PRL secretion rhythm was similar in all seasons. However, under RF conditions, the PRL rhythm oscillated with high frequency in summer and low frequency in winter, indicating a seasonal change in rhythm. The present study demonstrates that hormone secretion rhythms change under different environments and management techniques.

  9. Modulation of the epithelial barrier by dexamethasone and prolactin in cultured Madin-Darby canine kidney (MDCK) cells.

    PubMed

    Peixoto, E B M I; Collares-Buzato, C B

    2006-02-01

    Glucocorticoids and prolactin (PRL) have a direct effect on the formation and maintenance of tight junctions (TJs) in cultured endothelial and mammary gland epithelial cells. In this work, we investigated the effect of a synthetic glucocorticoid dexamethasone (DEX) and PRL on the paracellular barrier function in MDCK renal epithelial cells. DEX (4 microM)+PRL (2 microg/ml) and DEX alone increased significantly the transepithelial electrical resistance after chronic treatment (4 days) of confluent MDCK monolayers or after 24 h treatment of subconfluent monolayers. Immunoblotting and immunocytochemistry revealed no changes in the expression and distribution of TJ-associated proteins occludin, ZO-1 and claudin-1 in confluent monolayers after hormone addition. However, a marked increase in junctional content for occludin and ZO-1 with no changes in their total expression was observed in subconfluent MDCK monolayers 24 h exposed to DEX or DEX+PRL. No change in cell proliferation/growth was detected at subconfluent conditions following hormone treatment. An increase in the total number of viable cells was observed only in confluent MDCK monolayers after exposure to DEX+PRL suggesting that the main effect of these hormones on already established barrier may be associated with the inhibition of cell death. In conclusion, our data suggest that these hormones (specially dexamethasone) have an effect on TJ structure and function only during the formation of MDCK epithelial barrier by probably modulating the localization, stability or assembly of TJ proteins to membrane sites of intercellular contact.

  10. An Atypical Acidophil Cell Line Tumor Showing Focal Differentiation Toward Both Growth Hormone and Prolactin Cells.

    PubMed

    Naritaka, Heiji; Kameya, Toru; Sato, Yuichi; Furuhata, Shigeru; Okui, Junichi; Kamiguchi, Yuji; Otani, Mitsuhiro; Toya, Shigeo

    1995-01-01

    We report a case of giant pituitary adenoma in a child. Computerized tomography (CT) scan revealed a suprasellar extension tumor mass with hydrocephalus. There was no clinical evidence of acromegaly, gigantism, and other hormonal symptoms. Endocrinologic studies showed within normal value of serum growth hormone (GH: 4.2 ng/mL) and slightly increased levels of prolactin (PRL: 78 ng/mL) and other pituitary hormone values were within normal range. On suppression test by bromocryptin, both GH and PRL levels were reduced. Histopathological findings revealed that the tumor consisted of predominantly chromophobic and partly eosinophilic adenoma cells. Immunohistochemical staining detected GH and PRL in a small number of distinctly different adenoma cells, respectively. Nonradioactive in situ hybridization (ISH) also showed GH and PRL mRNA expression in identical immunopositive cells. Electron microscopy (EM) demonstrated adenoma cells with moderate or small numbers of two types of dense granules and without fibrous body which are characteristic of sparsely granulated GH-cell adenomas. The adenoma does not fit into any classification but may be an atypical acidophil cell line tumor showing focal differentiation toward both GH and PRL cells. PMID:12114745

  11. Prolactin-releasing peptide is a potent mediator of the innate immune response in leukocytes from Salmo salar.

    PubMed

    Romero, Alex; Manríquez, René; Alvarez, Claudio; Gajardo, Cristina; Vásquez, Jorge; Kausel, Gudrun; Monrás, Mónica; Olavarría, Víctor H; Yáñez, Alejandro; Enríquez, Ricardo; Figueroa, Jaime

    2012-06-30

    Prolactin (PRL)-releasing peptide (PrRP) is a strong candidate stimulator of pituitary PRL transcription and secretion in teleosts. However, the role in control of extrapituitary PRL expression or its effects on innate immunity are unclear even in mammals. To study the possible presence of PrRP in peripheral organs, PrRP expression patterns and their effect on innate immunity were characterised in SHK-1 cells and head kidney (HK) leukocytes purified from the salmonid, Salmo salar. We detected immunoreactive cells in leukocytes from blood and HK of S. salar and found that PrRP mRNA was abundantly expressed in these cells. We have recently reported that physiological concentrations of native PRL, downstream of neuropeptide PrRP were able to induce expression of pro-inflammatory cytokines and the production of reactive oxygen species (ROS) in HK leukocytes and macrophages from S. salar and Sparus aurata. It is of interest to note that in this work we have revealed that synthetic PrRP was able to induce expression of pro-inflammatory cytokines (interleukins) IL-1β, IL-6, IL-8, IL-12 and PRL. We also show here that PrRP increased both (ROS) production and phagocytosis. Taken together, our results demonstrate for the first time that PrRP may be a local modulator of innate immune responses in leukocytes from S. salar.

  12. Hypothalamic pituitary adrenal axis and prolactin abnormalities in suicidal behavior.

    PubMed

    Pompili, Maurizio; Serafini, Gianluca; Palermo, Mario; Seretti, Maria Elena; Stefani, Henry; Angeletti, Gloria; Lester, David; Amore, Mario; Girardi, Paolo

    2013-11-01

    Hypothalamic-Pituitary-Adrenal (HPA) axis hyperactivity measured with the dexamethasone suppression test and the dexamethesone/CRH test may have some predictive power for suicidal behavior in patients with mood disorders. Increased prolactin (PRL) levels may be related both to physiological and pathological conditions. HPA-axis abnormalities and increased levels of PRL may coexist, and common neuroendocrine changes may activate both HPA axis and PRL release. HPA-axis hyperactivity is presumably present in a large subpopulation of depressed subjects. Suicidal behavior is considered to be a form of inward-directed aggression, and aggressive behavior has been connected to high androgen levels. However, lower plasma total testosterone levels have also been reported in subjects with depression and higher suicidality. Lipid/immune dysregulations, the increased ratio of blood fatty acids, and increased PRL levels may each be associated with the increased production of pro-inflammatory cytokines, which have been reported in patients with major depression and patients engaging in suicidal behavior. Although no studies have been done to determine whether ante-mortem physical stress may be detected by raised post-mortem PRL, this would be of great interest for physicians.

  13. Moderate hyperprolactinemia is associated with survival in patients with acute graft-versus-host disease after allogeneic stem cell transplantation.

    PubMed

    Parra, Adalberto; Ramírez-Peredo, Jorge; Reyes, Enrique; Hidalgo, Rocío; Macías-Gallardo, Julio; Lutz-Presno, Julia; Ruiz-Argüelles, Alejandro; Garza, Eduardo; Infante, Eduardo; Gutiérrez-Aguirre, César H; Salazar-Riojas, Rosario; Villarreal, Jesús Z; Gómez-Almaguer, David; Ruiz-Argüelles, Guillermo J

    2012-03-01

    Fasting serum prolactin (PRL) levels in response to metoclopramide (MCP) and lymphocyte cytokine profiles was studied in patients given allografts and their donors. Thirty normoprolactinemic volunteers (12-59 years) were studied: group 1, 10 healthy men; group 2, 8 males and 2 females with various hematologic diseases; and group 3, 3 males and 7 females HLA-identical sibling donors: PRL and cytokines were measured. Four surviving recipients developed acute graft-versus-host disease (GVHD) (+), and six did not. Before transplant Fasting PRL concentrations were higher in 'future' GVHD(+) recipients than in their donors (P < 0.001). The opposite was seen in response to MCP (P = 0.01). Donors had a predominant T-helper type 1 (Th1) cytokine profile compared with recipients (P ≤ 0.02), and GVHD(+) recipients had a greater tumor necrosis factor (TNF) value than GVHD(-) (P = 0.05). After transplant On days +30 and +100, a mild sustained rise in fasting PRL levels occurred only in GVHD(+) recipients (P ≤ 0.05) simultaneously with a transient rise in Th1 cytokines. GVHD(-) recipients had no changes. Donors with a Th1 cytokine profile might be more prone to induce GVHD in their recipients, and a mild sustained rise in PRL concentrations after transplantation in recipients GVHD(+) might participate in the amelioration of the severity of GVHD.

  14. [Effect of bromocriptine on the endocrine profile during pregnancy].

    PubMed

    Kubota, T; Yaoi, Y; Suzuki, A; Nishi, N; Saito, M; Kumasaka, T

    1982-10-01

    In this paper, we revealed the changes in maternal plasma concentration of PRL, HCG, HPL, progesterone (P), estradiol-17 beta (E2), estriol (E3), estetrol (E4) and dehydroepiandrosterone-sulfate (DHEA-S) after the administration of bromocriptine during pregnancy. Blood samples were collected from 23 women with gestation ranging from 7 to 28 weeks. Sixteen patients had therapeutic abortion and other 7 patients had inevitable abortion. PRL, HCG, HPL, P, E2, E3, E4 and DHEA-S were measured by radioimmunoassay. The PRL decreased significantly at 120 and 180 minutes after the administration of bromocriptine in any case. In 4 cases out of 10 cases in early normal pregnancy, plasma E2 level decreased to 50% lower than the basal level, but no significant change of E2 occurred after bromocriptine in early and mid pregnancy. Bromocriptine made no change in HCG, HPL, P, E3, E4 and DHEA-S for any group. Our data suggested that bromocriptine had effect on only plasma PRL level, and this drug or the change of PRL level had no effect on P, estrogen, DHEA-S, HPL and HCG concentration during pregnancy. PMID:7175275

  15. A Histopathological Study of Multi-hormone Producing Proliferative Lesions in Estrogen-induced Rat Pituitary Prolactinoma

    PubMed Central

    Takekoshi, Susumu; Yasui, Yuzo; Inomoto, Chie; Kitatani, Kanae; Nakamura, Naoya; Osamura, Robert Yoshiyuki

    2014-01-01

    Rats with estrogen-induced prolactin-producing pituitary adenoma (E2-PRLoma) have been employed as an animal model of human PRL-producing pituitary adenoma in a large number of studies. Presently, we found that long-term administration of estrogen to SD rats resulted in the development of E2-PRLomas, some of which included multi-hormone producing nodules. We herein report results of histopathological analyses of these lesions. PRLoma models were created in female SD rats by 22 weeks or longer administration of a controlled-release preparation of estradiol at a dose of 10 mg/kg/2 weeks. Ten of the 11 PRLoma model rats had proliferative nodular lesions composed of large eosinophilic cells like gonadotrophs inside the PRLoma. These lesions were positive for PRL, TSHβ, and α subunits and were negative for GH, LHβ, ACTH, and S-100. Double immunostaining revealed that these large eosinophilic cells showed coexpression of PRL and TSHβ, PRL and α subunits, and TSHβ and α subunits. Those results clarified that long-term estrogen administration to female SD rats induced multi-hormone producing neoplastic pituitary nodules that expressed PRL, TSHβ, and α subunits. We studied these neoplastic nodules obtained by laser microdissection to acquire findings similar to those of the immuno­histochemical analysis. We consider that this animal model is useful for pathogenesis analyses and therapeutic agent development concerning human multi-hormone producing pituitary adenomas. PMID:25392569

  16. Circulating LH, FSH, prolactin, testosterone, delta 4-androstenedione, dehydroepiandrosterone sulfate and cortisol levels in the fetus in late gestation and in newborn male and female lambs.

    PubMed

    Savoie, S; Bourel, B; Hamel, R; Buithieu, M; Jéquier, J C; Bertrand, J; Saez, J M; Collu, R; Ducharme, J R

    1981-01-01

    Gonadotropins, prolactin (PRL), testosterone (T), delta 4-androstenedione, dehydroepiandrosterone sulfate and cortisol (F) levels were determined from 14 days before birth to term in 3 female and 3 male ovine fetuses with a chronically implanted venous catheter, and in the same animals from birth to 72 h of age. In both sexes, plasma gonadotropins and androgens were low throughout the period of study while plasma F increased with gestational age. After birth, plasma gonadotropins and PRL tended to increase progressively with time while PRL concentrations were significantly higher in female than in male lambs. F and T concentrations decreased significantly within the first 12 and 6 h of postnatal life. Higher T values were again observed at 36 h in male lambs. These data indicate that the fetal hypothalamic-pituitary-gonadal axis is relatively quiescent in the last 14 days of gestation but is activated within the first 72 h after birth.

  17. Effects of sulpiride induced hyperprolactinaemia in patients with Turner's syndrome.

    PubMed

    Loli, P; Riolo, A; Bonomo, M; Ronzoni, M; Botalla, L; Gelli, D

    1980-07-01

    In order to evaluate the interference of prolactin (PRL) on some aspects of pituitary-gonadal derangement observed in patients with hyperprolactinaemic amenorrhoea (HA), a GnRH stimulation test (100 micrograms i.v.) was performed on twenty-one patients with hyperprolactinaemia without evidence of pituitary tumour and in nine subjects with Turner's syndrome (TS) before and after sulpiride administration (200 mg/day orally, for 3 months). In patients with HA an enhanced response of gonadotrophins to GnRH was observed. In patients with TS a further increase of the gonadotrophin hyper-responsiveness to the releasing hormone occurred when hyperprolactinaemia was induced by chronic sulpiride administration. Since, in these patients, appreciable ovarian steroidogenesis is lacking, a direct effect of the increased plasma PRL at the hypothalamo-pituitary level is likely. In hyperprolactinaemic amenorrhoea pituitary hyper-responsiveness may not be due to PRL effects on ovarian steroidogenesis.

  18. Plasma prolactin concentrations in lead exposed workers.

    PubMed

    Govoni, S; Battaini, F; Fernicola, C; Castelletti, L; Trabucchi, M

    1987-01-01

    Plasma Prolactin (Prl) Zinc protoporphyrin (Zpp) and blood lead concentrations (PbB) were measured in 76 exposed male workers. All of them were employed in small (not more than 30 persons) pewter factories and were randomly selected from those regularly controlled by the National Health Service, Occupational Health Unit of Brescia (USSL 41). Although all plasma Prl values were within the normal range, the mean value of the subgroup having Zpp and PbB higher than 40 micrograms/dl was significantly higher (+47%) than that observed in the group of workers having Zpp and PbB less than 40 micrograms/dl. The data indicate the possibility of a lead-induced Prl secretion dysfunction, probably mediated by a decrease in dopaminergic inhibitory control.

  19. Plasma prolactin concentrations in lead exposed workers.

    PubMed

    Govoni, S; Battaini, F; Fernicola, C; Castelletti, L; Trabucchi, M

    1987-01-01

    Plasma Prolactin (Prl) Zinc protoporphyrin (Zpp) and blood lead concentrations (PbB) were measured in 76 exposed male workers. All of them were employed in small (not more than 30 persons) pewter factories and were randomly selected from those regularly controlled by the National Health Service, Occupational Health Unit of Brescia (USSL 41). Although all plasma Prl values were within the normal range, the mean value of the subgroup having Zpp and PbB higher than 40 micrograms/dl was significantly higher (+47%) than that observed in the group of workers having Zpp and PbB less than 40 micrograms/dl. The data indicate the possibility of a lead-induced Prl secretion dysfunction, probably mediated by a decrease in dopaminergic inhibitory control. PMID:3598878

  20. Up‐modulation of interferon‐γ mediates the enhancement of spontanous cytotoxicity in prolactin‐activated natural killer cells

    PubMed Central

    Matera, L; Contarini, M; Bellone, G; Forno, B; Biglino, A

    1999-01-01

    Prolactin (PRL) has been shown to participate in lymphocyte activation. In particular, the constitutive natural killer (NK) and the lymphokine‐activated killer (LAK) cytotoxicity of CD56+ CD16+ cells is increased by its physiological to supraphysiological concentrations. As PRL has been shown to up‐regulate the production of interferon‐γ (IFN‐γ) by peripheral blood mononuclear cells, we studied its effect on IFN‐γ production by NK cells as a possible mechanism of autocrine activation of cytotoxicity. Released and intracellular IFN‐γ, as well as IFN‐γ mRNA expression, were increased by pituitary and recombinant human PRL, which stimulated optimal NK and LAK cytotoxicity. Treatment with blocking anti‐IFN‐γ monoclonal antibody (mAb) selectively affected PRL‐increased killing of K562 targets, demonstrating that PRL‐mediated enhancement of spontaneous cytotoxicity depends, at least in part, on up‐regulation of IFN‐γ. PMID:10583598

  1. Transformation of a Microprolactinoma into a Mixed Growth Hormone and Prolactin-Secreting Pituitary Adenoma

    PubMed Central

    Dessimoz, Cédric; Browaeys, Patrick; Maeder, Philippe; Lhermitte, Benoît; Pitteloud, Nelly; Momjian, Shahan; Pralong, François P.

    2012-01-01

    Combined prolactin (PRL) and growth hormone (GH) secretion by a single pituitary tumor can occur in approximately 5% of cases. However, in all previously reported patients, combined secretion of both hormones was present at the time of diagnosis. Here we describe a patient initially diagnosed with a pure prolactin-secreting microadenoma, who experienced the progressive apparition of symptomatic autonomous GH secretion while on intermittent long term dopamine agonist therapy. She was operated on, and immunohistochemical analysis of tumor tissue confirmed the diagnosis of pituitary adenoma with uniform co-staining of all cells for both GH and PRL. This patient represents the first documented occurrence of asynchronous development of combined GH and PRL secretion in a pituitary adenoma. Although pathogenic mechanisms implicated remain largely speculative, it emphasizes the need for long term hormonal follow up of patients harboring prolactinomas. PMID:22654846

  2. Modeling Island-Growth Capture Zone Distributions (CZD) with the Generalized Wigner Distribution (GWD): New Developments in Theory and Experiment

    NASA Astrophysics Data System (ADS)

    Pimpinelli, Alberto; Einstein, T. L.; González, Diego Luis; Sathiyanarayanan, Rajesh; Hamouda, Ajmi Bh.

    2011-03-01

    Earlier we showed [PRL 99, 226102 (2007)] that the CZD in growth could be well described by P (s) = asβ exp (-bs2) , where s is the CZ area divided by its average value. Painstaking simulations by Amar's [PRE 79, 011602 (2009)] and Evans's [PRL 104, 149601 (2010)] groups showed inadequacies in our mean field Fokker-Planck argument relating β to the critical nucleus size. We refine our derivation to retrieve their β ~ i + 2 [PRL 104, 149602 (2010)]. We discuss applications of this formula and methodology to experiments on Ge/Si(001) and on various organics on Si O2 , as well as to kinetic Monte Carlo studies homoepitaxial growth on Cu(100) with codeposited impurities of different sorts. In contrast to theory, there can be significant changes to β with coverage. Some experiments also show temperature dependence. Supported by NSF-MRSEC at UMD, Grant DMR 05-20471.

