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Sample records for protein-3 luteinizing hormone

  1. Luteinizing hormone (LH) blood test

    MedlinePlus

    ICSH - blood test; Luteinizing hormone - blood test; Interstitial cell stimulating hormone - blood test ... medicines you take. These include: Birth control pills Hormone therapy Testosterone DHEA (a supplement) If you are ...

  2. Luteinizing hormone (LH) blood test

    MedlinePlus

    ICSH - blood test; Luteinizing hormone - blood test; Interstitial cell stimulating hormone - blood test ... to temporarily stop medicines that may affect the test results. Be sure to tell your provider about ...

  3. Naloxone does not Affect the Luteinizing Hormone-Releasing Hormone-Induced Inhibition of Luteinizing Hormone Secretion in Sheep.

    PubMed

    Naylor, A M; Porter, D W; Lincoln, D W

    1989-06-01

    Abstract Injection of luteinizing hormone-releasing hormone (21 pmol) into the third cerebral ventricle of long-term ovariectomized ewes caused a marked inhibition of luteinizing hormone secretion. Mean luteinizing hormone levels and luteinizing hormone pulse frequency were reduced significantly when compared with the control responses to saline (50 mul). A notable characteristic of the response was the delayed and sustained nature of the luteinizing hormone-releasing hormone-induced inhibition. In the presence of the opioid antagonist naloxone (4 +/- 25 mg iv), the central administration of luteinizing hormone-releasing hormone still produced a marked inhibition of luteinizing hormone secretion. Again, mean luteinizing hormone levels and luteinizing hormone pulse frequency were reduced significantly. When naloxone was injected iv, there was a significant rise in mean luteinizing hormone levels as a consequence of an increase in pulse frequency (in four out of five ewes) and a significant increase in luteinizing hormone pulse amplitude. In conclusion, these data suggest that central opioid pathways sensitive to blockade by naloxone are not involved in the luteinizing hormone-releasing hormone-induced inhibition of luteinizing hormone release. Furthermore, in the long-term ovariectomized ewe, endogenous opioid peptides exert a tonic inhibitory influence on luteinizing hormone-releasing hormone/luteinizing hormone secretion. PMID:19210459

  4. 21 CFR 862.1485 - Luteinizing hormone test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Luteinizing hormone test system. 862.1485 Section... Systems § 862.1485 Luteinizing hormone test system. (a) Identification. A luteinizing hormone test system is a device intended to measure luteinizing hormone in serum and urine. Luteinizing...

  5. 21 CFR 862.1485 - Luteinizing hormone test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Luteinizing hormone test system. 862.1485 Section... Systems § 862.1485 Luteinizing hormone test system. (a) Identification. A luteinizing hormone test system is a device intended to measure luteinizing hormone in serum and urine. Luteinizing...

  6. 21 CFR 862.1485 - Luteinizing hormone test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Luteinizing hormone test system. 862.1485 Section... Systems § 862.1485 Luteinizing hormone test system. (a) Identification. A luteinizing hormone test system is a device intended to measure luteinizing hormone in serum and urine. Luteinizing...

  7. 21 CFR 862.1485 - Luteinizing hormone test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Luteinizing hormone test system. 862.1485 Section... Systems § 862.1485 Luteinizing hormone test system. (a) Identification. A luteinizing hormone test system is a device intended to measure luteinizing hormone in serum and urine. Luteinizing...

  8. 21 CFR 862.1485 - Luteinizing hormone test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Luteinizing hormone test system. 862.1485 Section... Systems § 862.1485 Luteinizing hormone test system. (a) Identification. A luteinizing hormone test system is a device intended to measure luteinizing hormone in serum and urine. Luteinizing...

  9. 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.

  10. 21 CFR 522.1820 - Pituitary luteinizing hormone for injection.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Pituitary luteinizing hormone for injection. 522... ANIMAL DRUGS § 522.1820 Pituitary luteinizing hormone for injection. (a) Specifications. The drug is a... standard pituitary luteinizing hormone and is reconstituted for use by addition of 5 milliliters of...

  11. 21 CFR 522.1820 - Pituitary luteinizing hormone for injection.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Pituitary luteinizing hormone for injection. 522... ANIMAL DRUGS § 522.1820 Pituitary luteinizing hormone for injection. (a) Specifications. The drug is a... standard pituitary luteinizing hormone and is reconstituted for use by addition of 5 milliliters of...

  12. 21 CFR 522.1820 - Pituitary luteinizing hormone for injection.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Pituitary luteinizing hormone for injection. 522... ANIMAL DRUGS § 522.1820 Pituitary luteinizing hormone for injection. (a) Specifications. The drug is a... standard pituitary luteinizing hormone and is reconstituted for use by addition of 5 milliliters of...

  13. 21 CFR 522.1820 - Pituitary luteinizing hormone for injection.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Pituitary luteinizing hormone for injection. 522... ANIMAL DRUGS § 522.1820 Pituitary luteinizing hormone for injection. (a) Specifications. The drug is a... standard pituitary luteinizing hormone and is reconstituted for use by addition of 5 milliliters of...

  14. Regulation of luteinizing hormone-releasing hormone and luteinizing hormone secretion by hypothalamic amino acids.

    PubMed

    Donoso, A O; Seltzer, A M; Navarro, C E; Cabrera, R J; López, F J; Negro-Vilar, A

    1994-04-01

    1. The present review discusses the proposed roles of the amino acids glutamate and GABA in the central regulation of luteinizing hormone-releasing hormone (LHRH) and in luteinizing hormone (LH) secretion. 2. Descriptions of the mechanisms of action of these neurotransmitters have focused on two diencephalic areas, namely, the preoptic-anterior hypothalamic area where the cell bodies of LHRH neurons are located, and the medial basal hypothalamus which contains the nerve endings of the LHRH system. Increasing endogenous GABA concentration by drugs, GABA agonists, or blockade of glutamatergic neurotransmission by selective antagonists in rats and non-human primates prevents ovulation and pulsatile LH release, and blunts the LH surges induced by estrogen or an estrogen-progesterone combination. In contrast, glutamate and different glutamate agonists such as NMDA, AMPA and kainate, can increase LHRH/LH secretion. 3. The simultaneous enhancement of glutamatergic activity and a decrease of GABAergic tone may positively influence the maturation of the pituitary-gonadal system in rats and non-human primates. Administration of glutamate receptor agonists has been shown to significantly advance the onset of puberty. Conversely, glutamate antagonists or increased endogenous GABA levels may delay the onset of puberty. The physiological regulation of LHRH/LH secretion may thus involve a GABA-glutamate interaction and a cooperative action of the various types of ionotropic glutamate receptors. 4. The inhibitory actions of GABA on LH release and ovulation may be exerted at the level of afferent nerve terminals that regulate LHRH secretion. A likely candidate is noradrenaline, as suggested by the synaptic connections between noradrenergic nerve terminals and GABAergic interneurons in the preoptic area. Recent experiments have provided complementary evidence for the physiological balance between inhibitory and excitatory transmission resulting in modulation of the action of

  15. 21 CFR 522.1820 - Pituitary luteinizing hormone powder for injection.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Pituitary luteinizing hormone powder for injection... ANIMAL DRUGS § 522.1820 Pituitary luteinizing hormone powder for injection. (a) Specifications. The drug... milligrams of standard pituitary luteinizing hormone and is reconstituted for use by addition of...

  16. Luteinizing hormone release and androgen production of avian hybrids in response to luteinizing hormone releasing hormone injection.

    PubMed

    Mathis, G F; Burke, W H; McDougald, L R

    1983-04-01

    The levels of luteinizing hormone (LH) and androgens were measured in sterile avian hybrids. Guinea fowl-chicken and peafowl-guinea fowl hybrids were bled before and after injection with LH- releasing hormone (LHRH). The preinjection LH levels for the guinea fowl-chicken hybrids were below or at the very lower limit of the assay sensitivity and the peafowl-guinea fowl hybrids averaged 1.3 ng/ml. Within 10 min after LHRH injection, LH had increased dramatically in both hybrids and then began to slowly decline. Androgen levels in the guinea fowl-chicken hybrids increased from 16.2 pg/ml to 95.2 pg/ml and continued to increase, reaching 287 pg/ml at the last bleeding 60 min after injection. PMID:6346309

  17. Analogues of luteinizing hormone-releasing hormone containing cytotoxic groups.

    PubMed Central

    Janáky, T; Juhász, A; Bajusz, S; Csernus, V; Srkalovic, G; Bokser, L; Milovanovic, S; Redding, T W; Rékási, Z; Nagy, A

    1992-01-01

    In an attempt to produce better cytotoxic analogues, chemotherapeutic antineoplastic radicals including an alkylating nitrogen mustard derivative of D-phenylalanine (D-melphalan), reactive cyclopropane, anthraquinone derivatives [2-(hydroxymethyl)anthraquinone and the anticancer antibiotic doxorubicin], and an antimetabolite (methotrexate) were coupled to suitably modified agonists and antagonists of luteinizing hormone-releasing hormone (LH-RH). Analogues with D-lysine6 and D-ornithine6 or N epsilon-(2,3-diaminopropionyl)-D-lysine and N delta-(2,3-diaminopropionyl)-D-ornithine were used as carriers for one or two cytotoxic moieties. The enhanced biological activities produced by the incorporation of D amino acids into position 6 of the agonistic analogues were further increased by the attachment of hydrophobic cytotoxic groups, resulting in compounds with 10-50 times higher activity than LH-RH. Most of the monosubstituted agonistic analogues showed high affinities for the membrane receptors of human breast cancer cells, while the receptor binding affinities of peptides containing two cytotoxic side chains were lower. Antagonistic carriers [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,D-Lys6,D-Ala10] LH-RH [where Nal(2) is 3-(2-naphthyl)alanine], [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,N epsilon-(2,3-diaminopropionyl)-D-Lys6,D-Ala10]LH-RH, and their D-Pal(3)3 homologs [Pal(3) is 3-(3-pyridyl)alanine] as well as [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,Tyr5,N epsilon-(2,3-diamino-propionyl)-D-Lys6,D-Ala10]LH-RH were linked to cytotoxic compounds. The hybrid molecules inhibited ovulation in rats at doses of 10 micrograms and suppressed LH release in vitro. The receptor binding of cytotoxic analogues was decreased compared to the precursor peptides, although analogues with 2-(hydroxymethyl)anthraquinone hemiglutarate had high affinities. All of the cytotoxic analogues tested inhibited [3H]thymidine incorporation into DNA in cultures of human breast and prostate cancer cell lines

  18. Luteinizing hormone-releasing hormone and thyrotropin-releasing hormone in human and bovine milk.

    PubMed

    Amarant, T; Fridkin, M; Koch, Y

    1982-10-01

    Two hypothalamic peptide hormones, luteinizing hormone-releasing hormone (LHRH) and thyrotropin-releasing hormone (TRH), have been isolated from human milk and bovine colostrum. Acidified methanolic extracts, prepared from human milk, bovine colostrum and rat hypothalami, as well as synthetic LHRH and TRH markers were subjected to high-pressure liquid chromatography (HPLC). The eluates were tested for the presence of LHRH and TRH by specific radioimmunoassays. It was found that milk extracts contain significant amounts of LHRH (3.9 - 11.8 ng/ml) and TRH (0.16 - 0.34 ng/ml), which comigrate with the corresponding marker hormones and with those of hypothalamic origin. The HPLC-purified LHRH from both human and bovine milk was bioactive in a dose-response manner similar to synthetic LHRH. PMID:6816590

  19. Genetic Models for the Study of Luteinizing Hormone Receptor Function

    PubMed Central

    Narayan, Prema

    2015-01-01

    The luteinizing hormone/chorionic gonadotropin receptor (LHCGR) is essential for fertility in men and women. LHCGR binds luteinizing hormone (LH) as well as the highly homologous chorionic gonadotropin. Signaling from LHCGR is required for steroidogenesis and gametogenesis in males and females and for sexual differentiation in the male. The importance of LHCGR in reproductive physiology is underscored by the large number of naturally occurring inactivating and activating mutations in the receptor that result in reproductive disorders. Consequently, several genetically modified mouse models have been developed for the study of LHCGR function. They include targeted deletion of LH and LHCGR that mimic inactivating mutations in hormone and receptor, expression of a constitutively active mutant in LHCGR that mimics activating mutations associated with familial male-limited precocious puberty and transgenic models of LH and hCG overexpression. This review summarizes the salient findings from these models and their utility in understanding the physiological and pathological consequences of loss and gain of function in LHCGR signaling. PMID:26483755

  20. Active immunization to luteinizing hormone releasing hormone to inhibit the induction of mammary tumors in the rat

    SciTech Connect

    Ravdin, P.M.; Jordan, V.C.

    1988-01-01

    Immunization of female rats with a bovine serum albumin-luteinizing hormone releasing hormone conjugate results in suppression of dimethylbenzanthracene mammary tumor incidence. Tumor incidence was 1.3, and 1.29 tumors per rat in bovine serum albumin alone (n = 10) and unimmunized (n = 18) control groups, but no tumors were found in the bovine serum albumin-luteinizing hormone releasing hormone conjugate immunized animals (n = 10). In a second experiment immunization with bovine serum albumin-luteinizing hormone releasing hormone conjugates reduced tumor incidence to 0.3 tumors per rat (n = 10) from the 1.2 tumors per animal seen in the control animals (n = 10) immunized with bovine serum albumin alone. Bovine serum albumin-luteinizing hormone immunization caused the production of anti-LHRH antibodies, an interruption of estrous cycles, lowered serum estradiol and progesterone levels, and atrophy of the ovaries and uteri. Immunization BSA-hormone conjugates is a novel anti-tumor strategy.

  1. Clinical studies with d-Trp 6-luteinizing hormone-releasing hormone in anovulatory women.

    PubMed

    Jaramillo, C J; Charro-Salgado, A; Peréz-Infante, V; del Campo, G L; Botella-Llusiá, J; Coy, D H; Schally, A V

    1978-04-01

    Nine anovulatory patients with hypothalamic-pituitary dysfunction were treated with d-Trp6-luteinizing hormone-releasing hormone, an analog with far greater gonadotropin-releasing activity than luteinizing hormone-releasing hormone. Four of eight patients, who were formerly unsuccessfully treated with clomiphene, human chorionic gonadotropin, and human menopausal gonadotropin, ovulated after treatment with the peptide alone or with peptide preceded by clomiphene, and three became pregnant. The ninth patient, who had amenorrhea and anovulation due to excessive loss of weight caused by anorexia nervosa, also ovulated after treatment with the analog. These results demonstrate the effectiveness of this potent analog for induction of ovulation and pregnancy and point favorably toward clinical applications. PMID:348500

  2. Lutein

    MedlinePlus

    ... eye diseases including age-related macular degeneration (AMD), cataracts, and retinitis pigmentosa. Some people also use it ... lutein together with other ingredients shows conflicting results. Cataracts. Some studies suggest that eating higher amounts of ...

  3. Lutein

    MedlinePlus

    ... including age-related macular degeneration (AMD), cataracts, and retinitis pigmentosa. Some people also use it for preventing colon ... risk of respiratory infections An eye disease called retinitis pigmentosa. Some early evidence suggests that lutein might be ...

  4. Metabolic clearance of biologically active luteinizing hormone in man.

    PubMed Central

    Veldhuis, J D; Fraioli, F; Rogol, A D; Dufau, M L

    1986-01-01

    The plasma metabolic clearance of biologically active luteinizing hormone (bioactive LH) was studied using the rat interstitial cell testosterone (RICT) bioassay in six hypogonadotropic men after single bolus injection of highly purified human LH and during continuous steady-state infusions of three graded doses of LH. The LH bolus disappearance curves provided estimates of metabolic clearance rates (MCR) of 24.1 +/- 4.7 (+/- SD) ml/min for bioactive LH vs. 56.2 +/- 12 ml/min for immunoactive LH in the same men (P = 0.03). A lower MCR of bioactive LH compared with immunoactive LH was also observed during continuous infusions of physiological doses of LH; for example, the mean steady-state MCRs for bioactive and immunoactive LH were, respectively, 26.1 +/- 3.1 and 34.2 +/- 3.2 ml/min (P = 0.02). Moreover, the stepped-dose infusion regimens permitted us to demonstrate that increasing doses of pure human LH resulted in progressive and parallel decreases in the apparent MCRs of both bioactive and immunoactive LH. Based on the respective steady-state MCRs calculated at physiological plasma concentrations of immunoactive and bioactive LH, we estimate a mean endogenous production rate for bioactive hormone of 1,937 IU/24 h, and for immunoactive LH of 589 IU/24 h in normal men. These results indicate that previous estimates of LH production rates from immunoassay data alone markedly underestimate the quantity of biologically active hormone secreted in man. PMID:3958184

  5. Radioiodination of chicken luteinizing hormone without affecting receptor binding potency

    SciTech Connect

    Kikuchi, M.; Ishii, S. )

    1989-12-01

    By improving the currently used lactoperoxidase method, we were able to obtain radioiodinated chicken luteinizing hormone (LH) that shows high specific binding and low nonspecific binding to a crude plasma membrane fraction of testicular cells of the domestic fowl and the Japanese quail, and to the ovarian granulosa cells of the Japanese quail. The change we made from the original method consisted of (1) using chicken LH for radioiodination that was not only highly purified but also retained a high receptor binding potency; (2) controlling the level of incorporation of radioiodine into chicken LH molecules by employing a short reaction time and low temperature; and (3) fractionating radioiodinated chicken LH further by gel filtration using high-performance liquid chromatography. Specific radioactivity of the final {sup 125}I-labeled chicken LH preparation was 14 microCi/micrograms. When specific binding was 12-16%, nonspecific binding was as low as 2-4% in the gonadal receptors. {sup 125}I-Labeled chicken LH was displaced by chicken LH and ovine LH but not by chicken follicle-stimulating hormone. The equilibrium association constant of quail testicular receptor was 3.6 x 10(9) M-1. We concluded that chicken LH radioiodinated by the present method is useful for studies of avian LH receptors.

  6. Luteinizing hormone/human chorionic gonadotropin receptors in breast cancer.

    PubMed

    Meduri, G; Charnaux, N; Loosfelt, H; Jolivet, A; Spyratos, F; Brailly, S; Milgrom, E

    1997-03-01

    Recent studies have suggested that human choriogonadotropin (hCG), in addition to its function in regulating steroidogenesis, may also play a role as a growth factor. Immunocytochemistry using two different monoclonal antibodies (LHR29 and LHR1055) raised against the human luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptor allowed us to detect this receptor in breast cancer cell lines (T47D, MCF7, and ZR75) in individual cancer biopsies and in benign breast lesions. The receptor was also present in epithelial cells of normal human and sow breast. In the latter, its concentration increased after ovulation. The presence of LH/hCG receptor mRNA was confirmed by reverse transcription-PCR using primers extending over exons 2-4, 5-11, and 9-11. The proportion of LH/hCG-receptor positive cells and the intensity of the immunolabeling varied in individual biopsies, but there was no obvious correlation with the histological type of the cancer. These results are compatible with previous studies suggesting that during pregnancy, hCG is involved in the differentiation of breast glandular epithelium and that this hormone may play an inhibitory role in mammary carcinogenesis and in the growth of breast tumors. PMID:9041186

  7. 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.

  8. Regional differences in the pituitary distribution of luteinizing hormone in the gonadectomized and proestrous female rat

    EPA Science Inventory

    Previous data have shown regional differences in the presence of anterior pituitary luteinizing hormone (LH) that generally correlate with comparable disparities in the distribution of gonadotropes throughout the gland. In female rats, the differences are apparent over the estro...

  9. Inactivating mutations of luteinizing hormone beta-subunit or luteinizing hormone receptor cause oligo-amenorrhea and infertility in women.

    PubMed

    Arnhold, Ivo Jorge; Lofrano-Porto, Adriana; Latronico, Ana Claudia

    2009-01-01

    Women harbouring inactivating mutations in luteinizing hormone (LH) beta subunit (LHB) or LH receptor (LHCGR) genes have similar clinical manifestations characterized by female external genitalia, spontaneous breast and pubic hair development at puberty, and normal or late menarche followed by oligo-amenorrhea and infertility. Oestradiol and progesterone levels are normal for the early to midfollicular phase, but do not reach ovulatory or luteal phase levels, confirming lack of ovulation. Notably, serum LH levels are low in patients with LHB mutations and high in those with LHCGR mutations, whereas follicle-stimulating hormone levels are normal or only slightly increased. Pelvic ultrasound has demonstrated a small or normal uterus and normal or enlarged ovaries with cysts. Women with LHB mutations may be treated with hCG (human chorionic gonadotropin) or LH, whereas those with mutations in LHCGR are resistant. Lhb and Lhcgr knockout female mice are close phenocopies of the respective human mutations, and confirm that early follicular development, low levels of oestrogen production and theca cell development are independent of LH action, which is necessary for ovulation. Although inactivating mutations in LHB and LHCGR are rare in comparison to other genetic and non-genetic causes of hypogonadism, they should be considered in the differential diagnosis of oligo-amenorrhea and infertility. PMID:19129711

  10. Highly potent antagonists of luteinizing hormone-releasing hormone free of edematogenic effects.

    PubMed Central

    Bajusz, S; Kovacs, M; Gazdag, M; Bokser, L; Karashima, T; Csernus, V J; Janaky, T; Guoth, J; Schally, A V

    1988-01-01

    To eliminate the undesirable edematogenic effect of the luteinizing hormone-releasing hormone (LH-RH) antagonists containing basic D amino acids at position 6, exemplified by [Ac-D-Phe(pCl)1,2,D-Trp3,D-Arg6,D-Ala10]LH-RH [Phe(pCl) indicates 4-chlorophenylalanine], analogs with D-ureidoalkyl amino acids such as D-citrulline (D-Cit) or D-homocitrulline (D-Hci) at position 6 were synthesized and tested in several systems in vitro and in vivo. HPLC analysis revealed that the overall hydrophobicity of the D-Cit/D-Hci6 analogs was similar to that of the basic D-Arg6 antagonists. In vitro, most of the analogs completely inhibited LH-RH-mediated luteinizing hormone release in perfused rat pituitary cell systems at an antagonist to LH-RH molar ratio of 5:1. In vivo, the most active peptides, [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Trp3,D-Cit6,D-Ala10]LH-RH [Nal(2) indicates 3-(2-naphthyl)alanine] and its D-Hci6 analog, caused 100% inhibition of ovulation in cycling rats in doses of 3 micrograms and suppressed the luteinizing hormone level in ovariectomized female rats for 47 hr when administered at doses of 25 micrograms. Characteristically, these peptides did not exert any edematogenic effects even at 1.5 mg/kg. These properties of the D-Cit/D-Hci6 antagonists may make them useful clinically. PMID:3278323

  11. Immunoreactive luteinizing hormone-releasing hormone in the seminal plasma and human semen parameters

    SciTech Connect

    Izumi, S.; Makino, T.; Iizuka, R.

    1985-04-01

    A luteinizing hormone-releasing hormone (LH-RH)-like substance has been detected in human seminal plasma by a radioimmunoassay (RIA) with a highly specific anti-LH-RH antiserum. The seminal samples - not only the plasma itself but also the sample extracted by an acid/alcohol method - showed satisfactory displacement curves in our RIA system. The relationship between fertility and the LH-RH values in the seminal plasma was studied by comparing the peptide levels with sperm concentration and motility. By these two parameters, 103 samples were divided into four groups. In the low-concentration groups (oligozoospermic patients), the hormonal concentrations differed significantly between those specimens demonstrating good and poor motility. These data suggest that this immunoreactive LH-RH may play a role in human spermatogenesis.

  12. ASSESSMENT OF TOXICANT-INDUCED ALTERATIONS IN THE LUTEINIZING HORMONE CONTROL OF OVULATION IN THE RAT

    EPA Science Inventory

    In the female rat, the large surge of luteinizing hormone (LH) from the pituitary into the general circulation that takes place on the afternoon of the day of vaginal proestrus is both a measurable and functional hormonal event. ince its occurrence is necessary for the expression...

  13. Different follicle stimulating hormone/luteinizing hormone ratios for ovarian stimulation.

    PubMed

    Duijkers, I J; Vemer, H M; Hollanders, J M; Willemsen, W N; Bastiaans, L A; Hamilton, C J; Thomas, C M; Borm, G F

    1993-09-01

    The aim of the present study was to investigate whether reducing the amount of luteinizing hormone (LH) in gonadotrophic preparations impairs follicular growth in in-vitro fertilization (IVF) cycles during suppression of endogenous LH levels. A selected group of 20 IVF patients was randomly divided into two groups. One group was treated with Org 31338 [follicle stimulating hormone (FSH)/LH 3:1], the other group with Metrodin (purified FSH), both during pituitary down-regulation with buserelin. A fixed daily dose of 150 IU FSH i.m. was given. Serum concentrations of FSH, LH, oestradiol and progesterone were determined frequently and serial ultrasound examinations were performed. Multiple follicular growth with concomitant rise of oestradiol levels was observed in all cycles. The duration of the stimulation phase was shorter in the group treated with Org 31338 than in the group treated with Metrodin. The number of follicles and oocytes and the fertilization rate was larger and the mean embryo quality was higher in the Org 31338 group, but the differences did not reach statistical significance. No significant differences were found in hormonal values. In women with normal endocrine profiles, lowering of the LH activity in gonadotrophic preparations during gonadotrophin-releasing hormone agonist treatment results in adequate ovarian stimulation. However, a preparation with some LH needed a shorter stimulation than a purified FSH preparation. Whether the other beneficial effects of Org 31338 also occur in a larger population needs further investigation. PMID:8253923

  14. Luteinizing hormone secretion as influenced by age and estradiol in the prepubertal gilt

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The aim of this study was to determine if there is an age related reduction in the sensitivity of the negative feedback action of estradiol on luteinizing hormone (LH) secretion in the prepubertal gilt. Ovariectomized gilts at 90 (n = 12), 150 (n = 11) or 210 (n = 12) days of age received estradiol ...

  15. PREGNANCY LOSS IN THE F344 RAT CAUSED BY BROMODICHLOROMETHANE: EFFECTS ON SERUM LUTEINIZING HORMONE LEVELS

    EPA Science Inventory

    PREGNANCY LOSS IN THE F344 RAT CAUSED BY BROMODICHLOROMETHANE: EFFECTS ON SERUM LUTEINIZING HORMONE LEVELS
    Bielmeier1, S.R., D.S. Best2, and M.G. Narotsky2; 1University of North Carolina at Chapel Hill, Curriculum in Toxicology, 2Reproductive Toxicology Division, U.S. Enviro...

  16. SUPPRESSION OF THE LUTEINIZING HORMONE SURGE BY CHLORDIMEFORM IN OVARIECTOMIZED, STEROID-PRIMED FEMALE RATS

    EPA Science Inventory

    The midcycle surge of luteinizing hormone (LH) from the pituitary provides the physiological trigger in the mammalian female for the process of ovulation. ccordingly, any agent that compromises the LH surge could function as a reproductive toxicant. ince ovariectomized (OVX) rats...

  17. Glucose-regulated protein, 78-kilodalton is a modulator of luteinizing hormone receptor expression in luteinizing granulosa cells in rats.

    PubMed

    Kogure, Kayoko; Nakamura, Kazuto; Ikeda, Sadatomo; Kitahara, Yoshikazu; Nishimura, Toshio; Iwamune, Masayuki; Minegishi, Takashi

    2013-01-01

    Glucose-regulated protein, 78-kilodalton (GRP78) is a molecular chaperone that exists in the endoplasmic reticulum and is involved in the assembly, transportation, and folding of proteins. Previously, GRP78 was reported to associate with gonadotropin receptors. However, little is known about how GRP78 is involved in the regulation of luteinizing hormone receptor (LHR). Thus, in this study, we investigated the significance of GRP78 for the induction of LHR in rat luteinizing granulosa cells. Western blot analysis of rat LHR expressed in HEK293 cells revealed that the protein levels of LHR were increased, depending on the increment of GRP78 protein. In both in vivo and in vitro experiments, the GRP78 mRNA level peaked while LHR mRNA was down-regulated by human chorionic gonadotropin (hCG). To examine the time-dependent localization of GRP78 in vivo, immunohistochemistry was performed. GRP78 was expressed mainly in granulosa cells, and the GRP78 protein peaked 18 h after the ovulatory dose of hCG injection in equine chorionic gonadotropin-primed immature rats. To ascertain the role of GRP78 in LHR after down-regulation, small interfering GRP78 was transfected to cultured rat granulosa cells, demonstrating that knockdown of the GRP78 protein level impaired the recovery of cell surface LHR from down-regulation that negatively affected progesterone synthesis. Moreover, luciferase assays showed that CRE mediated the hCG-induced promoter activity of GRP78 in rat luteinizing granulosa cells. These results reveal a novel mechanism of LHR by GRP78 in the early stage of corpus lustrum formation, which may be an important factor in the recovery of LHR after the down-regulation. PMID:23175774

  18. Correlation of protein kinase activation and testosterone production after stimulation of Leydig cells with luteinizing hormone.

    PubMed Central

    Cooke, B A; Lindh, M L; Janszen, F H

    1976-01-01

    The effect of different doses of luteinizing hormone on activation of protein kinases, cyclic AMP and testosterone production was studied in purified rat testis Leydig-cell preparations in the presence of 3-isobutyl-1-methylxanthine (a phosphodiesterase inhibitor). In addition, the nature of the protein kinases present in these cells and other tissues was investigated. The following results were obtained. 1. With all the amounts of luteinizing hormone used (0.1-1000 ng/ml), both activation of protein kinase and stimulation of testosterone production were demonstrated. With the lowest amount of luteinizing hormone (0.1 ng/ml), an 8.4+/-0.9% (S.E.M.,n=6) stimulation of protein kinase activation occurred, increasing to 100% with 1000 ng/ml, compared with 3.2+/-1.0%(S.E.M.,n=7) and 100% stimulation of testosterone production with 0.1 and 100 ng/ml respectively. 2. With amounts of luteinizing hormone up to 1 ng/ml (which gave half-maximal stimulation of testosterone production) no detectable increases in net cyclic AMP production were obtained. With higher amounts of luteinizing hormone, cyclic AMP production increased, but maximal production was not reached with 1000 ng/ml. 3. Two isoenzymic forms of protein kinase were present in Leydig cells and seminiferous tubules; type I was eluted with 0.075 M-and type II with 0.22-0.25 m-NaCl from DEAE-cellulose columns. 4. The protein kinase activity was not affected by the presence of erythrocytes in the Leydig-cell preparation, but varied depending on the type of histone used as substrate (histone F2b greater than mixed greater than histone F1). PMID:189752

  19. Annual cycle of plasma luteinizing hormone and sex hormones in male and female mallards (Anas platyrhynchos)

    USGS Publications Warehouse

    Donham, R.S.

    1979-01-01

    Comparisons between 'wild'and 'game farm' mallards (Anas platyrhynchos) were made to assess the differences in the temporal changes of plasma hormones. Seasonal variation in the levels of immunoreactive luteinizing hormone (LH), testosterone, 5 -dihydrotestosterone (DHT), estrone, estradiol-17i?? and progesterone were measured in male and female mallards. In all birds there was a vernal increase in the concentrations of LH and testosterone in plasma which were correlated with the development of the testes and ovaries prior to and during the nesting season. The concentrations of estrogens in the plasma of the females were, in general, slightly higher during the nesting season but were much lower than the levels of testosterone. The highest levels of LH and testosterone in the females coincided precisely with the period of egg laying which occurred approximately one month earlier in game farm females than in wild females. The concentrations of LH and testosterone in the plasma of females decreased rapidly during incubation. In wild males, the decline in levels of these hormones temporally coincided with that of females. In contrast, plasma levels of LH and testosterone of males of the game farm stock remained elevated after the beginning of incubation in females to which they were paired. On the basis of these results and an examination of the literature, it appears that domestication results in: 1) increased reproductive potential through earlier initiation of nesting and by delay of the termination of reproduction until later in the summer; and 2) a decrease in the synchronization of the hormonal events supporting reproduction between the male and female of a pair. Testicular weights and plasma levels of testosterone become higher in game farm and domestic males than in the wild stock but levels of LH are similar.