  3. Prolactin levels and autoantibodies in female patients with systemic lupus erythematosus.

    PubMed

    Kozáková, D; Rovenský, J; Cebecauer, L; Bosák, V; Jahnová, E; Vigas, M

    2000-01-01

    We investigated the relationships between prolactin (PRL) levels and antibody occurrence in systemic lupus erythematosus (SLE). No significant association between PRL levels and the majority of the autoantibodies studied (anti-U1 RNP, anti-rRNP, anti-Sm, anti-dsDNA, anti-DNP, auto-LCA, anti-EACA) could be confirmed (P > 0.05), anti-Ro/SSA antibodies being an exception. Our results showed significantly increased frequencies of these antibodies in the group of female SLE patients with normal PRL levels (< 20 micrograms/L): anti Ro/SSA in 53% (P < 0.025, chi 2 = 5.80, RR = 4.0) and anti-Ro/SSA + anti-Ro/La in 60% (P < 0.05, chi 2 = 4.05) compared with female SLE patients with hyperprolactinemia. PMID:11155810

  4. Arthritis and prolactin: a phylogenetic viewpoint.

    PubMed

    Adán, Norma; Ledesma-Colunga, María G; Reyes-López, Ana L; Martínez de la Escalera, Gonzalo; Clapp, Carmen

    2014-07-01

    Arthritic disorders are family of diseases that have existed since vertebrate life began. Their etiology is multifactorial with genetic, environmental, and gender factors driving chronic joint inflammation. Prolactin is a sexually dimorphic hormone in mammals that can act to both promote and ameliorate rheumatic diseases. It is found in all vertebrate groups where it exerts a wide diversity of actions. This review briefly addresses the presence and features of arthritic diseases in vertebrates, the effects of PRL on joint tissues and immune cells, and whether PRL actions could have contributed to the ubiquity of arthritis in nature. This comparative approach highlights the value of PRL as a biologically conserved factor influencing the development and progression of arthritis.

  5. Biosynthesis of pulcherriminic acid

    PubMed Central

    MacDonald, J. C.

    1965-01-01

    1. Candida pulcherrima was grown on a complex medium to which various compounds had been added to determine their effect on the biosynthesis of pulcherriminic acid. Most of the pulcherriminic acid synthesized by C. pulcherrima PRL2019 was derived from the l-[1-14C]leucine added to the medium. 2. The cyclic dipeptide of l-leucine (cyclo-l-leucyl-l-leucyl) was shown, by trapping experiments involving cycloleucyl-leucyl isomers, to be synthesized by strain PRL2019. Cyclo-l-leucyl-l-leucyl was derived from l-leucine and was converted into pulcherriminic acid. Cyclo-l-leucyl-l-leucyl was a precursor of pulcherriminic acid in strain PRL2007 also. 3. The results supported the hypothesis that pulcherriminic acid is derived from l-leucine and that cyclo-l-leucyl-l-leucyl is an intermediate in the biosynthesis. PMID:5837792

  6. Association of serum prolactin and oxytocin with milk production in mothers of preterm and term infants.

    PubMed

    Hill, Pamela D; Aldag, Jean C; Demirtas, Hakan; Naeem, Villian; Parker, Noah P; Zinaman, Michael J; Chatterton, Robert T

    2009-04-01

    The present study was designed to compare milk production and hormone responses (prolactin [PRL], oxytocin [OT]) and to determine associations of hormone levels with milk production in mothers of preterm (PT) and term (TM) infants during the first 6 weeks postpartum. Mothers of PT infants (n = 95) were all pump dependent; mothers of TM infants (n = 98) were all feeding their infant at breast. Mothers of nonnursing PT infants produced less milk over time compared to mothers of TM infants. A higher proportion of PT mothers had lower basal PRL levels compared with TM mothers. PRL and frequency of breast stimulation combined positively influenced milk production in PT mothers. OT levels were higher in PT versus TM mothers, but OT was not related to milk production. Further study is warranted regarding interventions to enhance milk production, particularly in pump-dependent mothers of PT infants.

  7. Recent clinical aspects of hyperprolactinemia induced by antipsychotics.

    PubMed

    Milano, Walter; D'Acunto, Cosimo Walter; De Rosa, Michele; Festa, Michela; Milano, Luca; Petrella, Claudio; Capasso, Anna

    2011-01-01

    This review will address the current understanding of the relationship between hyperprolactinemia and antipsychotic drugs. Hyperprolactinemia is a frequent but often neglected side effect of typical, but also of many atypical antipsychotics. Release of PRL from lactotrope cells is influenced by several factors, such as stress, physical and sexual activity and food assumption. PRL secretion is regulated by hypothalamic-pituitary portal system and its homeostasis is the result of a complex balance between stimulating and inhibitory factors, both endogeneous and esogeneous. The main physiological control mechanism of secretion is played by the inhibitory action of dopamine. Conversely, among stimulation factors, serotonin is probably the main modulator of PRL release. An high number of drugs may cause PRL increase too, such as drugs that reduce dopaminergic functions at SNC level, or drugs with an antagonistic action towards dopaminergic receptors and those increasing serotonergic neurotransmission. Hyperprolactinemia is one of the most frequent endocrine pathologies of the hypothalamic-pituitary axis. Antipsychotics (AP) are the most common cause of druginduced hyperprolactinemia. Not all AP have the same impact on inducing hyperprolactinemia. In this review we will focus on the subdivision of AP in 'PRL-raising' (stimulators) and 'PRL-sparing' (sparers) and on their differences in inducing hyperprolactinemia. Finally we evaluated different complications in patients with antipsychotics induced hyperprolactinemia that may cause not only short-term side effects but also important systemic long-term effects. At the end of the review we finally report the possible options of treatment considering however that at present there are no ideal therapies or evaluations, and decisions have to be made on a case by case basis. PMID:20868350

  8. Short communication: retinoic acid plus prolactin to synergistically increase specific casein gene expression in MAC-T cells.

    PubMed

    Lee, H Y; Heo, Y T; Lee, S E; Hwang, K C; Lee, H G; Choi, S H; Kim, N H

    2013-06-01

    Mammary alveolar (MAC-T) cells, an established bovine mammary epithelial cell line, are frequently used to investigate differentiation. A lactogenic phenotype in these cells is induced by treatment with a combination of hydrocortisone, insulin, and prolactin (PRL). The effect of the vitamin A derivative retinoic acid (RA), which induces differentiation in many cells, has not been studied in MAC-T cells. The objective of this study was to evaluate the differentiation potential of RA (1 μM) in MAC-T cells and to examine the effect of combined treatment with RA (1 μM) and PRL (5 μg/mL). Although RA treatment alone inhibited MAC-T cell proliferation, co-treatment of RA with PRL increased cell growth compared with the control group (treated with 1 μg/mL hydrocortisone and 5 μg/mL insulin). The ratio of Bcl to Bax mRNA was decreased in the RA treatment compared with RA+PRL or control. Retinoic acid-induced differentiation of MAC-T cells was associated with an increase in the mRNA expression of αS1-casein (3.9-fold), αS2-casein (4.5-fold), and β-casein (4.4-fold) compared with the control group. Expression of αS1-casein, αS2-casein, and β-casein was increased 12.9-fold, 11.9-fold, and 19.3-fold, respectively, following treatment with RA and PRL combined compared with the control group. These results demonstrate that RA induces differentiation of MAC-T cells and acts synergistically with PRL to increase specific casein gene expression.

  9. The influence of hyperthyroidism on the hypothalamic-pituitary-gonadal axis.

    PubMed

    Zähringer, S; Tomova, A; von Werder, K; Brabant, G; Kumanov, P; Schopohl, J

    2000-01-01

    We have investigated the function of the hypothalamic-pituitary-gonadal (H-P-G)-axis in patients with severe, untreated Graves' disease. We studied 7 male and 6 female healthy volunteers, and 7 male and 7 female patients with Graves' disease. Hormone profiles were developed by blood sampling every 10 min for an 8 hour period. In women this was done in the early follicular phase of menstrual cycle. LH-, FSH-, and PRL levels were measured using immunoradiometric assays and testosterone (T), estradiol (E2), sex-hormone binding globulin (SHBG), and progesterone (P) were measured with standard assays. The pulsatility of LH, FSH and PRL was calculated using the programmes Pulsar, Cluster and Desade. The temporal relationship of plasma LH, FSH, and PRL pulses was also investigated using specific concordance analysis. Data were evaluated by means of non-parametric statistics. LH-secretion was increased in all hyperthyroid patients, while FSH-secretion was increased in hyperthyroid men only. Pulsatile characteristics of LH- and FSH-secretion (frequency, peak shape) in patients were not different from controls. No change in PRL-secretion was shown. Significant copulsatility occurred between LH and FSH, and LH and PRL. This was more pronounced in hyperthyroid than in healthy study subjects. Plasma levels of steroid hormones and sex-hormone-binding globulin were significantly (p<0.005) increased in hyperthyroid men. Free Androgen Index was significantly (p<0.005) decreased in hyperthyroid males. No other auto immune diseases were noticed. Our results indicate that the function of the H-P-G axis is not impaired in hyperthyroid patients, but gonadotropin levels are increased. Hyperthyroid men show relative primary gonadal insufficiency that may be due to exaggerated SHBG levels. The copulsatility of LH and FSH, and of LH and PRL was confirmed both in patients and controls.

  10. Neuroendocrine correlates of temperamental traits in humans.

    PubMed

    Gerra, G; Zaimovic, A; Timpano, M; Zambelli, U; Delsignore, R; Brambilla, F

    2000-07-01

    Studies investigating temperament traits in humans and their biological correlates have found high levels of novelty seeking (NS) linked with dopaminergic system changes, and particularly a deficit of dopamine transporter. Harm avoidance and reward dependence, on the other hand, appeared to be associated, respectively with serotonin and noradrenaline changes. In the present study, we have investigated the dopaminergic (DA), serotonergic (5-HT), and noradrenergic (NE) functions in healthy volunteers by challenging the monoamine systems with the DA agonist bromocriptine, the 5-HT agonist D-fenfluramine, and the NE agonist clonidine, respectively. Parallel to this investigation, we examined the temperament traits of our subjects by measuring NS, harm avoidance (HA) and reward dependence (RD) using the 'Three-dimensional Personality Questionnaire' (TPQ). The aims of the study were to see whether or not the monoamine functions were correlated with temperament traits. Bromocriptine challenge induced a significant GH increase and a significant suppression of PRL. D-fenfluramine test significantly increased PRL and cortisol plasma levels and Clonidine test induced a significant rise in GH values. NS scores showed a significant direct correlation with brom-stimulated GH values (r=0.426, P<0.05) and a significant inverse correlation with brom-inhibited PRL values (r=-0.498, P<0.01). HA scores correlated significantly with D-fen-stimulated PRL and CORT AUCs, (PRL: r=0.424, P<0.05; CORT: r=0. 595, P<0.005). RD scores correlated positively with clon-stimulated GH values (r=0.55; F=8.6; P<0.01) and negatively with brom-inhibited-PRL AUCs (r=-0.439, P<0.05). Our data support Cloninger theory concerning the biological correlates of temperamental traits, and evidence the link between the neuroendocrine responses to dynamic challenges and stable temperament features.

  11. Effect of various partial separations of the litters from their mother on plasma prolactin levels of lactating rats.

    PubMed

    Bánky, Z; Nagy, G M; Halász, B

    1994-01-01

    Removal of the pups results in an abrupt and marked depression in plasma prolactin (PRL) level of the lactating mother. The present studies were undertaken to investigate what kind of sensory input (smell, sound, visual, touch etc.) from the pups is essential for the mother to avoid the pituitary PRL response to pup-removal. Therefore, various partial separations were made and their effect on plasma PRL levels tested: a. The pups were placed into a small glass having holes on its cover; b. they were put into a long measuring tube not covered; c. the pups were placed into the feeding trough made of a wireframe; d. a dividing wall made of glass or metal was slowly let down when the mother spontaneously went away from her pups; e. the nipples were covered by a cotton plaster. Pituitary PRL responses were almost identical after all these separations and similar to that one obtained after removal of the pups from the cage. In addition, separation of the mother resulted in a rise in plasma corticosterone concentrations. The findings suggest that the pup-removal induced inhibition of PRL secretion is a very complex event for the mother and cannot be prevented by partial separations when the mother can see, smell her pups, or hear them or even can touch them with her nose. We assume that separation of the pups is a stress for the mother and cannot simply be due to the lack of just one kind of sensory input from the pups. This assumption is in line with our recent observations indicating that in lactating rat stress causes a decrease in plasma PRL level.

  12. The influence of transient hyperprolactinemia on hormonal parameters, oocyte recovery, and fertilization rates in in vitro fertilization.

    PubMed

    Gonen, Y; Casper, R F

    1989-06-01

    A detrimental effect of transient elevation of plasma prolactin (PRL) during in vitro fertilization (IVF) has not been proven; however, treatment with a dopamine agonist has been suggested. The present study was undertaken to determine if transient, midcycle hyperprolactinemia exerted a deleterious effect on the number of oocytes retrieved or on fertilization of oocytes in vitro. Fifty-three infertile patients with midcycle hyperprolactinemia (PRL greater than 20 micrograms/liter) during ovarian hyperstimulation for IVF were compared with 53 matched controls who remained normoprolactinemic. Mean (+/- SE) serum PRL levels on the day after hCG were significantly higher in the study group (29.5 +/- 1 micrograms/liter) than in the control (13.1 +/- 0.5 microgram/liter) (P less than 0.0005), whereas the mean estradiol (E2) concentrations on the same day were not significantly different (4822 +/- 287 and 4492 +/- 269 pmol/liters, respectively). Fertilization rates (72 +/- 4 and 70 +/- 4%, respectively) and the mean number of oocytes recovered (4.2 +/- 0.3 and 3.7 +/- 0.3, respectively) did not differ between the two groups. No correlation was observed between serum PRL and E2 levels, fertilization rates, or the number of oocytes retrieved in either group. Eleven patients with elevated PRL levels as a result of ovarian hyperstimulation were treated with 2.5 mg bromocriptine daily during the next IVF cycle. Serum PRL levels were significantly lower in the treated (5.6 +/- 1.8 micrograms/liter) than in the untreated cycles (35.6 +/- 3.1 micrograms/liter) (P less than 0.0005), whereas serum E2 concentrations did not differ.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Effect of constant-release melatonin implants and prolonged exposure to a long day photoperiod on prolactin secretion and hair growth in mouflon (Ovis gmelini musimon).

    PubMed

    Santiago-Moreno, J; López-Sebastián, A; del Campo, A; González-Bulnes, A; Picazo, R; Gómez-Brunet, A

    2004-05-01

    The aims of this study were to examine whether mouflons exposed to constant long and short day photoperiods are able to exhibit an annual cycle of hair growth and moult, and prolactin (PRL) secretion. Mouflon ewes were assigned to three groups of treatment. Ewes were maintained, either under natural photoperiod (control, n = 9), or received a series of subcutaneous melatonin implants from December to April (n = 8), or were exposed to a constant long day photoperiod (16-h light:8-h dark; 16L:8D) during 18 months (n = 7). Blood was collected weekly to determine PRL concentrations, and hair samples were clipped weekly from the base of the neck to measure the length of predominant hair. Under constant long days and with melatonin implants, mouflons expressed an annual rhythm of PRL secretion, even though these treatments modified the times of rise or falling of PRL concentrations throughout the year. Hair growth initiation was almost coincident with the summer solstice in both control and melatonin-implanted mouflons but occurred two months earlier in long day hold mouflons (P < 0.001). Long day hold mouflons had a lower hair growth rate than control and melatonin-implanted mouflons (P < 0.001), and at the end of the experiment, a shorter hair length (3.4 +/- 0.24 cm; P < 0.01) than control (4.3 +/- 0.17 cm), and melatonin-implanted mouflons (4.2 +/- 0.12 cm). Our data support the conclusion that in mouflon, an endogenous circannual rhythm of PRL secretion exists, and that the seasonal cycle of hair growth and moult appears to depend, at least in part, on circulating levels of PRL. PMID:15063923

  14. Is a stable or decreasing prolactin level in a patient with prolactinoma a surrogate marker for lack of tumor growth?

    PubMed

    Alkabbani, Abdulrahman G; Mon, Sann Y; Hatipoglu, Betul; Kennedy, Laurence; Faiman, Charles; Weil, Robert J; Hamrahian, Amir H

    2014-04-01

    The optimal interval for follow-up imaging of patients with prolactinomas is unclear. We wish to determine the likelihood of tumor enlargement in patients with prolactinomas who have a stable or reduced prolactin (PRL) level over time, whether or not they are treated with a dopamine agonist (DA). We identified 80 patients with prolactinomas (34 men, 46 women) who had at least two paired sets of serum PRL levels and pituitary MRIs, 3 or more months apart. Patients with hyperprolactinemia due to drug or stalk effects were excluded. The median (range) age was 45 (25-77) years. Sixty-three patients (78.8%) were treated with DA. PRL levels (ng/mL) at the initial and latest sets were 114 (0.3-15,732) and 16 (0.3-1,204), respectively. In patients with identifiable tumors, the maximum tumor diameters (mm) at the initial and latest MRI studies were 12.5 (2-60) and 12.5 (2-39) respectively, with an interval of 2.9 (0.3-9.7) years. Sixty percent of patients (n = 48) had a macroadenoma. Forty-two (52.5%) patients had either disappearance of the tumor (n = 22) or reduction (n = 20) in tumor size. In the remainder, tumor size was stable in 35 but increased in 3 patients. One of these patients, observed off therapy had a concomitant rise in PRL level. The other 2 had evidence of pituitary hemorrhage with no PRL increase. Tumor growth in prolactinoma patients with a stable or decreasing PRL level, regardless of size, is a rare event. Repetitive pituitary imaging in these patients may not be warranted.

  15. Vertebral fractures in males with prolactinoma.

    PubMed

    Mazziotti, Gherardo; Porcelli, Teresa; Mormando, Marilda; De Menis, Ernesto; Bianchi, Antonio; Mejia, Carola; Mancini, Tatiana; De Marinis, Laura; Giustina, Andrea

    2011-06-01

    Data on osteoporotic fractures in hyperprolactinemia are limited. An increased prevalence of radiological vertebral fractures was recently observed in women with prolactin (PRL)-secreting adenoma, whereas it is unknown whether this observation may reflect a more general increased risk of fractures in this disease and whether the prevalence of fractures in males is affected by gonadal status. Thirty-two males (median age 47 years, range: 22-79) with PRL-secreting pituitary adenoma (10 with microadenoma and 22 with macroadenoma) and 64 control males, with normal PRL values and with comparable age to patients with hyperprolactinemia, were evaluated for vertebral fractures by a morphometric approach and for bone mineral density (BMD) by a dual-energy X-ray absorptiometry at lumbar spine. Vertebral fractures were shown in 12 patients with PRL-secreting adenoma (37.5%) and in 5 controls (7.8%, P < 0.001). Fractured patients had lower BMD T-score (P = 0.007) and longer duration of disease (P < 0.001) as compared to patients who did not fracture. Fractures occurred more frequently (P = 0.03) in patients with untreated hyperprolactinemia versus patients treated with cabergoline whose frequency of vertebral fractures was still higher than control subjects. The prevalence of vertebral fractures was not significantly different between eugonadal and hypogonadal patients (33.3% vs. 38.5%; P = 0.8). Moreover, no significant (P = 0.4) difference in serum testosterone values was found between fractured and not fractured males. Hyperprolactinemia is associated with high prevalence of radiological vertebral fractures in men with PRL-secreting adenoma. These findings would also suggest that PRL excess may produce negative skeletal effects independently of hypogonadism.

  16. Women with prolactinomas presented at the postmenopausal period.

    PubMed

    Shimon, Ilan; Bronstein, Marcello D; Shapiro, Jonathan; Tsvetov, Gloria; Benbassat, Carlos; Barkan, Ariel

    2014-12-01

    In women, prolactinomas (mainly microprolactinomas) are commonly diagnosed between 20-40-year old. In postmenopausal women, prolactinomas are rarely encountered and usually do not present with hyperprolactinemia-related symptoms as these are dependent on intact ovarian function. Therefore, the true incidence of prolactin (PRL)-secreting adenomas in postmenopausal woman is unknown. Our study objective was to characterize these rare and unique pituitary tumors. A retrospective study including a consecutive group of postmenopausal women followed and treated at 3 Endocrine academic clinics. Baseline clinical characteristics (PRL and gonadotropins levels, other pituitary hormones, adenoma size and invasiveness, visual fields) and response to treatment are reported. The cohort included 14 postmenopausal women with prolactinomas (mean age at diagnosis, 63.6 ± 7.1 years; range, 54-75 years). Mean adenoma size at presentation was 25.6 ± 12.4 mm (range, 8-50 mm). Six out of the 14 women had significant visual fields damage. Mean baseline PRL level was 1,783 ng/ml, and median PRL was 827 ng/ml (range, 85-6,732 ng/ml). Medical treatment with cabergoline was given to twelve of the patients. Cabergoline normalized/near-normalized PRL in eleven women; one woman was dopamine agonist-resistant. Five of the six subjects with visual disturbances normalized or improved their vision, and a pre-treatment diplopia in another patient disappeared. Two large pituitary tumors disappeared on MRI following long-term dopamine agonist therapy. All other treated prolactinomas, except the resistant adenoma, shrank following medical treatment. Prolactinomas are rarely diagnosed in postmenopausal women. These women usually harbor large and invasive macroadenomas, secreting high PRL levels, and usually respond to dopamine agonist treatment.

  17. POLYMORPHISM OF THE PROLACTIN GENE AND ITS EFFECT ON FIBER TRAITS IN GOAT.

    PubMed

    Shamsalddini, S; Mohammadabadi, M R; Esmailizadeh, A K

    2016-04-01

    The prolactin gene (PRL) is a potential candidate gene for the goat cashmere traits in marker-assisted selection. Thus, the aim of this study was to detect PRL gene polymorphism and its association with fiber traits in 200 Raini cashmere goats native to the south-east of Iran. A 196-bp fragment encoding exon 5 within the goat PRL gene was amplified using PCR specific primers. The amplification products were subjected to the single stranded conformation polymorphism (SSCP) analysis. Three different SSCP banding patterns (CC, AC and AA) were observed in exon 5 of the caprine PRL gene. The pattern frequencies for CC, AC and AA were 0.39, 0.38 and 0.23 and frequencies of the A and C alleles were 0.42 and 0.58, respectively. The genotypic distributions did not deviate from the Hardy-Weinberg equilibrium (P> 0.05). The number of observed alleles, number of effective alleles, expected heterozygosity, observed heterozygosity, mean of heterozygosity, expected homozygosity, observed homozygosity, Nei's index and Shanon's index were 2.0, 1.9, 0.48, 0.38, 0.48, 0.51, 0.61, 0.48 and 0.68, respectively. Results of association between genotypes and fiber traits indicated that the CC genotype had the highest fiber length compared with the AA and AC genotypes (P < 0.05) while there was no significant association between the PRL gene genotypes and fiber diameter. These results imply that the PRL gene polymorphism can be used as a molecular marker to improve fiber production without a negative effect on fiber diameter. PMID:27529980

  18. Selective oxytocin receptor activation in the ventrolateral portion of the ventromedial hypothalamus is required for mating-induced pseudopregnancy in the female rat.

    PubMed

    Northrop, Lesley E; Erskine, Mary S

    2008-02-01

    The ventrolateral region of the ventromedial hypothalamus (VMHvl) plays an essential role in female sexual behavior. Oxytocin (OT) is released from the paraventricular nucleus to downstream sites such as the VMHvl to facilitate female sexual behavior and shows characteristics of a prolactin (PRL)-releasing factor. During mating, vaginal cervical stimulation (VCS) received from a vasectomized male triggers twice-daily PRL surges that persist up to 12+ d, a period known as pseudopregnancy (PSP). To determine whether OT is involved in PSP by acting within the VMHvl, female rats were infused bilaterally with an oxytocin receptor antagonist (OTR-A), a vasopressin receptor-1a antagonist (V(1a)-A), or artificial cerebral spinal fluid 30 min before mating. All females received a sufficient amount of VCS, 15 intromissions, to induce PSP. Females infused with OTR-A (20 ng/0.4 microl) with implants targeting the VMHvl showed only a 22% induction of PSP, as measured using vaginal diestrus and serum PRL concentrations. In contrast, controls and V(1a)-A (80 ng/0.4 microl) infused females exhibited 100% induction of PSP. Females infused with OTR-A returned to estrus after 5 d, whereas females infused with either artificial cerebral spinal fluid or V(1a)-A remained in diestrus for 12-13 d in both the correct and missed placement groups. Although OT can act as a PRL releasing factor, the PRL surge does not begin until 18-24 h after mating. Together, our results suggest that OT release in the VMHvl mediates the effects of VCS on the induction of the PRL secretion needed to establish PSP.

  19. Diurnal variation of serum progesterone, but not relaxin, prolactin, or estradiol-17 beta in the pregnant bitch.

    PubMed

    Steinetz, B G; Goldsmith, L T; Hasan, S H; Lust, G

    1990-09-01

    The concentrations of progesterone (P), relaxin (Rlx), estradiol (E2) and PRL were measured by specific RIAs in serum samples collected twice daily at 8:00 am and 3:00 pm at weekly intervals after mating and until whelping in five Labrador Retriever bitches. From weeks 3 to 6 of pregnancy, P exhibited a conspicuous and statistically significant diurnal pattern (P less than 0.05), its serum concentration being approximately twice as high at 8:00 am as at 3:00 pm. A similar but nonsignificant trend was observed weeks 2, 7, and 8, and the overall ratio of the am/pm P concentrations was 2.4 +/- 0.28 (P less than 0.001). Rlx, E2, and PRL did not show a diurnal pattern at any time during pregnancy. The glandular sources and regulation of secretion of Rlx were further investigated. Rlx bioactivity was detected in canine placentas and ovaries, providing supportive evidence that these organs may be a dual source of the hormone in canine pregnancy. Injection of ovine PRL in three pseudopregnant bitches significantly increased serum P concentration as compared with seven untreated pseudopregnant controls, but Rlx was not detectable in serum before, during or after PRL treatment. The data support the view that Rlx and P are independently regulated in the bitch; PRL may be a regulator of P, but not of Rlx secretion. However, as PRL showed no diurnal changes in concentration, it does not appear to be directly responsible for the diurnal pattern exhibited by P.

  20. Bait-delivered pimozide causes precocious embryo implantation in mink: a fertility control option for the exotic stoat?

    PubMed

    Marks, Clive A; Lindeberg, Heli; Van Cleeff, Judy

    2006-01-01

    Stoats (Mustela erminea), an exotic pest in New Zealand, threaten the conservation of several ground-nesting bird species and broad-scale methods for their control are sought. Females are seasonally monestrous, show a 9-month period of obligatory diapause and usually do not breed more than once in their lives. A bait-delivered agent that terminates diapause and results in a non-viable embryo may have a significant impact on their reproductive success. Prolactin (PRL) is hypothesised to be the only gonadotrophin required for renewal of luteal activity and blastocyst implantation in some mustelids. We investigated the effects of bait-delivered dopamine (DA) antagonists (which stimulate the release of PRL) using a mink model (Mustela vison), a species that maintains a short period of diapause. A bait dose of 0.8 mg kg(-1) of pimozide was more effective in elevating PRL levels than equivalent doses of fluphenazine, sulpiride (P < 0.01) or haloperidol (P < 0.05). Bait doses of 1.6 mg kg(-1) pimozide given at Days 0, 3, 9 and 11 after mating caused a significant reduction in the length of pregnancy compared with a positive control and placebo (46 days v. 51 days), indicating early termination of diapause (P < 0.01). Pimozide doses caused higher elevations in PRL concentration relative to the oral placebo by Day 12, but mean PRL levels fell below all other groups by Day 18. A borderline significant increase in progesterone (P4) secretion compared with the oral placebo was detected at Day 18. These results suggest that bait-delivered pimozide can elevate PRL outside of the normal breeding season and doses of 1.6 mg kg(-1) are effective in terminating embryonic diapause in mink. The implications and limitations of these data are discussed with reference to the use of bait-delivered DA antagonists as a possible means to affect the reproductive success of wild stoats. PMID:16930517

  1. Regenerative capacity of the adult pituitary: multiple mechanisms of lactotrope restoration after transgenic ablation.

    PubMed

    Fu, Qiuli; Vankelecom, Hugo

    2012-12-10

    In a recent study, we showed that the adult pituitary gland is capable of regenerating transgenically ablated growth hormone-producing (GH(+)) somatotropes. Here, we investigated whether the gland's regenerative capacity is more general and also applies to the other major hormonal cell type, the prolactin-producing (PRL(+)) lactotropes. We set up the transgenic PRLCre/inducible diphtheria toxin receptor (iDTR) mouse model, in which the PRL promoter drives expression of Cre that induces DTR in lactotropes. Injection of female mice with DT for different periods causes a gradual ablation of PRL(+) cells, reaching a maximum of 70% after 10-day DT treatment. During the following weeks, lactotropes progressively reappear achieving a 60% restoration after 6 weeks. The Sox2(+) stem/progenitor cell compartment displays a prompt reaction to the DT-triggered cell ablation injury, including expansion of the marginal-zone niche and coexpression of PRL, the latter only very rarely observed in control pituitary. Throughout the regeneration period (2-6 weeks), Sox2(+) as well as double Sox2(+)/PRL(+) cells continue to be more abundant than in control pituitary. In addition to this stem cell reaction, surviving or newborn lactotropes increase their proliferative activity, and bihormonal PRL(+)/GH(+) cells become detectable suggesting somatotrope-to-lactotrope transdifferentiation. In conclusion, the adult pituitary gland is capable of restoring lactotrope cells after destruction, further confirming its regenerative competence. Repair of lactotropes appears to be driven by a combination of mechanisms, including recruitment from stem cells, proliferation of lactotropes, and transdifferentiation of somatotropes.

  2. The osmoregulatory effects of rearing Mozambique tilapia in a tidally changing salinity.

    PubMed

    Moorman, Benjamin P; Inokuchi, Mayu; Yamaguchi, Yoko; Lerner, Darren T; Grau, E Gordon; Seale, Andre P

    2014-10-01

    The native distribution of Mozambique tilapia, Oreochromis mossambicus, is characterized by estuarine areas subject to salinity variations between fresh water (FW) and seawater (SW) with tidal frequency. Osmoregulation in the face of changing environmental salinity is largely mediated through the neuroendocrine system and involves the activation of ion uptake and extrusion mechanisms in osmoregulatory tissues. We compared plasma osmolality, plasma prolactin (PRL), pituitary PRL mRNA, and mRNA of branchial ion pumps, transporters, channels, and PRL receptors in tilapia reared in FW, SW, brackish water (BW) and in tidally-changing salinity, which varied between FW (TF) and SW (TS) every 6h. Plasma PRL was higher in FW tilapia than in SW, BW, TF, and TS tilapia. Unlike tilapia reared in FW or SW, fish in salinities that varied tidally showed no correlation between plasma osmolality and PRL. In FW fish, gene expression of PRL receptor 1 (PRLR1), Na(+)/Cl(-) cotransporter (NCC), aquaporin 3 (AQP3) and two isoforms of Na(+)/K(+)-ATPase (NKA α1a and NKA α1b) was higher than that of SW, BW or tidally-changing salinity fish. Gene expression of the Na(+)/K(+)/2Cl(-) cotransporter (NKCC1a), and the cystic fibrosis transmembrane conductance regulator (CFTR) were higher in fish in SW, BW or a tidally-changing salinity than in FW fish. Immunocytochemistry revealed that ionocytes of fish in tidally-changing salinities resemble ionocytes of SW fish. This study indicated that tilapia reared in a tidally-changing salinity can compensate for large changes in external osmolality while maintaining osmoregulatory parameters within a narrow range closer to that observed in SW-acclimated fish.

  3. Somatotropic, lactotropic and adrenocortical responses to insulin-induced hypoglycemia in patients with rheumatoid arthritis.

    PubMed

    Rovensky, Jozef; Bakosová, Jana; Koska, Juraj; Ksinantová, Lucia; Jezová, Daniela; Vigas, Milan

    2002-06-01

    Neuroendocrine mechanisms have been suggested to play an important role in the onset and progression of rheumatoid arthritis (RA). The aim of this study was to evaluate hypothalamic-pituitary functions in RA patients by measurement of hormone responses to insulin-induced hypoglycemia. Insulin-hypoglycemia (Actrapid HM 0.1 IU/kg, i.v. as a bolus) was induced in 17 male patients and in 11 age-, gender-, and weight-matched healthy subjects. Concentrations of growth hormone (GH), prolactin (PRL) and cortisol were analyzed in plasma. PRL release after thyreoliberin stimulation (TRH, 200 g, i.v.) was determined in 21 patients with active forms of RA and in 12 control subjects to evaluate pituitary lactotropic response. In RA patients, basal concentrations of glucose, GH, PRL, and cortisol were in the normal range and they were comparable to those in the control group. Stress of hypoglycemia induced significant elevation of GH, PRL, and cortisol concentrations in all groups. Cortisol responses to hypoglycemia were comparable in patients and in control subjects. GH release during hypoglycemia was increased (p < 0.05) and PRL response was attenuated (p < 0.05) in RA patients versus control subjects. After TRH administration, PRL response was the same in patients as in healthy subjects. In conclusion, the present study revealed an altered hypothalamic-pituitary function in patients with RA, namely, an enhanced somatotropic and reduced lactotropic activation in response to insulin-induced hypoglycemia. Basal hormone levels and cortisol release during hypoglycemia were similar to those in healthy subjects. PMID:12114282

  4. POLYMORPHISM OF THE PROLACTIN GENE AND ITS EFFECT ON FIBER TRAITS IN GOAT.

    PubMed

    Shamsalddini, S; Mohammadabadi, M R; Esmailizadeh, A K

    2016-04-01

    The prolactin gene (PRL) is a potential candidate gene for the goat cashmere traits in marker-assisted selection. Thus, the aim of this study was to detect PRL gene polymorphism and its association with fiber traits in 200 Raini cashmere goats native to the south-east of Iran. A 196-bp fragment encoding exon 5 within the goat PRL gene was amplified using PCR specific primers. The amplification products were subjected to the single stranded conformation polymorphism (SSCP) analysis. Three different SSCP banding patterns (CC, AC and AA) were observed in exon 5 of the caprine PRL gene. The pattern frequencies for CC, AC and AA were 0.39, 0.38 and 0.23 and frequencies of the A and C alleles were 0.42 and 0.58, respectively. The genotypic distributions did not deviate from the Hardy-Weinberg equilibrium (P> 0.05). The number of observed alleles, number of effective alleles, expected heterozygosity, observed heterozygosity, mean of heterozygosity, expected homozygosity, observed homozygosity, Nei's index and Shanon's index were 2.0, 1.9, 0.48, 0.38, 0.48, 0.51, 0.61, 0.48 and 0.68, respectively. Results of association between genotypes and fiber traits indicated that the CC genotype had the highest fiber length compared with the AA and AC genotypes (P < 0.05) while there was no significant association between the PRL gene genotypes and fiber diameter. These results imply that the PRL gene polymorphism can be used as a molecular marker to improve fiber production without a negative effect on fiber diameter.

  5. Pituitary adenomas: immunohistology and ultrastructural analysis of 118 tumors.

    PubMed

    Esiri, M M; Adams, C B; Burke, C; Underdown, R

    1983-01-01

    An analysis is presented of the immunohistological and ultrastructural features in a series of 118 surgically removed pituitary adenomas all of which were studied immunohistologically using antisera to growth hormone (GH), prolactin (PRL) ACTH, beta FSH, beta LH and beta TSH, and 75 of which were studied ultrastructurally. Results were analysed according to the mode of presentation of patients. Forty-one (35%) of the tumours were from patients with acromegaly or gigantism, ten (9%) from patients with Cushing's syndrome or Nelson's syndrome, 19 (16%) from patients with clinical features associated with hyperprolactinaemia and 48 (40%) from patients with space occupying lesions which appeared clinically to be overtly endocrinologically functionless. By light microscopy, using the immunoperoxidase (PAP) technique, immunoreactive GH was demonstrated in all the tumours from patients with acromegaly or gigantism, immunoreactive ACTH in all tumours from patients with Cushing's syndrome or Nelson's syndrome and immunoreactive PRL in 95% of tumours associated with effects of hyperprolactinaemia. Forty-five percent of the tumours from acromegalic patients contained some PRL-positive cells as well as GH-positive cells. Among the tumours which appeared clinically to be endocrinologically functionless were three tumours (from males) uniformly stained for immunoreactive PRL. Of the remainder, 60% were negative for immunoreactive hormones and 40% contained small numbers of cells which were positive for a variety of immunoreactive hormones. ACTH-cell and PRL-cell tumours had ultrastructural features as described in previous studies. Fifty percent of GH-cell tumours examined at the EM level contained fibrous bodies, while in the remainder these structures were not identified. Tumours with fibrous bodies were more likely to contain PRL as well as GH with immunoperoxidase. All tumours that were endocrinologically functionless and which were examined at the EM level contained

  6. Prolactin and growth hormone affect metaphase-II chromosomes in aging oocytes via cumulus cells using similar signaling pathways

    PubMed Central

    Lebedeva, Irina Y.; Singina, Galina N.; Lopukhov, Alexander V.; Shedova, Ekaterina N.; Zinovieva, Natalia A.

    2015-01-01

    General senescence of the adult organism is closely connected with reproductive one. Meanwhile, the age-related reduction in the female fertility is primarily associated with a decline in the gamete quality. Molecular and cellular changes in oocytes of old mammalian females are very similar to those occurring during aging of matured ova of their young counterparts, suggesting similarities in underlying mechanisms. The aim of the present work was to study actions of two related pituitary hormones, prolactin (PRL) and growth hormone (GH), on age-associated modifications of metaphase-II (M-II) chromosomes in bovine oocytes using a model of the prolonged culture. We analyzed: (1) effects of PRL and GH on abnormal changes in the chromosome morphology in aging matured oocytes and the role of cumulus cells in these effects and (2) signaling pathways involved in the hormone actions. During the prolonged culture of oocytes, a gradual rise in the frequency of destructive modifications of M-II chromosomes was revealed. In the case of cumulus-enclosed oocytes (CEOs), PRL and GH exerted dose-dependent biphasic effects on the frequency of these modifications. Both PRL (50 ng/ml) and GH (10 ng/ml) decelerated the abnormal chromosome changes in CEOs, but did not affect the chromosome configuration in denuded oocytes. Concurrently, the presence of PRL and GH receptors in cumulus cells surrounding matured oocytes was demonstrated. Attenuating effects of both hormones on the chromosome modifications in aging CEOs were abolished by PP2 (an inhibitor of Src-family tyrosine kinases), triciribine (an inhibitor of Akt kinase), and calphostin C (a protein kinase C inhibitor). Our findings indicate that PRL and GH can exert the similar decelerating action on age-associated alterations in the M-II chromosome morphology in bovine ova, which is mediated by cumulus cells and may be related to activation of Src-family tyrosine kinases as well as Akt- and protein kinase C-dependent signal

  7. A 32,000-molecular weight protein from bovine placenta with placental lactogen-like activity in radioreceptor assays

    SciTech Connect

    Eakle, K.A.; Arima, Y.; Swanson, P.; Grimek, H.; Bremel, R.D.