  20. Substantial expression of luteinizing hormone-releasing hormone (LHRH) receptor type I in human uveal melanoma

    PubMed Central

    Schally, Andrew V.; Block, Norman L; Dezso, Balazs; Olah, Gabor; Rozsa, Bernadett; Fodor, Klara; Buglyo, Armin; Gardi, Janos; Berta, Andras; Halmos, Gabor

    2013-01-01

    Uveal melanoma is the most common primary intraocular malignancy in adults, with a very high mortality rate due to frequent liver metastases. Consequently, the therapy of uveal melanoma remains a major clinical challenge and new treatment approaches are needed. For improving diagnosis and designing a rational and effective therapy, it is essential to elucidate molecular characteristics of this malignancy. The aim of this study therefore was to evaluate as a potential therapeutic target the expression of luteinizing hormone-releasing hormone (LHRH) receptor in human uveal melanoma. The expression of LHRH ligand and LHRH receptor transcript forms was studied in 39 human uveal melanoma specimens by RT-PCR using gene specific primers. The binding charachteristics of receptors for LHRH on 10 samples were determined by ligand competition assays. The presence of LHRH receptor protein was further evaluated by immunohistochemistry. The expression of mRNA for type I LHRH receptor was detected in 18 of 39 (46%) of tissue specimens. mRNA for LHRH-I ligand could be detected in 27 of 39 (69%) of the samples. Seven of 10 samples investigated showed high affinity LHRH-I receptors. The specific presence of full length LHRH receptor protein was further confirmed by immunohistochemistry. A high percentage of uveal melanomas express mRNA and protein for type-I LHRH receptors. Our results support the merit of further investigation of LHRH receptors in human ophthalmological tumors. Since diverse analogs of LHRH are in clinical trials or are already used for the treatment of various cancers, these analogs could be considered for the LHRH receptor-based treatment of uveal melanoma. PMID:24077773

  1. Specific protein synthesis in isolated rat testis leydig cells. Influence of luteinizing hormone and cycloheximide.

    PubMed Central

    Janszen, F H; Cooke, B A; van der Molen, H J

    1977-01-01

    The effect of luteinizing hormone (luteotropin) and cycloheximide on specific protein synthesis in rat testis Leydig cells has been investigated. Proteins were labelled with either I114C]leucine, [3H]leucine or [35S]methionine during incubation with Leydig-cell suspensions in vitro. Total protein was extracted from the cells and separated by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. No detectable increase in the synthesis of specific proteins could be observed after incubation of Leydig cells with luteinizing hormone for up to 1 h. However, after a 2h incubation period, an increase in [35S]methionine incorporation was observed in a protein with an apparent mol.wt. of 21000 (referred to as 'protein 21"). When, after labelling of this protein with [35S]-methionine, Leydig cells were incubated for another 30min with cycloheximide, no decrease in radioactivity of this protein band was observed, indicating that it does not have a short half-life. However, another protein band was detected, which after incubation with cycloheximide disappeared rapidly, the reaction following first-order kinetics, with a half-life of about 11 min. This protein, with an apparent mol.wt. of 33000 (referred to as "protein 33"), was found to be located in the particulate fraction of the Leydig cell, and could not be demonstrated in other rat testis-cell types or blood cells. No effect of luteinizing hormone on molecular weight, subcellular localization or half-life of protein 33 was observed. A possible role for protein 33 and protein 21 in the mechanism of action of luteinizing hormone on testosterone production of Leydig cells is discussed. Images PLATE 4 PLATE 1 PLATE 2 PLATE 3 PMID:849289

  2. Responses of luteinizing hormone, follicle-stimulating hormone, and prolactin to prolonged administration of the dopamine antagonist in normal women and women with low-weight amenorrhea.

    PubMed

    Larsen, S

    1981-06-01

    The responses of luteinizing hormone, follicle-stimulating hormone, and prolactin to prolonged administration of the dopamine receptor antagonist metoclopramide (5 mg twice daily) were investigated in six normal women and six women with low-weight amenorrhea (LWA). In contrast to the normal group, the LWA group showed no significant changes in the mean basal prolactin level or the mean prolactin response to stimulation with thyrotropin-releasing hormone, but there was an significant elevation of the mean net increase in luteinizing hormone after stimulation with gonadotropin-releasing hormone. On the basis of these data, the possibility of increased central dopaminergic activity in women with LWA is discussed. PMID:6788608

  3. Follicle-stimulating hormone potentiates the steroidogenic activity of chorionic gonadotropin and the anti-apoptotic activity of luteinizing hormone in human granulosa-lutein cells in vitro.

    PubMed

    Casarini, Livio; Riccetti, Laura; De Pascali, Francesco; Nicoli, Alessia; Tagliavini, Simonetta; Trenti, Tommaso; La Sala, Giovanni Battista; Simoni, Manuela

    2016-02-15

    Luteinizing hormone (LH) and choriogonadotropin (hCG) are glycoprotein hormones regulating ovarian function and pregnancy, respectively. Since these molecules act on the same receptor (LHCGR), they were traditionally assumed as equivalent in assisted reproduction techniques (ART), although differences between LH and hCG were demonstrated at molecular and physiological level. In this study, we demonstrated for the first time that co-treatment with a follicle-stimulating hormone (FSH) dose in the ART therapeutic range potentiates different LH- and hCG-dependent responses in vitro, measured in terms of cAMP, phospho-CREB, -ERK1/2 and -AKT activation, gene expression, progesterone and estradiol production in human granulosa-lutein cells (hGLC). We show that in the presence of FSH, hCG biopotency is about 5-fold increased, in the presence of FSH, in terms of cAMP activation. Accordingly, CREB phosphorylation and steroid production is increased under hCG and FSH co-treatment. LH effects, evaluated as steroidogenic cAMP/PKA pathway activation, do not change in the presence of FSH, which, however, increases LH-dependent ERK1/2 and AKT, but not CREB phosphorylation, resulting in anti-apoptotic effects. The different modulatory activity of FSH on LH and hCG action in vitro corresponds to their different physiological functions, reflecting proliferative effects exerted by LH during the follicular phase and before trophoblast development, and the high steroidogenic potential of hCG requested to sustain pregnancy from the luteal phase onwards. PMID:26690776

  4. Plasma luteinizing hormone concentration in mares treated with gondotropin-releasing hormone and estradiol.

    PubMed

    Garcia, M C; Ginther, O J

    1975-11-01

    Three experiments were performed to study the luteinizing hormone (LH) and ovulatory responses to various doses and methods of administration of gonadotropin-releasing hormone (GnRH) in estrous pony mares and the influence of estradiol-17beta (E2-17beta) on LH response to GnRH treatment. In experiment 1, single injections of synthetic GnRH were subcutaneously given to 5 groups of estrous (day 2) mares (3 mares/group) on a body weight basis as follows: group A--isotonic saline solution; group B--GnRH, 0.14 mug/kg; group C--GnRH, 0.28 mug/kg; group D--KGnRH, 0.59 mug/kg; and group E--GnRH, 2.37 mug/kg. Significant increase of plasma LH concentration lasting for approximately 2 hours occurred only in mares of group E given the largest dose of GnRH (2.37 mug/kg). Plasma LH concentration increase at 1 hour after treatment approached significane (P less than 0.10) in mares of group D given the next smaller dose. In experiment 2, GnRH (2.37 mug/kg) was intravenously infused for 24 hours to a group of 6 mares (group F); 6 other mares (group G) were given saline solution infusion. Mean plasma LH concentration was increased at 3 hours, continued to increase until 6 hours, and remained at approximately the 6-hour concentration throughout the period of GnRH infusion. In the 3rd experiment, 3 groups of mares (4 mares/group) were subcutaneously given the following treatments on days 2 and 3 of estrus, respectively: group H--corn oil and saline solution; group I--corn oil and GnRH, 0.59 mug/kg; and group J--estradiol-17beta, 0.5 mg, and GnRH, 0.59 mug/kg. Plasma LH response was not seen in group H mares given corn oil and saline solution. Mean plasma LH concentration at 1 hour after administration of GnRH approached significance (P less than 0.10) in group I mares given corn oil and GnRH. For the mares in group J given E2-17beta and GnRH, E2-17beta pretreatment increased plasma LH after 24 horus; significnat increases of plasma LH concentration were seen from 1 to 6 hours after

  5. Metabolism of testosterone by human granulosa cells in culture: influence of follicle-stimulating hormone and luteinizing hormone

    SciTech Connect

    Moon, Y.S.; Duleba, A.; Leung, P.C.; Gomel, V.

    1982-03-15

    Human granulosa cells were isolated from follicles (8 to 15 mm) and cultivated for 24 hours in the presence or absence of follicle-stimulating hormone (NIH-FSH-HS-1, 1 microgram/ml) and luteinizing hormone (NIAMDD-hLH-1, 1 microgram/ml). Testosterone -4-14C was added subsequently to all cultures for 4-, 6-, and 24-hour periods. Of the seven metabolites of testosterone studied, 17 beta-estradiol (E2) and estrone (E1) were the major products. In all patients, levels of E2 were three to ten times higher than those of E1. Production of E2, but not E1, was stimulated by either follicle-stimulating hormone (FSH) or luteinizing hormone (LH). The cells of the largest follicle (15 mm) showed greater response to LH than to FSH. Production of the other C19 and C18 metabolites was very low or negligible. These results further suggest that FSH regulates the aromatization of testosterone in human granulosa cells, and that LH may have the same effect on the matured follicle during the preovulatory period.

  6. Synthesis and in vitro anti-cancer evaluation of luteinizing hormone-releasing hormone-conjugated peptide.

    PubMed

    Deng, Xin; Qiu, Qianqian; Ma, Ke; Huang, Wenlong; Qian, Hai

    2015-11-01

    Luteinizing hormone-releasing hormone (LHRH) is a decapeptide hormone released from the hypothalamus and shows high affinity binding to the LHRH receptors. It is reported that several cancer cells also express LHRH receptors such as breast, ovarian, prostatic, bladder and others. In this study, we linked B1, an anti-cancer peptide, to LHRH and its analogs to improve the activity against cancer cells with LHRH receptor. Biological evaluation revealed that TB1, the peptide contains triptorelin sequence, present favorable anti-cancer activity as well as plasma stability. Further investigations disclosed that TB1 trigger apoptosis by activating the mitochondria-cytochrome c-caspase apoptotic pathway, it also exhibited the anti-migratory effect on cancer cells. PMID:26058357

  7. Effect of a combination of norethynodrel and mestranol on plasma luteinizing hormone in normal women.

    PubMed

    Abraham, G E; Klaiber, E L; Broverman, D

    1969-08-01

    Plasma luteinizing hormone (LH) levels were measured by radioimmunoassay in 6 normal nulliparous women (ages 21-25) during 2 consecutive menstrual cycles. Cycle 1 served as the control, while a combination of 5 mg norethynodrel and .075 mg mestranol (Enovid) was administered daily during the second cycle. Midcycle LH peaks observed in all subjects during the control cycle were completely suppressed in the treated cycle. Basal LH levels during the treated cycle were significantly lower than during the follicular phase of control cycles. Mechanisms by which Enovid could affect plasma LH include decreased synthesis or release of LH and different sites of drug action with different dosages. PMID:5794834

  8. Organophosphorus insecticide induced decrease in plasma luteinizing hormone concentration in white-footed mice

    USGS Publications Warehouse

    Rattner, B.A.; Michael, S.D.

    1985-01-01

    Oral intubation of 50 and 100 mg/kg acephate inhibited brain acetylcholinesterase (AChE) activity by 45% and 56%, and reduced basal luteinizing hormone (LH) concentration by 29% and 25% after 4 h in white-footed mice (Peromyscus leucopus noveboracensis). Dietary exposure to 25, 100, and 400 ppm acephate for 5 days substantially inhibited brain AChE activity, but did not affect plasma LH concentration. These preliminary findings suggest that acute exposure to organophosphorus insecticides may affect LH secretion and possibly reproductive function.

  9. Leap of Faith: Does serum luteinizing hormone always accurately reflect central reproductive neuroendocrine activity?

    PubMed Central

    Moenter, Suzanne M.

    2015-01-01

    Function of the central aspects of the hypothalamo-pituitary-gonadal axis has been assessed in a number of ways including direct measurements of hypothalamic output and indirect measures using gonadotropin release from the pituitary as a bioassay for reproductive neuroendocrine activity. Here, methods for monitoring these various parameters are briefly reviewed and then examples presented of both concordance and discrepancy between central and peripheral measurements, with a focus on situations in which elevated GnRH neurosecretion is not reflected accurately by pituitary luteinizing hormone release. Implications for interpretation of gonadotropin data are discussed. PMID:26278916

  10. AGE-RELATED ALTERATIONS IN THE STIMULATED RELEASE IN VITRO OF CATECHOLAMINES AND LUTEINIZING HORMONE-RELEASING HORMONE FROM THE MALE RAT HYPOTHALAMUS

    EPA Science Inventory

    Using an in vitro perifusion system, the present study investigated the possibility that alterations in catecholamine and luteinizing hormone-releasing hormone (LHRH) secretion from the male rat mediobasal hypothalamus are present during the period of middle-age. The results indi...

  11. Effect of carp pituitary extract and luteinizing hormone releasing analog hormone on reproductive indices and spawning of 3-year-old channel catfish

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The efficacy of carp pituitary extract (CPE) and luteinizing hormone releasing hormone (LHRHa) treatments to induce spawning in young-adult channel catfish undergoing first oogenesis just prior to the spawning season was evaluated in four commercial strains of channel catfish. Prior to injection of ...

  12. The effect of luteinizing hormone releasing hormone analog regime and stage of oocyte maturity for induced ovulation of channel catfish Ictalurus punctatus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effective LHRHa (luteinizing hormone releasing hormone analog) dose based on the gonadal maturity of channel catfish, Ictalurus punctatus to optimize channel x blue hybrid catfish production was evaluated in 4 trials (twice in early part of the season and twice in the peak spawning season) in a ...

  13. Luteinizing hormone and follicle stimulating hormone synergy: A review of role in controlled ovarian hyper-stimulation

    PubMed Central

    Raju, Gottumukkala Achyuta Rama; Chavan, Rahul; Deenadayal, Mamata; Gunasheela, Devika; Gutgutia, Rohit; Haripriya, Geetha; Govindarajan, Mirudhubashini; Patel, Nayana Hitesh; Patki, Ameet Shashikant

    2013-01-01

    Luteinizing hormone (LH) in synergy with follicle stimulating hormone (FSH) stimulates normal follicular growth and ovulation. FSH is frequently used in assisted reproductive technology (ART). Recent studies have facilitated better understanding on the complementary role of the LH to FSH in regulation of the follicle; however, role of LH in stimulation of follicle, optimal dosage of LH in stimulation and its importance in advanced aged patients has been a topic of discussion among medical fraternity. Though the administration of exogenous LH with FSH is obligatory for controlled ovarian stimulation in patients with hypogonadotropic hypogonadism, there is still a paucity of information of its usage in other patient population. In this review we looked in to the multiple roles that LH plays complementary to FSH to better understand the LH requirement in patients undergoing ART. PMID:24672160

  14. Luteinizing hormone-releasing hormone (LH-RH) as a diagnostic and research tool in gynecologic endocrinology.

    PubMed

    Taymor, M L; Thompson, I E; Berger, M J; Patton, W

    1974-11-15

    A study is reported on the effects of 150 mcg. of luteinizing hormone-releasing hormone (LH-RH), administered iv to 48 women with 5 types of secondary oligoamenorrhea, on the serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) Levels. At Time 0, patients with pituitary disease showed a markedly diminished LH response and patients with polycystic ovarian disease with enlarged ovaries showed a brisk, elevated LH response. FSH levels in patients with pituitary disease and polycystic ovarian disease showed a negligible rise at Time 0. 9 of 10 patients with pituitary disease and 5 of 9 patients with dietary amenorrhea had a low LH response 30 minutes after LH-RH administration. FSH response 60 minutes after injection in patients with pituitary disease and polycystic ovarian disease seemed to be lowered though too much overlap prevented a complete diagnosis. The conclusion of this initial study is that through baseline determinations of FSH and LH, along with a LH-RH stimulation test, useful data are provided for determining whether amenorrhea is due to ovarian or pituitary failure. A 2nd study evaluated the effects of 150 mcg of LH-RH administered iv before and after the im administration of various dosages of estrogen and progesterone to anovulatory women. A vigorous response in pituitary gonadotropin, particularly LH, was observed with LH-RH administered only. The effect with estrogen and progesterone was diminished pituitary response in terms of LH production. It is concluded that estrogen and progesterone exert a negative feedback effect on gonadotropin secretion at the hypothalamic and pituitary levels. PMID:4611213

  15. The problem of anti-doping control of luteinizing hormone in boxing.

    PubMed

    Llouquet, Jean Louis; Crepin, Nathalie; Lasne, Françoise

    2013-04-01

    Luteinizing hormone (LH) is physiologically produced by the anterior pituitary gland. Male athletes may use pharmaceutical LH for doping since it increases the production of testosterone by testes. This hormone is thus on the World Anti-Doping Agency (WADA) list of substances prohibited for males. Anti-doping laboratories perform the assay of this hormone in urine and report abnormally elevated results. We observed a highly significant prevalence of abnormal results in samples taken after a boxing match. Comparison of the descriptive statistics for 426 LH values observed in boxing and other sports showed significant differences. An experimental study comparing urinary LH levels in 17 boxers before and after a match demonstrated a clear increase after the match. The same observation was made for urinary follicle stimulating hormone (FSH) in all of the eight boxers tested for this other pituitary gonadotropin. These observations have consequences for anti-doping controls, as the reference range for urinary LH levels must take into account the specificities of boxers. They also suggest consequences for the health of boxers. Although to our knowledge such observations have never been described, other pituitary disorders have been reported. Our results deserve further investigation from a medical point of view. PMID:23315937

  16. Effect of naloxone treatment on luteinizing hormone and testosterone concentrations in boars with high and low libido

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective was to determine the effects of naloxone, an opioid peptide receptor antagonist on circulating concentrations of luteinizing hormone (LH) and testosterone in boars characterized as having high (n = 8) or low libido (n = 8) based on the willingness to mount an artificial sow and allow s...

  17. Luteinizing hormone receptors in human ovarian follicles and corpora lutea during the menstrual cycle

    SciTech Connect

    Yamoto, M.; Nakano, R.; Iwasaki, M.; Ikoma, H.; Furukawa, K.

    1986-08-01

    The binding of /sup 125/I-labeled human luteinizing hormone (hLH) to the 2000-g fraction of human ovarian follicles and corpora lutea during the entire menstrual cycle was examined. Specific high affinity, low capacity receptors for hLH were demonstrated in the 2000-g fraction of both follicles and corpora lutea. Specific binding of /sup 125/I-labeled hLH to follicular tissue increased from the early follicular phase to the ovulatory phase. Specific binding of /sup 125/I-labeled hLH to luteal tissue increased from the early luteal phase to the midluteal phase and decreased towards the late luteal phase. The results of the present study indicate that the increase and decrease in receptors for hLH during the menstrual cycle might play an important role in the regulation of the ovarian cycle.

  18. Depression of plasma luteinizing hormone concentration in quail by the anticholinesterase insecticide parathion

    USGS Publications Warehouse

    Rattner, B.A.; Clarke, R.N.; Ottinger, M.A.

    1986-01-01

    To examine the effects of parathion on basal plasma luteinizing hormone (LH) concentration, male Japanese quail (Coturnix japonica) were orally intubated with 0, 5 or 10 mg/kg parathion and sacrificed after 4, 8 and 24 hr. At the 5 mg/kg dose, plasma LH levels were reduced at 4 and 8 hr, but returned to control values by 24 hr. Brain acetylcholinesterase activity was substantially reduced by 10 mg/kg parathion (52, 75 and 37% inhibition at 4, 8 and 24 hr, respectively) and plasma LH concentration remained depressed through the 24-hr period. These findings suggest that the organophosphorus insecticide parathion may alter plasma LH concentration in a manner which might impair reproductive activity, and provide indirect evidence for a cholinergic component in the regulation of LH secretion in quail.

  19. Luteinizing hormone (LH) levels in male workers exposed to urban stressors.

    PubMed

    Tomao, Enrico; Tomei, Gianfranco; Rosati, Maria Valeria; Caciari, Tiziana; Danese, Daniele; Gamberale, Daniele; Vacca, Daniele; Palermo, Paola; Anzelmo, Vincenza; Tomei, Francesco

    2009-08-01

    The aim of the study is to evaluate if occupational exposure to urban stressors could cause alterations in luteinizing hormone (LH) plasma levels in male traffic policemen vs. administrative staff of Municipal Police.After excluding the subjects with the main confounding factors, male traffic police and administrative staff of Municipal Police were matched by age, working life, body mass index (BMI), alcohol drinking habit, cigarette smoking habit and habitual consumption of Italian coffee.In 166 male traffic police mean LH values were significantly higher compared to 166 male administrative employees. The distribution of LH values in traffic police and in administrative employees was statistically significant.Our results suggest that recent exposure to urban stressors (chemical, physical and psycho-social) can alter the plasma concentration of LH. In agreement with our previous research, levels of plasma LH may be used as early biological markers, valuable for the group, used in occupational set before the appearance of the disease. PMID:19477485

  20. Association of luteinizing hormone receptor gene expression with cell cycle progression in granulosa cells

    PubMed Central

    Cannon, Jennifer D.; Seekallu, Srinivas V.; VandeVoort, Catherine A.; Chaffin, Charles L.

    2009-01-01

    During hormonally induced ovarian follicle growth, granulosa cell proliferation increases and returns to baseline prior to the administration of an ovulatory stimulus. Several key genes appear to follow a similar pattern, including the luteinizing hormone receptor (LHCGR), suggesting an association between cell cycle progression and gene expression. The expression of LHCGR mRNA in granulosa cells isolated from immature rats and treated in culture with FSH increased in a time-dependent manner, whereas administration of the cell cycle inhibitor mimosine completely suppressed expression. Although forskolin was able to induce luteinization in cells treated with mimosine, human chorionic gonadotropin had no effect, indicating the functional loss of LHCGR. The effects of mimosine on cell cycle progression and LHCGR mRNA expression were reversible within 24 h of mimosine removal. Cell cycle inhibition did not alter the stability of LHCGR mRNA, indicating that the primary effect was at the transcriptional level. To determine whether the relationship between LHCGR expression and cell cycle were relevant in vivo, immature rats were given a bolus of PMSG, followed by a second injection of either saline or PMSG 24 h later to augment levels of proliferation. The expression of LHCGR mRNA was elevated in the ovaries of animals receiving a supplement of PMSG. Mimosine also blocked cell cycle progression and LHCGR mRNA expression in macaque granulosa cells isolated following controlled ovarian stimulation cycles and in two different mouse Leydig tumor lines. These data collectively indicate that LHCGR mRNA is expressed as a function of the passage of cells across the G1-S phase boundary. PMID:19293332

  1. Evaluation of an immunoenzymometric assay (IEMA) using automated system for determination of luteinizing hormone and follicle stimulating hormone.

    PubMed

    Fonseca, E; Mason, M; Galván, R E; Pascoe, D; Ochoa, R; Hernández, M; Zárate, A

    1997-01-01

    It has been proposed that automated systems for immunoenzymometric assay (IEMA) may substitute traditional radioimmunoassay (RIA) for measurement of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in blood due to the advantage of being more rapid, higher sensitivity, lower cost and not requiring radioactive reagents. The study was designed to evaluate both systems using serum samples to determine luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations. The automatic system (ES-300) for IEMA utilized two monoclonal antibodies, one of them on the solid phase was the specific extractant for the antigen, and the other was a peroxidase labeled antibody which recognizes a different epitope in the antigen molecule, specifically bound in linear proportion to the antigen concentration. Blood samples were obtained from patients who were treated at the hospital for various clinical problems ("problem group") as well as blood samples from patients in whom FSH and LH concentrations were already known ("high", "medium" and "low" levels) by previous RIA ("control group"). IEMA showed a higher sensitivity, 0.42 and 0.96 mIU/ml for FSH and LH, respectively, whereas RIA was 1.95 mIU/ml for both hormones. Intra- and interassay coefficient of variation were below 10% within the range of 15-150 mIU/ml for FSH and 5-100 mIU/ml for LH; however, the coefficient of variation was 15-25% at lower concentrations of FSH and LH. Accuracy of IEMA was evaluated by recovery percentage, thus when high and medium concentrations of FSH and LH were analyzed the recovery was between 99-104%. On the other hand, the recovery was 110% when low levels of FSH and LH were used. In conclusion, IEMA resulted reliable when FSH and LH concentrations are in the middle and high range; likewise, the detection limit of IEMA was lower than RIA, particularly for FSH. On the bases of these results, IEMA showed several advantages over RIA, but its reliability diminishes when serum

  2. Hypothalamic multiunit activity and pulsatile luteinizing hormone release in the castrated male rat.

    PubMed

    Goubillon, M L; Kaufman, J M; Thalabard, J C

    1995-11-01

    Using chronically implanted microelectrodes, multiunit electrical activity (MUA) was recorded from the arcuate nucleus of freely moving gonadectomized male rats. Intermittent increases in MUA activity (MUA volleys) closely associated with luteinizing hormone pulses measured in the peripheral circulation were observed, which confirms that this experimental approach can be used for monitoring the activity of the gonadotropin-releasing hormone-associated hypothalamic pulse generator in the male rat. The mean MUA volley frequency was 22.2 min (range 13-38 min), whereas the mean MUA volley duration was 2.7 +/- 0.8 min (standard deviation). In addition to a large inter-individual variability. MUA volley intervals also showed an important intra-individual variability. This observation suggests that, beside the mean frequency of pulse generator activation, the degree of variability in gonadotropin-releasing hormone-associated pulse generator activity might be an additional relevant parameter in the characterization of the reproductive function in the male rat. PMID:7581989

  3. Plasma and urinary luteinizing hormone levels in the diagnosis of endocrine disease.

    PubMed

    Wikramanayake, R; Keenan, J R; Spathis, G S; Nabarro, J D; Leonard, P J; Gallagher, M J

    1972-03-25

    The diagnostic value of measurements of plasma and urinary luteinizing hormone (LH) has been studied in 209 patients with endocrine disease. In 44 patients puberty was either delayed or had failed to occur. In those with chromosomal abnormalities the LH levels were often within the normal range, whereas those with a pituitary cause usually had low levels. In boys with delayed puberty plasma LH levels rose before physical changes occurred and had prognostic value. In patients with later gonadal failure, men with impotence or infertility, and women with secondary amenorrhoea LH assays proved of little value, although in one case a premature menopause was suspected and six patients with anorexia nervosa had low LH levels.Sixty patients with disorders of the hypothalamicpituitary area were studied. Levels of LH were measured and considered in relation to the other anterior pituitary hormones. Impairment of LH secretion was one of the first effects on hormone production of disease affecting this area, and this was, of course, most readily detected in postmenopausal women.The normal ranges of both plasma and urine LH are wide and there seems to be considerable day-to-day variation, especially of urinary output. Several samples should, therefore, be measured if therapeutic decisions are involved. PMID:5014251

  4. Targeted overexpression of luteinizing hormone in transgenic mice leads to infertility, polycystic ovaries, and ovarian tumors.

    PubMed Central

    Risma, K A; Clay, C M; Nett, T M; Wagner, T; Yun, J; Nilson, J H

    1995-01-01

    Hypersecretion of luteinizing hormone (LH) is implicated in infertility and miscarriages in women. A lack of animal models has limited progress in determining the mechanisms of LH toxicity. We have recently generated transgenic mice expressing a chimeric LH beta subunit (LH beta) in gonadotropes. The LH beta chimera contains the C-terminal peptide of the human chorionic gonadotropin beta subunit. Addition of this peptide to bovine LH beta resulted in a hormone with a longer half-life. Furthermore, targeted expression of the LH beta chimera led to elevated LH levels and infertility in female transgenics. These mice ovulated infrequently, maintained a prolonged luteal phase, and developed pathologic ovarian changes such as cyst formation, marked enlargement of ovaries, and granulosa cell tumors. Testosterone and estradiol levels were increased compared to nontransgenic littermates. An unusual extragonadal phenotype was also observed: transgenic females developed hydronephropathy and pyelonephritis. The pathology observed demonstrates a direct association between abnormal secretion of LH and infertility and underscores the utility of the transgenic model for studying how excess LH leads to cyst formation, ovarian tumorigenesis, and infertility. Images Fig. 2 Fig. 3 Fig. 5 PMID:7877975

  5. Streptozotocin-induced diabetes blocks the positive feedback release of luteinizing hormone in the female rat.

    PubMed

    Kienast, S G; Fadden, C; Steger, R W

    1993-01-01

    The effects of streptozotocin-induced (STZ) diabetes on the release of gonadotropins was studied in female rats. In the first experiment, rats were ovariectomized and 2 days later were injected with STZ. Three weeks later rats were treated with estrogen and progesterone and blood samples were taken via intraatrial cannulae for luteinizing hormone (LH) assay. Afternoon surges of LH were seen in 4/5 control but 0/8 STZ rats. Pituitary responses to LH-releasing hormone in vitro did not differ. In the 2nd experiment, ovariectomized estrogen-primed rats were killed prior to and during a progesterone-induced LH surge. As in Experiment 1, STZ-treatment inhibited the LH surge but did not effect the afternoon rise in median eminence norepinephrine turnover which has previously been shown to be important in stimulating LH release. Turnover of norepinephrine in the anterior hypothalamus was depressed in the diabetic rats both prior to and during the expected time of the LH surge. Dopamine turnover was depressed in all three brain regions studied. It can be concluded that the positive feedback control of LH release is severely attenuated in diabetic rats but the mechanism explaining the loss is not clear. Diabetes-induced alterations in hypothalamic catecholamine metabolism may be involved but further work is needed to more carefully define these relationships. PMID:8221130

  6. Thecal cell sensitivity to luteinizing hormone and insulin in polycystic ovarian syndrome.

    PubMed

    Cadagan, David; Khan, Raheela; Amer, Saad

    2016-03-01

    This study examined whether a defect of steroid synthesis in ovarian theca cells may lead to the development of PCOS, through contributions to excess androgen secretion. Polycystic ovarian syndrome (PCOS) is one of the leading causes of infertility worldwide affecting around 1 in 10 of women of a reproductive age. One of the fundamental abnormalities in this syndrome is the presence of hormonal irregularities, including hyperandrogenemia, hyperinsulinemia and hypersecretion of luteinizing hormone (LH). Studies suggest that insulin treatment increases progesterone and androstenedione secretion in PCOS theca cells when compared to insulin treated normal theca cells. Furthermore the augmented effects of LH and insulin have been seen to increase ovarian androgen synthesis in non-PCOS theca cultures whilst also increasing the expression of steroidogenic enzymes specific to the PI3-K pathway. Our examination of primary thecal cultures showed an increase in both the expression of the steroidogenic enzyme CYP17 and androgen secretion in PCOS theca cells under basal conditions, when compared to non-PCOS cells. This was increased significantly under treatments of LH and insulin combined. Our results support the previous reported hypothesis that a dysfunction may exist within the PI3-K pathway. Specifically, that sensitivity exists to physiological symptoms including hyperinsulinemia and hyper secretion of LH found in PCOS through co-stimulation. The impact of these findings may allow the development of a therapeutic target in PCOS. PMID:26952754

  7. Hypersecretion of luteinizing hormone and ovarian steroids in women with recurrent early miscarriage.

    PubMed

    Watson, H; Kiddy, D S; Hamilton-Fairley, D; Scanlon, M J; Barnard, C; Collins, W P; Bonney, R C; Franks, S

    1993-06-01

    Polycystic ovary syndrome is associated with hypersecretion of luteinizing hormone (LH) which has been implicated in the aetiology of early pregnancy loss. Although 82% of women with recurrent early loss have polycystic ovaries on ultrasound imaging, random serum LH concentrations are normal. In the present study, we have obtained further information from serial samples concerning the cyclical patterns of gonadotrophin and sex steroid secretion in these women. Twenty-one women with recurrent early pregnancy loss and 10 multiparous controls were investigated; 81% of them and one of ten control subjects had polycystic ovaries. Mean mid-follicular and mid-luteal serum LH and follicle stimulating hormone (FSH) levels were similar in both groups. Seventeen women with pregnancy loss had either raised urinary LH excretion or a premature LH surge; one control subject had a premature LH surge. Total LH excretion during the cycle and mean follicular phase serum testosterone was significantly greater with early pregnancy loss than in the control group, the difference in LH being greatest in the early luteal phase. Urinary oestrone-3-glucuronide excretion was raised in the early luteal phase of the cycle in the group with early pregnancy loss; there was no difference between the groups in pregnanediol-3 alpha-glucuronide excretion. These data demonstrate abnormalities in LH secretion in 81% of women with recurrent fetal loss. Inappropriately raised LH levels may have adverse effects on the developing oocyte or endometrium either directly, or indirectly by causing an elevation in testosterone and oestrogen levels. PMID:8345070

  8. Exogenous action of 5-lipoxygenase by its metabolites on luteinizing hormone release in rat pituitary cells.

    PubMed

    Przylipiak, A; Kiesel, L; Habenicht, A J; Przylipiak, M; Runnebaum, B

    1990-02-12

    The stimulatory effect of exogenously administered potato 5-lipoxygenase (0.1-0.3 U/2 ml) on luteinizing hormone (LH) release was demonstrated in rat anterior pituitary cells in a superfusion system. Nordihydroguaiaretic acid (NDGA), an inhibitor of 5-lipoxygenase, abolished the effect of the enzyme on LH secretion. The secretory effect on LH after 5-lipoxygenase administration was biphasic and dependent on Ca2+ indicating that 5-lipoxygenase affects LH release through its oxygenation reaction. Another series of experiments demonstrated that activation of 5-lipoxygenase, expressed as production of leukotriene (LT) B4 and C4 (728 +/- 127 pg/10(6) cells and 178 +/- 23 pg/10(6) cells, respectively) occurs in rat pituitary cells after addition of Ca2+ ionophore A23187. However, LTB4 and LTC4 were not formed by pituitary cells that had previously been desensitized by gonadotropin-releasing hormone (GnRH), the physiological ligand of LH release. These results are consistent with a role of 5-lipoxygenase metabolites in the mechanism of GnRH-induced LH secretion. PMID:2157615

  9. The goldfish nervus terminalis: a luteinizing hormone-releasing hormone and molluscan cardioexcitatory peptide immunoreactive olfactoretinal pathway.