    1982-05-01

    Considerable discrepancies exist in the literature concerning the size and activity of bovine placental lactogen. Our bovine placental lactogen purification preparations were 20% as active as bovine PRL (bPRL) on a per weight basis when compared to bPRL in a lactogenic radioreceptor assay. To identify the active component in these preparations, the proteins were radioiodinated and bound to membrane receptors in the presence and absence of competing hormones, bPRL, and bovine GH (bGH). After centrifugation, membrane pellets were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the gels were autoradiographed. Only one radioiodinated protein band was present. This protein was displaced in the presence of competing hormone and comigrated with a major component of the purification preparations. In radioreceptor assays the active component was as active as bPRL and bGH. From the migration of protein standards included with the radioiodinated purification preparations in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, we estimate that the protein is 32,000 mol wt--about 10,000 mol wt larger than placental lactogens isolated in other species. The possibility that the active molecule was a precursor protein was investigated by examining proteins secreted by bovine placenta tissue cultures. The binding activity in these secretions, as well as in the purification preparations, eluted between ovalbumin (43,000 mol wt) and bPRL (22,000 mol wt) under nondenaturing conditions using high performance gel filtration chromatography. Analysis of this secreted protein, also by binding to membrane receptors, showed that the protein had the same molecular weight as that isolated from the purification preparations and was specifically displaced by the same hormones.

  8. A 32,000-molecular weight protein from bovine placenta with placental lactogen-like activity in radioreceptor assays.

    PubMed

    Eakle, K A; Arima, Y; Swanson, P; Grimek, H; Bremel, R D

    1982-05-01

    Considerable discrepancies exist in the literature concerning the size and activity of bovine placental lactogen. Our bovine placental lactogen purification preparations were 20% as active as bovine PRL (bPRL) on a per weight basis when compared to bPRL in a lactogenic radioreceptor assay. To identify the active component in these preparations, the proteins were radioiodinated and bound to membrane receptors in the presence and absence of competing hormones, bPRL, and bovine GH (bGH). After centrifugation, membrane pellets were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the gels were autoradiographed. Only one radioiodinated protein band was present. This protein was displaced in the presence of competing hormone and comigrated which a major component of the purification preparations. In radioreceptor assays the active component was as active as bPRL and bGH. From the migration of protein standards included with the radioiodinated purification preparations in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, we estimate that the protein is 32,000 mol wt--about 10,000 mol wt larger than placental lactogens isolated in other species. The possibility that the active molecule was a precursor protein was investigated by examining proteins secreted by bovine placenta tissue cultures. The binding activity in these secretions, as well as in the purification preparations, eluted between ovalbumin (43,000 mol wt) and bPRL (22,000 mol wt) under nondenaturing conditions using high performance gel filtration chromatography. Analysis of this secreted protein, also by binding to membrane receptors, showed that the protein had the same molecular weight as that isolated from the purification preparations and was specifically displaced by the same hormones. PMID:7075536

  9. Prolactin inhibits the increased cytokine gene expression in Kupffer cells following haemorrhage.

    PubMed

    Zhu, X H; Zellweger, R; Ayala, A; Chaudry, I H

    1996-02-01

    Kupffer cells are an important source of proinflammatory cytokines and contribute to the systemic inflammatory response observed following haemorrhagic shock. The systemic release of cytokines, such as TNF-alpha, IL-1 beta, IL-6, etc., has been associated with the decreased host immune and organ dysfunction following hypotension. Studies indicate that anterior pituitary hormone prolactin (PRL) plays an important role in the regulation of lymphocyte proliferation and macrophage function in vivo, as well as in vitro. However, it is not known what effects PRL administration has on Kupffer cells proinflammatory mediator release following haemorrhage. Therefore, it was the aim of this study to determine the effect of in vivo PRL administration on cytokine gene expression in Kupffer cells after haemorrhage. To study this, C3H/HeN male mice were bled to and maintained at a mean arterial pressure of 35 mmHg for 60 minutes, then resuscitated with shed blood, and segregated into two groups: one group was treated with PRL (100 micrograms/25 g body weight subcutaneously) while the other group received saline-vehicles. This was followed with lactated Ringer's solution (2 x the volume of shed blood). Two hours thereafter, the animals were sacrificed, Kupffer cells were isolated and stimulated with or without 10 micrograms/ml LPS for 1 hour. Total RNA was extracted and cytokine mRNA was detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The results demonstrated that haemorrhage markedly increased the level of mRNA for IL-1 beta, IL-6, TGF-beta and TNF-beta in Kupffer cells. However, in vivo PRL treatment significantly decreased the cytokine gene expression in Kupffer cells following haemorrhage. This indicates that PRL may be useful in blunting the systemic inflammatory response associated with cell and organ depression following shock.

  10. Placebo-controlled study of effects of epimestrol on the pituitary-testicular axis in normal men.

    PubMed

    Luisi, M; Kicóvíc, P M; Franchi, F

    1980-01-01

    Twenty healthy male volunteers were randomly allocated to the treatment with either 15 mg/day of epimestrol or placebo for 10 days. The plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), oestradiol (E2) and prolactin (PRL) were measured before, during and 4 days after the medication by radioimmunoassays. Data were statistically evaluated by means of an analysis of covariance. Circulating LH and FSH, and also T and E2 significantly increased in the epimestrol treated subjects. In the placebo treated subjects no significant changes in the plasma hormone levels were observed. There were no significant changes in the plasma levels of PRL in either group.

  11. Presence and possible site of action of secretin in the rat pituitary and hypothalamus

    SciTech Connect

    Samson, W.K.; Lumpkin, M.D.; McCann, S.M.

    1984-01-09

    Secretin-like immunoreactivity was detected in extracts of several rat brain structures by radioimmunoassay, most notably in the pituitary, hypothalamus, pineal and septum. Its localization to these structures suggested that it might play a role in neuroendocrine events similar to its structural homolog vasoactive intestinal peptide. Dose-related stimulations (MED, 10/sup -7/ M) of prolactin (PRL) release were observed after incubation of synthetic secretin with dispersed, cultured pituitary cells from male and ovariectomized (OVX) female rats. Secretin can now be added to the growing list of putative PRL-releasing agents.

  12. Maturation of the prolactin and proopiomelanocortin-derived peptide responses to ether stress and morphine: neurochemical analysis.

    PubMed

    Johnston, C A; Negro-Vilar, A

    1986-02-01

    The hormonal and neurochemical responses to acute ether stress, morphine, and/or naloxone were analyzed in infantile (13-day-old) and prepubertal (36-day-old) male CD rats in an attempt to identify a possible neurochemical correlate(s) for the previously demonstrated requisite maturation of the PRL response to ether stress. Neuronal serotonin (5-HT), norepinephrine (NE), and dopamine (DA) activities were examined in the medial preoptic hypothalamic area (MPOH), medial basal hypothalamic area (MBH), and median eminence (ME). Ether stress increased plasma PRL, ACTH, and beta-endorphin-like immunoreactivity (beta end) as well as NE metabolism in the MPOH and MBH and neuronal 5-HT activity in the MBH, and decreased neuronal DA activity in the ME of prepubertal animals. Ether stress elicited similar changes in infantile animals, with the important exceptions that plasma PRL, neuronal 5-HT activity in the MBH, and neuronal DA synthesis in the ME were not affected at this earlier age. Morphine increased plasma PRL, ACTH, and beta end levels, elevated neuronal NE and 5-HT activities in the MPOH and MBH, and decreased DA synthesis in the ME in both infantile and prepubertal animals. Naloxone administration did not alter basal hormone concentrations or neuronal monoamine activity in any brain area, but did prevent all of the morphine-induced changes as well as the ether stress-induced changes in PRL, MBH neuronal 5-HT activity, and DA synthesis in the ME of prepubertal animals. In addition, naloxone augmented the ether stress-induced increases in ACTH and beta end in prepubertal rats. Indirect stimulation of 5-HT neurons by administration of the amino acid precursor of 5-HT, 5-hydroxytryptophan, resulted in decreased DA synthesis in the ME of infantile animals and increased plasma PRL levels in that age group, indicating that this portion of the neurochemical connection is already present in infantile animals. Furthermore, the 5-hydroxytryptophan-induced increase in PRL was

  13. Localization of the aromatase enzyme expression in the human pituitary gland and its effect on growth hormone, prolactin, and thyroid stimulating hormone axis.

    PubMed

    Caglar, Asli Sezgin; Kapucu, Aysegul; Dar, Kadriye Akgun; Ozkaya, Hande Mefkure; Caglar, Erkan; Ince, Haluk; Kadioglu, Pinar

    2015-08-01

    The aim of this study is to evaluate aromatase expression in prolactin (PRL), thyroid stimulating hormone (TSH), and growth hormone (GH) secreting cells. Nontumoral human pituitary specimens were obtained from autopsy samples. Aromatase co-expression was determined by double immunohistochemical staining and assessed using H scores. H scores for GH-aromatase co-expression (GH-aromatase), TSH-aromatase co-expression (TSH-aromatase), and PRL-aromatase co-expression (PRL-aromatase) were 83.1 ± 13.1, 95.6 ± 16.1, and 83.7 ± 14.5, respectively. TSH producing cells exhibited the highest H score for co-expression of aromatase (p < 0.001). There was no gender difference in terms of H scores for aromatase expression and double immunohistochemical staining results (p > 0.05 for all). There was a negative correlation between the H scores for aromatase and PRL-aromatase, GH-aromatase and TSH-aromatase, respectively (r = -0.592, p < 0.001; r = -0.593, p < 0.001; r = -0.650, p < 0.001, respectively). Also, H scores for aromatase co-expression of each hormone were negatively correlated with the H scores for the corresponding hormone (r = -0.503, p < 0.001 for PRL-aromatase and PRL; r = -0.470, p < 0.001 for GH-aromatase, and GH; r = -0.641, p < 0.001 for TSH-aromatase and TSH). H scores for mean aromatase, GH-aromatase, TSH-aromatase were invariant of age (p > 0.05 for all). Age was negatively correlated with PRL-aromatase H score (r = -0.373, p = 0.008). Our study demonstrated significant aromatase co-expression in PRL, GH, and TSH secreting cells of the human anterior pituitary gland. The mutual paracrinal regulation between aromatase and three adenohypophyseal hormones indicates that aromatase may have a regulatory role on the synthesis and secretion of these hormones.

  14. Electrophoretic separation of kidney and pituitary cells on STS-8

    NASA Technical Reports Server (NTRS)

    Morrison, D. R.; Nachtwey, D. S.; Barlow, G. H.; Cleveland, C.; Lanham, J. W.; Farrington, M. A.; Hatfield, J. M.; Hymer, W. C.; Grindeland, R.; Lewis, M. L.

    1984-01-01

    Specific secretory cells were separated from suspensions of cultured primary human embryonic cells and rat pituitary cells in microgravity conditions, with an objective of isolating the subfractions of kidney cells that produce the largest amount of urakinase, and the subfractions of rat pituitary cells that secrete growth hormones (GH), prolactin (PRL), and other hormones. It is inferred from the experimental observations that the surface charge distributions of the GH-containing cells differ from those of the PRL-containing cells, which is explained by the presence of secretory products on the surface of pituitary cells. For kidney cells, the electrophoretic mobility distributions in flight experiments were spread more than the ground controls.

  15. Prolactin: the initial luteotropic stimulus of pseudopregnancy in the rat.

    PubMed

    Smith, M S; McLean, B K; Neill, J D

    1976-06-01

    The luteotropic stimuli necessary to transform the corpus luteum of the estrous cycle into a corpus luteum of psuedopregnancy on the morning of diestrus-2 (Day 2), as reflected by a dramatic divergence in progesterone secretion, were studied (Day 1 was taken as the first day of diestrus of pseudopregnancy). The requirement of prolactin (PRL) as a luteotropic stimulus was determined by inhibiting the diurnal and nocturnal PRL surges that occur immediately before and during the divergence in progesterone. Following cervical stimulation, 1 mg of 2-Br-alpha-ergocryptine (EC) was injected at 1100 and 2300 h on Day 1 (lights on 0600-1800 h), and the animals were decapitated at 2-4 h intervals from 1100 h on Day 1 to 1700 h on Day 2. In the control animals, the PRL surges on Day 1 and Day 2 were associated with an increase in progesterone secretion on Day 2. However, the regimen of EC treatment resulted in an inhibition of PRL surges, prolactin remaining at baseline values from 1100 h on Day 1 to 1700 h on Day 2. The inhibition of PRL secretion was associated with a fall in progesterone concentration to reach baseline values by 1700h on Day 2. Furthermore, a group of animals similarly treated with EC returned to vaginal estrus 2 days later. LH concentrations did not differ in control and EC-treated animals. The effect of EC on corpus luteum function could be completely reversed by the simultaneous administration of PRL. In addition, if PRL was administered at 1100 h and 2300 h on diestrus-1 of the estrous cycle, in an attempt to mimic the surges os pseudopregnancy, regression of the corpora lutea did not occur. Progesterone levels increased to reach values comparable to those observed in pseudopregnancy on diestrus-2. The role of LH was studied by administering a dose of LH antiserum at 110 and 2300 h on Day 1 of pseudopregnancy. This treatment failed to inhibit the increase in progesterone observed on Day 2. These results demonstrate that the surges of plasma PRL

  16. Global phase diagram of bilayer quantum Hall ferromagnets

    NASA Astrophysics Data System (ADS)

    Abolfath, Ramin; Radzihovsky, Leo; MacDonald, Allan

    2002-03-01

    We present a microscopic study of the interlayer spacing d versus in-plane magnetic field B_allel phase diagram for bilayer quantum Hall (QH) pseudo-ferromagnets [1]. In addition to the interlayer charge balanced commensurate and incommensurate states studied previously [2], we nalyze microscopically the corresponding interlayer charge unbalanced canted QH states, predicted in Ref. [3]. We predict a large anomaly in the bilayer capacitance at the canting transition and the formation of dipole stripe domains with periods exceeding 1 micron in the canted state. [1] M. Abolfath et al. cond-mat/0110049. [2] Yang et al. PRL 72, 732 (1994). [3] Leo Radzihovsky PRL 87, 236802 (2001).

  17. Technology for return of planetary samples

    NASA Technical Reports Server (NTRS)

    1975-01-01

    Technological requirements of a planetary return sample mission were studied. The state-of-the-art for problems unique to this class of missions was assessed and technological gaps were identified. The problem areas where significant advancement of the state-of-the-art is required are: life support for the exobiota during the return trip and within the Planetary Receiving Laboratory (PRL); biohazard assessment and control technology; and quarantine qualified handling and experimentation methods and equipment for studying the returned sample in the PRL. Concepts for solving these problems are discussed.

  18. Spectroscopic studies on the interaction between Pr(III) complex of an ofloxacin derivative and bovine serum albumin or DNA

    NASA Astrophysics Data System (ADS)

    Xu, Min; Ma, Zhao-Rong; Huang, Liang; Chen, Feng-Juan; Zeng, Zheng-zhi

    2011-01-01

    The binding properties on [PrL 2(NO 3)](NO 3) 2 (L = 9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperaziny)-7-oxo-7Hpyrido[1,2,3-de]-1,4-benzoxazine-6-carbaldehyde benzoyl hydrazone) to bovine serum albumin (BSA) have been studied for the first time using fluorescence spectroscopy in combination with UV-Vis absorbance spectroscopy. The results showed that [PrL 2(NO 3)](NO 3) 2 strongly quenched the intrinsic fluorescence of BSA through a static quenching procedure, and non-radiation energy transfer happened within molecules. The number of binding site was about 1, and the efficiency of Förster energy transfer provided a distance of 4.26 nm between tryptophan and [PrL 2(NO 3)](NO 3) 2 binding site. At 288, 298, 310 K, the quenching constants of BSA-[PrL 2(NO 3)](NO 3) 2 system were 5.11 × 10 4, 4.33 × 10 4 and 3.71 × 10 4 l M -1. Δ H, Δ S and Δ G were obtained based on the quenching constants and thermodynamic theory (Δ H < 0, Δ S > 0 and Δ G < 0). These results indicated that hydrophobic and electrostatic interactions are the mainly binding forces in the [PrL 2(NO 3)](NO 3) 2-BSA system. In addition, the CD spectra have proved that BSA secondary structure changed in the presence of [PrL 2(NO 3)](NO 3) 2 in aqueous solution. Moreover, the interaction between [PrL 2(NO 3)](NO 3) 2 and calf thymus DNA (CT DNA) was studied by spectroscopy and viscosity measurements, which showed that the binding mode of the [PrL 2(NO 3)](NO 3) 2 with DNA is intercalation. The DNA cleavage results show that in the absence of any reducing agent, the [PrL 2(NO 3)](NO 3) 2 can cleave plasmid pBR322 DNA and its hydrolytic mechanism was demonstrated with hydroxyl radical scavengers and singlet oxygen quenchers.

  19. Prolactin gene expression and gill chloride cell activity in fugu Takifugu rubripes exposed to a hypoosmotic environment.

    PubMed

    Lee, Kyung Mi; Kaneko, Toyoji; Katoh, Fumi; Aida, Katsumi

    2006-12-01

    To evaluate a possible involvement of prolactin (PRL) in low-salinity tolerance of a marine pufferfish Takifugu rubripes, or fugu, gene-expression profiles of PRL in the pituitary and PRL receptor (PRLR) in the osmoregulatory organs were investigated in fish exposed to 25%-dilute seawater (SW). Following transfer from full-strength (100%) SW to 25% SW, plasma osmolality and Na(+) and Cl(-) levels were slightly decreased on day 1, which were restored on days 3 and 7. Expression levels of PRL mRNA in the pituitary was significantly increased in response to 25% SW transfer, which was in sharp contrast with a remarkable decrease in growth hormone (GH) mRNA levels. These profiles suggest that PRL and GH are involved in hyper- and hypoosmoregulation, respectively, as is the case with euryhaline teleosts. Expression levels of PRLR mRNA in the gill and intestine were not significantly different from the initial levels, whereas, PRLR mRNA expression in the kidney was significantly higher on day 7 than the initial levels. Although transfer to 25% SW did not affect the average size of Na(+)/K(+)-ATPase-immunoreactive chloride cells in the gills, both size and density of apical openings of chloride cells became significantly smaller after transfer to 25% SW. These findings suggest that the possible hypoosmotic action of PRL is mediated by PRLR expressed in the osmoregulatory organs, and that low-salinity tolerance of fugu may involve reduction of an ion-secreting function of gill chloride cells. To further evaluate long-term effects of the low-salinity environment on growth and osmoregulation, fugu were raised in 25% and 100% SW for a prolonged period of 8 weeks. They grew similarly in 25% and 100% SW, and there was no significant difference in body weight and standard length at any weekly sampling point. The plasma osmolality was maintained at about 345mOsm/kg.H(2)O in both media, whereas the gill Na(+)/K(+)-ATPase activity was significantly lower in 25% SW than 100% SW. Gene

  20. Identification of somatomammotroph cells in lactating goats (Capra hircus) by fluorescence and immunogold techniques.

    PubMed

    Sánchez, J; Navarro, J A; Bernabé, A; Gómez, S; Garcés, B; Gómez, M A

    1994-01-01

    The occurrence and ultrastructural morphology of somatomammotroph cells, in the anterior pituitary tissue of the goat, is studied using fluorescence microscopic double staining and two methods of double immunogold staining combined with electron microscopy. Under the fluorescence microscope numerous monohormonal cells, either mammotroph cells (prolactin, PRL, cells) or somatotroph cells (growth hormone, GH, cells) are observed, but cells containing both hormones (somatomammotroph or SMT cells) are scarce. SMT cells do not differ ultrastructurally from monohormonal cells, and the cytoplasm contains two populations of granules, each reactive only for one of the antisera, either antisheep GH or antisheep PRL.

  1. Identical changes in Bax expression, but not Fas ligand expression, occur in structural luteolysis in gonadotropin releasing hormone agonist- and prolactin-treated superovulated rats.

    PubMed

    Endo, Toshiaki; Kiya, Tamotsu; Kitajima, Yoshimitsu; Honnma, Hiroyuki; Chida, Manabu; Hayashi, Takumi; Henmi, Hirofumi; Yamazaki, Kiyohiro; Hayashi, Takuhiro; Manase, Kengo; Kudo, Ryuichi

    2005-03-25

    Structural luteolysis induced by gonadotropin releasing hormone agonist (GnRHa) or prolactin (PRL) is defined as histological involution of the corpus luteum. We reported that one of the mechanisms of structural luteolysis induced by PRL was tissue remodeling by matrix metalloproteinase (MMP) and also apoptosis in superovulated rats. We also reported that GnRHa induced structural luteolysis with elevation of MMP. In this study, we investigated whether GnRHa caused apoptosis in mature corpus luteum of superovulated rats and also examined the expression of apoptosis-related molecules (Fas, Fas ligand (FasL), Bcl-2, Bax). We gave 4-day GnRHa treatment 5 days after hCG injection to immature female rats treated with pregnant mare surum gonadotrophin (PMSG) and hCG to induce structural involution of mature corpus luteum. PMSG-hCG-treated rats without GnRHa treatment, rats treated with bromocryptine (Brom) to induce functional luteolysis and rats treated with Brom followed by PRL (Brom+PRL) to mimic the PRL surge to induce structural luteolysis as we previously reported were used for comparison. GnRHa treatment caused structural luteolysis characterized by structural involution, a decrease in the serum progestin level, and apoptotic bodies as well as structural luteolysis induced by Brom+PRL. FasL expression in corpora lutea was elevated after Brom treatment, but there was no elevation of FasL after GnRHa treatment started. FasL expression decreased and Bax expression increased in structural luteolysis induced by GnRHa as well as Brom+PRL treatment, although Fas and Bcl-2 expression did not change throughout the luteal phase. In summary, both GnRHa and Brom+PRL caused structural luteolysis, one of whose mechanisms was apoptosis with an increase in Bax expression, but not with an identical change in FasL expression. It is speculated that the significance in alteration of FasL may involve some mechanism other than apoptosis. PMID:15733931

  2. Immunocytochemical localization of human growth hormone- and prolactin-like antigenic determinants in the insects, Locusta migratoria and Sarcophaga bullata.

    PubMed

    Swinnen, K; Broeck, J V; Verhaert, P; De Loof, A

    1990-01-01

    1. By use of the peroxidase-antiperoxidase immunocytochemical method, substances immunoreactive to antisera directed against human growth hormone (hGH) and prolactin (hPrl) were localized in the nervous system of larval and adult Locusta migratoria and of adult Sarcophaga bullata belonging to different age groups. 2. No major differences in the distribution of cerebral immunoreactive materials were observed between males and females or between juvenile and adult insects. 3. Differential immuno-labeling of alternating tissue sections demonstrated that materials resembling hGH or hPrl are present in distinct neurons in the locust, whereas neurons immunoreactive to both antisera were detected in the fleshfly (Sarcophaga).

  3. Delayed Adrenarche may be an Additional Feature of Immunoglobulin Super Family Member 1 Deficiency Syndrome.

    PubMed

    Van Hulle, Severine; Craen, Margarita; Callewaert, Bert; Joustra, Sjoerd; Oostdijk, Wilma; Losekoot, Monique; Wit, Jan Maarten; Turgeon, Marc Olivier; Bernard, Daniel J; De Schepper, Jean

    2016-03-01

    Immunoglobulin super family member 1 (IGSF1) deficiency syndrome is characterized by central hypothyroidism, delayed surge in testosterone during puberty, macro-orchidism, and in some cases, hypoprolactinemia and/or transient growth hormone (GH) deficiency. Our patient was a 19-year-old male adolescent who had been treated since the age of 9 years with GH and thyroxine for an idiopathic combined GH, thyroid-stimulating hormone (TSH), and prolactin (PRL) deficiency. His GH deficiency proved to be transient, but deficiencies of TSH and PRL persisted, and he had developed macro-orchidism since the end of puberty. Brain magnetic resonance imaging and PROP1 and POU1F1 sequencing were normal. A disharmonious puberty (delayed genital and pubic hair development, bone maturation, and pubertal growth spurt, despite normal testicular growth) was observed as well as a delayed adrenarche, as reflected by very low dehydroepiandrosterone sulfate and delayed pubarche. Direct sequencing of the IGSF1 gene revealed a novel hemizygous mutation, c.3127T>C, p.Cys1043Arg. Pathogenicity of the mutation was demonstrated in vitro. Male children with an idiopathic combined GH, PRL, and TSH deficiency, showing persistent central hypothyroidism but transient GH deficiency upon retesting at adult height, should be screened for mutations in the IGSF1 gene, especially when macro-orchidism and/or hypoprolactinemia are present. We suspect that delayed adrenarche, as a consequence of PRL deficiency, might be part of the clinical phenotype of patients with IGSF1 deficiency. PMID:26757742

  4. MATERNAL ATRAZINE (ATR) ALTERS HYPOTHALAMIC DOPAMINE (HYP-DA) AND SERUM PROLACTIN (SPRL) IN MALE PUPS

    EPA Science Inventory

    Maternal Atrazine (ATR) alters hypothalamic dopamine (HYP-DA) and serum prolactin (sPRL) in male pups. 1Christopher Langdale, 2Tammy Stoker and 2Ralph Cooper. 1 Dept. of Cell Biology, North Carolina State University College of Veterinary Medicine, Raleigh, NC. 2 Endocrinology ...

  5. Late presentation of acromegaly in medically controlled prolactinoma patients

    PubMed Central

    Manuylova, Ekaterina; Calvi, Laura M; Hastings, Catherine; Vates, G Edward; Johnson, Mahlon D; Cave, William T

    2016-01-01

    Summary Co-secretion of growth hormone (GH) and prolactin (PRL) from a single pituitary adenoma is common. In fact, up to 25% of patients with acromegaly may have PRL co-secretion. The prevalence of acromegaly among patients with a newly diagnosed prolactinoma is unknown. Given the possibility of mixed GH and PRL co-secretion, the current recommendation is to obtain an insulin-like growth factor-1 (IGF-1) in patients with prolactinoma at the initial diagnosis. Long-term follow-up of IGF-1 is not routinely done. Here, we report two cases of well-controlled prolactinoma on dopamine agonists with the development of acromegaly 10–20 years after the initial diagnoses. In both patients, a mixed PRL/GH-cosecreting adenoma was confirmed on the pathology examination after transsphenoidal surgery (TSS). Therefore, periodic routine measurements of IGF-1 should be considered regardless of the duration and biochemical control of prolactinoma. Learning points: Acromegaly can develop in patients with well-controlled prolactinoma on dopamine agonists. The interval between prolactinoma and acromegaly diagnoses can be several decades. Periodic screening of patients with prolactinoma for growth hormone excess should be considered and can 
lead to an early diagnosis of acromegaly before the development of complications.

  6. Effect of prolactin, beta-lactoglobulin, and kappa-casein genotype on milk yield in East Friesian sheep.

    PubMed

    Staiger, E A; Thonney, M L; Buchanan, J W; Rogers, E R; Oltenacu, P A; Mateescu, R G

    2010-04-01

    The effect of prolactin (PRL), beta-lactoglobulin (beta-LG), and kappa-casein (CSN3) on milk yield was estimated in an East Friesian dairy sheep population from Old Chatham Sheepherding Company, New York. Genotypes were determined by PCR amplification followed by digestion with HaeIII and RsaI for PRL and beta-LG, respectively, and by PCR amplification for CSN3. Monthly milking records and pedigree information were used to evaluate the effect of each polymorphism on milk yield. Results indicated that PRL genotype had a significant effect on milk yield. Ewes carrying one A allele produced 110.6g more milk per day than ewes with no A alleles. There was no statistical difference between ewes with only one A allele and ewes with 2 A alleles. No association among polymorphisms at the beta-LG and CSN3 loci and milk yield was found. The results presented in this study indicate that the PRL gene is a potential marker that could be used in selection programs for improving milk yield in dairy sheep.

  7. Effect of pulse frequency and amplitude of D-Trp6-luteinizing hormone-releasing hormone on the pulsatile secretion of prolactin and LH.

    PubMed

    Rodriguez, T; Bordiu, E; Rubio, J A; Duran, A; Charro, A L

    1993-09-01

    This work analyzes the effect of the pulse amplitude and frequency of a potent LHRH analog, D-Trp6-LHRH, in a perfusion system of isolated rat pituitary cells. To this purpose, we studied the LH and PRL secretion in different conditions: basal secretion, secretion after increasing concentrations of D-Trp6-LHRL (0.001, 0.01, 0.1 and 1 nM) secretion in function of the pulses frequency (2,3, and 4 pulses per h) and amplitude (0.1, 1 and 10 nM). The principal findings were: 1. The basal LH and PRL secretions was pulsatile; 2. The stimulation of LH by the analog was not dose-dependent; 3. When more than 2 pulses per h were administered, a rapid desensitization of gonadotroph to release LH (at 20-30 min) occurred; 4. There was a loss of pulsatility of PRL secretion with an increase in the pulse frequency and amplitude of the D-Trp6-LHRH, which was produced parallelly to the desensitization of the gonadotroph to release LH. In summary, these findings suggest that a rapid loss of pulsatility of the PRL when the D-Trp6-LHRH pulse frequency and amplitude is increased might be due to the early desensitization of the gonadotroph to the analog.

  8. Potentially Pathogenic Immune Cells and Networks in Apparently Healthy Lacrimal Glands

    PubMed Central

    Mircheff, Austin K.; Wang, Yanru; Ding, Chuanqing; Warren, Dwight W.; Schechter, Joel E.

    2014-01-01

    Lacrimal glands of people over 40 years old frequently contain lymphocytic infiltrates. Relationships between histopathological presentation and physiological dysfunction are not straightforward. Data from rabbit studies have suggested that at least two immune cell networks form in healthy lacrimal glands, one responding to environmental dryness, the other to high temperatures. New findings indicate that mRNAs for several chemokines and cytokines are expressed primarily in epithelial cells; certain others are expressed in both epithelial cells and immune cells. Transcript abundances vary substantially across glands from animals that have experienced the same conditions, allowing for correlation analyses, which detect clusters that map to various cell types and to networks of coordinately functioning cells. A core network—expressing mRNAs including IL-1α, IL-6, IL-17A, and IL-10—expands adaptively with exposure to dryness, suppressing IFN-γ, but potentially causing physiological dysfunction. High temperature elicits concurrent increases of mRNAs for prolactin (PRL), CCL21, and IL-18. PRL is associated with crosstalk to IFN-γ, BAFF, and IL-4. The core network reacts to the resulting PRL-BAFF-IL-4 network, creating a profile reminiscent of Sjögren’s disease. In a warmer, moderately dry setting, PRL-associated increases of IFN-γ are associated with suppression of IL-10 and augmentations of IL-1α and IL-17, creating a profile reminiscent of severe chronic inflammation. PMID:25557346

  9. Perinatal activity of the hypothalamic-pituitary-gonadal axis in the lamb. III. LH, testosterone and prolactin secretory pattern in newborn lambs.

    PubMed

    Savoie, S; Polychronakos, C; Forest, M G; Haour, F; Collu, R; Ducharme, J R

    1981-01-01

    Crossbred male and female lambs from Suffolk rams and Dorset-Finnish ewes born in January and February were studied at 1, 3, 7, 21 and 28 days of age and female lambs at 14 days. Ultradian variations in plasma luteinizing hormone (LH), prolactin (PRL) and testosterone were studied at 30-min intervals during a 4-hour period. In female lambs LH secretory peaks were observed at 7 days of age the amplitude of LH peaks increasing 8-fold between 7 and 14 days and 2-fold between 21 and 28 days. The number of secretory peaks also increased with age. Ultradian variations in PRL were observed from 1 day of age, the amplitude of the PRL peaks increasing also with age. In male lambs, LH and testosterone peaks were observed at 3 days of age, the testosterone peak being preceded by or concomitant with LH peaks. The amplitude of LH peaks increased with age together with basal testosterone levels although the amplitude of testosterone peaks was unchanged. This study demonstrates pulsatile secretion of LH and PRL in lambs of both sexes and of testosterone in male lambs in the first week of postnatal life. In addition, since the ovine testis is responsive to endogenous gonadotropic stimulation at this period, it is suggested that the hypothalamic-pituitary-gonadal axis is already operative at this age. It can be concluded that the hypothalamic activity concerned with pulsatile LH and prolactin secretion is present very early in the lamb neonate.

  10. Diurnal profiles of testosterone and pituitary hormones suggest different mechanisms for menstrual disturbances in endurance athletes.

    PubMed

    Rickenlund, Anette; Thorén, Marja; Carlström, Kjell; von Schoultz, Bo; Hirschberg, Angelica Lindén

    2004-02-01

    The aim of this study was to evaluate the diurnal pattern of testosterone and pituitary hormones in endurance female athletes with different types of menstrual disorder. Age- and body mass index-matched groups of endurance athletes with amenorrhea (n = 10) and oligomenorrhea (n = 6), regularly cycling athletes (n = 8), and sedentary controls (n = 8) were compared with respect to 24-h hormonal profiles of testosterone, LH, prolactin (PRL), GH, insulin, IGF binding protein 1 (IGFBP-1), and cortisol. The 24-h hormone profiles in amenorrheic athletes were characterized by decreased LH pulsatility and peak amplitude of PRL and increased baseline levels of GH and cortisol. However, oligomenorrheic athletes displayed a significantly different pattern with higher diurnal testosterone secretion than all other groups. Furthermore, LH, PRL, GH, and cortisol secretions were comparable with regularly menstruating subjects. In the combined group of athletes with menstrual disturbances, diurnal secretions of testosterone, LH, and PRL were positively, whereas cortisol was negatively correlated with the number of menstruations the last year. Although this could be explained by a gradual inhibition of the hypothalamic-pituitary-gonadal axis, our results indicate that the symptoms of amenorrhea and oligomenorrhea may reflect two hormonally distinct conditions. Thus, amenorrheic athletes displayed a hormonal pattern in agreement with hypothalamic inhibition due to energy deficiency, whereas oligomenorrheic athletes demonstrated increased diurnal secretion of testosterone, suggesting a different mechanism, e.g. essential hyperandrogenism.

  11. THE EFFECT OF ATRAZINE ON PUBERTY IN THE MALE WISTAR RATS: AN EVALUATION IN THE PROTOCOL FOR THE ASSESSMENT OF PUBERTAL DEVELOPMENT AND THYROID FUNCTION

    EPA Science Inventory

    Since atrazine (ATR), a chlorotriazine herbicide, has been shown previously to alter the secretion of luteinizing hormone (LH) and prolactin (PRL) through a direct effect on the central nervous system (CNS), we hypothesized that exposure to ATR in the EDSTAC male pubertal protoco...

  12. Developmental expression and estrogen responses of endocrine genes in juvenile yellow perch (Perca flavescens)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present study examines the expression of growth-regulating genes (gh, prl, smtl and igf1b), the estrogen receptors (esr1 and esr2a) and aromatase (cyp19a1a) in developing yellow perch. To gain an initial understanding into the endocrine control of growth preceding and involved with sexual size d...

  13. Neonatal androgenization increases vasoactive intestinal peptide levels in rat anterior pituitary: possible involvement of vasoactive intestinal peptide in the neonatal androgenization-induced hyperprolactinemia.

    PubMed

    Watanobe, H; Sasaki, S; Takebe, K

    1991-11-01

    Accumulating evidence suggests that vasoactive intestinal peptide (VIP) may be a physiological PRL-releasing factor. In the present study, we examined a possible involvement of VIP in the neonatal androgenization (NA)-induced hyperprolactinemia. Twenty-four hours after birth, newborn female rats were injected sc with 1,000 micrograms of testosterone (NA) or with oil vehicle only (control). Both groups were sacrificed at 8 weeks of age. Compared to controls, NA rats showed significantly higher plasma PRL levels (7.3 fold), anterior pituitary (AP) PRL content (2.1 fold) and plasma estradiol levels (2.1 fold). AP VIP content was extremely higher (61 fold) in NA rats than in controls. However, NA did not affect VIP content in the suprachiasmatic nucleus, paraventricular nucleus or median eminence. These results suggest that the NA-induced hyperprolactinemia may be mediated, at least in part, by paracrine and/or autocrine effects of the increased AP VIP on PRL secretion. However, since the potentiation by NA of the AP VIP content was extremely marked compared to those of the other parameters, the possibility was also raised that the increased AP VIP may be involved in other endocrine and/or nonendocrine events occurring in the AP. PMID:1802925

  14. ZBTB20 is required for anterior pituitary development and lactotrope specification.

    PubMed

    Cao, Dongmei; Ma, Xianhua; Cai, Jiao; Luan, Jing; Liu, An-Jun; Yang, Rui; Cao, Yi; Zhu, Xiaotong; Zhang, Hai; Chen, Yu-Xia; Shi, Yuguang; Shi, Guang-Xia; Zou, Dajin; Cao, Xuetao; Grusby, Michael J; Xie, Zhifang; Zhang, Weiping J

    2016-01-01

    The anterior pituitary harbours five distinct hormone-producing cell types, and their cellular differentiation is a highly regulated and coordinated process. Here we show that ZBTB20 is essential for anterior pituitary development and lactotrope specification in mice. In anterior pituitary, ZBTB20 is highly expressed by all the mature endocrine cell types, and to some less extent by somatolactotropes, the precursors of prolactin (PRL)-producing lactotropes. Disruption of Zbtb20 leads to anterior pituitary hypoplasia, hypopituitary dwarfism and a complete loss of mature lactotropes. In ZBTB20-null mice, although lactotrope lineage commitment is normally initiated, somatolactotropes exhibit profound defects in lineage specification and expansion. Furthermore, endogenous ZBTB20 protein binds to Prl promoter, and its knockdown decreases PRL expression and secretion in a lactotrope cell line MMQ. In addition, ZBTB20 overexpression enhances the transcriptional activity of Prl promoter in vitro. In conclusion, our findings point to ZBTB20 as a critical regulator of anterior pituitary development and lactotrope specification. PMID:27079169

  15. Dynamics of prolactin, gonadotropin, and of sex steroids in the blood serum of parturients during laser therapy

    NASA Astrophysics Data System (ADS)

    Kovalyov, M. I.

    2001-04-01

    An investigation was made of the effect (lambda) equals 0.63 micrometers diode laser radiation with the energy density of 0.6 to 0.8 J cm-2 on parturients affected by nipples' rhagades. In our experiments, we determined the content of prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and of progesterone (P) in the parturients' blood serum. It was found that laser radiation produced an insignificant effect on the prolactic (PRL) content in parturients with the normal lactation level. On the contrary, it produced a stimulating effect on the PRL level in parturients with hypogalactia. Possibly, laser radiation promoted the decrease in the FSH level in the parturients' blood serum. It was also found that this laser radiation produced an insignificant effect on the levels of LH, estradiol (E2), and of progesterone. Women subsequently affected by mastitis exhibited a significantly higher PRL level in their blood serum, as compared with women of the control group.

  16. Consumption of endophyte-infected fescue seed during the dry period does not decrease milk production in the following lactation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ergot alkaloids in endophyte-infected grasses inhibit prolactin (PRL) secretion and may reduce milk production of cows consuming endophyte-infected grasses. We investigated the effects of consuming endophyte-infected fescue during late lactation and the dry period on mammary growth, differentiation ...