    PubMed Central

    Stell, W K; Walker, S E; Chohan, K S; Ball, A K

    1984-01-01

    Antisera to two putative neurotransmitters, luteinizing hormone-releasing hormone (LHRH) and molluscan cardioexcitatory tetrapeptide (H-Phe-Met-Arg-Phe-NH2; FMRF-amide), bind specifically to neurites in the inner nuclear and inner plexiform layers of the goldfish retina. Retrograde labeling showed that intraocular axon terminals originate from the nervus terminalis, whose cell bodies are located in the olfactory nerves. Double immunocytochemical and retrograde labeling showed that some terminalis neurons project to the retina; others may project only within the brain. All terminalis neurons having proven retinal projections were both LHRH- and FMRF-amide-immunoreactive. The activity of retinal ganglion cells was recorded with microelectrodes in isolated superfused goldfish retinas. In ON- and OFF-center double-color-opponent cells, micromolar FMRF-amide and salmon brain gonadotropin-releasing factor ( [Trp7, Leu8] LHRH) caused increased spontaneous activity in the dark, loss of light-induced inhibition, and increased incidence of light-entrained pulsatile response. The nervus terminalis is therefore a putatively peptidergic retinopetal projection. Sex-related olfactory stimuli may act through it, thereby modulating the output of ganglion cells responsive to color contrast. Images PMID:6199789

  10. Is radiation-induced ovarian failure in rhesus monkeys preventable by luteinizing hormone-releasing hormone agonists?: Preliminary observations

    SciTech Connect

    Ataya, K.; Pydyn, E.; Ramahi-Ataya

    1995-03-01

    With the advent of cancer therapy, increasing numbers of cancer patients are achieving long term survival. Impaired ovarian function after radiation therapy has been reported in several studies. Some investigators have suggested that luteinizing hormone-releasing hormone agonists (LHRHa) can prevent radiation-induced ovarian injury in rodents. Adult female rhesus monkeys were given either vehicle or Leuprolide acetate before, during, and after radiation. Radiation was given in a dose of 200 rads/day for a total of 4000 rads to the ovaries. Frequent serum samples were assayed for estradiol (E{sub 2}) and FSH. Ovariectomy was performed later. Ovaries were processed and serially sectioned. Follicle count and size distribution were determined. Shortly after radiation started, E{sub 2} dropped to low levels, at which it remained, whereas serum FSH level, which was low before radiation, rose soon after starting radiation. In monkeys treated with a combination of LHRHa and radiation, FSH started rising soon after the LHRHa-loaded minipump was removed (after the end of radiation). Serum E{sub 2} increased after the end of LHRHa treatment in the non-irradiated monkey, but not in the irradiated monkey. Follicle counts were not preserved in the LHRHa-treated monkeys that received radiation. The data demonstrated no protective effect of LHRHa treatment against radiation-induced ovarian injury in this rhesus monkey model. 58 refs., 2 figs., 1 tab.

  11. Inhibition of progesterone secretion during the luteal phase by two luteinizing hormone-releasing hormone agonists in Macaca fascicularis.

    PubMed

    Raynaud, J P; Mary, I; Moguilewsky, M; Mouren, M; Labrie, F

    1980-12-01

    The administration of 200 microgram of the potent luteinizing hormone-releasing hormone (LHRH) agonist [D-Leu6,des-Gly-NH2(10)]LHRH ethylamide on day 6 following the plasma estradiol peak to 11 female monkeys (Macaca fascicularis) during two consecutive menstrual cycles decreased plasma progesterone levels by 40.0% +/- 3.9% as compared with previous control cycles. The plasma estradiol profile and the cycle length were not affected significantly by the treatment. Similar results were obtained with 25 microgram of [D-Ser(TBU)6,des-Gly-NH2(10)]LHRH ethylamide administered to one monkey at the same period of the cycle, such treatment leading to a 41% inhibition of circulating progesterone levels. Although plasma progesterone levels were still reduced in the two post-treatment cycles in monkeys treated with the high dose (200 microgram) of [D-Leu6,des-Gly-NH2(10)]LHRH ethylamide, the recovery cycle was normal after the administration of a lower dose (25 microgram) of [D-Ser(TBU)6, des-Gly-NH2(10)] LHRH ethylamide. The M. fascicularis monkey thus appears as a valid model with which to study the inhibitory effects of LHRH agonists on luteal function. PMID:6778718

  12. Cadmium affects the episodic luteinizing hormone secretion in male rats: possible age-dependent effects.

    PubMed

    Lafuente, A; Márquez, N; Piquero, S; Esquifino, A I

    1999-01-11

    Cadmium affects luteinizing hormone (LH) secretion through unknown mechanisms. The present study was undertaken to assess whether chronic exposure to low concentrations of cadmium may affect the episodic secretion of LH and if these effects are age-dependent. Male rats were given cadmium at a dose of 50 ppm in the drinking water, from day 30 to 60 or from day 60 to 90 of life. Age-matched rats with access to cadmium-free water were used as controls. At the end of the treatment, blood samples were collected every 7 min for 3 h, from 10:30 to 13.30 in conscious, freely moving rats. In control animals, mean serum LH levels and pulse duration increased with age (P < or = 0.001), and pulse frequency and the relative amplitude of LH pulses decreased (P < or = 0.001). Cadmium administration, from day 30 to 60 of life, decreased the pulse frequency and mean half-life of the hormone (P < or = 0.05, P < or = 0.01, respectively). However, no changes in any other parameters studied were observed as compared to the control group. When cadmium was administered from day 60 to 90, mean serum LH levels and the duration of LH pulses decreased (P < or = 0.05), whereas the pulse frequency increased (P < or = 0.05). The absolute and relative amplitude of the LH peaks and the mean half-life of the hormone were not changed after cadmium administration from day 60 to 90. These results indicate that low doses of cadmium change the pulsatile secretion of LH in male rats and that the effect of cadmium on episodic LH release was age-dependent. PMID:10048746

  13. Luteinizing hormone/human chorionic gonadotrophin receptors in various epidermal structures.

    PubMed

    Venencie, P Y; Méduri, G; Pissard, S; Jolivet, A; Loosfelt, H; Milgrom, E; Misrahi, M

    1999-09-01

    Two different monoclonal antibodies recognizing different epitopes were used to study the localization of luteinizing hormone/human chorionic gonadotrophin (LH/hCG) receptors in human skin. Immunolabelling was observed only in the epidermis and derived structures but not in the dermis. The basal, spinal and granular layers were stained, whereas no receptors were detected in the non-nucleated horny cells. In the growing (anagen) hair, immunostaining was found in the inner root sheath below the level of the sebaceous glands and in the outer root sheath above this level. In the resting (telogen) hair, only the latter staining was observed. In the sebaceous glands, only the thin cells close to the walls of the ducts were immunolabelled. In the eccrine sweat glands, the external clear cells were stained in the secretory portion of the gland, whereas only the cells close to the lumen were labelled in the ducts. The distribution of LH/hCG receptors was compared with that of steroidogenic enzymes (side chain cleavage cytochrome P450, adrenodoxin, 3-beta-hydroxy-5-ene steroid dehydrogenase Delta5-Delta4 isomerase, 17-hydroxylase cytochrome P450 and cytochrome P450 aromatase). Only partial overlaps were observed. The presence of LH receptor mRNA in the skin was confirmed by reverse transcription-polymerase chain reaction. Monoclonal antibodies raised against the human follicle-stimulating hormone receptor failed to detect the latter in the epidermal structures and in the dermis. The role of LH and hCG in skin modifications occurring during pregnancy and after the menopause is unknown. These hormones may possibly act by regulating steroidogenic enzymes or by modulating cell growth and differentiation. PMID:10583046

  14. Effects of external radiation therapy for cancer of the prostate on the serum concentrations of testosterone, follicle-stimulating hormone, luteinizing hormone and prolactin

    SciTech Connect

    Tomic, R.; Bergman, B.; Damber, J.E.; Littbrand, B.; Loefroth, P.O.

    1983-08-01

    Testosterone, luteinizing hormone, follicle-stimulating hormone and prolactin were analyzed in serum from 31 patients with carcinoma of the prostate treated primarily with megavoltage radiation therapy. The total tumor dose varied between 58 and 71 gray (mean 63.5 gray). Absorbed doses to the testes were measured at approximately 1 to more than 10 gray. We investigated retrospectively 17 patients 3 to 60 months (mean 20 months) after therapy and found significantly lower serum testosterone concentrations and significantly higher luteinizing and follicle-stimulating hormone concentrations than in age-matched controls. Of the patients, 14 were followed before and after radiation treatment. Testosterone concentrations were reduced significantly 1 week as well as 3 months after treatment but pre-treatment values were found on analysis 6 and 12 months after treatment. The values for luteinizing and follicle-stimulating hormones were significantly higher 3, 6 and 12 months after radiation treatment compared to pre-treatment values. The follicle-stimulating hormone value already increased after 1 week. The greatest observed testosterone alteration occurred 1 week after treatment in patients who received more than 10 gray over the gonads. The use of lead shields protecting the testes reduced the dose absorbed to the gonads by approximately 50 percent.

  15. Differential thermal stability of human, bovine and ovine Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH) quaternary structures.

    PubMed

    Haj Hassan, Maya; Cahoreau, Claire; Jégot, Gwenhael; Jouanny, Camille; Mariot, Julie; Lecompte, François; Klett, Danièle; Combarnous, Yves

    2015-02-01

    Quaternary structure of human, bovine and ovine Follicle-Stimulating Hormones (hFSH, bFSH and oFSH) and Luteinizing Hormone was assessed in sandwich ELISAs using monoclonal anti-oFSHβ or anti-oLHβ antibodies, respectively, for capture and a biotinylated anti-hFSHα (α4 epitope) for detection. Neither free subunit gave any signal in this assay so that it was possible to measure the residual heterodimeric fraction after thermal treatment of the gonadotropins under study. The hormones were subjected to 5-min heating between 37 and 90 °C before rapid cooling in melting ice before ELISA. The data show half-dissociation of natural and recombinant human and ovine FSH preparations between 68 and 74 °C whereas bovine FSH preparations exhibited lower stability in these conditions with half-dissociation between 61 and 64 °C. Moreover, whereas all human and bovine as well as most ovine FSH preparations were fully dissociated at temperatures above 80 °C, one natural oFSH and one recombinant hLH preparations contained an important fraction that resisted dissociation even at 93 °C and retained in vitro bioactivity. This suggests the existence of gonadotropin αβ heterodimer with covalently linked subunits. Similarly, about 20% of the recombinant hLH preparation was also found withstand heat denaturation and also probably to have cross-linked subunits. The origin and chemical nature of these inter-subunit bonds remain to be determined. PMID:24732063

  16. Mutational analysis of the luteinizing hormone receptor gene in two individuals with Leydig cell tumors.

    PubMed

    Canto, Patricia; Söderlund, Daniela; Ramón, Guillermo; Nishimura, Elisa; Méndez, Juan Pablo

    2002-03-01

    Inactivating mutations of the luteinizing hormone receptor (LHR) gene in males induce Leydig cell agenesis or hypoplasia, while activating mutations cause testotoxicosis. Recently, it was demonstrated that a somatic heterozygous activating mutation of the LHR gene (Asp578His), limited to the tumor, was the cause of Leydig cell adenomas in three unrelated patients. We describe the molecular study of two unrelated boys with gonadotropin-independent hypersecretion of testosterone due to Leydig cell adenomas. Genomic DNA was extracted from the tumor, the adjacent normal testis tissue, and blood leukocytes. Both individuals exhibited an heterozygous missense mutation, limited only to the tumor, consisting of a guanine (G) to cytosine (C) substitution at codon 578 (GAT to CAT), turning aspartic acid into histidine. The presence of the same mutation in different ethnic groups demonstrates the existence of a mutational hot spot in the LHR gene. Indeed, this mutation occurs at the conserved aspartic acid residue at amino acid 578, where a substitution by glycine is the most common mutation observed in testotoxicosis and where a substitution by tyrosine has been linked to a more severe clinical phenotype where diffuse Leydig cell hyperplasia is found. Our results confirm the fact that somatic activating mutations of gonadotropin receptors are involved in gonadal tumorigenesis. PMID:11857565

  17. Ovine luteinizing hormone heterogeneity: androgens increase the percentage of less basic isohormones.

    PubMed

    Christianson, S L; Zalesky, D D; Grotjan, H E

    1998-03-01

    The heterogeneity of luteinizing (LH) is hormonally regulated with androgens having been reported to increase the percentage of extremely basic LH isohormones in the ovine pituitary. This study re-examined the effects of androgens on the heterogeneity of LH in the ovine pituitary because the extremely basic isoforms of LH reported previously were subsequently demonstrated to be artifacts resulting from the conditions used for chromatofocusing. Pituitary extracts from wethers, rams, and dihydrotestosterone (DHT)-implanted wethers were desalted by flow dialysis and chromatofocused on pH 10.5 to 7.0 gradients. LH was quantitated by radioimmunoassays. When compared with rams, wethers had increased percentages of LH isoforms eluting between pH 9.6 and 10. Patterns of intrapituitary LH isohormones were comparable in rams and DHT-implanted wethers except that rams had a higher percentage of LH eluting at pH 9.2 (20.9 +/- 2.1% vs. 13.3 +/- 1.3%). In contrast to what was previously reported, rams and DHT-implanted wethers had higher percentages of ovine LH isoforms eluting at pH's 9.4 or lower. Thus, androgens alter LH heterogeneity yielding increased percentages of isohormones eluting at pH's of 9.4 or lower. PMID:9532422

  18. Selective optogenetic activation of arcuate kisspeptin neurons generates pulsatile luteinizing hormone secretion

    PubMed Central

    Han, Su Young; McLennan, Timothy; Czieselsky, Katja; Herbison, Allan E.

    2015-01-01

    Normal reproductive functioning in mammals depends upon gonadotropin-releasing hormone (GnRH) neurons generating a pulsatile pattern of gonadotropin secretion. The neural mechanism underlying the episodic release of GnRH is not known, although recent studies have suggested that the kisspeptin neurons located in the arcuate nucleus (ARN) may be involved. In the present experiments we expressed channelrhodopsin (ChR2) in the ARN kisspeptin population to test directly whether synchronous activation of these neurons would generate pulsatile luteinizing hormone (LH) secretion in vivo. Characterization studies showed that this strategy targeted ChR2 to 70% of all ARN kisspeptin neurons and that, in vitro, these neurons were activated by 473-nm blue light with high fidelity up to 30 Hz. In vivo, the optogenetic activation of ARN kisspeptin neurons at 10 and 20 Hz evoked high amplitude, pulse-like increments in LH secretion in anesthetized male mice. Stimulation at 10 Hz for 2 min was sufficient to generate repetitive LH pulses. In diestrous female mice, only 20-Hz activation generated significant increments in LH secretion. In ovariectomized mice, 5-, 10-, and 20-Hz activation of ARN kisspeptin neurons were all found to evoke LH pulses. Part of the sex difference, but not the gonadal steroid dependence, resulted from differential pituitary sensitivity to GnRH. Experiments in kisspeptin receptor-null mice, showed that kisspeptin was the critical neuropeptide underlying the ability of ARN kisspeptin neurons to generate LH pulses. Together these data demonstrate that synchronized activation of the ARN kisspeptin neuronal population generates pulses of LH. PMID:26443858

  19. Effect of supplemental light on growth, prolactin, progesterone and luteinizing hormone in water buffalo ( Bubalus bubalis)

    NASA Astrophysics Data System (ADS)

    Perera, K. S.; Gwazdauskas, F. C.; Akers, R. M.; McGilliard, M. L.

    1989-06-01

    Fifty non-pregnant Surti buffalo heifers aged between 17 and 42 months ( n=24, <24 months; n=26, >24 months) were randomly assigned to groups subject to either natural daylight +4h supplemental light ( n=25) or natural day light ( n=25), to study changes in growth, serum prolactin (Prl), progesterone (P4) and luteinizing hormone (LH) to supplemental lighting. Ambient temperatures (T) and relative humidity (RH) generally were >27° C and <70% during the day-time, respectively. Light-supplemented heifers had 16.2 kg net body weight (BW) gain at 9 weeks compared to 20.8 kg for controls, but higher mean Prl after 6.5 weeks ( P<0.01), and higher P4 (0.41 vs 0.19 ng/ml; P<0.06) than control heifers. Older heifers had 39.7% greater BW ( P<0.01), but a net 4.3% BW gain compared to a 10.1% gain for younger heifers at 10 weeks. Older, light-supplemented heifers had higher mean P4 (0.63 vs 0.19 ng/ml; P<0.07) than the other groups. These weight and hormonal changes suggest that 4 h supplemental light can alter growth and endocrine function in buffaloes under similar planes of nutrition. While light supplementation did not have a positive effect on body wieght during the 10 week study, body weight and endocrine changes due to supplemental light may be important factors for initiation of reproductive cyclicity.

  20. Central estrogen action sites involved in prepubertal restraint of pulsatile luteinizing hormone release in female rats

    PubMed Central

    UENOYAMA, Yoshihisa; TANAKA, Akira; TAKASE, Kenji; YAMADA, Shunji; PHENG, Vutha; INOUE, Naoko; MAEDA, Kei-ichiro; TSUKAMURA, Hiroko

    2015-01-01

    The present study aimed to determine estrogen feedback action sites to mediate prepubertal restraint of gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) release in female rats. Wistar-Imamichi strain rats were ovariectomized (OVX) and received a local estradiol-17β (estradiol) or cholesterol microimplant in several brain areas, such as the medial preoptic area (mPOA), paraventricular nucleus, ventromedial nucleus and arcuate nucleus (ARC), at 20 or 35 days of age. Six days after receiving the estradiol microimplant, animals were bled to detect LH pulses at 26 or 41 days of age, representing the pre- or postpubertal period, respectively. Estradiol microimplants in the mPOA or ARC, but not in other brain regions, suppressed LH pulses in prepubertal OVX rats. Apparent LH pulses were found in the postpubertal period in all animals bearing estradiol or cholesterol implants. It is unlikely that pubertal changes in responsiveness to estrogen are due to a change in estrogen receptor (ER) expression, because the number of ERα-immunoreactive cells and mRNA levels of Esr1, Esr2 and Gpr30 in the mPOA and ARC were comparable between the pre- and postpubertal periods. In addition, kisspeptin or GnRH injection overrode estradiol-dependent prepubertal LH suppression, suggesting that estrogen inhibits the kisspeptin-GnRH cascade during the prepubertal period. Thus, estrogen-responsive neurons located in the mPOA and ARC may play key roles in estrogen-dependent prepubertal restraint of GnRH/LH secretion in female rats. PMID:26004302

  1. 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. PMID:25687742

  2. Treatment of nitrosamine-induced pancreatic tumors in hamsters with analogs of somatostatin and luteinizing hormone-releasing hormone

    SciTech Connect

    Paz-Bouza, J.I.; Redding, T.W.; Schally, A.V.

    1987-02-01

    Pancreatic ductal adenocarcinoma was induced in female Syrian golden hamsters by injecting N-nitrosobis(2-oxopropyl)amine (BOP) once a week at a dose of 10 mg per kg of body weight for 18 weeks. Hamsters were then treated with somatostatin analog (RC-160) or with (6-D-tryptophan)luteinizing hormone-releasing hormone ((D-Trp/sup 6/)LH-RH) delayed delivery systems. After 18 weeks of BOP administration, the hamsters were divided into three groups of 10-20 animals each. Group I consisted of untreated controls, group II was injected with RC-160, and group III was injected with (D-Trp/sub 2/)LH-RH. A striking decrease in tumor weight and volume was obtained in animals treated with (D-Trp/sup 6/)LH-RH or with the somatostatin analog RC-160. After 45 days of treatment with either analog, the survival rate was significantly higher in groups II and III (70%), as compared with the control group (35%). The studies, done by light microscopy, high-resolution microscopy, and electron microscopy, showed a decrease in the total number of cancer cells and changes in the epithelium, connective tissue, and cellular organelles in groups II and III treated with the hypothalamic analogs as compared to controls. These results in female hamsters with induced ductal pancreatic tumors confirm and extend the authors findings, obtained in male animals with transplanted tumors, that (D-Trp/sub 6/)LH-RH and somatostatin analogs inhibit the growth of pancreatic cancers.

  3. Ability of luteinizing hormone releasing hormone-Pseudomonas aeruginosa exotoxin 40 binding to LHRH receptor on human liver cancer cells

    PubMed Central

    Gong, Shou-Liang; Zhao, Gang; Zhao, Hong-Guang; Lü, Wen-Tian; Liu, Guang-Wei; Zhu, Ping

    2004-01-01

    AIM: To explore the ability of recombinant toxin luteinizing hormone releasing hormone-Pseudomonas aeruginosa exotoxin 40 (LHRH-PE40) and LHRH binding to LHRH receptor (LHRHR) on the membrane surface of human liver cancer HEPG cells. METHODS: LHRH was labeled by using 125I with enzymatic reaction. The affinity and receptor volume of LHRH-PE40 and LHRH binding to LHRHR on the membrane surface of human liver cancer cells were measured with radioligand receptor assay. RESULTS: The specific activity of LHRH labeled with 125I was 2.7 × 104 kBq/μL, and its radiochemical purity reached to 99.2%-99.7%. The binding of 125I to LHRH was maximal for 240 min in the warm cultivation, and this binding was stabilized. The inhibiting rates of 125I-LHRH and LHRH on the proliferation of human liver cancer HEPG cells were not significantly different. On the basis of the saturation curve of 125I-LHRH binding to the membrane LHRHR of HEPG cells, 125I-LHRH of 1 × 105 cpm was selected for radioligand receptor assay. The affinity constants (Kd) of LHRH-PE40 and LHRH binding to the membrane LHRHR of HEPG cells were 0.43 ± 0.12 nmol/L and 4.86 ± 1.47 nmol/L, respectively, and their receptor volumes were 0.37 ± 0.15 μmol/g and 0.42 ± 0.13 μmol/g, respectively. The binding of LHRH-PE40 to the membrane protein of normal liver cells was not observed. CONCLUSION: The recombinant toxin LHRH-PE40 binding to the membrane surface of LHRHR of human liver cancer HEPG cells was very strong, while the specific binding of it to normal liver cells was not observed. The results provide an important experimental basis for the clinical application of LHRH-PE. PMID:15334689

  4. Effect of permeation enhancer pretreatment on the iontophoresis of luteinizing hormone releasing hormone (LHRH) through human epidermal membrane (HEM).

    PubMed

    Smyth, Hugh D C; Becket, Gordon; Mehta, Samir

    2002-05-01

    A 2 x 2 factorial design was performed to determine the effect of a permeation enhancer (oleic acid/propylene glycol), iontophoresis (2 V), and the combination of the two treatments on the permeation enhancement of a model peptide, LHRH (luteinizing hormone releasing hormone), through human epidermal membrane (HEM). In parallel studies, TEAB (tetraethylammonium bromide, a small ionic solute) and sucrose (an electroosmotic flow marker) were also investigated. Structural changes in the HEM were monitored via conductance measurements, differential scanning calorimetry (DSC), and infrared (IR) spectroscopy experiments. LHRH enhancement due to enhancer in combination with iontophoresis (I + E; 29.5 times passive permeability, P), was greater than during iontophoresis alone (I; 14.3) and enhancer treatment alone (E; 3.5). I + E had an additive effect of I and E, indicating the mechanisms of action of the individual enhancement strategies were likely to be located at different sites in the skin. Also, no synergistic enhancement was observed with I + E for either TEAB or sucrose. For TEAB, permeability enhancement due to I (approximately 1400) was much higher than that due to E (14.9), and no additive effect could be detected. For sucrose, E had no effect on either passive or iontophoretic permeability, eliminating the possibility that electroosmosis could explain increases in LHRH permeability. Evidence of synergy between E and I was found, with conductance measurements indicating that I + E synergistically increased the membrane permeability to conducting ions (Na+ and Cl-). It appears these pathways were not available for transport for the solutes used in the current study. DSC and IR investigations showed significant changes in stratum corneum lipid structure following E treatment but not following I. These findings probably arise from the localized action of iontophoresis compared with the bulk action of enhancer. In summary, increased LHRH delivery through HEM in

  5. Association of Luteinizing Hormone Chorionic Gonadotropin Receptor Gene Polymorphism (rs2293275) with Polycystic Ovarian Syndrome

    PubMed Central

    Kodati, Vijayalakshmi; Erukkambattu, Jayashankar; Addepally, Uma; Qurratulain, Hasan

    2015-01-01

    Background: Polycystic ovaries and irregular menstruation/anovulation are important diagnostic criteria along with hyperandrogenism as per the Androgen Excess Society–2006 criteria for polycystic ovarian syndrome (PCOS). In the etiopathogenesis of PCOS, one of the candidate genes causing ovarian failure is the luteinizing hormone (LH) chorionic gonadotropin hormone receptor (LHCGR). Our aim was to study the association of LHCGR polymorphism (rs2293275) with PCOS in our study population. Materials and Methods: Genetic case–control study from multiple gynecological centers from Hyderabad, a cosmopolitan city in South India. The study involved 204 women with PCOS and 204 healthy, sex-, and age-matched controls. Anthropometric and biochemical profiles were taken in a well-designed pro forma. Isolation of deoxyribonucleic acid (DNA) and genotype analysis were done for the entire study population using the polymerase chain reaction–restriction fragment length polymorphism method followed by 12% polyacrylamide gel electrophoresis. Results: In this study, we have demonstrated an association between LHCGR (rs2293275) polymorphism and PCOS. The frequency of the G allele was 0.60 in PCOS and 0.49 in controls (odds ratio [OR] 1.531, confidence interval [CI] 1.16–2.01, and p-value=0.0026), which indicates that the G allele is associated with PCOS in our population. The GG genotype conferred a significant risk of developing PCOS (OR 3.36, CI 1.96–5.75, and p-value<0.0001). We found a significant association of the GG allele with body–mass index, waist to hip ratio, insulin resistance, LH, and LH/follicle-stimulating hormone (FSH) ratio in PCOS when compared with controls. The AA allele showed high basal FSH levels. Conclusions: This study suggests that LHCGR (rs2293275) polymorphism is associated with PCOS and could be used as a relevant molecular marker to identify women with the risk of developing PCOS in our population and may provide an understanding about the

  6. Effects of ionizing radiation and pretreatment with (D-Leu6,des-Gly10) luteinizing hormone-releasing hormone ethylamide on developing rat ovarian follicles

    SciTech Connect

    Jarrell, J.; YoungLai, E.V.; McMahon, A.; Barr, R.; O'Connell, G.; Belbeck, L.

    1987-10-01

    To assess the effects of a gonadotropin-releasing hormone agonist, (D-Leu6,des-Gly10) luteinizing hormone-releasing hormone ethylamide, in ameliorating the damage caused by ionizing radiation, gonadotropin-releasing hormone agonist was administered to rats from day 22 to 37 of age in doses of 0.1, 0.4, and 1.0 microgram/day or vehicle and the rats were sacrificed on day 44 of age. There were no effects on estradiol, progesterone, luteinizing, or follicle-stimulating hormone, nor an effect on ovarian follicle numbers or development. In separate experiments, rats treated with gonadotropin-releasing hormone agonist in doses of 0.04, 0.1, 0.4, or 1.0 microgram/day were either irradiated or sham irradiated on day 30 and all groups sacrificed on day 44 of age. Irradiation produced a reduction in ovarian weight and an increase in ovarian follicular atresia. Pretreatment with the agonist prevented the reduction in ovarian weight and numbers of primordial and preantral follicles but not healthy or atretic antral follicles. Such putative radioprotection should be tested on actual reproductive performance.

  7. Augmentation of Metastin/Kisspeptin mRNA Expression by the Proestrous Luteinizing Hormone Surge in Granulosa Cells of Rats: Implications for Luteinization.