  17. Increased milk production by Holstein cows consuming endophyte-infected fescue seed during the dry period.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ergot alkaloids in endophyte-infected grasses inhibit prolactin (PRL) secretion and may reduce milk production of cows consuming endophyte-infected grasses. We hypothesized that consumption of endophyte-infected fescue during the dry period inhibits mammary differentiation and subsequent milk produ...

  18. Association between endometriosis and hyperprolactinemia in infertile women

    PubMed Central

    Esmaeilzadeh, Seddigheh; Mirabi, Parvaneh; Basirat, Zahra; Zeinalzadeh, Mahtab; Khafri, Soraya

    2015-01-01

    Background: The association of endometriosis with hyperprolactinemia is controversial. Objective: The present study aimed to determine the frequency of endometriosis and association of prolactin with endometriosis in infertile women. Materials and Methods: 256 infertile women who underwent diagnostic laparoscopy for the evaluation of infertility, referred to Fatemezahra Infertility and Reproductive Health Research Center were included in a cross-sectional study. The presence of endometriosis was evaluated. To investigate the association of endometriosis with hyperprolactinemia, the patients whose infertility was not caused by endometriosis were included as control group. Serum prolactin (PRL) level was measured in both groups. The comparison of basal serum PRL levels between the two groups was performed, using independent t-test. One way ANOVA was used to determine PRL association with endometriosis stages. Results: The frequency of endometriosis was found to be 29%. PRL levels were significantly higher in endometriosis group compared to control group (23.02±1.25 vs. 17.22±1.22 respectively, p=0.004). Statistically significant associations were found between staging of endometriosis and prolactin levels (p=0.01). Conclusion: Hyperprolactinemia may be associated with endometriosis and its progression. PMID:26000006

  19. 8 CFR 324.4 - Women restored to United States citizenship by the act of June 25, 1936, as amended by the act of...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Women restored to United States citizenship... NATURALlZED: WOMEN WHO HAVE LOST UNITED STATES CITIZENSHIP BY MARRIAGE AND FORMER CITIZENS WHOSE NATURALIZATION IS AUTHORIZED BY PRlVATE LAW § 324.4 Women restored to United States citizenship by the act...

  20. Epigenetic modification of PKMζ rescues aging-related cognitive impairment.

    PubMed

    Chen, Chen; Meng, Shi-Qiu; Xue, Yan-Xue; Han, Ying; Sun, Cheng-Yu; Deng, Jia-Hui; Chen, Na; Bao, Yan-Ping; Zhang, Fei-Long; Cao, Lin-Lin; Zhu, Wei-Guo; Shi, Jie; Song, Wei-Hong; Lu, Lin

    2016-03-01

    Cognition is impacted by aging. However, the mechanisms that underlie aging-associated cognitive impairment are unclear. Here we showed that cognitive decline in aged rats was associated with changes in DNA methylation of protein kinase Mζ (PKMζ) in the prelimbic cortex (PrL). PKMζ is a crucial molecule involved in the maintenance of long-term memory. Using different behavioral models, we confirmed that aged rats exhibited cognitive impairment in memory retention test 24 h after training, and overexpression of PKMζ in the PrL rescued cognitive impairment in aged rats. After fear conditioning, the protein levels of PKMζ and the membrane expression of GluR2 increased in the PrL in young and adult rats but not in aged rats, and the levels of methylated PKMζ DNA in the PrL decreased in all age groups, whereas the levels of unmethylated PKMζ DNA increased only in young and adult rats. We also found that environmentally enriched housing reversed the hypermethylation of PKMζ and restored cognitive performance in aged rats. Inactivation of PKMζ prevented the potentiating effects of environmental enrichment on memory retention in aged rats. These results indicated that PKMζ might be a potential target for the treatment of aging-related cognitive impairment, suggesting a potential therapeutic avenue.

  1. Adaptation to a simulated central scotoma during visual search training.

    PubMed

    Walsh, David V; Liu, Lei

    2014-03-01

    Patients with a central scotoma usually use a preferred retinal locus (PRL) consistently in daily activities. The selection process and time course of the PRL development are not well understood. We used a gaze-contingent display to simulate an isotropic central scotoma in normal subjects while they were practicing a difficult visual search task. As compared to foveal search, initial exposure to the simulated scotoma resulted in prolonged search reaction time, many more fixations and unorganized eye movements during search. By the end of a 1782-trial training with the simulated scotoma, the search performance improved to within 25% of normal foveal search. Accompanying the performance improvement, there were also fewer fixations, fewer repeated fixations in the same area of the search stimulus and a clear tendency of using one area near the border of the scotoma to identify the search target. The results were discussed in relation to natural development of PRL in central scotoma patients and potential visual training protocols to facilitate PRL development. PMID:24456805

  2. Daily illuminance levels affect pituitary prolactin in male rats.

    PubMed

    Laakso, M L; Porkka-Heiskanen, T; Alila, A; Kajander, S; Stenberg, D; Johansson, G

    1989-04-01

    The 24-h patterns of melatonin, PRL, and gonadotropins in male rats maintained under natural lighting conditions have been found to differ from the patterns in rats kept under artificial lighting. In the present experiments we studied the role of different daily illuminances as a possible causative factor for the variation of the hormonal patterns. Three groups of male rats were kept under artificial lighting conditions (12 h on/12 h off), where the daily illuminance was 550, 110 or 25 lux. After a 7-day adaptation period the pineal content of melatonin, the serum levels of LH, FSH and PRL, and the pituitary content of these hormones were measured by RIAs in samples taken at 10.00, 13.00, 22.00 and 01.00 h. The patterns of pineal melatonin were equal in all three groups. The variation of daily illuminance did not change the serum levels of LH, FSH and PRL or the pituitary content of the gonadotropins. However, the pituitary content of PRL during the light phase was inversely related to the illuminance. The results suggest that the intensity of daily lighting in the studied range does not affect the patterns of melatonin or gonadotropins, but the synthesis of prolactin may be significantly regulated by the daily illuminance level.

  3. Membrane protein CNNM4–dependent Mg2+ efflux suppresses tumor progression

    PubMed Central

    Funato, Yosuke; Yamazaki, Daisuke; Mizukami, Shin; Du, Lisa; Kikuchi, Kazuya; Miki, Hiroaki

    2014-01-01

    Intracellular Mg2+ levels are strictly regulated; however, the biological importance of intracellular Mg2+ levels and the pathways that regulate them remain poorly understood. Here, we determined that intracellular Mg2+ is important in regulating both energy metabolism and tumor progression. We determined that CNNM4, a membrane protein that stimulates Mg2+ efflux, binds phosphatase of regenerating liver (PRL), which is frequently overexpressed in malignant human cancers. Biochemical analyses of cultured cells revealed that PRL prevents CNNM4-dependent Mg2+ efflux and that regulation of intracellular Mg2+ levels by PRL and CNNM4 is linked to energy metabolism and AMPK/mTOR signaling. Indeed, treatment with the clinically available mTOR inhibitor rapamycin suppressed the growth of cancer cells in which PRL was overexpressed. In ApcΔ14/+ mice, which spontaneously form benign polyps in the intestine, deletion of Cnnm4 promoted malignant progression of intestinal polyps to adenocarcinomas. IHC analyses of tissues from patients with colon cancer demonstrated an inverse relationship between CNNM4 expression and colon cancer malignancy. Together, these results indicate that CNNM4-dependent Mg2+ efflux suppresses tumor progression by regulating energy metabolism. PMID:25347473

  4. Adrenal influence on the persistence of pseudopregnancy in rats.

    PubMed

    Kawaminami, Mitsumori; Yoshida, Makoto; Moriai, Yutaka; Kurusu, Shiro; Hashimoto, Inoru

    2002-06-01

    The effect of adrenalectomy on the duration of pseudopregnancy was investigated in rats. When adrenalectomy was performed three days before cervical stimulation or when it was done on the first day (day 1, day of estrus) or day 2 of pseudopregnancy, the duration of the pseudopregnancy was significantly prolonged (3.0, 2.5 and 1.8 days respectively). This effect of adrenalectomy was not seen when operation was delayed until day 4 of pseudopregnancy. Adrenalectomy on day 2 of pseudopregnancy significantly increased prolactin (PRL) release at the time of the nocturnal PRL surge (5:00) on day 7. When rats were ovariectomized simultaneously with adrenalectomy on day 1, the stimulating effect of adrenalectomy on PRL release was more evident. The effect of active immunization against corticosterone on the continuation of pseudopregnancy was also examined. Neutralization of plasma corticosterone extended the duration of pseudopregnancy and the binding activity of the antiserum positively correlated with the length of continuing diestrus (P < 0.05). These results indicate the negative effect of the adrenal glands, which is probably due to corticosterone, on PRL release in pseudopregnant rats and that the early relief of this inhibition extends the duration of pseudopregnancy.

  5. Prolactin and breast cancer: The need to avoid undertreatment of serious psychiatric illnesses in breast cancer patients: A review.

    PubMed

    Froes Brandao, Denise; Strasser-Weippl, Kathrin; Goss, Paul E

    2016-01-15

    Hyperprolactinemia, defined as a sustained elevation of prolactin (PRL) levels greater than 530 mIU/L in women and greater than 424 mIU/L in men, has been implicated for a long time in breast cancer etiology and prognosis. Elevated PRL values (approximately 2-3 times higher than the reference values) are a common adverse effect of antipsychotic medications, especially with first-generation drugs, and most antipsychotics carry a standard warning regarding PRL elevations on their US product labels. These associations foster undertreatment of serious psychiatric illnesses in both otherwise healthy patients and cancer patients. This review assesses both the preclinical and clinical evidence that has led to the hypothesis of PRL's role in breast cancer risk or breast cancer progression. It is concluded that taken together, the published data are unconvincing and insufficient to deprive cancer patients in general and breast cancer patients specifically of potentially effective antipsychotic or antidepressant medications for serious psychiatric indications. We thus call on revised medication guidelines to avoid the existing undertreatment of serious psychiatric illnesses among cancer patients based on an unproven contraindication to psychiatric medications. Cancer 2016;122:184-188. © 2015 American Cancer Society. PMID:26457577

  6. Effects of pterostilbene on treating hyperprolactinemia and related mechanisms

    PubMed Central

    Zhang, Haoru; Wang, Changhua; Li, Xiaokun; Zhang, Yong

    2016-01-01

    Hyperprolactinemia (HPRL) frequently causes primary menopause and reproductive disorders. Pterostilbene is known to have anti-inflammation and modulation on cell apoptosis. However, its role in treating HPRL and potential mechanisms remain unclear yet. Healthy female virgin SD rats were randomly assigned into control, HPRL model group, bromocriptine treatment group, and low (20 mg/kg) and high (40 mg/kg) pterostilbene treatment groups. All groups except control ones received metoclopramide hydrochloride injection for generating HPRL model. Uterus and ovarian index in all animals were monitored. Prolactin (PRL), estradiol (E2), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were quantified by ELISA. Caspase 3 activity was assayed, with real time PCR measuring Bcl-2 and Bax mRNA levels. HPRL rats had lower uterus and ovarian index, accompanied with elevated PRL, caspase 3 activity, Bax expression, and decreased FSH, LH, E2 and Bcl-2 expression as compared to control group (p<0.05). Pterostilbene treatment significantly increased uterus and ovarian index, FSH, LH, E2 and Bcl-2 expression, and decreased PRL, caspase 3 activity and Bax expression as compared to control group (p<0.05). 40 mg/kg pterostilbene had similar efficacy as those of bromocriptine. Pterostilbene exerts its function in the treatment of HPRL via modulating apoptosis-anti-apoptosis homeostasis, inhibiting serum PRL level, and regulating secretion of gonadotropin hormones. PMID:27508025

  7. Delayed Adrenarche may be an Additional Feature of Immunoglobulin Super Family Member 1 Deficiency Syndrome

    PubMed Central

    Hulle, Severine Van; Craen, Margarita; Callewaert, Bert; Joustra, Sjoerd; Oostdijk, Wilma; Losekoot, Monique; Wit, Jan Maarten; Turgeon, Marc Olivier; Bernard, Daniel J.; Schepper, Jean De

    2016-01-01

    Immunoglobulin super family member 1 (IGSF1) deficiency syndrome is characterized by central hypothyroidism, delayed surge in testosterone during puberty, macro-orchidism, and in some cases, hypoprolactinemia and/or transient growth hormone (GH) deficiency. Our patient was a 19-year-old male adolescent who had been treated since the age of 9 years with GH and thyroxine for an idiopathic combined GH, thyroid-stimulating hormone (TSH), and prolactin (PRL) deficiency. His GH deficiency proved to be transient, but deficiencies of TSH and PRL persisted, and he had developed macro-orchidism since the end of puberty. Brain magnetic resonance imaging and PROP1 and POU1F1 sequencing were normal. A disharmonious puberty (delayed genital and pubic hair development, bone maturation, and pubertal growth spurt, despite normal testicular growth) was observed as well as a delayed adrenarche, as reflected by very low dehydroepiandrosterone sulfate and delayed pubarche. Direct sequencing of the IGSF1 gene revealed a novel hemizygous mutation, c.3127T>C, p.Cys1043Arg. Pathogenicity of the mutation was demonstrated in vitro. Male children with an idiopathic combined GH, PRL, and TSH deficiency, showing persistent central hypothyroidism but transient GH deficiency upon retesting at adult height, should be screened for mutations in the IGSF1 gene, especially when macro-orchidism and/or hypoprolactinemia are present. We suspect that delayed adrenarche, as a consequence of PRL deficiency, might be part of the clinical phenotype of patients with IGSF1 deficiency. PMID:26757742

  8. Functional components of fibroblast growth factor (FGF) signal transduction in pituitary cells. Identification of FGF response elements in the prolactin gene.

    PubMed

    Schweppe, R E; Frazer-Abel, A A; Gutierrez-Hartmann, A; Bradford, A P

    1997-12-01

    Fibroblast growth factors (FGFs) have been implicated in pituitary lactotroph tumorigenesis; however, little is known about the molecular mechanisms of FGF signal transduction. We used a transient transfection approach, in GH4 cells, to identify components of the FGF signaling pathway leading to activation of the rat prolactin (rPRL) promoter. Using dominant-negative constructs of p21(Ras), Raf-1 kinase, and mitogen-activated protein (MAP) kinase, we show that FGF activation of the rPRL promoter is independent of Ras and Raf-1 but requires MAP kinase. Furthermore, MAP kinase but not Raf-1 kinase catalytic activity is stimulated by FGFs. The rPRL promoter FGF response maps to two Ets binding sites, centered at -212 (FRE1) and -96 (FRE2), and co-transfection of dominant-negative Ets inhibits FGF activation. FRE1 co-localizes with a composite, Ets/GHF-1, Ras response element. However, overexpression of Ets-1 and GHF-1, which potentiate the Ras response, inhibits FGF stimulation of the rPRL promoter, implying that Ras and FGF signaling pathways target distinct factors to elicit their effects. These data suggest that Ets factors serve to sort and integrate MAP kinase-dependent growth factor signals, allowing highly specific transcriptional responses to be mediated via the interaction of distinct Ets proteins and cofactors at common response elements.

  9. 8 CFR 324.5 - Former citizen of the United States whose naturalization by taking the oath is authorized by a...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... naturalization by taking the oath is authorized by a private law. 324.5 Section 324.5 Aliens and Nationality...: WOMEN WHO HAVE LOST UNITED STATES CITIZENSHIP BY MARRIAGE AND FORMER CITIZENS WHOSE NATURALIZATION IS AUTHORIZED BY PRlVATE LAW § 324.5 Former citizen of the United States whose naturalization by taking the...

  10. 8 CFR 324.2 - Former citizen at birth or by naturalization.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... naturalization. 324.2 Section 324.2 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY NATIONALITY... BY MARRIAGE AND FORMER CITIZENS WHOSE NATURALIZATION IS AUTHORIZED BY PRlVATE LAW § 324.2 Former citizen at birth or by naturalization. (a) Eligibility. To be eligible for naturalization under...

  11. Developmental atrazine exposure suppresses immune function in male, but not female Sprague-Dawley rats.

    PubMed

    Rooney, Andrew A; Matulka, Raymond A; Luebke, Robert W

    2003-12-01

    Each year, 75 million pounds of the broadleaf herbicide atrazine (ATR) are applied to crops in the United States. Despite limited solubility, ATR is common in ground and surface water, making it of regulatory concern. ATR suppresses the immunomodulatory hormones prolactin (PRL) and the thyroid hormones (THs), with developmental exposure to ATR permanently disrupting PRL regulation. We hypothesized that ATR may cause developmental immunotoxicity through its disruption of PRL or THs. To test this hypothesis, pregnant Sprague-Dawley (SD) rats were exposed to 35-mg ATR/kg/d from gestational day (GD) 10 through postnatal day (PND) 23. Separate groups were exposed to bromocryptine (BCR) at 0.2 mg/kg/2x/day to induce hypoprolactinemia or to propylthiouracil (PTU) at 2 mg/kg/day to induce hypothyroidism. After the offspring reached immunologic maturity (at least 7 weeks old), the following immune functions were evaluated: natural killer (NK) cell function; delayed-type hypersensitivity (DTH) responses; phagocytic activity of peritoneal macrophages; and antibody response to sheep erythrocytes (SRBC). ATR decreased the primary antibody and DTH responses in male offspring only. Neither PTU nor BCR caused immunosuppression in any measured variable, although PTU increased phagocytosis by peritoneal macrophages. These results demonstrate that developmental exposure to ATR produced gender-specific changes in immune function in adult rats and suggest that immune changes associated with ATR are not mediated through the suppression of PRL or THs.

  12. Effects of induced parturition in goats on immunoglobulin G and chitotriosidase activity in colostrum and plasma and on plasma concentrations of prolactin.

    PubMed

    Castro, N; Capote, J; Batista, M; Bruckmaier, R M; Argüello, A

    2011-05-01

    The effect of induction of parturition with a PGF(2)α analog on plasma concentration of prolactin (PRL) and its effects on colostrum concentration of IgG and chitotriosidase (ChT) activity were studied in 16 pregnant Majorera goats. Treated goats, those in which parturition was induced, had greater concentrations of PRL than control goats 24 h before parturition (P < 0.05) and 48 h after parturition (P < 0.05). Control goats had greater concentrations of PRL than treated goats 96 h after parturition (P < 0.05). Plasma concentration of IgG did not differ between groups during the experimental period, but colostrum concentrations of IgG were greater in control goats than in treated goats at parturition (P < 0.05). Plasma ChT activity decreased during the period 72 h before parturition to 24 h after parturition in control and treated goats. Time evolution after partum affected the colostrum ChT activity, being greater at parturition than after parturition in both groups (P < 0.05). In summary, concentration of IgG in colostrum is slightly diminished if parturition is induced. Induction of parturition causes an early increase in PRL, which is most likely responsible for preterm suppression of IgG transport into mammary secretions.