    PubMed

    Laoharatchatathanin, Titaree; Terashima, Ryota; Yonezawa, Tomohiro; Kurusu, Shiro; Kawaminami, Mitsumori

    2015-07-01

    Variations in mRNA levels and sources of metastin/kisspeptin, neurokinin B (NKB), dynorphin, and kisspeptin receptor GPR54 were examined in the ovaries of cycling rats. Kisspeptin and dynorphin mRNAs dramatically increased at 2000 h of the proestrous day. NKB mRNA also increased, but the peak was delayed by 6 h. GPR54 mRNA declined inversely with kisspeptin. Whole-ovary expressions of kisspeptin and dynorphin mRNAs, but not of NKB mRNA, were augmented by the administration of human chorionic gonadotropin (hCG). By means of laser-capture microdissection, kisspeptin mRNA was shown mostly in follicles at 2000 h of proestrus, whereas NKB and dynorphin were expressed mainly in interstitial tissues. GPR54 mRNA was detected equally in follicles, corpora lutea, and interstitial tissues. The hCG stimulated the follicular expression of kisspeptin and interstitial tissue expression of dynorphin mRNA. In primary cultures of granulosa cells prepared from equine chorionic gonadotropin-pretreated immature rats, hCG stimulated the expression of kisspeptin, dynorphin, and NKB mRNAs. Distortion of the corpus luteum and surrounding tissue borders was sometimes seen after intra-ovarian bursa administration of kisspeptin antagonist p234 for 3 days from proestrus. Progesterone production stimulated by hCG in granulosa cell culture was suppressed by p234. These data demonstrate that significant amounts of kisspeptin are synthesized in granulosa cells and dynorphin in interstitial tissues, in response to the proestrous luteinizing hormone surge, whereas granulosa cells also contain dynorphin and NKB, suggesting at least a role for kisspeptin in the luteinization of granulosa cells. PMID:25995272

  8. Kisspeptin receptor agonist (FTM080) increased plasma concentrations of luteinizing hormone in anestrous ewes

    PubMed Central

    Daniel, Joseph A.; Amelse, Lisa L.; Tanco, Valeria M.; Chameroy, Kelly A.; Schrick, F. Neal

    2015-01-01

    Kisspeptin receptor (KISS1R) agonists with increased half-life and similar efficacy to kisspeptin in vitro may provide beneficial applications in breeding management of many species. However, many of these agonists have not been tested in vivo. These studies were designed to test and compare the effects of a KISS1R agonist (FTM080) and kisspeptin on luteinizing hormone (LH) in vivo. In experiment 1 (pilot study), sheep were treated with FTM080 (500 pmol/kg BW) or sterile water (VEH) intravenosuly. Blood was collected every 15 min before (1 h) and after (1 h) treatment. In experiment 2, sheep were treated with KP-10 (human Metastin 45-54; 500 pmol/kg BW), one of three dosages of FTM080 (500 (FTM080:500), 2500 (FTM080:2500), or 5000 (FTM080:5000) pmol/kg BW), or VEH intravenously. Blood was collected every 15 min before (1 h) and after (4 h) treatment. In experiment 1, FTM080:500 increased (P < 0.05) plasma LH concentrations when compared to VEH. The area under the curve (AUC) of LH following FTM080:500 treatment was also increased (P < 0.05). In experiment 2, plasma LH concentrations increased (P < 0.05) following treatment with KP-10 and FTM080:5000 when compared to VEH and FTM080:500. The AUC of LH following KP-10 was greater than (P < 0.05) all other treatments and the AUC of LH following FTM080:5000 was greater than (P < 0.05) all treatments except KP-10. These data provide evidence to suggest that FTM080 stimulates the gonadotropic axis of ruminants in vivo. Any increased half-life and comparable efficacy of FTM080 to KP-10 in vitro does not appear to translate to in vivo in sheep. PMID:26587345

  9. Induction of the expressions of antioxidant enzymes by luteinizing hormone in the bovine corpus luteum.

    PubMed

    Kawaguchi, Syota; Sakumoto, Ryosuke; Okuda, Kiyoshi

    2013-01-01

    Luteoprotective mechanisms of luteinizing hormone (LH) involved in the maintenance of bovine corpus luteum (CL) function have not been completely clarified. Since antioxidant enzymes are well documented as antiapoptotic factors in the CL of many mammals, we hypothesized that the luteoprotective action of LH is mediated by stimulating the local production and action of antioxidant enzymes. To test the above hypothesis, in the present study, we examined the mechanisms involved in the luteoprotective actions of LH. Cultured bovine luteal cells obtained from the CL at the mid-luteal stage (days 8-12 of the estrous cycle) were treated with LH (10 ng/ml), onapristone (OP; a specific progesterone receptor antagonist, 100 μM) and diethyldithiocarbamate [DETC; an inhibitor of superoxide dismutase (SOD), 100 μM] for 24 h. LH in combination with or without OP significantly increased the mRNA and protein expressions of manganese SOD (Mn-SOD) and catalase (CATA) and SOD activity. While LH alone significantly increased the mRNA and protein expressions of SOD containing copper and zinc (Cu,Zn-SOD), OP in combination with or without LH significantly decreased the mRNA and protein expressions of Cu,Zn-SOD. In addition, Cu,Zn-SOD, Mn-SOD and CATA mRNA expressions were higher at the mid luteal phase than the other luteal phases. LH in combination with DETC significantly decreased LH-increased cell viability. The overall results suggest that LH increases cell viability by LH-increased antioxidant enzymes, resulting in maintenance of CL function during the luteal phase in cattle. PMID:23386101

  10. Noradrenaline concentrations in the hypothalamus of anoestrus ewes following the ram-induced luteinizing hormone release.

    PubMed

    Fabre-Nys, Claude; Kendrick, Keith M

    2015-05-01

    Sheep are seasonal breeders, but exposure of anoestrus ewes to rams results in a rapid increase in luteinizing hormone (LH) secretion, eventually leading to surge in LH. Although LH secretion is known to be under the control of many neurotransmitters, noradrenaline (NA) is of particular importance for the LH surge in induced ovulators, although little is known about its role in LH secretion induced by males in spontaneous ovulators. To address this question, anoestrus ewes fitted with guide-tubes in the medial preoptic area (MPOA) or the ventromedial hypothalamus were subjected to microdialysis and blood sampling every 15 min for an hour before and 2 h after exposure to rams, and the concentrations of LH, monoamine and amino acid transmitters were measured. In ewes implanted in the posterior MPOA that responded to the ram by an increase in LH pulses, NA concentrations changed after exposure to the ram (P<0.018) and were higher at 15 (P<0.054) and 45 min (P<0.03) after male introduction than before. By contrast, no change in NA could be detected in ewes implanted in the same region, but not responding to the ram, or in those showing increased LH pulsatility, but implanted in the anterior MPOA or in the ventromedial hypothalamus. No changes were observed in other neurotransmitters or when the ewes were exposed to male odour alone. These results suggest that NA release in the posterior MPOA is selectively involved in the triggering of LH secretion by rams in anoestrus ewes. PMID:25839177

  11. MicroRNA Expression and Regulation in Human Ovarian Carcinoma Cells by Luteinizing Hormone

    PubMed Central

    Cui, Juan; Eldredge, Joanna B.; Xu, Ying; Puett, David

    2011-01-01

    Background MicroRNAs have been widely-studied with regard to their aberrant expression and high correlation with tumorigenesis and progression in various solid tumors. With the major goal of assessing gonadotropin (luteinizing hormone, LH) contributions to LH receptor (LHR)-positive ovarian cancer cells, we have conducted a genome-wide transcriptomic analysis on human epithelial ovarian cancer cells to identify the microRNA-associated cellular response to LH-mediated activation of LHR. Methods Human ovarian cancer cells (SKOV3) were chosen as negative control (LHR−) and stably transfected to express functional LHR (LHR+), followed by incubation with LH (0–20 h). At different times of LH-mediated activation of LHR the cancer cells were analyzed by a high-density Ovarian Cancer Disease-Specific-Array (DSA, ALMAC™), which profiled ∼100,000 transcripts with ∼400 non-coding microRNAs. Findings In total, 65 microRNAs were identified to exhibit differential expression in either LHR expressing SKOV3 cells or LH-treated cells, a few of which have been found in the genomic fragile regions that are associated with abnormal deletion or amplification in cancer, such as miR-21, miR-101-1, miR-210 and miR-301a. By incorporating the dramatic expression changes observed in mRNAs, strong microRNA/mRNA regulatory pairs were predicted through statistical analyses coupled with collective computational prediction. The role of each microRNA was then determined through a functional analysis based on the highly-confident microRNA/mRNA pairs. Conclusion The overall impact on the transcriptome-level expression indicates that LH may regulate apoptosis and cell growth of LHR+ SKOV3 cells, particularly by reducing cancer cell proliferation, with some microRNAs involved in regulatory roles. PMID:21765906

  12. Supression of the steroid-primed luteinizing hormone surge in the female rat by sodium dimethyldithiocarbamate: Relationship to hypothalamic catecholamines and GnRH neuronal activation

    EPA Science Inventory

    In female rodents, hypothalamic norepinephrine (NE) has a role in stimulating the secretion of gonadotropin-releasing hormone (GnRH) that triggers the ovulatory surge of luteinizing hormone (LH). NE synthesis from dopamine requires the presence of dopamine--hydroxylase (DH) an...

  13. Pregnancy rates to timed artificial insemination in dairy cows treated with gonadotropin-releasing hormone or porcine luteinizing hormone.

    PubMed

    Colazo, M G; Gordon, M B; Rajamahendran, R; Mapletoft, R J; Ambrose, D J

    2009-07-15

    We compared the effects of porcine luteinizing hormone (pLH) versus gonadotropin-releasing hormone (GnRH) on ovulatory response and pregnancy rate after timed artificial insemination (TAI) in 605 lactating dairy cows. Cows (mean+/-SEM: 2.4+/-0.08 lactations, 109.0+/-2.5 d in milk, and 2.8+/-0.02 body condition score) at three locations were assigned to receive, in a 2x2 factorial design, either 100 microg GnRH or 25mg pLH im on Day 0, 500 microg cloprostenol (PGF) on Day 7, and GnRH or pLH on Day 9, with TAI 14 to 18h later. Ultrasonographic examinations were performed in a subset of cows on Days 0, 7, 10, and 11 to determine ovulations, presence of corpus luteum, and follicle diameter and in all cows 32 d after TAI for pregnancy determination. In 35 cows, plasma progesterone concentrations were determined 0, 3, 4, 5, 6, 7, and 12 d after ovulation. The proportion of noncyclic cows and cows with ovarian cysts on Day 0 were 12% and 6%, respectively. Ovulatory response to first treatment was 62% versus 44% for pLH and GnRH and 78% versus 50% for noncyclic and cyclic cows (P<0.01). Location, ovulatory response to first pLH or GnRH, cyclic status, presence of an ovarian cyst, and preovulatory follicle size did not affect pregnancy rate. Plasma progesterone concentrations after TAI did not differ among treatments. Pregnancy rate to TAI was greater (P<0.01) in the GnRH/PGF/pLH group (42%) than in the other three groups (28%, 30%, and 26% for GnRH/PGF/GnRH, pLH/PGF/GnRH, and pLH/PGF/pLH, respectively). Although only 3% of cows given pLH in lieu of GnRH on Day 9 lost their embryo versus 7% in those subjected to a conventional TAI using two GnRH treatments, the difference was not statistically significant. In summary, pLH treatment on Day 0 increased ovulatory response but not pregnancy rate. Cows treated with GnRH/PGF/pLH had the highest pregnancy rate to TAI, but progesterone concentrations after TAI were not increased. In addition, preovulatory follicle diameter did not

  14. Identification, cDNA Cloning, and Characterization of Luteinizing Hormone Beta Subunit (lhb) Gene in Catla catla.

    PubMed

    Rather, Mohd Ashraf; Bhat, Irfan Ahmad; Sharma, Rupam

    2016-07-01

    Reproductive hormones play a significant role in the gonadal development and gametogenesis process of animals. In the present study luteinizing hormone beta, (lhb) subunit gene was cloned and characterized from the brain of Catla catla. The lhb full-length of cDNA sequence is 629 bp which consists of 43bp 5'-UTR (untranslated region) 447bp, ORF(open reading frame) and 139 bp of 3'-UTR respectively. The coding region of lhb gene encoded a peptide of 148 amino acids. The coding sequence of lhb gene consist of a single N-linked glycosylation site (NET) and 12 cysteine knot residues. Phylogenetic analysis of C. catla Lhβ deduced amino acid sequence showed high similarity with Carassius auratus followed by Gobiocypris rarus. 3D structure Lhβ protein comprises of five β-sheets and six coils/loops. The qPCR results revealed lhb mRNA is mainly expressed in the pituitary, ovary while moderate expression was observed in brain and testis. To best our knowledge, this is the first report on the identification, molecular characterization and structural information regarding luteinizing hormone in Indian major carp. PMID:26980432

  15. Inhibition of growth of a prolactin and growth hormone-secreting pituitary tumor in rats by D-tryptophan-6 analog of luteinizing hormone-releasing hormone.

    PubMed Central

    Torres-Aleman, I; Redding, T W; Schally, A V

    1985-01-01

    The effect of long-term administration of analogs of luteinizing hormone-releasing hormone (LH-RH) and somatostatin on the growth of the growth hormone (GH)- and prolactin (PRL)-secreting rat pituitary GH3 tumor was investigated. Daily administration of [D-Trp6]LH-RH (50 micrograms/day), early after inoculation of the GH3 tumor, inhibited tumor growth by more than 90% as compared to controls. Similarly, in two experiments, a single once-a-month injection of long-acting [D-Trp6]LH-RH microcapsules (in a dose calculated to release about 25 micrograms/day for 30 days) inhibited the growth of GH3 pituitary tumor by more than 50% 6 or 13 wk after transplantation, when the tumors were fully developed. Serum GH and PRL levels also were reduced markedly by treatment with [D-Trp6]LH-RH. On the other hand, the administration of an antagonistic analog of LH-RH, N-Ac-[D-Phe(4Cl)1,2, D-Trp3, D-Arg6, D-Ala10]LH-RH, did not significantly reduce the growth of this tumor, and the treatment with two different analogs of somatostatin, cyclo(Pro-Phe-D-Trp-Lys-Thr-Phe) and D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr NH2, appeared to enhance it. These results are in agreement with previous findings of growth inhibition of 7315a pituitary tumors with different hormone-secreting characteristics by agonistic analogs of LH-RH. The collective data from experimental work with rat pituitary tumor models support the contention that the use of [D-Trp6]LH-RH might be considered for the treatment of some patients with pituitary tumors who failed to respond to conventional therapy. PMID:2858096

  16. Pubertal development in the male pig: effects of treatment with a long-acting gonadotropin-releasing hormone agonist on plasma luteinizing hormone, follicle stimulating hormone and testosterone.

    PubMed Central

    Trudeau, V L; Meijer, J C; Erkens, J H; van de Wiel, D F; Wensing, C J

    1992-01-01

    The effects of a long-acting gonadotropin-releasing hormone (GnRH) agonist, [D-Trp6]-GnRH (GnRH-A) on developmental profiles of plasma luteinizing hormone (LH), follicle stimulation hormone (FSH) and testosterone (T), and pituitary responsiveness to exogenous GnRH were studied in male Dutch Landrace x Large White crossbred pigs from 1 to 30 wk of age. Group 1 control animals (control; n = 12) were injected subcutaneously in the neck with vehicle at 1 and 16 wk of age. Group 2 animals (early treatment; n = 10) were injected with 600 micrograms [D-Trp6]-GnRH at 1 wk and with vehicle at 16 wk. Group 3 animals (late treatment; n = 8) were injected with vehicle and 3 mg GnRH-A at 1 and 16 wk, respectively. Group 4 animals (early plus late treatment; n = 9) were injected at both 1 and 16 wk with GnRH-A. Blood was collected by brachiocephalic puncture at weekly or biweekly intervals, and through brachiocephalic cannulae, to determine longitudinal profiles of LH, FSH and T, and plasma gonadotropin responses to intravenous injection of GnRH (0.1 microgram/kg), respectively. In control animals, LH and FSH declined over the first 5 wk of postnatal life and peaked again at 10-14 wk. Levels of both hormones were basal from 18 to 30 wk. Plasma T was high in the first week, declined progressively over the next few weeks and remained low until 24 wk when a transient increment was noted. The LH and FSH responses to acute GnRH stimulation were similar at 7 and 14 wk and declined significantly at 23 wk of age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1534270

  17. Cloning and functional expression of the equine luteinizing hormone/chorionic gonadotrophin receptor.

    PubMed

    Saint-Dizier, Marie; Foulon-Gauze, Florence; Lecompte, François; Combarnous, Yves; Chopineau, Maryse

    2004-12-01

    Pituitary equine luteinizing hormone (eLH) and fetal chorionic gonadotrophin (eCG) have identical polypeptidic chains, but different linked carbohydrates. In equine tissues, eCG and eLH bind only to the LH/CG receptor (eLH/CG-R) and have no FSH activity. However, radio-receptor assays on equine luteal or testicular tissues have shown that eCG binds to the eLH/CG-R with only 2-4% of the binding activity of eLH. In order to study the structure-function relationship of eLH and eCG in a homologous system, we undertook the cloning and functional expression of the eLH/CG-R. Based on sequence homologies among mammalian sequences for the LH/CG-R, overlapping partial fragments of LH/CG-R cDNAs were obtained from mare luteal RNA using reverse transcription-PCR and 5'-rapid amplification of cDNA ends. Ligations of the partial cDNA fragments encoded a part of the signal peptide followed by a putative 672 amino acid eLH/CG-R mature protein. The mature eLH/CG-R displayed 88.2-92.8% overall sequence homology with the other mammalian LH/CG-Rs and contained one unique seventh N-glycosylation site in its extracellular domain. COS-7 cells were transiently transfected with a cDNA construct encoding an engineered complete signal peptide and the mature eLH/CG-R. Membrane preparations from transfected COS-7 cells bound 125I-eLH with high affinity (Kd 3.8 x 10(-10) M). On a molar basis, eCG competed with 125I-eLH on membrane preparations with only 12.4% of the eLH binding activity. In transfected COS-7, both eLH and eCG increased the extracellular cAMP concentration in a dose-dependent manner, whereas eFSH did not. Furthermore, on a molar basis, eCG stimulated cAMP production with only 13.9% of the eLH stimulating activity. We conclude that the cloned cDNA encodes a The differences functional eLH/CG-R. between eLH and eCG activities towards this receptor will be useful in studies of the influence of carbohydrates on gonadotrophin receptor binding and activation. PMID:15590981

  18. Regulation of gene expression in ovarian cancer cells by luteinizing hormone receptor expression and activation

    PubMed Central

    2011-01-01

    Background Since a substantial percentage of ovarian cancers express gonadotropin receptors and are responsive to the relatively high concentrations of pituitary gonadotropins during the postmenopausal years, it has been suggested that receptor activation may contribute to the etiology and/or progression of the neoplasm. The goal of the present study was to develop a cell model to determine the impact of luteinizing hormone (LH) receptor (LHR) expression and LH-mediated LHR activation on gene expression and thus obtain insights into the mechanism of gonadotropin action on ovarian surface epithelial (OSE) carcinoma cells. Methods The human ovarian cancer cell line, SKOV-3, was stably transfected to express functional LHR and incubated with LH for various periods of time (0-20 hours). Transcriptomic profiling was performed on these cells to identify LHR expression/activation-dependent changes in gene expression levels and pathways by microarray and qRT-PCR analyses. Results Through comparative analysis on the LHR-transfected SKOV-3 cells exposed to LH, we observed the differential expression of 1,783 genes in response to LH treatment, among which five significant families were enriched, including those of growth factors, translation regulators, transporters, G-protein coupled receptors, and ligand-dependent nuclear receptors. The most highly induced early and intermediate responses were found to occupy a network impacting transcriptional regulation, cell growth, apoptosis, and multiple signaling transductions, giving indications of LH-induced apoptosis and cell growth inhibition through the significant changes in, for example, tumor necrosis factor, Jun and many others, supportive of the observed cell growth reduction in in vitro assays. However, other observations, e.g. the substantial up-regulation of the genes encoding the endothelin-1 subtype A receptor, stromal cell-derived factor 1, and insulin-like growth factor II, all of which are potential therapeutic

  19. Seasonal variation in plasma testosterone, luteinizing hormone concentrations and LH-RH responsiveness in mature, male rusa deer (Cervus rusa timorensis).

    PubMed

    van Mourik, S; Stelmasiak, T; Outch, K H

    1986-01-01

    Plasma testosterone and luteinizing hormone (LH) concentrations in immobilized or yarded rusa stags (Cervus rusa timorensis) were investigated over a two-year period. Testosterone concentrations showed a minor elevation in autumn (May) and reached maximal levels in late winter-early spring (August) coinciding with the rut. Luteinizing hormone in plasma was only detectable from January to May. Maximal responsiveness of the pituitary-gonadal axis to LH-RH stimulation was recorded in August. The combination of Fentaz (fentanylcitrate and azaperone) and Rompun (xylazine hydrochloride) for immobilizing deer influences hypothalamic function. PMID:2869876

  20. Growth hormone, luteinizing hormone, and follicle-stimulating hormone regulation by neuropeptide Y in both sexes of the cichlid fish, Cichlasoma dimerus.

    PubMed

    Di Yorio, M P; Delgadin, T H; Pérez Sirkin, D I; Vissio, P G

    2015-08-01

    Neuropeptide Y (NPY) is considered the most potent orexigenic peptide, increasing before meal time and during fasting. In teleost, most studies on NPY action upon growth hormone (GH) and luteinizing hormone (LH) were conducted in females or group of animals without sex discrimination. The aim of this study was to evaluate whether NPY modulates the expression and release of GH and gonadotropins in both sexes of Cichlasoma dimerus. By double-label immunofluorescence, we first determined the association between NPY fibers and pituitary cells. In addition, we performed in vitro studies to evaluate the effect of NPY on GH and gonadotropins expression by real-time PCR, and release by Western blot, in males and females separately. Contacts between NPY fibers and GH and follicle-stimulating hormone (FSH)-producing cells were detected, indicating possible functional relationships. We observed an increase in GH release in the culture medium at 2 nM for males (p = 0.043) and 20 nM for females (p = 0.028). Pituitary FSH release was stimulated at 20 nM (p = 0.026) and 200 nM (p = 0.033) for males and females, respectively. Finally, NPY only increased β-LH mRNA expression at 20 nM in females (p = 0.028) and its release at 2 nM (p = 0.049) and 200 nM for males (p = 0.005) and 200 nM for females (p = 0.018). In conclusion, NPY acts as a GH-, LH- and FSH-releasing factor, in a dose- and sex-dependent way. PMID:25869217

  1. Control of gonadotrophin secretion by steroid hormones in castrated male transsexuals. I. Effects of oestradiol infusion on plasma levels of follicle-stimulating hormone and luteinizing hormone.

    PubMed

    Goh, H H; Chew, P C; Karim, S M; Ratnam, S S

    1980-02-01

    Twenty-four infusions of oestradiol (E2) in graded doses ranging from 0--200 micrograms administered over a period of 7 hours were carried out in eleven healthy male transsexuals who had undergone sex reassignment at least 3 months previously. Plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and E2 were analysed by radioimmunoassay, while sex hormone binding globulin (SHBG) was measured using 3H-testosterone as the saturating ligand. Infusion of 5--200 micrograms of E2 raised plasma E2 to levels ranging from 38.4--367.8 pg/ml which present 83%--800% of levels found in a control group of sixty-three normal males. SHBG capacity remained unchanged at all doses of E2 studied. No change in plasma levels of FSH and LH was observed in control infusions and infusion of 5 micrograms of E2. From 10 micrograms-200 micrograms, suppression of plasma levels of FSH was noted at the 5--7 hour period. The suppression increased up to 20 micrograms and thereafter the levels of FSH remained constant. On the other hand, the suppression of LH increased up to the highest E2 dose (200 micrograms) studied. Further, significant suppression of LH occurred earlier than the 5--7 hours as the dose of E2 increased. These observations are consistent with the conclusions that: (1) E2 plays a part in the regulation of secretion of FSH and LH in men; and (2) at doses higher than physiological, E2 exerts a differential effect on the secretion of FSH and LH. PMID:6772356

  2. Stimulation of cholesterol side-chain cleavage by a luteinizing-hormone-releasing hormone (luliberin) agonist (ICI 118630) in rat Leydig cells.

    PubMed Central

    Sullivan, M H; Cooke, B A

    1983-01-01

    The action of a luliberin (luteinizing-hormone-releasing hormone) agonist (ICI 118630) and lutropin (luteinizing hormone) on the activity of the cytochrome P-450 cholesterol side-chain cleavage enzyme in rat Leydig cells has been investigated. This has been carried out by studying the metabolism of exogenous (22R)-22- and 25-hydroxycholesterol to testosterone. It was found that both hydroxycholesterols increased testosterone production to higher levels than achieved by lutropin alone. Addition of luliberin agonist but not lutropin was found to increase further the metabolism of the hydroxycholesterol to testosterone; this occurred in the presence of saturating and subsaturating levels of the hydroxycholesterols. This effect of luliberin agonist was potentiated in the presence of lutropin. The protein synthesis inhibitor, cycloheximide, inhibited the luliberin agonist-induced stimulation of the hydroxycholesterol metabolism. At low calcium levels (1.1 microM), testosterone production was increased by addition of (22R)-22-hydroxycholesterol but the luliberin agonist effect was negated. The calmodulin inhibitor trifluoperazine inhibited (22R)-22-hydroxycholesterol-stimulated steroidogenesis and negated the luliberin agonist effect. These results indicate that luliberin agonist specifically increases the synthesis of the cytochrome P-450 cholesterol side-chain cleavage enzyme in rat testis Leydig cells. PMID:6230077

  3. First attempt to monitor luteinizing hormone and reproductive steroids in urine samples of the Amazonian manatee (Trichechus inunguis).

    PubMed

    Amaral, Rodrigo S; Rosas, Fernando C W; Graham, Laura H; da Silva, Vera M F; Oliveira, Claudio A

    2014-12-01

    The aims of this study were to validate an enzyme immunoassay (EIA) for the measurement of luteinizing hormone (LH) in urine samples of Amazonian manatees (Trichechus inunguis; Mammalia: Sirenia) and to monitor urinary LH and reproductive steroids during the ovarian cycle in this species. Urine samples were collected from two captive males following a hormonal challenge with a gonadotropin-releasing hormone (GnRH) analogue. The urinary LH results from hormonal challenge were compared with urinary androgens for the purpose of EIA validation. Furthermore, urine samples were collected daily, over a 12-wk period, from two captive adult females, for 2 consecutive yr. The urinary LH pattern from females was compared with the patterns of urinary progestagens and estrogen conjugates throughout the ovarian cycle. An LH peak was observed in both male Amazonian manatees after the hormonal challenge, occurring prior to or together with peak androgen levels. In the females, the ovarian cycle ranged from 40 to 48 days (mean of 43.7 days). Two distinct peaks of estrogen conjugates were observed across all cycles analyzed, and the urinary LH peaks observed were accompanied by peaks of urinary estrogen conjugates. The EIA was validated as a method for the quantification of urinary LH from Amazonian manatees, as it was able to detect variations in the levels of LH in urine samples. These results suggest that T. inunguis exhibits a peculiar hormonal pattern during the ovarian cycle. Therefore, further studies are desirable and necessary to clarify the relationship between this hormonal pattern and morphological changes, as well as mating behavior, in Amazonian manatee. PMID:25632672

  4. Testosterone antagonist (flutamide) blocks ovulation and preovulatory surges of progesterone, luteinizing hormone and oestradiol in laying hens.

    PubMed

    Rangel, P L; Sharp, P J; Gutierrez, C G

    2006-06-01

    The preovulatory release of luteinizing hormone (LH) in the domestic hen occurs after the initiation of a preovulatory surge of testosterone. The objective of this study was to determine whether this testosterone surge has functional significance in the endocrine control of ovulation. Groups of laying hens (n = 10-22) were treated with the androgen receptor antagonist, flutamide, at 8 h intervals for 24 h at doses of 0, 31.25, 62.5, 125 and 250 mg. All doses reduced egg laying (P < 0.001), with the highest dose being the most effective. In a second study, laying hens (n = 9) were treated with 250 mg flutamide at 8 h intervals for 24 h with a control group being given placebo (n = 10). Blood samples were taken for hormone measurements at 2 h intervals for 18 h starting 4 h before the onset of darkness. The percentage of hens laying per day did not differ between groups before treatment (control, 88% vs flutamide, 86%). Ovulation was blocked in all hens treated with flutamide within 2 days while the control hens continued to lay at the pretreatment rate (80%). Preovulatory surges of plasma testosterone, progesterone, oestradiol and LH were observed in control hens but with the exception of testosterone, flutamide treatment blocked the progesterone, oestradiol and LH surges. LH concentrations declined progressively with time in the flutamide-treated hens. It is concluded that inhibition of testosterone action blocks egg laying and the preovulatory surges of progesterone, luteinizing hormone and oestradiol demonstrating a key role for the preovulatory release of testosterone in the endocrine control of ovulation in the domestic hen. PMID:16735550

  5. Characterization of recombinant DNA derived-human luteinizing hormone in vitro and in vivo: efficacy in ovulation induction and corpus luteum support

    SciTech Connect

    Simon, J.A.; Danforth, D.R.; Hutchison, J.S.; Hodgen, G.D.

    1988-06-10

    The present data are the first, to the authors knowledge, to demonstrate the production feasibility of a commercially available medication of pure human luteinizing hormone from recombinant DNA technology (rechLH). The rechLH preparation achieved ovulation induction and corpus luteum support in the primate menstrual cycle. The observations described herein indicate the opportunity for significant improvement in the treatment of infertile women and men who require gonadal stimulation. Recombinant DNA-derived gonadotropin products, rechLH in this case, will have several therapeutic advantages compared with current medications extracted from urine. These advantages include (1) better reliability of an available supply of hormone and (2) improved treatment flexibility in determining the optimal dose ratio of follicle-stimulating hormone and luteinizing hormone or avoidance of the long-acting effects of human chorionic gonadotropin, as the needs of individual patients may dictate.

  6. Gonadotropin-releasing hormone, estradiol, and inhibin regulation of follicle-stimulating hormone and luteinizing hormone surges: implications for follicle emergence and selection in heifers.

    PubMed

    Haughian, James M; Ginther, O J; Diaz, Francisco J; Wiltbank, Milo C

    2013-06-01

    Mechanisms regulating gonadotropin surges and gonadotropin requirements for follicle emergence and selection were studied in heifers. Experiment 1 evaluated whether follicular inhibins regulate the preovulatory luteinizing hormone (LH)/follicle-stimulating hormone (FSH) surges elicited by gonadotropin-releasing hormone (GnRH) injection (Hour = 0) and the subsequent periovulatory FSH surge. Treatments included control (n = 6), steroid-depleted bovine follicular fluid (bFF) at Hour -4 (n = 6), and bFF at Hour 6 (n = 6). Gonadotropins in blood were assessed hourly from Hours -6 to 36, and follicle growth tracked by ultrasound. Consistent with inhibin independence, bFF at Hour -4 did not impact the GnRH-induced preovulatory FSH surge, whereas treatment at Hour 6 delayed onset of the periovulatory FSH surge and impeded growth of a new follicular wave. Experiment 2 examined GnRH and estradiol (E2) regulation of the periovulatory FSH surge. Treatment groups were control (n = 8), GnRH-receptor antagonist (GnRHr-ant, n = 8), and E2 + GnRHr-ant (n = 4). GnRHr-ant (acyline) did not reduce the concentrations of FSH during the periovulatory surge and early follicle development (<7.0 mm) was unaffected, although subsequent growth of a dominant follicle (>8.0 mm) was prevented by GnRHr-ant. Addition of E2 delayed both the onset of the periovulatory FSH surge and emergence of a follicular wave. Failure to select a dominant follicle in the GnRHr-ant group was associated with reduced concentrations of LH but not FSH. Maximum diameter of F1 in controls (13.3 ± 0.5 mm) was greater than in both GnRHr-ant (7.7 ± 0.3 mm) and E2 + GnRHr-ant (6.7 ± 0.8 mm) groups. Results indicated that the periovulatory FSH surge stems from removal of negative stimuli (follicular E2 and inhibin), but is independent of GnRH stimulation. Emergence and early growth of follicles (until about 8 mm) requires the periovulatory FSH surge but not LH pulses. However, follicular deviation and late-stage growth of

  7. Heterodimers and homodimers of inhibin subunits have different paracrine action in the modulation of luteinizing hormone-stimulated androgen biosynthesis

    SciTech Connect

    Hsueh, A.J.W.; Dahl, K.D.; Vaughan, J.; Tucker, E.; Rivier, J.; Bardin, C.W.; Vale, W.

    1987-07-01

    Inhibin, a gonadal hormone capable of preferential suppression of pituitary follicle-stimulating hormone (FSH) secretion, has recently been purified. The major form of this protein is an ..cap alpha beta.. heterodimer encoded by two separate genes. In contrast to the FSH-suppressing action of the ..cap alpha beta.. heterodimer, the ..beta beta.. homodimer stimulates FSH secretion. Luteinizing hormone (LH)-secreting pituitary cells and gonadal androgen-producing cells have long been shown to form a closed-loop feedback axis. Based on recent studies demonstrated the FSH stimulation of inhibin biosynthesis by ovarian granulosa and testis Sertoli cells, an additional closed-loop feedback axis exists between pituitary FSH- and gonadal inhibin-producing cells. Because uncharacterized Sertoli cell factors have been suggested to either stimulate or inhibit androgen production by testicular Leydig cells, the authors have tested the intragonadal paracrine actions of heterodimers and homodimers of inhibin subunits. In primary cultures of testis cells, the ..cap alpha beta.. heterodimer of inhibin enhances Leydig cell androgen biosynthesis stimulated by LH, whereas the ..beta beta.. homodimer suppresses androgen production. The data indicate that the inhibin-related gene products synthesized by Sertoli and granulosa cells may form heterodimers or homodimers to serve as intragonadal paracrine signals in the modulation of LH-stimulated androgen biosynthesis and allow cross-communication between the two feedback loops.

  8. Radioimmunoassay for 6-D-tryptophan analog of luteinizing hormone-releasing hormone: measurement of serum levels after administration of long-acting microcapsule formulations

    SciTech Connect

    Mason-Garcia, M.; Vigh, S.; Comaru-Schally, A.M.; Redding, T.W.; Somogyvari-Vigh, A.; Horvath, J.; Schally, A.V.

    1985-03-01

    A sensitive and specific radioimmunoassay for (6-D-tryptophan)luteinizing hormone-releasing hormone ((D-Trp/sup 6/)LH-RH) was developed and used for following the rate of liberation of (D-Trp/sup 6/)LH-RH from a long-acting delivery systems based on a microcapsule formulation. Rabbit antibodies were generated against (D-Trp/sup 6/)LH-RH conjugated to bovine serum albumin with glutaraldehyde. Crossreactivity with LH-RH was less than 1%; there was no significant cross-reactivity with other peptides. The minimal detectable dose of (D-Trp/sup 6/)LH-RH was 2 pg per tube. In tra- and interassay coefficients of variation were 8% and 10%, respectively. The radioimmunoassay was suitable for direct determination of (D-Trp/sup 6/)LH-RH in serum, permitting the study of blood levels of the analog after single injections into normal men and after one-a-month administration of microcapsules to rats. In men, 90 min after subcutaneous injection of 250 ..mu..g of the peptide, serum (D-Trp/sup 6/)LH-RH rose to 6-12 ng/ml. Luteinizing hormone was increased 90 min and 24 hr after the administration of the analog. Several batches of microcapsules were tested in rats and the rate of release of (D-Trp/sup 6/)LH-RH was followed. The improved batch of microcapsules of (D-Trp/sup 6/)LH-RH increased serum concentrations of the analog for 30 days or longer after intramuscular injection.

  9. Luteinizing hormone downregulation but not estrogen replacement improves ovariectomy-associated cognition and spine density loss independently of treatment onset timing.

    PubMed

    Blair, Jeffrey A; Palm, Russell; Chang, Jaewon; McGee, Henry; Zhu, Xiongwei; Wang, Xinglong; Casadesus, Gemma

    2016-02-01

    Age-related changes in reproductive hormone levels are a well-known risk factor for the development of cognitive dysfunction and dementia in women. We and others have shown an important contribution of gonadotropins in this process. Lowering serum gonadotropin levels is able to rescue cognitive function in Alzheimer's disease and menopause models, but whether this is time-dependent and the exact mechanism through which gonadotropins regulate cognitive function is unknown. We show that pharmacologically lowering serum levels of luteinizing hormone lead to cognitive improvement immediately after ovariectomy and with a 4month interval after ovariectomy, when the benefits of 17β-estradiol are known to disappear in rodents. Importantly, we show that these improvements are associated with spine density changes at both time points. These findings suggest a role of luteinizing hormone in learning and memory and neuroplasticity processes as well as provide an alternative therapeutic strategy of menopause associated cognitive loss. PMID:26497249

  10. CREB Binding Protein (CBP) Activation Is Required for Luteinizing Hormone Beta Expression and Normal Fertility in Mice

    PubMed Central

    Miller, Ryan S.; Wolfe, Andrew; He, Ling; Radovick, Sally

    2012-01-01

    Normal function of the hypothalamic-pituitary-gonadal axis is dependent on gonadotropin-releasing hormone (GNRH)-stimulated synthesis and secretion of luteinizing hormone (LH) from the pituitary gonadotroph. While the transcriptional coactivator CREB binding protein (CBP) is known to interact with Egr-1, the major mediator of GNRH action on the Lhb gene, the role of CBP in Lhb gene expression has yet to be characterized. We show that in the LβT2 gonadotroph cell line, overexpression of CBP augmented the response to GNRH and that knockdown of CBP eliminated GNRH responsiveness. While GNRH-mediated phosphorylation of CBP at Ser436 increased the interaction with Egr-1 on the Lhb promoter, loss of this phosphorylation site eliminated GNRH-mediated Lhb expression in LβT2 cells. In vivo, loss of CBP phosphorylation at Ser436 rendered female mice subfertile. S436A knock-in mice had disrupted estrous cyclicity and reduced responsiveness to GNRH. Our results show that GNRH-mediated phosphorylation of CBP at Ser436 is required for Egr-1 to activate Lhb expression and is a requirement for normal fertility in female mice. As CBP can be phosphorylated by other factors, such as insulin, our studies suggest that CBP may act as a key regulator of Lhb expression in the gonadotroph by integrating homeostatic information with GNRH signaling. PMID:22508984

  11. Negative energy balance in a male songbird, the Abert's towhee, constrains the testicular endocrine response to luteinizing hormone stimulation

    PubMed Central

    Davies, Scott; Gao, Sisi; Valle, Shelley; Bittner, Stephanie; Hutton, Pierce; Meddle, Simone L.; Deviche, Pierre

    2015-01-01

    ABSTRACT Energy deficiency can suppress reproductive function in vertebrates. As the orchestrator of reproductive function, endocrine activity of the hypothalamo-pituitary–gonadal (HPG) axis is potentially an important mechanism mediating such effects. Previous experiments in wild-caught birds found inconsistent relationships between energy deficiency and seasonal reproductive function, but these experiments focused on baseline HPG axis activity and none have investigated the responsiveness of this axis to endocrine stimulation. Here, we present data from an experiment in Abert's towhees, Melozone aberti, using gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) challenges to investigate whether energy deficiency modulates the plasma testosterone responsiveness of the HPG axis. Wild-caught birds were either ad libitum fed or energetically constrained via chronic food restriction during photoinduced reproductive development. Energy deficiency did not significantly affect the development of reproductive morphology, the baseline endocrine activity of the HPG axis, or the plasma testosterone response to GnRH challenge. Energy deficiency did, however, decrease the plasma testosterone responsiveness to LH challenge. Collectively, these observations suggest that energy deficiency has direct gonadal effects consisting of a decreased responsiveness to LH stimulation. Our study, therefore, reveals a mechanism by which energy deficiency modulates reproductive function in wild birds in the absence of detectable effects on baseline HPG axis activity. PMID:26333925

  12. Commercial radioimmunoassay for beta subunit of human chorionic gonadotropin: falsely positive determinations due to elevated serum luteinizing hormone

    SciTech Connect

    Fowler, J.E. Jr.; Platoff, G.E.; Kubrock, C.A.; Stuzman, R.E.

    1982-01-01

    Among 17 men who had received seemingly curative treatment for unilateral non-seminomatous germ cell tumors for the testis and who had consistently normal serum human chorionic gonadotropin (HCG) levels at a reference laboratory, 7 (41%) had at least one falsely positive commercial serum HCG determination. To investigate the cause of these falsely positive determinations the authors measured the cross reactivity of luteinizing hormone (LH) and follicle stimulating hormone (FSH) standards in the commercial HCG assay, and studied the relationships between commercial HCG levels and serum LH levels, serum FSH levels and gonadal status in men with and without normal gonadal function. The falsely positive HCG determinations appeared to be due to elevated serum LH levels and cross reactivity of LH in the commercial HCG assay because: 1) there was substantial cross reactivity of the LH standards in the commercial assay, 2) the serum LH was elevated in four of six men with solitary testes, 3) there was a striking correlation between elevated serum LH levels and falsely elevated commercial HCG levels in ten men with solitary or absent testes, and 4) there were no falsely positive HCG determinations in 13 normal men but there were falsely positive HCG determinations in seven of ten anorchid men.

  13. Interleukin 1. alpha. inhibits prostaglandin E sub 2 release to suppress pulsatile release of luteinizing hormone but not follicle-stimulating hormone

    SciTech Connect

    Rettori, V.; McCann, S.M. ); Gimeno, M.F. ); Karara, A. ); Gonzalez, M.C. )

    1991-04-01

    Interleukin 1{alpha} (IL-1{alpha}), a powerful endogenous pyrogen released from monocytes and macrophages by bacterial endotoxin, stimulates corticotropin, prolactin, and somatotropin release and inhibits thyrotropin release by hypothalamic action. The authors injected recombinant human IL-1{alpha} into the third cerebral ventricle, to study its effect on the pulsatile release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in conscious, freely moving, ovariectomized rats. Intraventricular injection of 0.25 pmol of IL-1{alpha} caused an almost immediate reduction of plasma LH concentration. To determine the mechanism of the suppression of LH release, mediobasal hypothalamic fragments were incubated in vitro with IL-1{alpha} (10 pM) and the release of LH-releasing hormone (LHRH) and prostaglandin E{sub 2} into the medium was measured by RIA in the presence or absence of nonrepinephrine. 1{alpha} reduced basal LHRH release and blocked LHRH release induced by nonrepinephrine. In conclusion, IL-1{alpha} suppresses LH but not FSH release by an almost complete cessation of pulsatile release of LH in the castrated rat. The mechanism of this effect appears to be by inhibition of prostaglandin E{sub 2}-mediated release of LHRH.

  14. Molecular and biological interaction between major histocompatibility complex class I antigens and luteinizing hormone receptors or beta-adrenergic receptors triggers cellular response in mice.

    PubMed Central

    Solano, A R; Cremaschi, G; Sánchez, M L; Borda, E; Sterin-Borda, L; Podestá, E J

    1988-01-01

    Purified IgG from BALB/c mouse anti-C3H serum exerts positive inotropic and chronotropic effects in C3H mouse atria and induces testosterone synthesis in C3H mouse Leydig cells. The effect depends on IgG concentration and can be abolished by beta-adrenergic-receptor and luteinizing hormone-receptor antagonists. IgG interferes with the binding of dihydroalprenolol and luteinizing hormone. Monoclonal antibodies against major histocompatibility complex class I antigens were active on the Leydig cells of C3H and BALB/c mice. There was a parallelism between the effect of each individual monoclonal antibody with specificity for a particular haplotype and the response of the target cell from the strains carrying such haplotypes. These antibodies could precipitate the soluble luteinizing hormone-receptor complex. The results suggested that bound hormone triggers the association of major histocompatibility class I antigen with the receptor, thereby activating the respective target cells. PMID:2839829

  15. Pituitary self-priming actions of gonadotropin-releasing hormone. Kinetics of estradiol's potentiating effects on gonadotropin-releasing hormone-facilitated luteinizing hormone and follicle-stimulating hormone release in healthy postmenopausal women.

    PubMed

    Veldhuis, J D; Evans, W S; Rogol, A D; Kolp, L; Thorner, M O; Stumpf, P

    1986-06-01

    We examined the kinetically distinct characteristics of estradiol's effects upon pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release in response to pulses of exogenous gonadotropin-releasing hormone (GnRH) in healthy postmenopausal individuals. The putative self-priming actions of GnRH on LH and FSH release were tested by intravenous injections of equal paired doses of GnRH (10 micrograms) before and after 1, 5, 10, and 30 d of pure estradiol-17 beta delivery via an intravaginal silastic ring. Self-priming actions of GnRH, as defined by heightened gonadotropin release in response to the second pulse of GnRH compared with the first, were completely absent in the hypoestrogenemic state. However, estradiol administration unmasked GnRH self-priming in a time-dependent fashion, with maximal expression after 5 and 10 d of steroid replacement, followed by attenuation by 30 d. Since estradiol's modulation of GnRH action was expressed differentially on LH and FSH release, we suggest that such facilitation of GnRH-stimulated pituitary LH and FSH release may provide an additional mechanism for dissociated secretion of gonadotropic hormones in health or disease. PMID:3086382

  16. Age-Related Mercury Contamination and Relationship with Luteinizing Hormone in a Long-Lived Antarctic Bird

    PubMed Central

    Tartu, Sabrina; Bustamante, Paco; Goutte, Aurélie; Cherel, Yves; Weimerskirch, Henri; Bustnes, Jan Ove; Chastel, Olivier

    2014-01-01

    Seabirds, as long-lived top predators, accumulate contaminants such as mercury (Hg), an established endocrine disruptor. In long lived species hormonal secretion varies with age; therefore, Hg-induced endocrine disruption may be exacerbated in some age classes. Here we investigated relationships between blood total Hg and luteinizing hormone (LH, a key pituitary hormone for the onset of breeding), in pre-laying known-age (11–45 years old) snow petrels (Pagodroma nivea) from Adélie Land, Antarctica. We predicted that 1) blood Hg would increase with advancing age as a consequence of bio-accumulation; and that 2) increasing blood Hg would be related to decreased concentrations of LH in the most Hg-contaminated individuals. Hg concentrations were higher in females than in males (p<0.001), and contrary to our prediction, decreased with advancing age in males (p = 0.009) and tended to do so in females (p = 0.06). The analysis of stable isotopes (δ13C and δ15N) suggested that this unexpected pattern could originate from age and sex-related variations in trophic niche, and hence Hg exposure. Regarding LH, our prediction was only supported in young birds (≤23 years) where baseline LH was inversely correlated with Hg concentrations (p = 0.04). Hg burden did not predict baseline LH or GnRH-induced LH in birds that were more than 23 years old. These results show that age and contaminants may interfere with major endocrine mechanisms and, together with other recent studies, support the view that Hg could be connected to LH secretion and could then impair the fitness of long-lived birds. PMID:25072936

  17. Heterodimers and homodimers of inhibin subunits have different paracrine action in the modulation of luteinizing hormone-stimulated androgen biosynthesis.

    PubMed Central

    Hsueh, A J; Dahl, K D; Vaughan, J; Tucker, E; Rivier, J; Bardin, C W; Vale, W

    1987-01-01

    Inhibin, a gonadal hormone capable of preferential suppression of pituitary follicle-stimulating hormone (FSH) secretion, has recently been purified. The major form of this protein is an alpha beta heterodimer encoded by two separate genes. In contrast to the FSH-suppressing action of the alpha beta heterodimer, the beta beta homodimer stimulates FSH secretion. Luteinizing hormone (LH)-secreting pituitary cells and gonadal androgen-producing cells have long been shown to form a closed-loop feedback axis. Based on recent studies demonstrating the FSH stimulation of inhibin biosynthesis by ovarian granulosa and testis Sertoli cells, an additional closed-loop feedback axis exists between pituitary FSH- and gonadal inhibin-producing cells. Because uncharacterized Sertoli cell factors have been suggested to either stimulate or inhibit androgen production by testicular Leydig cells, we have tested the intragonadal paracrine actions of heterodimers and homodimers of inhibin subunits. In primary cultures of testis cells, the alpha beta heterodimer of inhibin enhances Leydig cell androgen biosynthesis stimulated by LH, whereas the beta beta homodimer suppresses androgen production. Furthermore, similar modulatory actions of inhibin-related proteins were found in cultured ovarian theca-interstitial cells and theca explants treated with LH. In contrast, treatment with the inhibin-related proteins alone did not affect gonadal steroidogenesis. Our data indicate that the inhibin-related gene products synthesized by Sertoli and granulosa cells may form heterodimers or homodimers to serve as intragonadal paracrine signals in the modulation of LH-stimulated androgen biosynthesis and allow cross-communication between the two feedback loops. PMID:3474640

  18. Identification of major urinary metabolites of nafarelin acetate, a potent agonist of luteinizing hormone-releasing hormone, in the rhesus monkey

    SciTech Connect

    Chan, R.L.; Chaplin, M.D.

    1985-09-01

    Nafarelin acetate (less than Glu-His-Trp-Ser-Tyr-3-(2-naphthyl)-D-Ala-Leu-Arg-Pro-Gly-NH2) is a potent agonistic analogue of luteinizing hormone-releasing hormone. After a single iv administration of nafarelin acetate (with UC label at C-3 of 3-(2-naphthyl)-D-Ala) to female rhesus monkeys, about 80% of the radioactivity was eliminated in urine. Five major radioactive urinary metabolites were isolated and purified by reversed phase HPLC. Four of these metabolites, identified by amino acid analysis, were short peptides: the 5-10-hexapeptide amide, the 6-10-pentapeptide amide, the 5-7-tripeptide, and the 6-7-dipeptide. The fifth metabolite, which accounted for about 15% of the radioactivity administered, was shown by NMR and mass spectrometry to be 2-naphthylacetic acid. A possible pathway of its formation is by oxidative deamination of 3-(2-napthyl)-D-Ala to give the corresponding alpha-keto acid, followed by oxidative decarboxylation of the alpha-keto acid. These five metabolites together accounted for about 70% of the radioactivity recovered in the urine of rhesus monkeys, or more than half of the radioactivity in the administered dose. Nafarelin acetate was also present in small amounts. Several of these metabolites were also present in plasma of the rhesus monkey.

  19. Luteinizing hormone-releasing hormone targeted poly(methyl vinyl ether maleic acid) nanoparticles for doxorubicin delivery to MCF-7 breast cancer cells.

    PubMed

    Varshosaz, Jaleh; Jahanian-Najafabadi, Ali; Ghazzavi, Jila

    2016-08-01

    The purpose of this study was to design a targeted anti-cancer drug delivery system for breast cancer. Therefore, doxorubicin (DOX) loaded poly(methyl vinyl ether maleic acid) nanoparticles (NPs) were prepared by ionic cross-linking method using Zn(2+) ions. To optimise the effect of DOX/polymer ratio, Zn/polymer ratio, and stirrer rate a full factorial design was used and their effects on particle size, zeta potential, loading efficiency (LE, %), and release efficiency in 72 h (RE72, %) were studied. Targeted NPs were prepared by chemical coating of tiptorelin/polyallylamin conjugate on the surface of NPs by using 1-ethyl-3-(3-dimethylaminopropyl) carboiimid HCl as cross-linking agent. Conjugation efficiency was measured by Bradford assay. Conjugated triptorelin and targeted NPs were studied by Fourier-transform infrared spectroscopy (FTIR). The cytotoxicity of DOX loaded in targeted NPs and non-targeted ones were studied on MCF-7 cells which overexpress luteinizing hormone-releasing hormone (LHRH) receptors and SKOV3 cells as negative LHRH receptors using Thiazolyl blue tetrazolium bromide assay. The best results obtained from NPs prepared by DOX/polymer ratio of 5%, Zn/polymer ratio of 50%, and stirrer rate of 960 rpm. FTIR spectrum confirmed successful conjugation of triptorelin to NPs. The conjugation efficiency was about 70%. The targeted NPs showed significantly less IC50 for MCF-7 cells compared to free DOX and non-targeted NPs. PMID:27463791

  20. Profile of follitropin alpha/lutropin alpha combination for the stimulation of follicular development in women with severe luteinizing hormone and follicle-stimulating hormone deficiency

    PubMed Central

    Rinaldi, Leonardo; Selman, Helmy

    2016-01-01

    A severe gonadotropin deficiency together with chronic estradiol deficiency leading to amenorrhea characterizes patients suffering from hypogonadotropic hypogonadism. Administration of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to these patients has been shown to be essential in achieving successful stimulation of follicular development, ovulation, and rescue of fertility. In recent years, the availability of both recombinant FSH (rFSH) and recombinant LH (rLH) has provided a new therapeutic option for the stimulation of follicular growth in hypopituitary–hypogonadotropic women (World Health Organization Group I). In this article, we review the data reported in the literature to highlight the role and the efficacy of using recombinant gonadotropins, rFSH and rLH, in the treatment of women with severe LH/FSH deficiency. Although the studies on this issue are limited and the experiences available in the literature are few due to the small number of such patients, it is clearly evident that the recombinant gonadotropins rFSH and rLH are efficient in treating patients affected by hypogonadotropic hypogonadism. The results observed in the studies reported in this review suggest that recombinant gonadotropins are able to induce proper follicular growth, oocyte maturation, and eventually pregnancy in this group of women. Moreover, the clinical use of recombinant gonadotropins in this type of patients has given more insight into some endocrinological aspects of ovarian function that have not yet been fully understood. PMID:27307766

  1. Infertility in Female Mice with a Gain-of-Function Mutation in the Luteinizing Hormone Receptor Is Due to Irregular Estrous Cyclicity, Anovulation, Hormonal Alterations, and Polycystic Ovaries.

    PubMed

    Hai, Lan; McGee, Stacey R; Rabideau, Amanda C; Paquet, Marilène; Narayan, Prema

    2015-07-01

    The luteinizing hormone receptor, LHCGR, is essential for fertility in males and females, and genetic mutations in the receptor have been identified that result in developmental and reproductive defects. We have previously generated and characterized a mouse model (KiLHR(D582G)) for familial male-limited precocious puberty caused by an activating mutation in the receptor. We demonstrated that the phenotype of the KiLHR(D582G) male mice is an accurate phenocopy of male patients with activating LHCGR mutations. In this study, we observed that unlike women with activating LHCGR mutations who are normal, female KiLHR(D582G) mice are infertile. Mice exhibit irregular estrous cyclicity, anovulation, and precocious puberty. A temporal study from 2-24 wk of age indicated elevated levels of progesterone, androstenedione, testosterone, and estradiol and upregulation of several steroidogenic enzyme genes. Ovaries of KiLHR(D582G) mice exhibited significant pathology with the development of large hemorrhagic cysts as early as 3 wk of age, extensive stromal cell hyperplasia and hypertrophy with luteinization, numerous atretic follicles, and granulosa cell tumors. Ovulation could not be rescued by the addition of exogenous gonadotropins. The body weights of the KiLHR(D582G) mice were higher than wild-type counterparts, but there was no increase in the body fat composition or metabolic abnormalities such as impaired glucose tolerance and insulin resistance. These studies demonstrate that activating LHCGR mutations do not produce the same phenotype in female mice as in humans and clearly illustrate species differences in the expression and regulation of LHCGR in the ovary, but not in the testis. PMID:26040673

  2. Isolation and characterization of testis-specific cDNAs for luteinizing hormone beta-subunit in the rat.

    PubMed

    Zhang, F P; Rannikko, A; Huhtaniemi, I

    1995-05-25

    To study further the unexpected expression of the luteinizing hormone (LH) beta-subunit in the rat testis, we identified in a rat testicular cDNA library three LH beta clones with lengths of 3.2, 2.4 and 0.86 kb (TLH beta 1, TLH beta 2 and TLH beta 3). The clones were identified using a 32P-labeled cDNA probe complimentary to the known rat pituitary LH beta mRNA. Clone TLH beta 2 corresponds in size to the main LH beta mRNA species (2.7 kb) detected by Northern hybridization in the rat testis. Sequence analysis indicated that the different sizes of the three clones are due to alternative RNA splicing and differences at the 5' ends of transcripts. The sequence of one open reading frame deduced from TLH beta 1 is almost identical with the pituitary LH beta peptide, differing only in three amino acids in the putative signal peptide. It might encode a functional testis-specific LH beta peptide. Shorter transcripts from clones TLH beta 2 and TLH beta 3 may correspond to short testicular LH beta peptides. The present findings provide further evidence in the rat for expression of testis-specific mRNA variants of the LH beta gene. Their translation products may form a novel class of testicular para/autocrine factors. PMID:7763258

  3. Luteinizing hormone/chorionic gonadotrophin receptor overexpressed in granulosa cells from polycystic ovary syndrome ovaries is functionally active.

    PubMed

    Kanamarlapudi, Venkateswarlu; Gordon, Uma D; López Bernal, Andrés

    2016-06-01

    Polycystic ovarian syndrome (PCOS) is associated with anovulatory infertility. Luteinizing hormone/chorionic gonadotrophin receptor (LHCGR), which is critical for ovulation, has been suggested to be expressed prematurely in the ovarian follicles of women with PCOS. This study aimed to analyse the expression and activity of LHCGR in ovarian granulosa cells from PCOS patients and the involvement of ARF6 small GTPase in LHCGR internalization. Granulosa cells (GC) isolated from follicular fluid collected during oocyte retrieval from normal women (n = 19) and women with PCOS (n = 17) were used to study differences in LHCGR protein expression and activity between normal and PCOS patients. LHCGR expression is up-regulated in GC from PCOS women. LHCGR in PCOS GC is functionally active, as shown by increased cAMP production upon human gonadotrophin (HCG)-stimulation. Moreover, ARF6 is highly expressed in GC from PCOS patients and HCG-stimulation increases the concentrations of active ARF6. The inhibition of ARF6 activation attenuates HCG-induced LHCGR internalization in both normal and PCOS GC, indicating that there are no alterations in LHCGR internalisation in GC from PCOS. In conclusion, the expression and activation of LHCGR and ARF6 are up-regulated in GC from PCOS women but the mechanism of agonist-induced LHCGR internalization is unaltered. PMID:27061682

  4. A controlled study of human chorionic gonadotrophin induced ovulation versus urinary luteinizing hormone surge for timing of intrauterine insemination.

    PubMed

    Martinez, A R; Bernadus, R E; Voorhorst, F J; Vermeiden, J P; Schoemaker, J

    1991-10-01

    Forty-eight patients in a programme of intrauterine insemination (IUI) were randomized in a cross-over study. All were stimulated with clomiphene citrate (CC) and inseminated either after follicular rupture induced by human chorionic gonadotrophin (HCG) or after a spontaneous urinary luteinizing hormone (LH) surge. The HCG was administered when follicles of 18-22 mm in diameter were observed on ultrasound and IUI was performed 37-40 h thereafter. The monitoring of a urinary LH peak was carried out using a rapid urinary LH test. IUI took place approximately 22 h after detection of the LH surge. Overall, the pregnancy rates were 9.3% (4/43) after HCG induced ovulation and 20.5% (9/44) after spontaneous ovulation (P = 0.12). Analysis of mid-cycle events showed that following sonographic criteria, the HCG injection was performed significantly earlier in the cycle compared with the spontaneous LH surge. In addition, the mean diameter of the preovulatory follicles was significantly smaller and insemination was substantially earlier in the HCG induced cycles. These findings suggest that a beneficial effect arises from allowing the natural process of final follicular maturation to occur. PMID:1752926

  5. Thyrotropin-luteinizing hormone/chorionic gonadotropin receptor extracellular domain chimeras as probes for thyrotropin receptor function

    SciTech Connect

    Nagayama, Yuji; Wadsworth, H.L.; Chazenbalk, G.D.; Russo, D.; Seto, Pui; Rapoport, B. Univ. of California, San Francisco )

    1991-02-01

    To define the sites in the extracellular domain of the human thyrotropin (TSH) receptor that are involved in TSH binding and signal transduction the authors constructed chimeric thyrotropin-luteinizing hormone/chorionic gonadotropin (TSH-LH/CG) receptors. The extracellular domain of the human TSH receptor was divided into five regions that were replaced, either singly or in various combinations, with homologous regions of the rat LH/CG receptor. The chimeric receptors were stably expressed in Chinese hamster ovary cells. The data obtained suggest that the carboxyl region of the extracellular domain (amino acid residues 261-418) and particularly the middle region (residues 171-260) play a role in signal transduction. The possibility is also raised of an interaction between the amino and carboxyl regions of the extracellular domain in the process of signal transduction. In summary, these studies suggest that the middle region and carboxyl half of the extracellular domain of the TSH receptor are involved in signal transduction and that the TSH-binding region is likely to span the entire extracellular domain, with multiple discontinuous contact sites.

  6. A new variant in signal peptide of the human luteinizing hormone receptor (LHCGR) affects receptor biogenesis causing leydig cell hypoplasia.

    PubMed

    Vezzoli, Valeria; Duminuco, Paolo; Vottero, Alessandra; Kleinau, Gunnar; Schülein, Ralf; Minari, Roberta; Bassi, Ivan; Bernasconi, Sergio; Persani, Luca; Bonomi, Marco

    2015-11-01

    The human luteinizing hormone/chorionic gonadotropin receptor (LHCGR) plays a fundamental role in male and female reproduction. In males, loss-of-function mutations in LHCGR have been associated with distinct degrees of impairment in pre- and postnatal testosterone secretion resulting in a variable phenotypic spectrum, classified as Leydig cell hypoplasia (LCH) type 1 (complete LH resistance and disorder of sex differentiation) and type 2 (partial LH resistance with impaired masculinization and fertility). Here, we report the case of an adolescent who came to the pediatric endocrinologist at the age of 12 years old for micropenis and cryptorchidism. Testis biopsy showed profound LCH and absent germinal line elements (Sertoli-only syndrome). The sequence analysis of the LHCGR gene showed the presence of a compound heterozygosity, being one variation, c.1847C>A p.S616Y, already described in association to Hypergonadotropic Hypogonadism, and the other, c.29 C>T p.L10P, a new identified variant in the putative signal peptide (SP) of LHCGR. Functional and structural studies provide first evidence that LHCGR have a functional and cleavable SP required for receptor biogenesis. Moreover, we demonstrate the pathogenic role of the novel p.L10P allelic variant, which has to be considered a loss-of-function mutation significantly contributing, in compound heterozygosity with p.S616Y, to the LCH type 2 observed in our patient. PMID:26246498

  7. Carboxymethylation of methionine residues in bovine pituitary luteinizing hormone and its subunits. Location of specifically modified methionine residues.

    PubMed Central

    Cheng, K W

    1976-01-01

    Bovine lutropin (luteinizing hormone) was carboxymethylated at pH3.0 for 12 h at 37 degrees C with iodoacetic acid for specific modification of methionine residues. To facilitate the location of preferentially modified methionine residues, iodoE114C]acetic acid was added as tracer. The alpha and beta subunits of bovine lutropin were carboxymethylated with a 2- or 5-fold molar excess of iodoacetic acid either in the presence or absence of their counterpart subunits. The modified subunits were separated and isolated by counter-current distribution followed by gel filtration on Sephadex G-100. To locate the modified methiones, the isolated alpha or beta chain was reduced. S-carboxymethylated and subjected to tryptic hydrolysis. The tryptic peptides were fractionated by gel filtration on Bio-Gel P-10. From analyses of the purified 14C-labelled tryptic peptides, it was observed that methionine-8 and -33 in bovine lutropin alpha chain and methionine-52 in the beta chain were preferentially modified. Similar results were obtained when isolated alpha and beta subunits were individually carboxymethylated in the absence of their counterpart subunit under identical conditions. The fact that a recombinant of native human lutropin alpha chain, in which a valine residue is present in the position corresponding to methionine-8 of bovine lutropin alpha chain, and carboxymethylated bovine lutropin beta chain regenerated a substantial amount of receptor-site-binding activity indicated that methionine-8 in bovine alpha chain was biologically not essential. These studies showed clearly that both methionine-33 in the alpha chain and methionine-52 in the beta subunit were involved for optimum binding between bovine lutropin and its receptors for expression of hormonal activity. Images PLATE 1 PMID:999646

  8. Luteinizing hormone, a reproductive regulator that modulates the processing of amyloid-beta precursor protein and amyloid-beta deposition.