  13. Seasonal Expression of Prolactin Receptor in the Scented Gland of Male Muskrat (Ondatra zibethicus)

    PubMed Central

    Cao, Han; Wang, Liang; Zhang, Shuo; Lu, Lu; Sheng, Xia; Han, Yingying; Yuan, Zhengrong; Weng, Qiang

    2015-01-01

    Prolactin (PRL) has numerous actions in mammalian biological systems including mammary development and biological processes. The aim of this study was to investigate the seasonal changes of prolactin receptor (PRLR) expression in the scented gland of muskrat during the breeding and nonbreeding seasons. Histologically, glandular cells, interstitial cells and excretory tubules were identified in the scented glands in both seasons, whereas epithelial cells were sparse in the nonbreeding season. PRLR was observed in glandular cells of scented glands during the breeding and nonbreeding seasons with stronger immunostaining during the breeding season. Consistent with the immunohistochemical results, both the mean of protein and mRNA levels of PRLR were higher in the scented glands of the breeding season, and relatively lower level in the nonbreeding season. In addition, differential seasonal changes were also detected in the expression profile of microRNAs (miRNAs) in the scented gland of muskrat. Besides, plasma PRL concentration was remarkably higher in the breeding season than that in the nonbreeding season. These results suggested that muskrat scented gland was the direct target organ of PRL, and stronger expression of PRLR in scented glands during the breeding season indicated that PRL may directly regulate scented glandular function of the muskrats. PMID:26477851

  14. "Physical Review Letters" in the Classroom

    ERIC Educational Resources Information Center

    Angiolillo, Paul J.; Lynch, Jonathan

    2010-01-01

    Ask any physicist what the preeminent journal in the field is, and I think the almost unanimous answer will be "Physical Review Letters" ("PRL"). This weekly journal of the American Physical Society publishes high-impact research from all the major subdisciplines of physics. This journal is not the one you would think is the first place a high…

  15. Probabilistic Reversal Learning in Schizophrenia: Stability of Deficits and Potential Causal Mechanisms.

    PubMed

    Reddy, Lena Felice; Waltz, James A; Green, Michael F; Wynn, Jonathan K; Horan, William P

    2016-07-01

    Although individuals with schizophrenia show impaired feedback-driven learning on probabilistic reversal learning (PRL) tasks, the specific factors that contribute to these deficits remain unknown. Recent work has suggested several potential causes including neurocognitive impairments, clinical symptoms, and specific types of feedback-related errors. To examine this issue, we administered a PRL task to 126 stable schizophrenia outpatients and 72 matched controls, and patients were retested 4 weeks later. The task involved an initial probabilistic discrimination learning phase and subsequent reversal phases in which subjects had to adjust their responses to sudden shifts in the reinforcement contingencies. Patients showed poorer performance than controls for both the initial discrimination and reversal learning phases of the task, and performance overall showed good test-retest reliability among patients. A subgroup analysis of patients (n = 64) and controls (n = 49) with good initial discrimination learning revealed no between-group differences in reversal learning, indicating that the patients who were able to achieve all of the initial probabilistic discriminations were not impaired in reversal learning. Regarding potential contributors to impaired discrimination learning, several factors were associated with poor PRL, including higher levels of neurocognitive impairment, poor learning from both positive and negative feedback, and higher levels of indiscriminate response shifting. The results suggest that poor PRL performance in schizophrenia can be the product of multiple mechanisms. PMID:26884546

  16. The hypothalamic-pituitary response in SLE. Regulation of prolactin, growth hormone and cortisol release.

    PubMed

    Rovenský, J; Blazícková, S; Rauová, L; Jezová, D; Koska, J; Lukác, J; Vigas, M

    1998-01-01

    It has been suggested that neuroendocrine regulation plays an important role in the pathogenesis and activation of autoimmune diseases. The aim of this investigation was to clarify the hypothalamic-pituitary response to a well-defined stimulus under standardised conditions in patients with SLE. Plasma concentrations of prolactin (PRL), growth hormone (GH) and cortisol were determined in venous blood drawn through an indwelling cannula during insulin-induced hypoglycaemia (0.1 U/kg b.w., i.v.) in ten patients and in 12 age-, gender- and weight-matched healthy subjects. Basal PRL concentrations were higher in patients vs healthy controls (12 vs 6 ng/ml, P < 0.01), though still within the physiological range. Insulin-induced plasma PRL and GH were significantly increased both in patients and healthy subjects; however, the increments or areas under the curves were not different in the two groups. Plasma cortisol response showed moderate attenuation in patients. Sensitivity of pituitary lactotrothrops to thyrotropin-releasing hormone (TRH) administration (200 microg, i.v.) was the same in patients and control subjects. In SLE patients with low activity of the disease the sensitivity of pituitary PRL release to TRH administration remained unchanged. The hypothalamic response to stress stimulus (hypoglycaemia) was comparable in patients and healthy subjects. PMID:9736325

  17. Comparative genomics reveals tissue-specific regulation of prolactin receptor gene expression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prolactin (PRL), acting via the prolactin receptor, fulfills a diversity of biological functions including the maintenance of solute balance and mineral homeostasis via tissues such as the heart, kidneys and intestine. Expression and activity of the prolactin receptor (PRLR) is regulated by various ...

  18. Enhancement of maternal lactation performance during prolonged lactation in the mouse by mouse GH and long-R3-IGF-I is linked to changes in mammary signaling and gene expression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    GH, prolactin (PRL), and IGF-I stimulate lactation-related metabolic processes in mammary epithelial cells. However, the ability of these factors to stimulate milk production in animals varies depending on species and experimental variables. Previous work in our laboratory demonstrated that transgen...

  19. Effects of metoclopramide-induced hyperprolactinemia on the prolactin and prolactin receptor expression of murine adrenal.

    PubMed

    do Amaral, Vinícius Cestari; da Silva, Priscilla Ludovico; Carvalho, Kátia Candido; Simoncini, Tommaso; Maciel, Gustavo Arantes Rosa; Soares-Jr, José Maria; Baracat, Edmund Chada

    2015-01-01

    The aim of this study was to evaluate the effects of metoclopramide-induced hyperprolactinemia on the prolactin (PRL) and prolactin receptor's (PRLR) expression in the adrenal. For this purpose, a total of 12 animals with intact ovaries were allocated to two groups: G1 (saline solution) and G2 (metoclopramide). A total of 30 oophorectomized animals was randomized to five subgroups: G3 (saline solution), G4 (metoclopramide), G5 (metoclopramide + 17β-estradiol), G6 (metoclopramide + progesterone), and G7 (metoclopramide + 17β-estradiol + progesterone). Immunohistochemical analyses were evaluated semi-quantitatively. For PRLR, the area fraction of labeled cells (ALC) varied from 1 (0-10%) to 3 (> 50%). Based on the mean of the immunostaining intensity, G2 and G4 showed strong expression; G6 and G7 presented a mild reaction; and G1, G3, and G5 exhibited a weak reaction. Concerning PRL, the ALC varied from 1 (0-10%) to 3 (> 50%), and groups G6 and G7 showed a strong reaction; G2, G4, and G5 showed a mild reaction; and G1 and G3 exhibited a weak reaction. These findings suggest that metoclopramide-induced hyperprolactinemia increases PRL expression in the adrenal glands of mice. Furthermore, progesterone alone or in association with estrogen also increases PRL expression, but to a lesser extent.

  20. A novel first exon directs hormone-sensitive transcription of the pig prolactin receptor

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Endocrine, paracrine, and autocrine prolactin (PRL) acts through its receptor (PRLR) to confer a wide range of biological functions, including its established role during lactation.We have identified a novel first exon of the porcine PRLR that gives rise to three different mRNA transcripts. Transcri...

  1. Seasonal Expression of Prolactin Receptor in the Scented Gland of Male Muskrat (Ondatra zibethicus).

    PubMed

    Cao, Han; Wang, Liang; Zhang, Shuo; Lu, Lu; Sheng, Xia; Han, Yingying; Yuan, Zhengrong; Weng, Qiang

    2015-01-01

    Prolactin (PRL) has numerous actions in mammalian biological systems including mammary development and biological processes. The aim of this study was to investigate the seasonal changes of prolactin receptor (PRLR) expression in the scented gland of muskrat during the breeding and nonbreeding seasons. Histologically, glandular cells, interstitial cells and excretory tubules were identified in the scented glands in both seasons, whereas epithelial cells were sparse in the nonbreeding season. PRLR was observed in glandular cells of scented glands during the breeding and nonbreeding seasons with stronger immunostaining during the breeding season. Consistent with the immunohistochemical results, both the mean of protein and mRNA levels of PRLR were higher in the scented glands of the breeding season, and relatively lower level in the nonbreeding season. In addition, differential seasonal changes were also detected in the expression profile of microRNAs (miRNAs) in the scented gland of muskrat. Besides, plasma PRL concentration was remarkably higher in the breeding season than that in the nonbreeding season. These results suggested that muskrat scented gland was the direct target organ of PRL, and stronger expression of PRLR in scented glands during the breeding season indicated that PRL may directly regulate scented glandular function of the muskrats.

  2. Maternal stress affects postnatal growth and the pituitary expression of prolactin in mouse offspring.

    PubMed

    Gao, Pengfei; Ishige, Atsushi; Murakami, Yu; Nakata, Hideyuki; Oka, Jun-Ichiro; Munakata, Kaori; Yamamoto, Masahiro; Nishimura, Ko; Watanabe, Kenji

    2011-03-01

    Maternal stress exerts long-lasting psychiatric and somatic on offspring, which persist into adulthood. However, the effect of maternal stress on the postnatal growth of pups has not been widely reported. In this study, we found that maternal immobilization stress (IS) during lactation resulted in low body weight of male mouse offspring, which persisted after weaning. Despite free access to chow, IS induced maternal malnutrition and decreased the serum insulin-like growth factor-1 (IGF-1) levels in the mothers and in the pups. mRNA expression analysis of anterior pituitary hormones in the pups revealed that growth hormone (GH) and prolactin (PRL), but no other hormones, were decreased by IS. Expression of the pituitary transcription factor PIT1 and isoforms of PITX2, which are essential for the development and function of GH-producing somatotropes and PRL-producing lactotropes, was decreased, whereas that of PROP1, which is critical for the earlier stages of pituitary development, was unchanged. Immunohistochemistry also showed a decrease in pituitary PRL protein expression. These results suggest that stress in a postpartum mother has persistent effects on the body weight of the offspring. Reduced PRL expression in the offspring's pituitary gland may play a role in these effects.

  3. Mechanism for ordered receptor binding by human prolactin.

    PubMed

    Sivaprasad, Umasundari; Canfield, Jeffrey M; Brooks, Charles L

    2004-11-01

    Prolactin, a lactogenic hormone, binds to two prolactin receptors sequentially, the first receptor binding at site 1 of the hormone followed by the second receptor binding at site 2. We have investigated the mechanism by which human prolactin (hPRL) binds the extracellular domain of the human prolactin receptor (hPRLbp) using surface plasmon resonance (SPR) technology. We have covalently coupled hPRL to the SPR chip surface via coupling chemistries that reside in and block either site 1 or site 2. Equilibrium binding experiments using saturating hPRLbp concentrations show that site 2 receptor binding is dependent on site 1 receptor occupancy. In contrast, site 1 binding is independent of site 2 occupancy. Thus, sites 1 and 2 are functionally coupled, site 1 binding inducing the functional organization of site 2. Site 2 of hPRL does not have a measurable binding affinity prior to hPRLbp binding at site 1. After site 1 receptor binding, site 2 affinity is increased to values approaching that of site 1. Corruption of either site 1 or site 2 by mutagenesis is consistent with a functional coupling of sites 1 and 2. Fluorescence resonance energy transfer (FRET) experiments indicate that receptor binding at site 1 induces a conformation change in the hormone. These data support an "induced-fit" model for prolactin receptor binding where binding of the first receptor to hPRL induces a conformation change in the hormone creating the second receptor-binding site.

  4. Seasonal Expression of Prolactin Receptor in the Scented Gland of Male Muskrat (Ondatra zibethicus).

    PubMed

    Cao, Han; Wang, Liang; Zhang, Shuo; Lu, Lu; Sheng, Xia; Han, Yingying; Yuan, Zhengrong; Weng, Qiang

    2015-01-01

    Prolactin (PRL) has numerous actions in mammalian biological systems including mammary development and biological processes. The aim of this study was to investigate the seasonal changes of prolactin receptor (PRLR) expression in the scented gland of muskrat during the breeding and nonbreeding seasons. Histologically, glandular cells, interstitial cells and excretory tubules were identified in the scented glands in both seasons, whereas epithelial cells were sparse in the nonbreeding season. PRLR was observed in glandular cells of scented glands during the breeding and nonbreeding seasons with stronger immunostaining during the breeding season. Consistent with the immunohistochemical results, both the mean of protein and mRNA levels of PRLR were higher in the scented glands of the breeding season, and relatively lower level in the nonbreeding season. In addition, differential seasonal changes were also detected in the expression profile of microRNAs (miRNAs) in the scented gland of muskrat. Besides, plasma PRL concentration was remarkably higher in the breeding season than that in the nonbreeding season. These results suggested that muskrat scented gland was the direct target organ of PRL, and stronger expression of PRLR in scented glands during the breeding season indicated that PRL may directly regulate scented glandular function of the muskrats. PMID:26477851

  5. Epigenetic modification of PKMζ rescues aging-related cognitive impairment

    PubMed Central

    Chen, Chen; Meng, Shi-Qiu; Xue, Yan-Xue; Han, Ying; Sun, Cheng-Yu; Deng, Jia-Hui; Chen, Na; Bao, Yan-Ping; Zhang, Fei-Long; Cao, Lin-Lin; Zhu, Wei-Guo; Shi, Jie; Song, Wei-Hong; Lu, Lin

    2016-01-01

    Cognition is impacted by aging. However, the mechanisms that underlie aging-associated cognitive impairment are unclear. Here we showed that cognitive decline in aged rats was associated with changes in DNA methylation of protein kinase Mζ (PKMζ) in the prelimbic cortex (PrL). PKMζ is a crucial molecule involved in the maintenance of long-term memory. Using different behavioral models, we confirmed that aged rats exhibited cognitive impairment in memory retention test 24 h after training, and overexpression of PKMζ in the PrL rescued cognitive impairment in aged rats. After fear conditioning, the protein levels of PKMζ and the membrane expression of GluR2 increased in the PrL in young and adult rats but not in aged rats, and the levels of methylated PKMζ DNA in the PrL decreased in all age groups, whereas the levels of unmethylated PKMζ DNA increased only in young and adult rats. We also found that environmentally enriched housing reversed the hypermethylation of PKMζ and restored cognitive performance in aged rats. Inactivation of PKMζ prevented the potentiating effects of environmental enrichment on memory retention in aged rats. These results indicated that PKMζ might be a potential target for the treatment of aging-related cognitive impairment, suggesting a potential therapeutic avenue. PMID:26926225

  6. Peritonitis activates transcription of the human prolactin locus in myeloid cells in a humanized transgenic rat model.

    PubMed

    Semprini, Sabrina; McNamara, Anne V; Awais, Raheela; Featherstone, Karen; Harper, Claire V; McNeilly, Judith R; Patist, Amanda; Rossi, Adriano G; Dransfield, Ian; McNeilly, Alan S; Davis, Julian R E; White, Michael R H; Mullins, John J

    2012-06-01

    Prolactin (PRL) is mainly expressed in the pituitary in rodents, whereas in humans, expression is observed in many extrapituitary sites, including lymphocytes. Due to the lack of adequate experimental models, the function of locally produced PRL in the immune system is largely unknown. Using transgenic rats that express luciferase under the control of extensive human PRL regulatory regions, we characterized immune cell responses to thioglycollate (TG)-induced peritonitis. Resident populations of myeloid cells in the peritoneal cavity of untreated rats expressed barely detectable levels of luciferase. In contrast, during TG-induced peritonitis, cell-specific expression in both neutrophils and monocytes/macrophages in peritoneal exudates increased dramatically. Elevated luciferase expression was also detectable in peripheral blood and bone marrow CD11b(+) cells. Ex vivo stimulation of primary myeloid cells showed activation of the human extrapituitary promoter by TNF-α, lipopolysaccharide, or TG. These findings were confirmed in human peripheral blood monocytes, showing that the transgenic rat provided a faithful model for the human gene. Thus, the resolution of an inflammatory response is associated with dramatic activation of the PRL gene promoter in the myeloid lineage.

  7. Individualized cosinor assessment of circadian hormonal variation in third trimester human pregnancy.

    PubMed

    Meis, P J; Buster, J E; Kundu, N; Magyar, D; Marshall, J R; Halberg, F

    1983-01-01

    Two clinically healthy pregnant women were studied in a single 24-h span during the third trimester. Blood drawn every 20 min was assayed for cortisol (F), dehydroepiandrosterone sulfate (DHEA-S), estriol (E3), and prolactin (PRL). Blood drawn hourly was assayed for progesterone (P), human placental lactogen (HPL) and 15alpha-hydroxyestriol (E4). Breast temperature (BT) was continuously monitored. Single cosinor analysis demonstrated statistically significant circadian rhythms for plasma concentrations of F, DHEA-S, and BT for both subjects, and of E3 for one subject. Statistically significant circadian rhythms in plasma concentrations of P, HPL, E4 or PRL could not be demonstrated in our third trimester subjects. However, analysis of data from subjects sampled at earlier gestational ages revealed highly significant PRL circadian rhythms. These results suggest that plasma concentrations of PRL show a progressive decrease in circadian amplitude despite a progressive increase in mesor with advancing gestational age. Frequent sampling and cosinor data analysis permit identification of circadian rhythms in BT. The use of BT as a potential marker for rhythms in plasma concentration of certain hormones awaits further scrutiny. The demonstration of several circadian endocrine rhythms in individual subjects in the third trimester of human pregnancy facilitates the usefulness of such marker rhythms. PMID:6221911

  8. Prolactin and breast cancer: The need to avoid undertreatment of serious psychiatric illnesses in breast cancer patients: A review.

    PubMed

    Froes Brandao, Denise; Strasser-Weippl, Kathrin; Goss, Paul E

    2016-01-15

    Hyperprolactinemia, defined as a sustained elevation of prolactin (PRL) levels greater than 530 mIU/L in women and greater than 424 mIU/L in men, has been implicated for a long time in breast cancer etiology and prognosis. Elevated PRL values (approximately 2-3 times higher than the reference values) are a common adverse effect of antipsychotic medications, especially with first-generation drugs, and most antipsychotics carry a standard warning regarding PRL elevations on their US product labels. These associations foster undertreatment of serious psychiatric illnesses in both otherwise healthy patients and cancer patients. This review assesses both the preclinical and clinical evidence that has led to the hypothesis of PRL's role in breast cancer risk or breast cancer progression. It is concluded that taken together, the published data are unconvincing and insufficient to deprive cancer patients in general and breast cancer patients specifically of potentially effective antipsychotic or antidepressant medications for serious psychiatric indications. We thus call on revised medication guidelines to avoid the existing undertreatment of serious psychiatric illnesses among cancer patients based on an unproven contraindication to psychiatric medications. Cancer 2016;122:184-188. © 2015 American Cancer Society.

  9. Purification and biological characterization of bacterially expressed recombinant buffalo prolactin.

    PubMed

    Panchal, Manoj; Muralidhar, Kambadur

    2010-01-01

    Recombinant prolactin (PRL) from water buffalo (Bubalus bubalis) has been cloned and expressed in a prokaryotic expression system. The hormone was also successfully refolded into a biologically active form. Total RNA was purified from buffalo pituitaries and the buPRL cDNA was synthesized using primers designed on bovine PRL sequence. This prolactin cDNA was cloned in a pET 28a vector and expressed in Escherichia coli strain BL21(DE3)pLysS. Most of the expressed protein was present as insoluble inclusion bodies. The inclusion bodies were solubilized and buPRL was purified by Ni-NTA column. The purified protein was refolded by gradually decreasing the concentration of denaturant during dialysis. Total yield of the refolded and soluble prolactin was 22 mg/L from 100 mL bacterial culture in LB medium. The recombinant prolactin was as active as native prolactin in stimulating growth of Nb2 lymphoma cells.

  10. Studies on the role of TRH and corticosterone in the regulation of prolactin and thyrotrophin secretion during lactation.

    PubMed

    van Haasteren, G A; van Toor, H; Klootwijk, W; Handler, B; Linkels, E; van der Schoot, P; van Ophemert, J; de Jong, F H; Visser, T J; de Greef, W J

    1996-02-01

    This study describes the effects of litter size and acute suckling on the synthesis and release of hypothalamic TRH, as indirectly estimated by determination of hypothalamic prothyrotrophin-releasing hormone (proTRH) mRNA and median eminence TRH content. The effects of litter size (five or ten pups) were studied throughout lactation, while suckling-induced acute changes were analyzed on day 13 of lactation in dams with ten pups. In view of the enhanced adrenal activity during lactation and recent evidence that corticosteroids have negative effects on hypothalamic TRH, we also studied adrenalectomized (ADX) dams treated with corticosterone to maintain basal plasma corticosterone levels. In addition to an increased plasma level of prolactin (PRL), adrenal weight and plasma corticosterone increased, while plasma TSH, tri-iodothyronine (T3), thyroxine (T4) and free T4 (FT4) levels decreased during lactation. Litter size correlated positively with plasma PRL, adrenal weight and plasma corticosterone. No effect of litter size was observed on plasma T3, but rats with ten pups had lower plasma TSH, T4 and FT4 than rats with a five-pup litter. Compared with dioestrous rats, lactating rats showed an increased hypothalamic proTRH mRNA content on day 2, but not on days 8 and 15 of lactation. Median eminence TRH in lactating rats gradually increased until day 15 and decreased thereafter. Acute suckling, after a 6-h separation of mother and pups, rapidly increased plasma PRL and corticosterone in the mothers, but had no effects on plasma TSH and thyroid hormone levels. Hypothalamic proTRH mRNA increased twofold after 0.5 h of suckling, and then gradually returned to presuckling values after 6 h. Compared with sham-operated rats, corticosterone-substituted ADX rats with ten pups had increased plasma PRL and TSH, hypothalamic proTRH mRNA and pituitary TSH beta mRNA on day 15 of lactation. Moreover, while acute suckling did not enhance TSH release in sham-operated rats, it provoked

  11. Role of the serotonergic axis in the reproductive failure associated with aging broiler breeder roosters.

    PubMed

    Avital-Cohen, N; Heiblum, R; Rosenstrauch, A; Chaiseha, Y; Mobarkey, N; Gumułka, M; Rozenboim, I

    2015-10-01

    Reproductive failure associated with aging is a well-known phenomenon. However, the mechanism by which this failure occurs in broiler breeder roosters is still unclear. A previous study conducted in our laboratory, comparing young and aging broiler breeder roosters, demonstrated an elevation in hypothalamic vasoactive intestinal peptide (VIP) and pituitary prolactin (PRL) gene expression accompanied by a deterioration of gonadal axis function. This resulted in a decrease in semen-quality variables as roosters aged. The objective of this study was to examine the involvement of the serotonergic axis in the age-associated reproductive failure in broiler breeder roosters. Cobb roosters aged 64 wk were divided into 3 groups (n = 20 each): parachlorophenylalanine (PCPA) administration, active immunization against chicken VIP, and controls. At 69 wk of age, each group was divided into 2 equal subgroups: 1 received ovine PRL and the other served as controls. Weekly semen volume, concentration and motility, and plasma testosterone, estradiol, and PRL concentrations were examined. At the end of the experiment, roosters were euthanized, testes were weighed, and hypothalamus and pituitary were removed to assay the expression of genes encoding hypothalamic GnRH-I, pituitary FSH, pituitary LH, hypothalamic VIP, and pituitary PRL. Both PCPA administration and active immunization against chicken VIP significantly increased testis weight, semen volume, sperm concentration, ejaculation grade, plasma testosterone level, and GnRH-I, FSH and LH gene expression compared with controls (P ≤ 0.05). In addition, a decrease in plasma estradiol and PRL concentrations and VIP and PRL gene expression was observed in PCPA- and VIP-immunized birds compared with controls (P ≤ 0.05). Administration of PRL in all groups decreased gonadal axis function and semen-quality variables (P ≤ 0.05). Collectively, these results suggest that the increasing expression levels of the serotonergic axis

  12. Enhancement of extinction learning attenuates ethanol-seeking behavior and alters plasticity in the prefrontal cortex.

    PubMed

    Gass, Justin T; Trantham-Davidson, Heather; Kassab, Amanda S; Glen, William B; Olive, M Foster; Chandler, L Judson

    2014-05-28

    Addiction is a chronic relapsing disorder in which relapse is often initiated by exposure to drug-related cues. The present study examined the effects of mGluR5 activation on extinction of ethanol-cue-maintained responding, relapse-like behavior, and neuronal plasticity. Rats were trained to self-administer ethanol and then exposed to extinction training during which they were administered either vehicle or the mGluR5 positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) or CDPPB. CDPPB treatment reduced active lever responding during extinction, decreased the total number of extinction sessions required to meet criteria, and attenuated cue-induced reinstatement of ethanol seeking. CDPPB facilitation of extinction was blocked by the local infusion of the mGluR5 antagonist 3-((2-methyl-4-thiazolyl)ethynyl) pyridine into the infralimbic (IfL) cortex, but had no effect when infused into the prelimbic (PrL) cortex. Analysis of dendritic spines revealed alterations in structural plasticity, whereas electrophysiological recordings demonstrated differential alterations in glutamatergic neurotransmission in the PrL and IfL cortex. Extinction was associated with increased amplitude of evoked synaptic PrL and IfL NMDA currents but reduced amplitude of PrL AMPA currents. Treatment with CDPPB prevented the extinction-induced enhancement of NMDA currents in PrL without affecting NMDA currents in the IfL. Whereas CDPPB treatment did not alter the amplitude of PrL or IfL AMPA currents, it did promote the expression of IfL calcium-permeable GluR2-lacking receptors in both abstinence- and extinction-trained rats, but had no effect in ethanol-naive rats. These results confirm changes in the PrL and IfL cortex in glutamatergic neurotransmission during extinction learning and demonstrate that manipulation of mGluR5 facilitates extinction of ethanol cues in association with neuronal plasticity.

  13. The Physiological Role of Thyrotropin-Releasing Hormone in the Regulation of Thyroid-Stimulating Hormone and Prolactin Secretion in the Rat

    PubMed Central

    Harris, Arthur R. C.; Christianson, Dana; Smith, M. Susan; Fang, Shih-Lieh; Braverman, Lewis E.; Vagenakis, Apostolos G.

    1978-01-01

    The physiological role of thyrotropin-releasing hormone (TRH) in the regulation of thyrotropin (thyroid-stimulating hormone, TSH) and prolactin (Prl) secretion has been assumed but not proven. Stimulation of their release requires pharmacologic doses of TRH. Lesions of the hypothalamus usually induce an inhibition of TSH secretion and an increase in Prl. To determine whether TRH is essential for TSH and Prl secretion in the rat, 0.1 ml of TRH antiserum (TRH-Ab) or normal rabbit serum was administered to normal, thyroidectomized, cold-exposed, and proestrus rats through indwelling atrial catheter. Serum samples were obtained before and at frequent intervals thereafter. Serum TSH concentrations in normal, thyroidectomized, cold-exposed, and proestrus rats were not depressed in specimens obtained up to 24 h after injection of normal rabbit serum. In contrast, serum TSH was significantly decreased after the administration of TRH-Ab in all normal (basal, 41±8 μU/ml [mean±SE]; 30 min, 6±2; 45 min, 8±3; 75 min, 4±2); thyroidectomized (basal, 642±32 μU/ml; 30 min, 418±32; 60 min, 426±36; 120 min, 516±146); coldstressed (basal, 68±19 μU/ml; 30 min, 4±3; 180 min, 16±8); and proestrus (basal, 11 a.m., 57±10 μU/ml; 1 p.m., 20±3; 3 p.m., 13±4; 5 p.m., 19±3) rats. However, 0.1 ml of TRH-Ab had no effect on basal Prl concentrations in normal or thyroidectomized rats and did not prevent the Prl rise in rats exposed to cold (basal, 68±7 ng/ml; 15 min, 387±121; 30 min, 212±132; 60 min, 154±114), or the Prl surge observed on the afternoon of proestrus (basal 11 a.m., 23±2 ng/ml; 1 p.m., 189±55; 3 p.m., 1,490±260; 5 p.m., 1,570±286). These studies demonstrate that TRH is required for TSH secretion in the normal, cold-exposed and proestrus rat and contributes, at least in part, to TSH secretion in the hypothyroid rat, but is not required for Prl secretion in these states. PMID:413840

  14. Effect of transsphenoidal surgery and standard care on fertility related indicators of patients with prolactinomas during child-bearing period

    PubMed Central

    Yan, Zhiyue; Wang, Yiming; Shou, Xuefei; Su, Jianguang; Lang, Liwei

    2015-01-01

    Objective: To explore the surgical therapeutic effects in the endocrine and reproductive system of women with prolactinoma at child-bearing age, and to investigate the potential influencing factors for therapeutic outcome. Methods: This retrospective study was performed using the medical records of 99 cases of female patients with pituitary PRL adenomas at child-bearing age, who underwent transsphenoidal surgery and took standard perioperative care from January, 2013 to June, 2013 in Huashan hospital, in which micro adenoma (≤1 cm) of 68 cases, large adenomas (> 1 cm) of 31 cases, 88 cases were total resection, 9 cases were subtotal resection, and 2 cases were massive resection. Retrospective study on the preoperative serum level of PRL, menstruation, galactorrhea and reproductive function, etc. Patients were followed up in 1, 3, 6 and 12 months after operation for endocrine indicators, the situation of menstruation and pregnancy. Results: Overall, 88.9%, 9.1%, and 2% patients underwent total, subtotal, and massive resection of prolactinoma in 99 cases of patients. Before accepting transsphenoidal surgery and standard care, all 99 cases with serum PRL level higher than normal 25 ng/ml, 71.7% (71 cases, all total resection) patients had their serum PRL < 25 ng/ml on the first day after surgery, and micro adenomas remission rate of 80.9% (55 cases) was significantly higher than 51.6% of large adenomas (16 cases) (P < 0.05); the postoperative PRL of 11 cases of total or massive resection in patients were not back to normal, Chi-square test results showed that the PRL remission rate after total resection were significantly higher than that of subtotal or massive resection (P < 0.01). 67.3% (66/98) irregular menstruation patients had menstruation recovery after surgery, in addition, total resection of the tumor, micro- adenoma, preoperative PRL < 200 ng/ml and first day of postoperative PRL ≤25 ng/ml were favorable factors for menstrual improvement (P < 0.05). 83

  15. The Pituitary in Gigantism.

    PubMed

    Scheithauer, Bernd W.; Kovacs, Kalman T.; Stefaneanu, Lucia; Horvath, Eva; Kane, Laurie A.; Young, William F.; Lloyd, Ricardo V.; Randall, Raymond V.; Davis, Dudley H.

    1995-01-01

    To compare the pituitary pathology of gigantism to that of acromegaly, 19 surgically resected lesions were studied from 10 males and 9 females, ages 13-49 (mean, 19 yr) with excessive height (>/=95th percentile), onset of disease prior to puberty, elevated growth hormone (GH) levels despite glucose suppression, and a pathologically confirmed GH-producing pituitary mass. One patient had MEN-I. The lesions included 18 adenomas and 1 case of pure hyperplasia. The median, mean, and range of serum GH and prolactin (PRL) levels were 64, 235, 5-1000 ng/mL and 47, 146, 29-770 ng/mL, respectively. Of the 8 adenoma specimens accompanied by nontumoral pituitary (i.e., tissue wherein the presence of hyperplasia was assessable), 3 (37%) demonstrated both. Of the 18 tumors, 78% were macroadenomas and 22% were grossly invasive; their immunophenotypes included GH (5%), GH and PRL (19%), and GHPRL and a glycoprotein hormone, usually TSH and/or a-subunit (76%). Of the 10 adenoma-containing lesions subject to electron microscopy (EM), 2 consisted of GH cells alone; 2 of mammosomatotroph (MS) cells alone; 1 of GH and MS cells; 1 of GH and PRL cells; 2 of GH, PRL, and MS cells; 1 of GH, PRL, and glycoprotein cells; and 1 was a subtype 3 adenoma. Ultrastructurally, GH cells and/or MS cells predominated in these lesions. Immuno-EM of one CH and PRL cell and of one GH-PR-MS tumor showed GH and PRL to be present not only in single cells but within the same granules. Nine of 12 adenoma-associated lesions subject to combined in situ hybridization (ISH) and immunostaining showed double labeling for PRL (or GH) mRNA and for GH (or PRL), respectively, features indicating MS differentiation. In the 4 lesions exhibiting hyperplasia, either alone (1) or in association with adenoma (3), EM showed MS cells in 3, and immuno-EM as well as combined immunohistochemistry and ISH showed double labeling for GH and PRL in both of the 2 cases studied. In summary, although in terms of their tinctorial

  16. Identification of bovine prolactin in seminal fluid, and expression and localization of the prolactin receptor and prolactin-inducible protein in the testis and epididymis of bulls exposed to ergot alkaloids.

    PubMed

    Pratt, S L; Calcatera, S M; Stowe, H M; Dimmick, M A; Schrick, F N; Duckett, S K; Andrae, J G

    2015-03-01

    The objectives of this study were to determine (1) the presence and expression levels of bovine prolactin receptor (PRLR) and prolactin-inducible protein (PIP) in bovine testis and epididymis, and (2) the presence and concentrations of prolactin (PRL) present in seminiferous fluid in bulls consuming diets with (E+) or without (E-) ergot alkaloids. Bulls (n = 8) were sacrificed after 126 days (group A) of E+ or E- treatment or 60 days after all bulls (n = 6) were switched to the E- ration (group B). End point and real-time quantitative reverse transcription-polymerase chain reaction and immunohistochemistry were conducted on testis and epididymis samples to establish the presence and relative expression of PRLR and PIP. Seminal fluid samples obtained from bulls consuming E- and E+ diets were subjected to RIA for PRL. Both PIP and PRLR were present in testis and epididymis as determined by reverse transcription-polymerase chain reaction and immunohistochemistry. Prolactin-inducible protein mRNA abundance was affected by time of slaughter in testis and epididymis head, respectively (P < 0.05). Prolactin receptor mRNA expression was affected by time of slaughter in the epididymis (P < 0.05) and differed in testis samples because of treatment (P < 0.05). Radioimmunoassay establishes the presence of PRL in seminal fluid; however, differences in the concentration of PRL over two separate studies were inconsistent, possibly because of differences in diet. The presence and localization of the PRLR are consistent with expression data reported for other species, and the presence of PIP and PRL in seminal fluid is consistent with data generated in humans.

  17. Activation and blockade of prelimbic 5-HT6 receptors produce different effects on depressive-like behaviors in unilateral 6-hydroxydopamine-induced Parkinson's rats.

    PubMed

    Zhang, Yu-Ming; Zhang, Li; Wang, Yong; Sun, Yi-Na; Guo, Yuan; Du, Cheng-Xue; Zhang, Jin; Yao, Lu; Yu, Shu-Qi; Liu, Jian

    2016-11-01

    The role of prelimbic (PrL) 5-HT6 receptors in depression is poorly understood, particularly in Parkinson's disease-related depression. Here we reported that 6-hydroxydopamine lesions in rats decreased sucrose preference and increased immobility time as measured by the sucrose preference and forced swim tests when compared to sham-operated rats, indicating the induction of depressive-like behaviors. Intra-PrL injection of 5-HT6 receptor agonist WAY208466 induced depressive-like responses in sham-operated rats, and produced antidepressant-like effects in the lesioned rats. However, 5-HT6 receptor antagonist SB258585 produced antidepressant-like effects in sham-operated rats, and increased the expression of depressive-like behaviors in the lesioned rats. Neurochemical results showed that intra-PrL injection of WAY208466 and SB258585 decreased or increased dopamine (DA) and noradrenaline (NA) levels in the medial prefrontal cortex, amygdala, habenula and ventral hippocampus in sham-operated and the lesioned rats, respectively. WAY208466 increased the firing rate of PrL glutamate neurons in the two groups of rats, while SB258585 decreased the firing rate of the neurons. Compared to sham-operated rats, the duration of WAY208466 and SB258585 action on the firing rate of glutamate neurons was markedly prolonged in the lesioned rats. The lesion did not change the co-localization of 5-HT6 receptor and glutamate neurons in the PrL. These findings indicate that 5-HT6 receptors in the PrL are involved in the regulation of depressive-like behaviors, which attribute to changes in DA and NA levels in the limbic and limbic-related brain regions. Additionally, the results suggest that the lesion leads to a supersensitization of 5-HT6 receptors on glutamate neurons in the PrL.

  18. The prolactin receptor mediates HOXA1-stimulated oncogenicity in mammary carcinoma cells.

    PubMed

    Hou, Lin; Xu, Bing; Mohankumar, Kumarasamypet M; Goffin, Vincent; Perry, Jo K; Lobie, Peter E; Liu, Dong-Xu

    2012-12-01

    The HOX genes are a highly conserved subgroup of homeodomain-containing transcription factors that are crucial to normal development. Forced expression of HOXA1 results in oncogenic transformation of immortalized human mammary cells with aggressive tumour formation in vivo. Microarray analysis identified that the prolactin receptor (PRLR) was significantly upregulated by forced expression of HOXA1 in mammary carcinoma cells. To determine prolactin (PRL) involvement in HOXA1‑induced oncogenicity in mammary carcinoma cells (MCF-7), we examined the effect of human prolactin (hPRL)-initiated PRLR signal transduction on changes in cellular behaviour mediated by HOXA1. Forced expression of HOXA1 in MCF-7 cells increased PRLR mRNA and protein expression. Forced expression of HOXA1 also enhanced hPRL-stimulated phosphorylation of both STAT5A/B and p44/42 MAPK, and increased subsequent transcriptional activity of STAT5A and STAT5B, and Elk-1 and Sap1a, respectively. Moreover, forced expression of HOXA1 in MCF-7 cells enhanced the hPRL‑stimulated increase in total cell number as a consequence of enhanced cell proliferation and cell survival, and also enhanced hPRL-stimulated anchorage-independent growth in soft agar. Increased anchorage-independent growth was attenuated by the PRLR antagonist ∆1-9-G129R‑hPRL. In conclusion, we have demonstrated that HOXA1 increases expression of the cell surface receptor PRLR and enhances PRLR-mediated signal transduction. Thus, the PRLR is one mediator of HOXA1‑stimulated oncogenicity in mammary carcinoma cells. PMID:23064471

  19. Progesterone receptor directly inhibits β-casein gene transcription in mammary epithelial cells through promoting promoter and enhancer repressive chromatin modifications.

    PubMed

    Buser, Adam C; Obr, Alison E; Kabotyanski, Elena B; Grimm, Sandra L; Rosen, Jeffrey M; Edwards, Dean P

    2011-06-01

    Differentiated HC-11 cells ectopically expressing progesterone receptor (PR) were used to explore the molecular mechanisms by which progesterone suppresses β-casein gene transcription induced by prolactin (PRL) and glucocorticoids in the mammary gland. As detected by chromatin immunoprecipitation assays, treatment of cells with the progestin agonist R5020 induced a rapid recruitment (5 min) of PR to the proximal promoter (-235 bp) and distal enhancer (-6 kb upstream of transcription start site) of β-casein. PR remained bound for 4 h and was dissociated by 24 h after treatment. Despite efficient binding, the hormone agonist-occupied PR did not stimulate transcription of the β-casein gene. Recruitment of signal transducer and activator of transcription 5a, glucocorticoid receptor, and the CCAAT enhancer binding protein β to the enhancer and proximal promoter of β-ca