    PubMed

    Bowen, Richard L; Verdile, Giuseppe; Liu, Tianbing; Parlow, Albert F; Perry, George; Smith, Mark A; Martins, Ralph N; Atwood, Craig S

    2004-05-01

    Hormonal changes associated with the dysregulation of the hypothalamic-pituitary-gonadal (HPG) axis following menopause/andropause have been implicated in the pathogenesis of Alzheimer's disease (AD). Experimental support for this has come from studies demonstrating an increase in amyloid-beta (Abeta) deposition following ovariectomy/castration. Because sex steroids and gonadotropins are both part of the HPG feedback loop, any loss in sex steroids results in a proportionate increase in gonadotropins. To assess whether Abeta generation was due to the loss of serum 17beta-estradiol or to the up-regulation of serum gonadotropins, we treated C57Bl/6J mice with the anti-gonadotropin leuprolide acetate, which suppresses both sex steroids and gonadotropins. Leuprolide acetate treatment resulted in a 3.5-fold (p < 0.0001) and a 1.5-fold (p < 0.024) reduction in total brain Abeta1-42 and Abeta1-40 concentrations, respectively, after 8 weeks of treatment. To further explore the role of gonadotropins in promoting amyloidogenesis, M17 neuroblastoma cells were treated with the gonadotropin luteinizing hormone (LH) at concentrations equivalent to early adulthood (10 mIU/ml) or post-menopause/andropause (30 mIU/ml). LH did not alter amyloid-beta precursor protein (AbetaPP) expression but did alter AbetaPP processing toward the amyloidogenic pathway as evidenced by increased secretion and insolubility of Abeta, decreased alphaAbetaPP secretion, and increased AbetaPP-C99 levels. These results suggest the marked increases in serum LH following menopause/andropause as a physiologically relevant signal that could promote Abeta secretion and deposition in the aging brain. Suppression of the age-related increase in serum gonadotropins using anti-gonadotropin agents may represent a novel therapeutic strategy for AD. PMID:14871891

  9. Altered regulation of luteinizing hormone secretion in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated male rats

    SciTech Connect

    Bookstaff, R.C.

    1989-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) severely decreases plasma androgen concentrations, yet plasma luteinizing hormone (LH) concentrations remain unchanged. The mechanism by which TCDD prevents the expected compensatory increase in plasma LH was investigated. No effect on the plasma disappearance rate of LH or on pituitary capacity to synthesize or secrete LH was detected. Rather, TCDD altered the regulation of LH secretion by substantially increasing the potency of both androgens and estrogens as feedback inhibitors of LH secretion. The mechanism by which TCDD alters androgen-regulated LH secretion was further investigated. Seven days after dosing, TCDD decreased plasma testosterone concentrations but prevented the expected compensatory increases in pituitary gonadotropin-releasing hormone (GnRH) receptor number, pituitary responsiveness to GnRH, and plasma LH concentrations as seen in similarly hypoandrogenic vehicle dosed rats. Furthermore, the TCDD dose-response relationships for preventing the compensatory increases in pituitary GnRH receptor number and plasma LH concentration were similar. However, in the absence of gonadal steroids (7 days after castration) TCDD did not affect the compensatory increases in pituitary GnRH receptor number, pituitary responsiveness to GnRH, or plasma LH concentration. All of these parameters increased substantially relative to intact TCDD treated rats, and to levels virtually identical to those seen in castrated control rats. Treatment of castrated rats with testosterone restored the ability of TCDD to prevent these compensatory increases. Taken together, these results demonstrate that the presence of androgens is required for TCDD to alter the regulation of pituitary GnRH receptors.

  10. A comparison of human chorionic gonadotropin and luteinizing hormone releasing hormone on the induction of spermiation and amplexus in the American toad (Anaxyrus americanus)

    PubMed Central

    2012-01-01

    Background Captive breeding programs for endangered amphibian species often utilize exogenous hormones for species that are difficult to breed. The purpose of our study was to compare the efficacy of two different hormones at various concentrations on sperm production, quantity and quality over time in order to optimize assisted breeding. Methods Male American toads (Anaxyrus americanus) were divided into three separate treatment groups, with animals in each group rotated through different concentrations of luteinizing hormone releasing hormone analog (LHRH; 0.1, 1.0, 4.0 and 32 micrograms/toad), human chorionic gonadotropin (hCG; 50, 100, 200, and 300 IU), or the control over 24 hours. We evaluated the number of males that respond by producing spermic urine, the sperm concentration, percent motility, and quality of forward progression. We also evaluated the effects of hCG and LHRH on reproductive behavior as assessed by amplexus. Data were analyzed using the Generalized Estimating Equations incorporating repeated measures over time and including the main effects of treatment and time, and the treatment by time interaction. Results The hormone hCG was significantly more effective at stimulating spermiation in male Anaxyrus americanus than LHRH and showed a dose-dependent response in the number of animals producing sperm. At the most effective hCG dose (300 IU), 100% of the male toads produced sperm, compared to only 35% for the best LHRH dose tested (4.0 micrograms). In addition to having a greater number of responders (P < 0.05), the 300 IU hCG treatment group had a much higher average sperm concentration (P < 0.05) than the treatment group receiving 4.0 micrograms LHRH. In contrast, these two treatments did not result in significant differences in sperm motility or quality of forward progressive motility. However, more males went into amplexus when treated with LHRH vs. hCG (90% vs. 75%) by nine hours post-administration. Conclusion There is a clear

  11. New insights on the role of luteinizing hormone releasing hormone agonists in premenopausal early breast cancer patients.

    PubMed

    Del Mastro, Lucia; Rossi, Giovanni; Lambertini, Matteo; Poggio, Francesca; Pronzato, Paolo

    2016-01-01

    Luteinising hormone releasing hormone agonists (LH-RHa) are effective in the treatment of advanced endocrine-sensitive breast cancer in premenopausal patients, but their role in the adjuvant setting has remained controversial for a long time. Tamoxifen for 5 years has been traditionally considered the standard endocrine therapy for premenopausal patients and this is still valid for many patients. However, the recently reported SOFT trial has suggested that adding ovarian function suppression (OFS) to tamoxifen could improve DFS in women at sufficient risk to warrant adjuvant chemotherapy and who remained premenopausal after this therapy. The administration of an aromatase inhibitor plus OFS represents an additional therapeutic option for hormone-receptor positive premenopausal breast cancer patients, according to the combined analysis of the SOFT and TEXT trials. Temporary ovarian suppression induced by LH-RHa has been recognized as an effective strategy to preserve ovarian function from the toxic effects of chemotherapy and is now recommended in young breast cancer patients with endocrine-insensitive tumors. In this review, we discuss recent data on the role of LH-RHa in combination with tamoxifen or with an aromatase inhibitor, and we comment on its role as a strategy to preserve ovarian function in young patients candidates for adjuvant or neo-adjuvant chemotherapy. PMID:26613834

  12. Total Androgen Blockade Versus a Luteinizing Hormone-Releasing Hormone Agonist Alone in Men With High-Risk Prostate Cancer Treated With Radiotherapy

    SciTech Connect

    Nanda, Akash; Moran, Brian J.; Braccioforte, Michelle H.; Dosoretz, Daniel; Salenius, Sharon; Katin, Michael; Ross, Rudi; D'Amico, Anthony V.

    2010-04-15

    Purpose: To assess whether short-course total androgen blockade vs. a luteinizing hormone-releasing hormone (LHRH) agonist alone affects the risk of prostate cancer-specific mortality (PCSM) in men with localized but high-risk disease treated with radiotherapy. Methods and Materials: The study cohort comprised 628 men with T1-T4, N0, M0 prostate cancer with high-risk disease (prostate-specific antigen level >20 ng/mL, Gleason score >=8, or clinical category >=T3) treated with 45 Gy of external beam radiotherapy followed by a brachytherapy boost in addition to receiving a median of 4.3 (interquartile range [IQR], 3.6-6.4) months of hormonal blockade with an LHRH agonist plus an antiandrogen or monotherapy with an LHRH agonist. Fine and Gray's multivariable regression analysis was used to determine whether combination androgen suppression therapy (AST) vs. monotherapy affected the risk of PCSM, adjusting for treatment year, duration of AST, age, and known prognostic factors. Results: After a median follow-up of 4.9 (IQR, 3.5-6.5) years, men receiving combination AST had a lower risk of PCSM than those treated with monotherapy (adjusted hazard ratio [AHR], 0.18; 95% confidence interval [CI], 0.04-0.90; p = 0.04). An increasing prostate-specific antigen level (AHR, 2.70; 95% CI, 1.64-4.45; p < 0.001) and clinical category T3/4 disease (AHR, 29.6; 95% CI, 2.88-303.5; p = 0.004) were also associated with an increased risk of PCSM. Conclusions: In men with localized but high-risk prostate cancer treated with external beam radiotherapy and brachytherapy, short-course AST with an LHRH agonist plus an antiandrogen is associated with a decreased risk of PCSM when compared with monotherapy with an LHRH agonist.

  13. Luteinizing Hormone-Induced RUNX1 Regulates the Expression of Genes in Granulosa Cells of Rat Periovulatory Follicles

    PubMed Central

    Jo, Misung; Curry, Thomas E.

    2006-01-01

    The LH surge induces specific transcription factors that regulate the expression of a myriad of genes in periovulatory follicles to bring about ovulation and luteinization. The present study determined 1) the localization of RUNX1, a nuclear transcription factor, 2) regulation of Runx1 mRNA expression, and 3) its potential function in rat ovaries. Up-regulation of mRNA and protein for RUNX1 is detected in preovulatory follicles after human chorionic gonadotropin (hCG) injection in gonadotropin-treated immature rats as well as after the LH surge in cycling animals by in situ hybridization and immunohistochemical and Western blot analyses. The regulation of Runx1 mRNA expression was investigated in vitro using granulosa cells from rat pre-ovulatory ovaries. Treatments with hCG, forskolin, or phorbol 12 myristate 13-acetate stimulated Runx1 mRNA expression. The effects of hCG were reduced by inhibitors of protein kinase A, MAPK kinase, or p38 kinase, indicating that Runx1 expression is regulated by the LH-initiated activation of these signaling mediators. In addition, hCG-induced Runx1 mRNA expression was inhibited by a progesterone receptor antagonist and an epidermal growth factor receptor tyrosine kinase inhibitor, whereas amphiregulin stimulated Runx1 mRNA expression, demonstrating that the expression is mediated by the activation of the progesterone receptor and epidermal growth factor receptor. Finally, knockdown of Runx1 mRNA by small interfering RNA decreased progesterone secretion and reduced levels of mRNA for Cyp11a1, Hapln1, Mt1a, and Rgc32. The hormonally regulated expression of Runx1 in periovulatory follicles, its involvement in progesterone production, and regulation of preovulatory gene expression suggest important roles of RUNX1 in the periovulatory process. PMID:16675540

  14. Human chorionic gonadotropin (a luteinizing hormone homologue) decreases spatial memory and increases brain amyloid-β levels in female rats

    PubMed Central

    Berry, Anne S.; Tomidokoro, Yasushi; Ghiso, Jorge; Thornton, Jan

    2008-01-01

    Numerous studies have suggested that estradiol (E) improves spatial memory as female rats with E perform better than those without E. However there is an inverse relationship between E and luteinizing hormone (LH) levels and LH could play a role. We examined whether treatment with the LH homologue human chorionic gonadotropin (hCG), would impair spatial memory of adult E-treated female rats. In the Object Location Memory Task, ovariectomized (ovxed) rats treated with E and either a single high dose (400IU/kg) or a lower repeated dose of hCG (75 IU/kg hourly for 8 hours) showed spatial memory disruption compared to ovxed rats treated with estradiol alone. Impairment was attributed to memory disruption as performance improved with shortened delay between task exposure and testing. Tests on another spatial memory task, the Barnes maze, confirmed that hCG (400IU/kg) can impair memory: although E + veh treated animals made significantly fewer hole errors across time, E + hCG treated did not. In humans, high LH levels have been correlated with Alzheimer’s Disease (AD). Because brain amyloid-beta (Aβ) species have been implicated as a toxic factor thought to cause memory loss in AD, we analyzed whether hCG-treated animals had increased Aβ levels. Levels of Aβ from whole brains or hippocampi were assessed by Western Blot. hCG treatment to E-implanted females significantly increased soluble Aβ40 and Aβ42 levels. These results indicate that high levels of LH/hCG can impair spatial memory, and an increase in brain Aβ species may account for the memory impairment in hCG-treated rats. PMID:18413150

  15. Genetic heterogeneity of activating mutations of the luteinizing hormone receptor gene in familial male-limited precocious puberty

    SciTech Connect

    Laue, L.; Chan, W.Y.; Wu, S.M.

    1994-09-01

    Familial male-limited precocious puberty (FMPP) is an autosomal dominant disorder characterized by elevated serum levels of testosterone, low levels of gonadotropins, and Leydig cell hyperplasia. Recently, 3 mutations have been found in FMPP families which encode substitution of Gly for Asp 578, Ile for Met 571, and Ile for Thr 577 in transmembrane helix 6 (TM 6) of the luteinizing hormone receptor (LHR). We have studied 28 additional unrelated FMPP families. Genomic DNA was isolated from affected males and PCR was performed to amplify a fragment of the LHR gene encoding amino acid residues 441 to 594. MspI restriction enzyme digests were positive for the Asp 578 to Gly mutation in 22 families. Four new mutations were found in the remaining 6 families: an A to C transition encoding substitution of Leu for Ile 542 in transmembrane helix 5 (TM 5), an A to G transition encoding substitution of Gly for Asp 564 in the third cytoplasmic loop, a G to T transition encoding substitution of Try for Asp 578 in TM 6, and a T to C transition encoding substitution of Arg for Cys 581 in TM 6 of the LHR. 293 cells transfected with cDNAs for each of the 4 mutant LHRs, created by site-directed mutagenesis of the wild-type LHR cDNA, exhibited markedly increased levels of basal cAMP production in the absence of agonist, indicating constitutive activation of the mutant LHRs. We conclude that substitution of residues at multiple sites with TM 5, TM 6, and the intervening third cytoplasmic loop of the LHR cause constitutive receptor activation resulting in FMPP. These findings allow future diagnosis of affected patients and provide the basis to study the receptor domains involved in G-protein activation.

  16. INTERACTION BETWEEN GABA AND NOREPINEPHRINE IN INTERLEUKIN-1β-INDUCED SUPPRESSION OF THE LUTEINIZING HORMONE SURGE

    PubMed Central

    Sirivelu, Madhu P.; Burnett, Robert; Shin, Andrew C.; Kim, Charlotte; MohanKumar, P.S.; MohanKumar, Sheba M.J.

    2009-01-01

    Interleukin-1β (IL-1β), a cytokine that is closely associated with inflammation and immune stress, is known to interfere with reproductive functions. Earlier studies have demonstrated that IL-1β inhibits the luteinizing hormone (LH) surge during the afternoon of proestrus in female rats. We have shown that this effect is most probably mediated through a reduction in norepinephrine (NE) levels in the medial preoptic area (MPA) of the hypothalamus. However, the mechanism by which IL-1β decreases NE levels in the MPA is unclear. We hypothesized that the inhibitory neurotransmitter, GABA could play a role in decreasing NE levels in the MPA. To test this, ovariectomized, steroid-primed rats were injected (i.p.) with either PBS-BSA (control) or 5 μg of IL-1β, alone or in combination with i.c.v. administration of GABA-A and GABA-B receptor antagonists, Bicuculline and CGP 35348 (CGP) respectively. Animals were subjected to push-pull perfusion of the MPA and perfusates collected at 30 min intervals were analyzed for both NE and GABA levels using HPLC-EC. Simultaneously, serial plasma samples were obtained through jugular catheters and were analyzed for LH levels using RIA. Compared to control rats, NE levels decreased significantly in the MPA in IL-1β-treated rats (p<0.05). Concurrently, there was a significant increase in GABA levels in the MPA (p<0.05). The GABA-A receptor antagonist, bicuculline, was able to reverse the effect of IL-1β on NE and LH, while the GABA-B receptor antagonist, CGP 35348 was without any effect. This leads us to conclude that the IL-1β-induced suppression of the LH surge is most probably mediated through an increase in GABA levels in the MPA which causes a reduction in NE levels. This is probably one of the mechanisms by which IL-1β inhibits reproductive functions. PMID:19014915

  17. The Naturally Occurring Luteinizing Hormone Surge Is Diminished in Mice Lacking Estrogen Receptor Beta in the Ovary1

    PubMed Central

    Jayes, Friederike L.; Burns, Katherine A.; Rodriguez, Karina F.; Kissling, Grace E.; Korach, Kenneth S.

    2013-01-01

    ABSTRACT Female ESR2-null mice (betaERKO) display defects in ovarian function and are subfertile. Follicular maturation is impaired and explains smaller litters, but betaERKO also produce fewer litters, which may be partially due to inadequate ovulatory signals. To test this, the amplitude and timing of the naturally occurring luteinizing hormone (LH) surge was measured in individual intact betaERKO and wild-type (WT) mice. Vaginal cytology was evaluated daily, and blood samples were taken from mice in proestrus. The amplitude of the LH surge was severely blunted in betaERKO mice compared to WT, but pituitary LH levels revealed no differences. The betaERKO mice did not produce a preovulatory estradiol surge. To determine if the smaller LH surges and the reduced number of litters in betaERKO were due to the lack of ESR2 in the hypothalamic-pituitary axis or due to the absence of ESR2 in the ovary, ovaries were transplanted from WT into betaERKO mice and vice versa. The size of the LH surge was reduced only in mice lacking ESR2 within the ovary, and these mice had fewer litters. Fertility and size of the LH surge were rescued in betaERKO mice receiving a WT ovary. These data provide the first experimental evidence that the LH surge is impaired in betaERKO females and may contribute to their reduced fertility. ESR2 is not necessary within the pituitary and hypothalamus for the generation of a normal LH surge and for normal fertility, but ESR2 is essential within the ovary to provide proper signals. PMID:24337314

  18. The effect of dietary monensin on th luteinizing hormone response of prepuberal heifers given a multiple gonadotropin-releasing hormone challenge.

    PubMed

    Randel, R D; Rhodes, R C

    1980-10-01

    Ten prepuberal Simmental X Brahman-Hereford heifers (average weight 208 +/- 4 kg) were randomly assigned to receive either 2.7 kg/head/day of ground milo containing 0 mg monensin sodium (C) or 2.7 kg/head/day of ground milo containing 200 mg monensin sodium (M). Both groups of animals (n = 5) received Coastal bermudagrass hay ad libitum throughout the trial. On day 21 of the feeding period all heifers were fitted with jugular cannulas. Immediately after cannulation, the heifers were injected IM with 100 microgram of gonadotropin-releasing hormone (GnRH) and blood was collected every 10 min for 4 hours. Four hours after the first GnRH challenge, a second 100-microgram GnRH injection was administered, and blood samples were collected at 10-min intervals for an additional 5 hours. Serum was stored at -20 C until radioimmunoassayed for luteinizing hormone (LH). The amount of LH released after each GnRH injection was greater in the heifers fed M than in the controls (P less than .05). Peak LH after the first GnRH challenge was greater (P less than .05) in heifers fed M than in controls. The area under th first GnRH induced LH curve tended (P less than .20) to be greater for the M group than for the controls. Peak LH concentration was greater in heifers fed M than in control heifers, as the duration (P less than .05) and area under the second GnRH-induced LH curve. In prepuberal heifers, dietary monensin appears to increase hypophyseal capability of releasing LH after a first and second GnRH challenge. PMID:7007307

  19. Evidence that cells expressing luteinizing hormone-releasing hormone mRNA in the mouse are derived from progenitor cells in the olfactory placode

    SciTech Connect

    Wray, S.; Grant, P.; Gainer, H. )

    1989-10-01

    In situ hybridization histochemistry and immunocytochemistry were used to study the prenatal expression of luteinizing hormone-releasing hormone (LHRH) cells in the mouse. Cells expressing LHRH mRNA and peptide product were first detected on embryonic day 11.5 (E11.5) in the olfactory pit. On E12.5, the majority of LHRH cells were located on tracks extending from the olfactory pit to the base of the telencephalon. From E12.5 to E15.5, LHRH cells were detected in a rostral-to-caudal gradient in forebrain areas. Prior to E12.5, cells expressing LHRH mRNA were not detected in forebrain areas known to contain LHRH cells in postnatal animals. Quantitation of cells expressing LHRH mRNA showed that the number of labeled cells on E12.5 (approximately 800) equaled the number of LHRH cells in postnatal animals, but more than 90% of these cells were located in nasal regions. Between E12.5 and E15.5, the location of LHRH cells shifted. The number of LHRH cells in the forebrain increased, while the number of LHRH cells in nasal regions decreased over this same period. These findings establish that cells first found in the olfactory pit and thereafter in forebrain areas express the LHRH gene and correspond to the position of LHRH immunopositive cells found at these developmental times. To further examine the ontogeny of the LHRH system, immunocytochemistry in combination with (3H)thymidine autoradiography was used to determine when LHRH cells left the mitotic cycle. We show that LHRH neurons exhibit a discrete time of birth, suggesting that they arise as a single neuronal population between E10.0 and E11.0. Postnatal LHRH neurons were birth-dated shortly after differentiation of the olfactory placode and before LHRH mRNA was expressed in cells in the olfactory pit.

  20. Intracerebroventricular infusion of neuropeptide Y up-regulates synthesis and accumulation of luteinizing hormone but not follicle stimulating hormone in the pituitary cells of prepubertal female lambs.

    PubMed

    Wańkowska, Marta; Lerrant, Yannick; Wójcik-Gładysz, Anna; Starzec, Anna; Counis, Raymond; Polkowska, Jolanta

    2002-02-01

    Neuropeptide Y (NPY) is a putative neuroregulator of the reproductive axis in the central nervous system. In this study we evaluated the effects of central infusion of exogenous NPY on the secretory activity of pituitary gonadotrophic cells in prepubertal lambs. Immature female Merino sheep (n=12) were infused of Ringer solution (control) or 50 microg of NPY to the third ventricle for 5 min and then slaughtered 3 h later. Immunoreactive luteinizing hormone (LH) and follicle stimulating hormone (FSH) cells were localised by immunohistochemistry using antibody raised against LHbeta and FSHbeta. Messenger RNA analyses were performed by in situ hybridisation using sense and antisense riboprobes produced from beta subunits of LH and FSH cDNA clones. The results were generated by computer image analysis to determine the area fraction occupied by immunoreactive and/or hybridising cells and optical density for immunostaining and hybridisation signal. LH in the blood plasma was determined by radioimmunoassay. It was found, that in the lambs infused with NPY the area fraction and optical density for immunoreactive LH cells and mRNA LHbeta-expressing cells increased significantly (P<0.001), compared to the vehicle-infused animals. The concentration of LH in the blood plasma did not differ between control and treated groups. The NPY infusions had no effect on the immunoreactivity of FSH cells or on expression of mRNA for FSHbeta. In conclusion we suggest that NPY may be an important component of mechanisms stimulating the synthesis and storage but not the release of LH in the pituitary gonadotrophs from prepubertal female sheep. In addition, this effect is specific for LH, no such effect was apparent on FSH. PMID:11841917

  1. Cytoplasmic kinases downstream of GPR30 suppress gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone secretion from bovine anterior pituitary cells

    PubMed Central

    RUDOLF, Faidiban O.; KADOKAWA, Hiroya

    2015-01-01

    GPR30 is known as a membrane receptor for picomolar concentrations of estradiol. The GPR30-specific agonist G1 causes a rapid, non-genomic suppression of gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) secretion from bovine anterior pituitary (AP) cells. A few studies have recently clarified that protein kinase A (PKA) and phosphorylated extracellular signal-regulated kinase (pERK) might be involved in cytoplasmic signaling pathways of GPR30 in other cells. Therefore, we tested the hypothesis that PKA and ERK kinase (MEK) are important cytoplasmic mediators for GPR30-associated non-genomic suppression of GnRH-induced LH secretion from bovine AP cells. Bovine AP cells (n = 8) were cultured for 3 days under steroid-free conditions. The AP cells were previously treated for 30 min with one of the following: 5000 nM of PKA inhibitor (H89), 1000 nM of MEK inhibitor (U0126), or a combination of H89 and U0126. Next, the AP cells were treated with 0.01 nM estradiol for 5 min before GnRH stimulation. Estradiol treatment without inhibitor pretreatment significantly suppressed GnRH-induced LH secretion (P < 0.01). In contrast, estradiol treatment after pretreatment with H89, U0126 or their combination had no suppressive effect on GnRH-induced LH secretion. The inhibitors also inhibited the G1 suppression of GnRH-induced LH secretion. Therefore, these data supported the hypothesis that PKA and MEK (thus, also pERK) are the intracellular mediators downstream of GPR30 that induce the non-genomic suppression of GnRH-induced LH secretion from bovine AP cells by estradiol or G1. PMID:26522383

  2. Alterations in RFamide-Related Peptide Expression Are Coordinated with the Preovulatory Luteinizing Hormone Surge

    PubMed Central

    Gibson, Erin M.; Humber, Stephanie A.; Jain, Sachi; Williams, Wilbur P.; Zhao, Sheng; Bentley, George E.; Tsutsui, Kazuyoshi; Kriegsfeld, Lance J.

    2008-01-01

    The preovulatory LH surge is triggered when the circadian pacemaker, the bilateral suprachiasmatic nucleus (SCN), stimulates the GnRH system in the presence of high estrogen concentrations (positive feedback). Importantly, during the remainder of the estrous cycle, estradiol inhibits LH release via negative feedback. We have recently documented the presence of a novel mammalian RFamide-related peptide (RFRP), a putative gonadotropin-inhibitory hormone (GnIH), that presumably acts upstream of GnRH to modulate the negative feedback effects of estrogen. The present series of studies used female Syrian hamsters to examine the possibility that, in addition to driving the LH surge positively, the SCN concomitantly coordinates the removal of steroid-mediated RFRP inhibition of the gonadotropic axis to permit the surge. We found that the SCN forms close appositions with RFRP cells, suggesting the possibility for direct temporal control of RFRP activity. During the time of the LH surge, immediate-early gene expression is reduced in RFRP cells, and this temporal regulation is estrogen dependent. To determine whether projections from the SCN regulate the timed reduction in activation of the RFRP system, we exploited the phenomenon of splitting. In split animals in which the SCN are active in antiphase, activation of the RFRP system is asymmetrical. Importantly, this asymmetry is opposite to the state of the GnRH system. Together, these findings point to novel circadian control of the RFRP system and potential participation in the circuitry controlling ovulatory function. PMID:18566114

  3. Protective effects of analogs of luteinizing hormone-releasing hormone against x-radiation-induced testicular damage in rats

    SciTech Connect

    Schally, A.V.; Paz-Bouza, J.I.; Schlosser, J.V.; Karashima, T.; Debeljuk, L.; Gandle, B.; Sampson, M.

    1987-02-01

    Possible protective effects of the agonist (D-Trp/sup 6/)LH-RH and antagonist N-Ac(D-Phe(pCl)/sup 1,2/,D-Trp/sup 3/,D-Arg/sup 6/,D-Ala/sup 10/)LH-RH against testicular damage caused by x-radiation were investigated in rats. Three months after being subjected to x-irradiation of the testes with 415 or 622 rads, control rats showed marked reduction in the weights of the testes and elevated levels of LH and follicle-stimulating hormone (FSH), indicating tubular damage. Histological studies demonstrated that, in testes of rats given 415 rads, most seminiferous tubules had only Sertoli cells and no germinal cells, and, in the group give 622 rads, the depression of spermatogenesis was even more marked. Rats pretreated for 50 days with LH-RH antagonist showed a complete recovery of testicular weights and spermatogenesis 3 months after 415 rads and showed partial recovery after 622 rads, and LH and FSH levels returned to normal in both of these groups. Three experiments were also carried out in which the rats were pretreated for 1-2 months with long-acting microcapsules of the agonist (D-Trp/sup 6/)LH-RH. Some rats were then subjected to gonadal irradiation with 415 or 622 rads and allowed a recovery period of 2-4 months. On the basis of testicular weights, histology, and gonadotropin levels, it could be concluded that the agonist (D-Trp/sup 6/)LH-RH did not protect the rat testes exposed to 622 rads and, at most, only partially protected against 415 rads. These results suggest that pretreatment with LH-RH antagonists and possibly agonists, might decrease the testicular damage caused by radiation and accelerate the recovery of reproductive functions.

  4. Differential effects of follicle-stimulating and luteinizing hormones on testosterone production by mouse testes.

    PubMed

    Dalterio, S L; Suter, D E; Schwartz, N B; Mayfield, D; Rettori, V B

    1986-07-01

    In adult mice, direct intratesticular injection of ovine follicle-stimulating hormone (o-FSH-13; AFP 2846-C, from NIAMDD, less than 1% LH contamination) at 10, 100 or 1000 ng significantly elevated concentrations of testosterone (T) within the testis. These effects were rapid, with peak values attained by 15 min, and transient, with return to values comparable to that in the contralateral, saline-injected testis within 90 min. Intratesticular injection of FSH (1 microgram) significantly increased testicular T levels in 15- and 60-day old mice. This contrasted with the effects of intratesticular administration of human chorionic gonadotropin (hCG), which stimulated T production significantly at 30 days of age through adulthood. In adult mice, the equivalent LH to the possible contamination in the FSH preparation (1 ng) had no effect. Intratesticular injection of 10 ng LH produced comparable stimulation to that by 100 ng FSH (approximately 7-fold). Systemic pre-treatment with a charcoal-treated porcine follicular fluid (PFF) extract for 2 days reduced plasma FSH levels [86 +/- 17 (5) vs 700 +/- 8 (6); P less than 0.05], but had no effect on plasma LH. Twenty-four hours after the last treatment, the response to intratesticular injection of hCG (2.5 mIU), FSH (100 ng) or LH (10 ng) was also significantly attenuated in these mice. Intratesticular injection of PFF had no direct effect on testicular T levels. In vitro T production in the presence of hCG, LH or FSH were differentially affected by the concentrations of calcium (Ca2+) or magnesium (Mg2+) in the incubation media. The stimulatory effects of FSH were apparent at significantly lower levels of Ca2+ or Mg2+, than were those of LH or hCG. The results of these studies indicate that FSH is capable of stimulating testicular T production. Furthermore, the responsiveness to FSH is qualitatively different than that to LH/hCG in terms of the age pattern, as well as the dependence on Ca2+ or Mg2+. In addition, plasma FSH

  5. Acute regulation of plasma insulin-like peptide 3 concentrations by luteinizing hormone in male goats.

    PubMed

    Hannan, M A; Kawate, N; Fukami, Y; Pathirana, I N; Büllesbach, E E; Inaba, T; Tamada, H

    2016-08-01

    Recently, it was reported that in bulls secretion of insulin-like peptide 3 (INSL3) in blood occurred in a pulsatile manner and was acutely regulated by LH. In the present study, the acute regulation of plasma INSL3 and its temporal relationships with LH and testosterone were examined in six sexually matured male goats using the following experimental design. (1) After stimulating LH release by administering a GnRH analogue, blood levels of LH, INSL3, and testosterone were monitored at 15-minute intervals for 2 hours followed by hourly intervals up to 8 hours. (2) After activation of the LH receptor by hCG blood levels of INSL3 and testosterone were determine at 15-minute intervals for 2 hours, followed by hourly intervals up to 8 hours, daily intervals up to Day 8, and finally on Day 12. (3) The release of LH, INSL3, and testosterone in normal physiology was established at 15-minute intervals for an 8-hour session. Concentrations of LH, INSL3, and testosterone in plasma were measured by enzyme-immunoassays. After GnRH treatment, mean plasma concentrations of all three hormones increased (P < 0.05) dramatically from 30 minutes and remained high until 120 minutes (LH), 75 minutes (INSL3), and 4 hours (testosterone) after treatment. After hCG treatment, mean plasma INSL3 concentrations increased (P < 0.05) from 30 minutes and remained elevated until the end of sampling on Day 12. An increase (P < 0.05) in mean plasma testosterone concentrations occurred from 15 minutes and remained high until Day 6. The mean increase (maximum per pretreatment concentration) of INSL3 concentrations after administration of GnRH and hCG was lower (P < 0.01) than that of testosterone. The secretory pattern of LH, INSL3, and testosterone in the general circulation was pulsatile with a frequency of 5.5 ± 0.6, 4.7 ± 0.5, and 2.2 ± 0.5, respectively, during the 8-hour period. Twenty out of 28 (71%) of these INSL3 pulses peaked within 1 hour after a peak of an LH

  6. Profiling of urinary testosterone and luteinizing hormone in exercise-stressed male athletes, using gas chromatography-mass spectrometry and enzyme immunoassay techniques.

    PubMed

    Yap, B K; Kazlauskas, R; Elghazi, K; Johnston, G A; Weatherby, R P

    1996-12-01

    Knowledge of the effects of episodic or short-term exercise-stress on endogenous testosterone and luteinizing hormone levels still remains fragmentary and inconclusive. In this study, an approach based on the absolute concentrations of urinary total testosterone (T), luteinizing hormone (LH) and the T/LH concentration ratios, was used to profile short-term exercise-stress responses in healthy drug-free male athletes. Testosterone and luteinizing hormone concentrations were measured using gas chromatography-mass spectrometry (GC-MS) and microparticle enzyme immunoassay (MEIA) techniques, respectively. Stress profiles derived from exercise-stress at VO2max, 68.1% VO2max and 51.6% VO2max were plotted using the concentrations of T, LH and the ratios of T/LH found under non-stressed and stressed conditions. Significant changes in LH concentrations (p < 0.005) and T/LH ratios (p < 0.005) levels were observed between the pre-stress and post-exercise conditions during acute exercise-stress at VO2max but the T concentration did not show any marked change relative to the non-stressed condition. Whilst exercise-stress appeared to reduce the change in T concentrations between the pre- and post-exercise states compared to that in the non-stressed control condition, the change in LH concentrations showed a moderate increase at submaximal oxygen uptake values. The stress profiles derived from this study facilitated an assessment of the relationship between the endogenous T, LH and T/LH ratio stress-responses over a short period of applied exercise-stress. PMID:9001959

  7. Association between genes encoding components of the Leutinizing hormone/Luteinizing hormone-choriogonadotrophin receptor pathway and polycystic ovary syndrome in Egyptian women.

    PubMed

    El-Shal, Amal S; Zidan, Haidy E; Rashad, Nearmeen M; Abdelaziz, Ahmed M; Harira, Mervat M

    2016-01-01

    Polycystic ovary syndrome (PCOS) is one of the most common endocrine-metabolic disorders; however, its pathophysiology is still unclear. Certain polymorphisms of luteinizing hormone beta-subunit (LHβ) and LH/choriogonadotrophin receptor (LHCGR) genes may lead to changes in the bioactivity of this hormone. We aimed to investigate possible associations between polymorphisms in the LHβ and LHCGR genes and PCOS among Egyptian women. We also aimed to shed light on the impact of these polymorphisms on LH level, hormonal, and metabolic features of PCOS. A case-control study included unrelated 210 patients with PCOS and 200 healthy controls, and they were stratified according to their body mass index into two subgroups: lean and obese. Polymorphisms of LHβ G1502A and LHCGR [G935A, and ins18LQ] genes were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Our results revealed that LHβ G1052A GA genotype and A allele, LHCGR G935A GA, AA genotypes, or A allele were significantly associated with PCOS risk, while the LHCGR ins18LQ polymorphism was not. Additionally, there is a synergism between LHβ G1052A minor A and minor A allele of LHCGR G935A or minor ins allele of LHCGR ins18LQ and susceptibility to PCOS. When we stratified PCOS women or controls into obese and lean subjects, we found that LHβ G1502A GA genotype and A allele being more frequent in the obese group when compared with lean patients with PCOS [The odds ratio and 95% confidence interval were 5.6 (1.30-24.56) and 5.15 (1.21-21.90), respectively, P = 0.01, for each group.] These results suggested that LHβ G1052A and LHCGR G935A genes polymorphisms are associated with increased risk of PCOS in Egyptian women especially in obese cases. There was a synergism between LHβ G1052A minor A allele and of LHCGR G935A minor A or minor ins alleles of LHCGR ins18LQ and PCOS risk. © 2015 IUBMB Life, 68(1):23-36, 2016. PMID:26662070

  8. Effect of priming injections of luteinizing hormone-releasing hormone on spermiation and ovulation in Gϋnther's Toadlet, Pseudophryne guentheri

    PubMed Central

    2011-01-01

    Background In the majority of vertebrates, gametogenesis and gamete-release depend on the pulsatile secretion of luteinizing hormone-releasing hormone (LHRH) from the hypothalamus. Studies attempting to artificially stimulate ovulation and spermiation may benefit from mimicking the naturally episodic secretion of LHRH by administering priming injections of a synthetic analogue (LHRHa). This study investigated the impact of low-dose priming injections of LHRHa on gamete-release in the Australian toadlet Pseudophryne guentheri. Methods Toadlets were administered a single dose of two micrograms per. gram LHRHa without a priming injection (no priming), or preceded by one (one priming) or two (two priming) injections of 0.4 micrograms per. gram LHRHa. Spermiation responses were evaluated at 3, 7 and 12 hrs post hormone administration (PA), and sperm number and viability were quantified using fluorescent microscopy. Oocyte yields were evaluated by stripping females at 10-11 hrs PA. A sub-sample of twenty eggs per female was then fertilised (with sperm obtained from testis macerates) and fertilisation success determined. Results No priming induced the release of the highest number of spermatozoa, with a step-wise decrease in the number of spermatozoa released in the one and two priming treatments respectively. Peak sperm-release occurred at 12 hrs PA for all priming treatments and there was no significant difference in sperm viability. Females in the control treatment failed to release oocytes, while those administered an ovulatory dose without priming exhibited a poor ovulatory response. The remaining two priming treatments (one and two priming) successfully induced 100% of females to expel an entire clutch. Oocytes obtained from the no, or two priming treatments all failed to fertilise, however oocytes obtained from the one priming treatment displayed an average fertilisation success of 97%. Conclusion Spermiation was most effectively induced in male P. guentheri by

  9. Degarelix monotherapy compared with luteinizing hormone-releasing hormone (LHRH) agonists plus anti-androgen flare protection in advanced prostate cancer: an analysis of two randomized controlled trials

    PubMed Central

    Iversen, Peter; Damber, Jan-Erik; Malmberg, Anders; Persson, Bo-Eric; Klotz, Laurence

    2015-01-01

    Objectives: The objective of this study was to assess differences in efficacy outcomes between luteinizing hormone-releasing hormone (LHRH) agonist plus antiandrogen (AA) flare protection and monotherapy with the gonadotrophin-releasing hormone antagonist degarelix in patients with prostate cancer. Methods: Data from 1455 patients were pooled from two prospective, phase III randomized 1-year clinical trials of degarelix versus LHRH agonist with or without AA. The AA bicalutamide was administered at the investigator’s discretion. Adjusted hazard ratios (HRs) were calculated using a Cox proportional hazards regression model and a conditional logistic regression model was used for a case-control analysis of odds ratios (ORs). Results: Patients received degarelix monotherapy (n = 972) or LHRH agonist (n = 483) of whom 57 also received AA. Overall, prostate-specific antigen progression-free survival (PSA PFS) was improved with degarelix versus LHRH agonist + AA (Cox proportional hazards regression model-adjusted HR for PSA PFS failure was 0.56 [95% confidence interval (CI) 0.33–0.97, p = 0.038]). To compensate for a higher proportion of patients with metastases, Gleason score 7–10, and PSA >20 ng/ml in the LHRH agonist + AA group, a case-control analysis using a conditional logistic regression model was utilized. This resulted in an OR for PSA PFS of 0.42 (95% CI 0.20–0.89; p = 0.023) in the overall population, and 0.35 (95% CI 0.13–0.96; p = 0.042) in patients with PSA >50 ng/ml at baseline, when treated with degarelix versus LHRH agonists + AA. There were a small number of deaths, 1.9% with degarelix and 7% with LHRH agonists + AA (case-control analysis OR = 0.37; p = 0.085). Conclusions: Degarelix monotherapy produced a more favorable effect on PSA PFS outcomes than a LHRH agonist + AA flare protection therapy in patients with prostate cancer when a case-control analysis was used to compensate for differences between treatment groups. PMID:27034720

  10. Combination of long-acting microcapsules of the D-tryptophan-6 analog of luteinizing hormone-releasing hormone with chemotherapy: investigation in the rat prostate cancer model.

    PubMed Central

    Schally, A V; Redding, T W

    1985-01-01

    The effect of combining hormonal treatment consisting of long-acting microcapsules of the agonist [D-Trp6]LH-RH (the D-tryptophan-6 analog of luteinizing hormone-releasing hormone) with the chemotherapeutic agent cyclophosphamide was investigated in the Dunning R-3327H rat prostate cancer model. Microcapsules of [D-Trp6]LH-RH formulated from poly(DL-lactide-co-glycolide) and calculated to release a controlled dose of 25 micrograms/day were injected intramuscularly once a month. Cyclophosphamide (Cytoxan) (5 mg/kg of body weight) was injected intraperitoneally twice a week. When the therapy was started 90 days after tumor transplantation--at the time that the cancers were well developed-and was continued for 2 months, tumor volume was significantly reduced by the microcapsules or Cytoxan given alone. The combination of these two agents similarly inhibited tumor growth but did not show a synergistic effect. In another study, the treatment was started 2 months after transplantation, when the developing tumors measured 60-70 mm3. Throughout the treatment period of 100 days, the microcapsules of [D-Trp6]LH-RH reduced tumor volume more than Cytoxan did, and the combination of the two drugs appeared to completely arrest tumor growth. Tumor weights also were diminished significantly in all experimental groups, the decrease in weight being smaller in the Cytoxan-treated group than in rats that received the microcapsules. The combination of Cytoxan plus the microcapsules was 10-100 times more effective than the single agents in reducing tumor weights. In both experiments, testes and ventral prostate weights were significantly diminished, serum testosterone was suppressed to undetectable levels, and prolactin values were reduced by administration of microcapsules of [D-Trp6]LH-RH alone or in combination with Cytoxan. These results in rats suggest that combined administration of long acting microcapsules of [D-Trp6]LH-RH with a chemotherapeutic agent, started soon after the

  11. The effects of 3 gonadorelin products on luteinizing hormone release, ovulation, and follicular wave emergence in cattle

    PubMed Central

    Martínez, Marcelo F.; Mapletoft, Reuben J.; Kastelic, John P.; Carruthers, Terry

    2003-01-01

    The objective was to determine luteinizing hormone (LH) secretion and follicular dynamics in cattle following administration of 3 gonadorelin formulations that are commercially available in Canada. In experiment 1, nonlactating Holstein cows (n = 4 per group) were randomly assigned to receive 100 μg gonadorelin diacetate tetrahydrate, intramuscularly (C; Cystorelin, or FE; Fertagyl). Blood samples (for LH analysis) were collected 0, 1, 2, and 4 hours after treatment. In experiment 2, nonlactating Holstein cows (n = 10 per group) were randomly allocated to receive 100 μg gonadorelin, intramuscularly as follows: 2 mL of C; 1 mL of FE; or 2 mL of Factrel (FA, gonadorelin hydrochloride). Gonadorelin treatment was done on days 6 or 7 after ovulation and blood samples for LH analysis were collected at 0, 1, 2, 4, and 6 hours after treatment. Ovaries were examined by ultrasonography, twice daily, to detect ovulation. A replicate was conducted using only C (n = 10) or FE (n = 10); blood samples were collected at 0, 1, 2, 3, and 4 hours. In experiment 3, beef heifers (n = 10 per group) were randomly assigned to receive 1 of 3 GnRH gonadorelin treatments (as in the first phase of experiment 2) on days 6 or 7 after ovulation and blood samples were collected at 0, 0.5, 1, 1.5, 2, and 4 hours. In experiments 2 and 3, both mean and mean peak plasma LH concentrations were higher (P < 0.05) in cattle treated with C. The proportion of dominant follicles that ovulated was higher (P < 0.02) in Holstein cows treated with C than in those treated with FE or FA (18/19, 11/19, and 4/7, respectively), but there was no significant difference among the products in beef heifers (6/10, 6/10, and 4/10, respectively). No significant differences were found in the interval from treatment to the emergence of the next follicular wave. In summary, C induced a greater LH release and this resulted in a higher ovulatory rate in Holstein cows but not in beef heifers. PMID:12650040

  12. Lead (Pb) alters the norepinephrine-induced secretion of luteinizing hormone releasing hormone from the median eminence of adult male rats in vitro

    SciTech Connect

    Bratton, G.R.; Hiney, J.K.; Dees, W.L. )

    1994-01-01

    In the present study, the authors evaluated the in vitro effects of lead (Pb) on basal and stimulated luteinizing hormone releasing hormone (LHRH) and Prostaglandin E[sub 2] (PGE[sub 2]) secretion. Median eminences (ME) were removed from brains of adult male rats and preincubated for 15 minutes in Krebs-Ringer bicarbonate glucose buffer in an atmosphere of 95% O[sub 2]-5% CO[sub 2]. These media were discarded and all MEs were subjected to one of the following experiments. In Experiment 1, all MEs were incubated for 30 minutes in medium only. These media were collected and replaced with medium only (controls) or with medium containing Pb doses ranging from 5 to 20 [mu]M. After this 60-minute incubation, media were collected, then replaced with new medium containing 60 [mu]M norepinephrine (NE), or NE plus each dose of Pb, then incubated for a final 30-minute period. Experiment 2 was conducted as above, except PGE[sub 2] (2.8 [mu]M) replaced the NE. In both experiments, the amounts of LHRH released was measured by RIA. In experiment 3, NE was again used for the challenge; however, this time, the amount of PGE[sub 2] released was measured by RIA. Results indicate that Pb did not alter basal LHRH release, but compared with controls, significantly blocked NE-induced LHRH release in a dose-related manner. Conversely, Pb had no effect on the PGE[sub 2]-induced release of LHRH. Additionally, Pb did not alter basal PGE[sub 2] release; however, it significantly blocked the NE-induced release of PGE[sub 2]. Since NE-induced LHRH release is mediated by PGE[sub 2], these results support the hypothesis that Pb is capable of altering the hypothalamus and suggest that this effect is due, at least in part, to the diminished PGE[sub 2] synthesis/release within the ME, resulting in diminished LHRH secretion.

  13. LH (Luteinizing Hormone) Test

    MedlinePlus

    ... LH and FSH may be ordered when a boy or girl does not appear to be entering puberty at ... pubic hair Growth of testicles and penis in boys Beginning of menstruation in girls ^ Back to top What does the test result ...

  14. Non-steroidal antiandrogen monotherapy compared with luteinizing hormone-releasing hormone agonists or surgical castration monotherapy for advanced prostate cancer: a Cochrane systematic review.

    PubMed

    Kunath, Frank; Grobe, Henrik R; Rücker, Gerta; Motschall, Edith; Antes, Gerd; Dahm, Philipp; Wullich, Bernd; Meerpohl, Joerg J

    2015-07-01

    To assess the effects of non-steroidal antiandrogen monotherapy compared with luteinizing hormone-releasing hormone agonists or surgical castration monotherapy for treating advanced hormone-sensitive stages of prostate cancer. We searched the Cochrane Prostatic Diseases and Urologic Cancers Group Specialized Register (PROSTATE), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Web of Science with Conference Proceedings, three trial registries and abstracts from three major conferences to 23 December 2013, together with reference lists, and contacted selected experts in the field and manufacturers. We included randomized controlled trials comparing non-steroidal antiandrogen monotherapy with medical or surgical castration monotherapy for men in advanced hormone-sensitive stages of prostate cancer. Two review authors independently examined full-text reports, identified relevant studies, assessed the eligibility of studies for inclusion, extracted data and assessed risk of bias as well as quality of evidence according to the GRADE working group guidelines. We used Review Manager 5.2 for data synthesis and the fixed-effect model as primary analysis (when heterogeneity was low with I(2) < 50%); we used a random-effects model when confronted with substantial or considerable heterogeneity (when I(2) ≥50%). A total of 11 studies involving 3060 randomly assigned participants were included in the present review. Use of non-steroidal antiandrogens resulted in lower overall survival times (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.05-1.48, six studies, 2712 participants) and greater clinical progression (1 year: risk ratio [RR] 1.25, 95% CI 1.08-1.45, five studies, 2067 participants; 70 weeks: RR 1.26, 95% CI 1.08-1.45, six studies, 2373 participants; 2 years: RR 1.14, 95% CI 1.04-1.25, three studies, 1336 participants), as well as treatment failure (1 year: RR 1.19, 95% CI 1.02-1.38, four studies, 1539 participants; 70 weeks: RR 1

  15. Sexual maturation, serum steroid concentrations, and mRNA expression of IGF-1, luteinizing and progesterone hormone receptors and survivin gene in Japanese quail hens.

    PubMed

    Shit, N; Sastry, K V H; Singh, R P; Pandey, N K; Mohan, J

    2014-03-15

    In avian species, sexual maturation represents the evidence of start laying, which is a consequence of the development of ovarian follicles. These follicles are the functional reproductive unit whose maturation and viability critically depends on endocrine, paracrine, and autocrine factors beyond the signals from the central nervous system. The present study was undertaken to investigate the correlation of sexual maturity with tissue growth, mRNA expression of certain genes, and serum steroid concentrations in Japanese quail hens. To carry out the present study, a total of forty Japanese quail hens (5 weeks) were housed individually under uniform husbandry condition with ad libitum quail layer ration and water at 14-hour photo schedule. On sixth week onwards, four birds were sacrificed at each time on 1, 3, 7, 10, 13, 16, 19, 22, 25, and 28 days. Serum was extracted aseptically to analyze the gonadal steroid hormones (estrogen and progesterone) and corticosterone to investigate the liaison with sexual maturation of the species. Expression analyses of four genes i.e., insulin-like growth factor-1, luteinizing hormone receptor, progesterone receptor, and survivin were carried out in the three largest ovarian yellow follicles. A significant (P < 0.05) increase in body weight gain and oviduct weight was recorded during the phase of sexual maturation. Smaller follicles revealed higher insulin-like growth factor-1 and survivin gene expression, whereas the reverse result was manifested in both the luteinizing and progesterone hormone receptors. In biochemical study, the gonadal steroids (estrogen and progesterone) were recorded higher at the first half of the experiment when a gradual decrease in corticosterone concentration was confirmed from the very beginning of this study. This result substantiated that sexual maturation in Japanese quail may be completed by the time of 8 weeks after its birth in support of the analyzed information studied in the current investigation

  16. The Luteinizing Hormone-Testosterone Pathway Regulates Mouse Spermatogonial Stem Cell Self-Renewal by Suppressing WNT5A Expression in Sertoli Cells.

    PubMed

    Tanaka, Takashi; Kanatsu-Shinohara, Mito; Lei, Zhenmin; Rao, C V; Shinohara, Takashi

    2016-08-01

    Spermatogenesis originates from self-renewal of spermatogonial stem cells (SSCs). Previous studies have reported conflicting roles of gonadotropic pituitary hormones in SSC self-renewal. Here, we explored the role of hormonal regulation of SSCs using Fshb and Lhcgr knockout (KO) mice. Although follicle-stimulating hormone (FSH) is thought to promote self-renewal by glial cell line-derived neurotrophic factor (GDNF), no abnormalities were found in SSCs and their microenvironment. In contrast, SSCs were enriched in Lhcgr-deficient mice. Moreover, wild-type SSCs transplanted into Lhcgr-deficient mice showed enhanced self-renewal. Microarray analysis revealed that Lhcgr-deficient testes have enhanced WNT5A expression in Sertoli cells, which showed an immature phenotype. Since WNT5A was upregulated by anti-androgen treatment, testosterone produced by luteinizing hormone (LH) is required for Sertoli cell maturation. WNT5A promoted SSC activity both in vitro and in vivo. Therefore, FSH is not responsible for GDNF regulation, while LH negatively regulates SSC self-renewal by suppressing WNT5A via testosterone. PMID:27509137

  17. MAPK3/1 is conducive to luteinizing hormone-mediated C-type natriuretic peptide decrease in bovine granulosa cells

    PubMed Central

    YANG, Lei; WEI, Qiang; GE, Junbang; ZHAO, Xiaoe; MA, Baohua

    2015-01-01

    C-type natriuretic peptide (CNP) plays a role as an oocyte maturation inhibitor (OMI) in many species, including the bovine. However, the effects of luteinizing hormone (LH) on CNP expression and its potential mechanisms have not reported in the bovine. In the present study, we aimed to study the effects of LH on CNP expression and to illuminate the potential molecular mechanism in this process. Our results showed that LH induced epidermal growth factor receptor (EGFR) phosphorylation, mitogen-activated protein kinase3/1 (MAPK3/1) activation and CNP mRNA decrease in cultured bovine granulosa cells. Further study revealed that LH suppressed CNP expression via the MAPK3/1 signaling pathway, which was activated by the EGFR pathway. In conclusion, our research suggested that MAPK3/1 is involved in LH-mediated decrease of CNP and that this process is related to the EGFR and MAPK3/1 signal pathways. PMID:26655567

  18. Effect of different seasons on concentration of plasma luteinizing hormone and seminal quality vis-à-vis freezability of buffalo bulls ( Bubalus bubalis)

    NASA Astrophysics Data System (ADS)

    Bahga, C. S.; Khokar, B. S.

    1991-12-01

    Seasonal variations in semen quality, freezability and plasma luteinizing hormone (LH) levels were studied between summer and spring. Semen volume, density and initial sperm motility did not differ significantly between different seasons. Plasma LH decreased between summer and spring but the differences were, however, not significant. Pre-freezing motility did not differ significantly but post-freezing motility varied significantly ( P<0.01) between seasons. Post-freezing motility was lowest during summer and highest during winter. It can be concluded that summer spermatozoa may be fragile and cannot withstand freezing stress. To increase reproductive efficiency in buffalo during summer, semen should be frozen during winter and spring and used during hot weather conditions. Seasonal variations in plasma LH levels were insignificant.

  19. Luteinizing hormone and follicle-stimulating hormone receptors and their transcribed genes (mRNA) are present in the lower urinary tract of intact male and female dogs.

    PubMed

    Ponglowhapan, S; Church, D B; Scaramuzzi, R J; Khalid, M

    2007-01-15

    In dogs, one of the side effects of neutering is the development of urinary incontinence. The relationship between neutering and urinary incontinence caused by acquired urethral sphincter mechanism incompetence (USMI) has been reported. Recently, GnRH analogue treatment that suppresses elevated plasma gonadotrophin concentrations post-spaying has been successfully used in incontinent bitches. These data and the fact that non-gonadal tissues may contain receptors for LH (LHR) and FSH (FSHR) suggest that there might be a functional relationship between gonadotrophins and the lower urinary tract in dogs. This study aimed to investigate the presence of LHR and FSHR in the lower urinary tract of intact male and female dogs. Four regions of the lower urinary tract, i.e. (i) body of the bladder, (ii) neck of the bladder, (iii) proximal urethra and (iv) distal urethra were collected from 10 healthy dogs (5 males and 5 anoestrous females). In situ hybridization and immunohistochemistry were performed to characterise the presence of receptor mRNA and receptor protein. Staining was rated semi-quantitatively, incorporating both the distribution and intensity of specific staining. The distribution of receptor expression in different tissue layers (epithelium, subepithelial stroma and muscle) in each region was statistically analyzed. Luteinizing hormone receptor and FSHR mRNA and protein were present in all four regions and in three tissue layers of males and females. Irrespective of region and layer, female dogs expressed significantly higher expression for LHR mRNA (P<0.001), LHR protein (P<0.05) and FSHR protein (P<0.001). The expression of LHR and FSHR mRNA and protein was not uniform and depended on region, tissue layer and gender. The expression of LHR mRNA was higher in the bladder, compared to the urethra (P<0.05). The FSHR mRNA significantly increased from the bladder to the urethra. Protein expression for LHR and FSHR was highest in the proximal urethra (P<0.05). The

  20. Carboxymethylation of methionine residues in bovine pituitary luteinizing hormone and its subunits. Effects on the binding activity with receptor sites and interactions between subunits.

    PubMed Central

    Cheng, K W

    1976-01-01

    The reaction of iodoacetic acid with bovine lutropin (luteinizing hormone) at pH 3.0 was specific for methionine residues; it was slow and reached its equilibrium after 12 h at 37 degrees C. The number of modified methionine residues increased proportionately with the amount of the alkylating reagent in the reaction mixture. In the presence of a 20-fold molar excess of iodoacetic acid with respect to methionine, essentially all methionine residues in both subunits of bovine lutropin were carboxymethylated. Studies of various recombinations of modified and native alpha and beta subunits showed that methionine residues in bovine lutropin were not essential for interactions between subunits. Various recombinants were characterized by polyacrylamide-gel electrophoresis and gel filtration of Sephadex G-100. Immunological cross-reactivity by radioimmunoassay of the recombinants of modified alpha and beta subunits was relatively similar to that of the native subunits. However, the biological activity measured by receptor-site binding of the recombinants of alpha and beta chains with a total of three alkylated methionine residues was less than 5% of the activity of native lutropin. It is noteworthy that recombinants of a modified subunit and a native counterpart subunit regenerated 20-30 % of biological activity. These findings suggested that at least 1-2 methionine residues in each subunit are involved in the hormone-receptor interaction for bovine lutropin. Images PLATE 1 PMID:187169

  1. Ontogeny of gene expression in the hypothalamic-pitutitary axis and luteinizing hormone secretion during pubertal development in the gilt

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The occurrence of puberty in the female is due to the interplay of central and peripheral mechanisms in which the hypothalamic-pituitary-ovarian axis regulates growth, gonadal function, as well as, adipocyte hormone secretion. Hypothalamic GnRH mRNA expression did not change. Concomitant with the ag...

  2. Effect of a calcium channel blocker on pituitary luteinizing hormone secretion in intact and castrated male and female rats

    SciTech Connect

    Babichev, V.N.; Sidneva, L.N.; Ozol', L.Yu.

    1987-08-01

    The authors study the effect of a calcium channel blocker on leuteinizing hormone (LH) secretion through experiments on rats. LH was determined by radioimmunoassay in two or three parallel tests and in two dilutions. The effect of verapamil on the LH level in rat blood serum and the pituitary gland is shown.

  3. Luteinizing hormone induces ovulation via tumor necrosis factor α-dependent increases in prostaglandin F2α in a nonmammalian vertebrate

    PubMed Central

    Crespo, Diego; Goetz, Frederick W.; Planas, Josep V.

    2015-01-01

    Ovulation is induced by the preovulatory surge of luteinizing hormone (LH) that acts on the ovary and triggers the rupture of the preovulatory ovarian follicle by stimulating proteolysis and apoptosis in the follicle wall, causing the release of the mature oocyte. The pro-inflammatory cytokine tumor necrosis factor α (TNFα) and prostaglandin (PG) F2α (PGF2α) are involved in the control of ovulation but their role mediating the pro-ovulatory actions of LH is not well established. Here we show that Lh induces PGF2α synthesis through its stimulation of Tnfα production in trout, a primitive teleost fish. Recombinant trout Tnfα (rTnfα) and PGF2α recapitulate the stimulatory in vitro effects of salmon Lh (sLh) on contraction, proteolysis and loss of cell viability in the preovulatory follicle wall and, finally, ovulation. Furthermore, all pro-ovulatory actions of sLh are blocked by inhibition of Tnfα secretion or PG synthesis and all actions of rTnfα are blocked by PG synthesis inhibitors. Therefore, we provide evidence that the Tnfα–dependent increase in PGF2α production is necessary for the pro-ovulatory actions of Lh. The results from this study shed light onto the mechanisms underlying the pro-ovulatory actions of LH in vertebrates and may prove important in clinical assessments of female infertility. PMID:26374476

  4. The effects of luteinizing hormone ablation/replacement versus steroid ablation/replacement on gene expression in the primate corpus luteum

    PubMed Central

    Bishop, Cecily V.; Hennebold, Jon D.; Stouffer, Richard L.

    2009-01-01

    This study was designed to provide a genome-wide analysis of the effects of luteinizing hormone (LH) versus steroid ablation/replacement on gene expression in the developed corpus luteum (CL) in primates during the menstrual cycle. On Days 9–11 of the luteal phase, female rhesus monkeys were left untreated (control) or received a GnRH antagonist Antide (A), A + LH, A + LH + the 3β-hydroxysteroid dehydrogenase inhibitor Trilostane (TRL) or A + LH + TRL + a progestin R5020. On Day 12 of the luteal phase, CL were removed and samples of RNA from individual CL were hybridized to Affymetrix™ rhesus macaque total genome microarrays. The greatest number of altered transcripts was associated with the ablation/replacement of LH, while steroid ablation/progestin replacement affected fewer transcripts. Replacement of LH during Antide treatment restored the expression of most transcripts to control levels. Validation of a subset of transcripts revealed that the expression patterns were similar between microarray and real-time PCR. Analyses of protein levels were subsequently determined for two transcripts. This is the first genome-wide analysis of LH and steroid regulation of gene transcription in the developed primate CL. Further analysis of novel transcripts identified in this data set can clarify the relative role for LH and steroids in CL maintenance and luteolysis. PMID:19168862

  5. /sup 125/I-luteinizing hormone (LH) binding to soluble receptors from the primate (Macaca mulatta) corpus luteum: effects of ethanol exposure

    SciTech Connect

    Danforth, D.R.; Stouffer, R.L.

    1988-01-01

    In the current study, we compared the effects of ethanol on gonadotropin receptors solubilized from macaque luteal membranes to those on receptors associated with the lipid bilayer. Treatment with 1% Triton X-100 for 30 min at 4C, followed by precipitation with polyethylene glycol, resulted in recovery of 50% more binding sites for /sup 125/I-human luteinizing hormone (hLH) than were available in particulate preparations. However, the soluble receptors displayed a 3-fold lower affinity for /sup 125/I-hLH. Conditions which enhanced LH binding to particulates, i.e., 1-8% ethanol at 25C, decreased specific /sup 125/I-hLH binding to soluble receptors. Steady-state LH binding to soluble receptors during incubation at 4C was half of that observed at 25C. The presence of 8% ethanol at 4C restored LH binding to levels observed in the absence of ethanol at 25C. Thus, LH binding sites in the primate corpus luteum can be effectively solubilized with Triton X-100. The different binding characteristics of particulate and soluble receptors, including the response to ethanol exposure, suggest that the lipid environment in the luteal membrane modulates the availability and affinity of gonadotropin receptors.

  6. Luteinizing hormone causes MAP kinase-dependent phosphorylation and closure of connexin 43 gap junctions in mouse ovarian follicles: one of two paths to meiotic resumption

    PubMed Central

    Norris, Rachael P.; Freudzon, Marina; Mehlmann, Lisa M.; Cowan, Ann E.; Simon, Alexander M.; Paul, David L.; Lampe, Paul D.; Jaffe, Laurinda A.

    2008-01-01

    SUMMARY Luteinizing hormone (LH) acts on ovarian follicles to reinitiate meiosis in prophase-arrested mammalian oocytes, and this has been proposed to occur by interruption of a meioisis-inhibitory signal that is transmitted through gap junctions into the oocyte from the somatic cells that surround it. To investigate this idea, we microinjected fluorescent tracers into live antral follicle-enclosed mouse oocytes, and demonstrate for the first time that LH causes a decrease in the gap junction permeability between the somatic cells, prior to nuclear envelope breakdown (NEBD). The decreased permeability results from MAP kinase-dependent phosphorylation of connexin 43 on serines 255, 262, and 279/282. We then tested whether inhibition of gap junction communication is sufficient and necessary for the reinitiation of meiosis. Inhibitors that reduced gap junction permeability caused NEBD, but an inhibitor of MAP kinase activation that blocked gap junction closure in response to LH did not prevent NEBD. Thus both MAP kinase-dependent gap junction closure and another redundant pathway function in parallel to ensure that meiosis resumes in response to LH. PMID:18776144

  7. Evidence for a daily rhythmicity in the acute release of luteinizing hormone in response to electrical stimulation in the Japanese quail.

    PubMed

    Konishi, H; Foster, R G; Follett, B K

    1987-08-01

    This study was undertaken to examine the effect of electrical stimulation of the hypothalamus at different times of day on luteinizing hormone (LH) secretion in male castrated quail on short days (8L:16D). The posterior hypothalamus was stimulated with square-wave pulses of 80 microA for 2 min through chronically-implanted platinum microelectrodes. Stimulation was carried out on each quail at 4 (treatment A), 10 (B), or 14 h (C) after dawn. Plasma LH levels were increased markedly within 2 min of ending the stimulation but reached basal levels again over the next 20 min or so. The absolute increase was significantly greater in treatment B (10 h after lights on) than at the other times tested. This is consistent with a rhythm in hypothalamic responsivity. The results are discussed in the context of the rhythm of photoinducibility which occurs early in the night and which is used by quail as a photoperiodic clock to regulate seasonal reproduction. PMID:3625579

  8. Luteinizing Hormone Reduces the Activity of the NPR2 Guanylyl Cyclase in Mouse Ovarian Follicles, Contributing to the Cyclic GMP Decrease that Promotes Resumption of Meiosis in Oocytes

    PubMed Central

    Robinson, Jerid W.; Zhang, Meijia; Shuhaibar, Leia C.; Norris, Rachael P.; Geerts, Andreas; Wunder, Frank; Eppig, John J.; Potter, Lincoln R.; Jaffe, Laurinda A.

    2012-01-01

    In preovulatory ovarian follicles of mice, meiotic prophase arrest in the oocyte is maintained by cyclic GMP from the surrounding granulosa cells that diffuses into the oocyte through gap junctions. The cGMP is synthesized in the granulosa cells by the transmembrane guanylyl cyclase natriuretic peptide receptor 2 (NPR2) in response to the agonist C-type natriuretic peptide (CNP). In response to luteinizing hormone (LH), cGMP in the granulosa cells decreases, and as a consequence, oocyte cGMP decreases and meiosis resumes. Here we report that within 20 minutes, LH treatment results in decreased guanylyl cyclase activity of NPR2, as determined in the presence of a maximally activating concentration of CNP. This occurs by a process that does not reduce the amount of NPR2 protein. We also show that by a slower process, first detected at 2 hours, LH decreases the amount of CNP available to bind to the receptor. Both of these LH actions contribute to decreasing cGMP in the follicle, thus signaling meiotic resumption in the oocyte. PMID:22546688

  9. The expression of the urinary forms of human luteinizing hormone beta fragment in various populations as assessed by a specific immunoradiometric assay.

    PubMed

    O'Connor, J F; Kovalevskaya, G; Birken, S; Schlatterer, J P; Schechter, D; McMahon, D J; Canfield, R E

    1998-04-01

    Human gonadotrophins undergo metabolic transformations which result in the presence of several smaller, structurally and immunologically related forms of gonadotrophins in the urine. For luteinizing hormone (LH), a beta core fragment (LHbeta cf) has been isolated from the pituitary and characterized. The corresponding urinary fragment is inferred from mass spectral and immunochemical analysis of chromatographically separated urinary forms. Physicochemical characteristics, primarily mass spectral and chromatographic, indicate that the pituitary and urinary forms of LHbeta cf have a different structure, probably in the carbohydrate moieties. This communication characterizes the expression of LHbeta cf in the urine of both reproductive and post-reproductive age women and in men, employing assays highly specific for the pituitary form of the fragment. It was found that LHbeta cf is the predominant LH associated molecular form in the urine during peri-ovulatory period, peaking 1-3 days later than intact LH and reaching a concentration of approximately 600 fmol/mg creatinine, 7-fold higher than either LH or LH free beta subunit. Corresponding concentrations of human chorionic gonadotrophin (HCG) beta cf were <1% that of LHbeta cf. LHbeta cf cross-reaction with some LH or LHbeta monoclonal antibodies may well interfere with the accurate estimation of the day of the LH surge when urinary tests are utilized. PMID:9619532

  10. Antibodies against the beta-subunit of ovine luteinizing hormone can decrease the clearance of human chorionic gonadotropin in rhesus monkeys.

    PubMed

    Yamamoto, Y; Gunsalus, G L; Sundaram, K; Thau, R B

    1984-06-01

    Contraceptive vaccines based on active immunization against gonadotropic hormones are being investigated in humans and other primates. Immunization against the beta-subunit of ovine luteinizing hormone (oLH beta) reduces fertility in rhesus monkeys by inducing inadequate luteal phases and preventing corpus luteum rescue by rhesus chorionic gonadotropin (rhCG). These effects result from the cross-reactions of the oLH beta-antibodies with rhCG and rhLH. We used human CG (hCG), which also cross-reacts strongly with anti-oLH beta to examine how the circulating oLH beta-antibodies affect the metabolic clearance rates (MCR) of hCG in rhesus monkeys. 125I-hCG was injected into four nonimmunized and seven immunized monkeys and blood was collected at frequent intervals over 7 days. Total and immunoprecipitable radioactivity did not differ significantly, suggesting that the radioactivity in the plasma consisted almost entirely of 125I-hCG. This was confirmed by column chromatography. The MCR (mean +/- SE) was significantly lower (p less than 0.001) in six immunized monkeys (0.35 +/- 0.06 liters/day) as compared to controls (1.19 +/- 0.09 liters/day). The hCG disappearance curve in control monkeys was best described by a two-compartmental system (slow and fast) while an additional third (intermediate) compartment of distribution was typical for immunized animals. The half-lives of hCG for the two exponentials corresponding to the slow and fast components of distribution were not significantly different between the two groups. One immunized monkey had a MCR (1.44 liters/day) that was much greater than the MCR of the other six.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6507705

  11. Studies on the metabolic clearance rate and production rate of human luteinizing hormone and on the initial half-time of its subunits in man.

    PubMed Central

    Pepperell, R J; Kretser, D M; Burger, H G

    1975-01-01

    The metabolic clearance rate (MCR) of human luteinizing hormone (hLH) has been determined in 10 normal men, 3 normal women, and in 12 women with ovulatory disorders resulting in oligomenorrhea or amenorrhea. The MCR was determined by the constant infusion technique using either iodinated or unlabeled highly purified hLH, and these results were compared to MCR determined by using crude pituitary preparations containing both follicle-stimulating hormone and hLH. Both preparations produced essentially similar results for the MCR of hLH and virtually identical results were obtained when complete or incomplete immunoprecipitation of the infused material was achieved. The MCR/body surface area of hLH was significantly greater in normal men (25.6 plus or minus 3.6 ml/min-m-2) than in normal premenopausal (19.2 plus or minus 0.9 ml/min-m-2) or postmenopausal women (17.4 plus or minus 1.9 ml/min-m-2). No difference was noted in the MCR of hLH in women with oligomenorrhea or amenorrhea. Production rates (PRs) were calculated by using a pituitary standard, the values being 85.1 plus or minus 21.5 IU/24 h in normal men, 39.9 plus or minus 12.6 IU/24 h in normal premenopausal women, and 294.6 plus or minus 61.9 IU/24 h in normal postmenopausal women. The initial half-times of disappearance of the alpha- and beta-subunits of hLH were measured in two normal men and found to be 15-18 min, respectively. The half-time of intact hLH was twice as great. PMID:1170215

  12. Editing of the Luteinizing Hormone Gene to Sterilize Channel Catfish, Ictalurus punctatus, Using a Modified Zinc Finger Nuclease Technology with Electroporation.

    PubMed

    Qin, Zhenkui; Li, Yun; Su, Baofeng; Cheng, Qi; Ye, Zhi; Perera, Dayan A; Fobes, Michael; Shang, Mei; Dunham, Rex A

    2016-04-01

    Channel catfish (Ictalurus punctatus) is the most important freshwater aquaculture species in the USA. Genetically enhanced fish that are sterile could both profit the catfish industry and reduce potential environmental and ecological risks. As the first step to generate sterile channel catfish, three sets of zinc finger nuclease (ZFN) plasmids targeting the luteinizing hormone (LH) gene were designed and electroporated into one-cell embryos, different concentrations were introduced, and the Cel-I assay was conducted to detect mutations. Channel catfish carrying the mutated LH gene were sterile, as confirmed by DNA sequencing and mating experiments. The overall mutation rate was 19.7 % for 66 channel catfish, and the best treatment was ZFN set 1 at the concentration 25 μg/ml. To our knowledge, this is the first instance of gene editing of fish via plasmid introduction instead of mRNA microinjection. The introduction of the ZFN plasmids may have reduced mosaicism, as mutated individuals were gene edited in every tissue evaluated. Apparently, the plasmids were eventually degraded without integration, as they were not detectable in mutated individuals using PCR. Carp pituitary extract failed to induce spawning and restoration of fertility, indicating the need for developing other hormone therapies to achieve reversal of sterility upon demand. This is the first sterilization achieved using ZFN technology in an aquaculture species and the first successful gene editing of channel catfish. Our results will help understand the roles of the LH gene, purposeful sterilization of teleost fishes, and is a step towards control of domestic, hybrid, exotic, invasive, and transgenic fishes. PMID:26846523

  13. Plasma levels of follicle-stimulating and luteinizing hormones during the reproductive cycle of wild and cultured Senegalese sole (Solea senegalensis).

    PubMed

    Chauvigné, François; Fatsini, Elvira; Duncan, Neil; Ollé, Judith; Zanuy, Silvia; Gómez, Ana; Cerdà, Joan

    2016-01-01

    The intensive culture of the Senegalese sole (Solea senegalensis) is hampered by the low or null fertilization rates exhibited by the first generation (F1) of reared males. To investigate the regulation of the reproductive processes in this species by the pituitary gonadotropins follicle-stimulating and luteinizing hormones (Fsh and Lh, respectively), we developed a highly sensitive and specific enzyme-linked immunosorbent assay (ELISA) for Lh measurements. Quantification of the Fsh and Lh plasma levels in cultured sole using the Lh ELISA developed here, and a previously developed ELISA for Fsh, indicated that in both males and females circulating Fsh steadily increased during autumn and winter and prior to the major spawning in spring, whereas an Lh surge occurred specifically during spawning. The increase in Fsh was associated with a rise of plasma levels of the steroid hormones testosterone (T), 11-ketotestosterone (11-KT) and estradiol-17β (E2), but that of Lh was concomitant with a strong decline of the levels of E2 in females and of 11-KT in males, possibly reflecting a rapid steroidogenic shift promoting the final maturation of gametes. Comparison of the plasma levels of gonadotropins and steroids between wild and F1 fish during autumn and spring revealed that F1 males showed significantly lower plasma Lh titres compared to wild males, whereas the levels of T and 11-KT were similar or more elevated in the F1 fish. These data suggest that an impaired Lh secretion during spawning, and perhaps altered Lh-mediated mechanisms in the testis, may be underlying causes for the low reproductive performance of Senegalese sole F1 males. PMID:26419696

  14. 11β-hydroxysteroid dehydrogenase types 1 and 2 in postnatal development of rat testis: gene expression, localization and regulation by luteinizing hormone and androgens

    PubMed Central

    Zhou, Hong-Yu; Chen, Xin-Xin; Lin, Han; Fei, Ai-Li; Ge, Ren-Shan

    2014-01-01

    11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and type 2 (11β-HSD2) are expressed in rat testis, where they regulate the local concentrations of glucocorticoids. Here, we investigated the expression and localization of 11β-HSD in rat testis during postnatal development, and the regulation of these genes by luteinizing hormone (LH) and androgens. mRNA and protein levels were analyzed by quantitative real-time-polymerase chain reaction and western blotting, respectively, in testes collected from rats at postnatal day (PND) 7, 14, 21, 35, and 90, and from rats treated with LH, 7α-methyl-19-nortestosterone (MENT) and testosterone at PND 21 and PND 90. Immunohistochemical staining was used to identify the localization of the 11β-HSD in rat testis at PND 7, 14, and 90. We found that 11β-HSD1 expression was restricted to the interstitial areas, and that its levels increased during rat testis development. In contrast, whereas 11β-HSD2 was expressed in both the interstitial areas and seminiferous tubules at PND 7, it was present only in the interstitial areas at PND 90, and its levels declined during testicular development. Moreover, 11β-HSD1 mRNA was induced by LH in both the PND 21 and 90 testes and by MENT at PND 21, whereas 11β-HSD2 mRNA was induced by testosterone and MENT in the PND 21 testis and by LH in the PND 90 testis. In conclusion, our study indicates that the 11β-HSD1 and 11β-HSD2 genes have distinct patterns of spatiotemporal expression and hormonal regulation during postnatal development of the rat testis. PMID:25038180

  15. Hyposmolar stimulation of in vitro pituitary secretion of luteinizing hormone: a potential clue to the secretory process.

    PubMed

    Greer, M A; Greer, S E; Opsahl, Z; McCafferty, L; Maruta, S

    1983-10-01

    Diluting the perifusion medium with water caused a striking prompt increase in LH secretion from perifused, acutely dispersed adenohypophseal cells. The minimum effective proportion of water was 4%; the quantity of hormone secreted was proportional to the dilution of the medium up to greater than 50% water. Secretion was not induced if the dilution was made with 5% aqueous mannitol to maintain isotonicity. The LH secretory responses to hyposmolarity or to LHRH were qualitatively indistinguishable. We suggest that expansion of the outer cell membrane may be an important initial component of the mechanism of secretion from adenohypophyseal cells. PMID:6413197

  16. In vitro effect of. Delta. sup 9 -tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E sub 2

    SciTech Connect

    Rettori, V.; Aguila, M.C.; McCann, S.M. ); Gimeno, M.F.; Franchi, A.M. )

    1990-12-01

    Previous in vivo studies have shown that {Delta}{sup 9}-tetrahydrocannabinol (THC), the principal active ingredient in marijuana, can suppress both luteinizing hormone (LH) and growth hormone (GH) secretion after its injection into the third ventricle of conscious male rats. The present studies were deigned to determine the mechanism of these effects. Various doses of THC were incubated with either stalk median eminence fragments (MEs) or mediobasal hypothalamic (MBH) fragments in vitro. Although THC (10 nM) did not alter basal release of LH-releasing hormone (LHRH) from MEs in vitro, it completely blocked the stimulatory action of dopamine or nonrepinephrine on LHRH release. The effective doses to block LHRH release were associated with a blockade of synthesis and release of prostaglandin E{sub 2} (PGE{sub 2}) from MBH in vitro. In contrast to the suppressive effect of THC on LHRH release, somatostatin release from MEs was enhanced in a dose-related manner with a minimal effective dose of 1 nM. Since PGE{sub 2} suppresses somatostatin release, this enhancement may also be related to the suppressive effect of THC on PGE{sub 2} synthesis and release. The authors speculate that these actions are mediated by the recently discovered THC receptors in the tissue. The results indicate that the suppressive effect of THC on LH release is mediated by a blockade of LHRH release, whereas the suppressive effect of the compound on growth hormone release is mediated, at least in part, by a stimulation of somatostatin release.

  17. Occurrence of D-aspartic acid and N-methyl-D-aspartic acid in rat neuroendocrine tissues and their role in the modulation of luteinizing hormone and growth hormone release.

    PubMed

    D'Aniello, A; Di Fiore, M M; Fisher, G H; Milone, A; Seleni, A; D'Aniello, S; Perna, A F; Ingrosso, D

    2000-04-01

    Using two specific and sensitive fluorometric/HPLC methods and a GC-MS method, alone and in combination with D-aspartate oxidase, we have demonstrated for the first time that N-methyl-D-aspartate (NMDA), in addition to D-aspartate (D-Asp), is endogenously present as a natural molecule in rat nervous system and endocrine glands. Both of these amino acids are mostly concentrated at nmol/g levels in the adenohypophysis, hypothalamus, brain, and testis. The adenohypophysis maximally showed the ability to accumulate D-Asp when the latter is exogenously administered. In vivo experiments, consisting of the i.p. injection of D-Asp, showed that D-Asp induced both growth hormone and luteinizing hormone (LH) release. However, in vitro experiments showed that D-Asp was able to induce LH release from adenohypophysis only when this gland was co-incubated with the hypothalamus. This is because D-Asp also induces the release of GnRH from the hypothalamus, which in turn is directly responsible for the D-Asp-induced LH secretion from the pituitary gland. Compared to D-Asp, NMDA elicits its hormone release action at concentrations approximately 100-fold lower than D-Asp. D-AP5, a specific NMDA receptor antagonist, inhibited D-Asp and NMDA hormonal activity, demonstrating that these actions are mediated by NMDA receptors. NMDA is biosynthesized from D-Asp by an S-adenosylmethionine-dependent enzyme, which we tentatively denominated as NMDA synthase. PMID:10744627

  18. Infertility in Female Mice with a Gain-of-Function Mutation in the Luteinizing Hormone Receptor Is Due to Irregular Estrous Cyclicity, Anovulation, Hormonal Alterations, and Polycystic Ovaries1

    PubMed Central

    Hai, Lan; McGee, Stacey R.; Rabideau, Amanda C.; Paquet, Marilène; Narayan, Prema

    2015-01-01

    The luteinizing hormone receptor, LHCGR, is essential for fertility in males and females, and genetic mutations in the receptor have been identified that result in developmental and reproductive defects. We have previously generated and characterized a mouse model (KiLHRD582G) for familial male-limited precocious puberty caused by an activating mutation in the receptor. We demonstrated that the phenotype of the KiLHRD582G male mice is an accurate phenocopy of male patients with activating LHCGR mutations. In this study, we observed that unlike women with activating LHCGR mutations who are normal, female KiLHRD582G mice are infertile. Mice exhibit irregular estrous cyclicity, anovulation, and precocious puberty. A temporal study from 2–24 wk of age indicated elevated levels of progesterone, androstenedione, testosterone, and estradiol and upregulation of several steroidogenic enzyme genes. Ovaries of KiLHRD582G mice exhibited significant pathology with the development of large hemorrhagic cysts as early as 3 wk of age, extensive stromal cell hyperplasia and hypertrophy with luteinization, numerous atretic follicles, and granulosa cell tumors. Ovulation could not be rescued by the addition of exogenous gonadotropins. The body weights of the KiLHRD582G mice were higher than wild-type counterparts, but there was no increase in the body fat composition or metabolic abnormalities such as impaired glucose tolerance and insulin resistance. These studies demonstrate that activating LHCGR mutations do not produce the same phenotype in female mice as in humans and clearly illustrate species differences in the expression and regulation of LHCGR in the ovary, but not in the testis. PMID:26040673

  19. Relative effectiveness of carp pituitary extract, luteinizing hormone releasing hormone analog LHRHa injections and LHRHa implants for producing hybrid catfish fry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adoption of the hybrid catfish (channel catfish, Ictalruus punctatus, female x blue catfish, I. furcatus, male) is increasing in the catfish industry. The most effective way to produce fry is hormone induced spawning of females coupled with hand stripping and in vitro fertilization. The success of...

  20. Effects of Ghrelin on Sexual Behavior and Luteinizing Hormone Beta-subunit Gene Expression in Male Rats

    PubMed Central

    Babaei-Balderlou, Farrin; Khazali, Homayoun

    2016-01-01

    Background: The hormones of hypothalamo-pituitary-gonadal (HPG) axis have facilitative effects on reproductive behavior in mammals. Ghrelin as a starvation hormone has an inhibitory effect on HPG axis’ function. Hence, it is postulated that ghrelin may reduce the sexual behavior through inhibiting of HPG axis. The aim of this study was to examine the effects of ghrelin and its antagonist, [D-Lys3 ]-GHRP-6, on sexual behavior and LH beta-subunit gene expression in male rats. Methods: In this experimental study, 128 male Wistar rats were divided into two groups. Each group was further subdivided into eight subgroups (n=8 rats/subgroup) including the animals that received saline, ghrelin (2, 4 or 8 nmol), [D-Lys3 ]-GHRP-6 (5 or 10 nmol) or co-administration of ghrelin (4 nmol) and [D-Lys3 ]-GHRP-6 (5 or 10 nmol) through the stereotaxically implanted cannula into the third cerebral ventricle. The sexual behavior of male rats encountering with females and the hypo-physeal LH beta-subunit gene expression were evaluated at two different groups. Data were analyzed by ANOVA and p<0.05 was considered statistically significant. Results: Ghrelin injection (4 and 8 nmol) significantly (p<0.01) increased the latencies to the first mount, intromission and ejaculation as well as the post-ejaculatory interval. Also, 4 and 8 nmol ghrelin significantly (p<0.05) increased the number of mount and decreased the number of ejaculation. In co-administrated groups, [D-Lys3 ]-GHRP-6 antagonized the effects of ghrelin. Ghrelin injection (4 and 8 nmol) reduced the LH beta-subunit gene expression while pretreatment with [D-Lys3 ]-GHRP-6 improved the gene expression. Conclusion: Ghrelin decreased the sexual behavior and LH beta-subunit gene expression in male rats, whereas [D-Lys3 ]-GHRP-6 antagonizes these effects. PMID:27141463

  1. Primary and secondary structural determinants in the receptor binding sequence. beta. -(38-57) from human luteinizing hormone

    SciTech Connect

    Keutmann, H.T.; Charlesworth, M.C.; Kitzmann, K.; Mason, K.A.; Johnson, L.; Ryan, R.J.

    1988-12-13

    The intercysteine loop sequence 38-57 in the ..beta.. subunit has been shown to be a determinant for expression of biological activity in human lutropin (hLH) and choriogonadotropin (hCG). Together with other sequences, the 38-57 region may contribute to a multicomponent receptor binding domain in hLH/hCG. Because the structural features influencing activity in this important region are not easy to evaluate in the full-length subunit, the authors have used analogues of hLH..beta..-(38-57) prepared by solid-phase synthesis. The peptides were tested for inhibition of /sup 125/I-labeled hCG binding to rat ovarian membrane receptors. Secondary structure was analyzed by circular dichroism (CD) and by reactivity with antibodies to the native 38-57 peptide. An analogue lacking the 38-57 disulfide linkage retained 20% receptor binding and full immunoreactivity. Far-ultraviolet CD profiles were essentially identical with those of the disulfide-intact peptide; a transition from 10% to 30% ..cap alpha..-helix in 90% trifluoroethanol was characteristic of both. The peptide thus appears not to require the disulfide bridge to retain a looped conformation with amphipathic secondary structure. An essential positive charge at position 43 was shown by complete loss of activity upon substitution of Asp or Ala for the Arg found in all known species of LH. These results indicate that the 38-57 sequence is a relatively rigid and structurally autonomous region, not merely a series of residues constrained passively into a loop by a disulfide linkage. It includes segments of ordered structure, probably including both amphipathic helical and turn sequences. Evidence from studies of other hormones suggests that this region may be important to binding and specificity in the glycoprotein hormones as a group.

  2. PPARγ co-activator-1α co-activates steroidogenic factor 1 to stimulate the synthesis of luteinizing hormone and aldosterone.

    PubMed

    Zhu, Liuluan; Ke, Yaojun; Shao, Di; Cui, Ying; Qiao, Aijun; Liu, Xiaojun; Fang, Fude; Chang, Yongsheng

    2010-12-15

    The orphan nuclear receptor SF-1 (steroidogenic factor 1) is highly expressed in the pituitary, gonad and adrenal glands and plays key roles at all levels of the hypothalamic-pituitary-steroidogenic tissue axis. In the present study, we show that PGC-1α [PPARγ (peroxisome-proliferator-activated receptor γ) co-activator 1α] interacts with and co-activates SF-1 to induce LHβ (luteinizing hormone β) and αGSU (α-glycoprotein subunit) gene expression, subsequently leading to the increased secretion of LH in pituitary gonadotrope-derived αT3-1 cells. PGC-1α co-activation of LHβ expression requires an SF-1-binding element [GSE (gonadotrope-specific element)] mapped to the promoter region of LHβ. Mammalian two-hybrid and co-immunoprecipitation assays, as well as GST (glutathione transferase) pull-down experiments demonstrated that PGC-1α interacts with SF-1 in vivo and in vitro. Additionally, PGC-1α stimulates the expression of Cyp11b2 (aldosterone synthase gene), Cyp11b1 (steroid 11β-hydroxylase gene) and P450scc (cholesterol side-chain cleavage enzyme), and the synthesis of aldosterone in adrenal-cortex-derived Y-1 cells. Chromatin immunoprecipitation assays confirmed that endogenous PGC-1α co-localizes with SF-1 in the LHβ and Cyp11b2 promoter region. Knockdown of endogenous SF-1 by siRNA (small interfering RNA) abolished the PGC-1α induction of LHβ and Cyp11b2 gene expression in αT3-1 and Y-1 cells respectively. Finally, we demonstrated that PGC-1α induces SF-1 gene expression in both αT3-1 and Y-1 cells. Taken together, our findings reveal the potential role of PGC-1α and suggest that it may play important roles in steroidogenesis, gonad development and sex differentiation through SF-1. PMID:21108604

  3. Novel C617Y mutation in the 7th transmembrane segment of luteinizing hormone/choriogonadotropin receptor in a Japanese boy with peripheral precocious puberty.

    PubMed

    Nagasaki, Keisuke; Katsumata, Noriyuki; Ogawa, Yohei; Kikuchi, Toru; Uchiyama, Makoto

    2010-01-01

    Testotoxicosis, also known as familial male-limited precocious puberty, is an autosomal dominant form of gonadotropin-independent precocious puberty caused by heterozygous constitutively activating mutations of the LHCGR gene encoding the luteinizing hormone/choriogonadotropin receptor (LH/CGR). The patient is an 8-year-old boy who started to develop pubic hair and penile enlargement at 6 years of age. The patient had elevated serum testosterone levels, but initially exhibited a prepubertal response of gonadotropins to GnRH, which was followed by central activation of the hypothalamo-pituitary-gonadal axis. The father reported having experienced precocious puberty, and is 158 cm tall. There is no history of short stature and precocious puberty in the family except for the father. The LHCGR gene was analyzed by direct DNA sequencing of amplified PCR products from the patient and his parents. The wild-type and mutant LH/CGRs were transiently expressed in COS-1 cells and cAMP levels in the cells were determined with or without hCG stimulation. Genetic analysis revealed a novel C617Y mutation of the LHCGR gene in the patient and his mother, while his father had no mutations. Functional expression study demonstrated around 15% increase in the basal intracellular cAMP level in cells expressing the mutant LH/CGR compared with that in cells expressing the wild-type receptor. We have reported the first missense C617Y mutation located in the 7th transmembrane segment of LH/CGR causing testotoxicosis. The modest phenotype of our patient may be explained, at least in part, by the modest increase in the intracellular cAMP level caused by the C617Y mutation. PMID:21060208

  4. Effects of hypophysectomy and administration of pituitary hormones on luteal function and uptake of high density lipoproteins by luteinized ovaries and adrenals of the rat

    SciTech Connect

    Murphy, B.D.; Rajkumar, K.; McKibbin, P.E.; Macdonald, G.J.; Buhr, M.M.; Grinwich, D.L.

    1985-04-01

    The role of plasma lipoproteins and hypophyseal hormones in the maintenance of progesterone secretion by the rat corpus luteum was investigated. In the first experiment, rats were treated daily from days 1-6 of pregnancy with 5 mg/kg 4-aminopyrozolopyramidine (4APP), a blocker of hepatic lipoprotein secretion, or with 5 mg/kg 4APP and 1 or 2 mg ovine PRL or 0.1 ml 0.5% phosphoric acid (4APP vehicle). The administration of 4APP reduced serum cholesterol and progesterone levels on days 2-6 of pregnancy and ovarian progesterone on day 6. The reduced progesterone secretion had no effect on embryo implantation. PRL, in the doses used, was incapable of abrogating the effects of 4APP on circulating or ovarian progesterone levels. Ovaries and adrenals, but not kidneys, of pseudopregnant rats exhibited specific and saturable uptake of porcine high density lipoprotein (HDL). Time-course studies indicated that the uptake of HDL was rapid in ovaries compared to that in adrenals. Ovaries from rats not only exhibited uptake of porcine HDL, but also were capable of using it for progesterone synthesis. Treatment with 4APP increased the adrenal uptake of HDL, but ovarian uptake was not different from that in the control group. Hypophysectomy reduced both adrenal and ovarian uptake of HDL. In adrenals only ACTH at the dose employed ameliorated reduction of HDL uptake induced by hypophysectomy, while in the ovaries, both PRL and LH reversed the effect of hypophysectomy. The effect of PRL on uptake was specific to (/sup 125/I)HDL and did not alter (/sup 125/I)albumin uptake. It is concluded that: 1) hypophysectomy reduces HDL uptake in the luteinized rat ovary; and 2) PRL and LH replacement therapy maintain ovarian uptake of HDL, suggesting a direct effect of these luteotropins on lipoprotein uptake.

  5. Dephosphorylation of juxtamembrane serines and threonines of the NPR2 guanylyl cyclase is required for rapid resumption of oocyte meiosis in response to luteinizing hormone.

    PubMed

    Shuhaibar, Leia C; Egbert, Jeremy R; Edmund, Aaron B; Uliasz, Tracy F; Dickey, Deborah M; Yee, Siu-Pok; Potter, Lincoln R; Jaffe, Laurinda A

    2016-01-01

    The meiotic cell cycle of mammalian oocytes starts during embryogenesis and then pauses until luteinizing hormone (LH) acts on the granulosa cells of the follicle surrounding the oocyte to restart the cell cycle. An essential event in this process is a decrease in cyclic GMP in the granulosa cells, and part of the cGMP decrease results from dephosphorylation and inactivation of the natriuretic peptide receptor 2 (NPR2) guanylyl cyclase, also known as guanylyl cyclase B. However, it is unknown whether NPR2 dephosphorylation is essential for LH-induced meiotic resumption. Here, we prevented NPR2 dephosphorylation by generating a mouse line in which the seven regulatory serines and threonines of NPR2 were changed to the phosphomimetic amino acid glutamate (Npr2-7E). Npr2-7E/7E follicles failed to show a decrease in enzyme activity in response to LH, and the cGMP decrease was attenuated; correspondingly, LH-induced meiotic resumption was delayed. Meiotic resumption in response to EGF receptor activation was likewise delayed, indicating that NPR2 dephosphorylation is a component of the pathway by which EGF receptor activation mediates LH signaling. We also found that most of the NPR2 protein in the follicle was present in the mural granulosa cells. These findings indicate that NPR2 dephosphorylation in the mural granulosa cells is essential for the normal progression of meiosis in response to LH and EGF receptor activation. In addition, these studies provide the first demonstration that a change in phosphorylation of a transmembrane guanylyl cyclase regulates a physiological process, a mechanism that may also control other developmental events. PMID:26522847

  6. Concentrations of progesterone, a metabolite of PGF2α, prolactin, and luteinizing hormone during development of idiopathic persistent corpus luteum in mares.

    PubMed

    Ginther, O J; Baldrighi, J M; Castro, T; Wolf, C A; Santos, V G

    2016-04-01

    In experiment 1, daily blood samples were available from Days 0 to 20 (Day 0 = ovulation) in mares with an interovulatory interval (IOI, n = 5) and in mares that developed idiopathic persistent corpus luteum (PCL, n = 5). The PCL was confirmed by maintenance of progesterone (P4) concentration until end of the experiment (Day 20). Significant interactions of group and day revealed the novel findings that luteinizing hormone (LH) was lower (P < 0.05) in the PCL group than that in the IOI group on Days 0 to 4, and prolactin was lower (P < 0.05) on Days 1, 4, 6, and 7. In experiment 2, treatment with a gonadotropin-releasing hormone antagonist (n = 6) significantly reduced LH on Days 1 to 6 compared with the controls (n = 6) but did not support the hypothesis that low LH during the postovulatory period increases the frequency of PCL. In experiment 3, P4, PGFM (a PGF2α metabolite), and prolactin concentrations on Days 12 to 20 from 2 reported experiments were combined to increase the number of mares with an IOI (n = 11) or a PCL (n = 11). An abrupt and complete decrease in P4 (luteolysis) began on Day 13 in the IOI group compared with a gradual and partial P4 decline after Day 12 in the PCL group. Concentrations of PGFM and prolactin were lower (P < 0.05) in the PCL group than those in the IOI group on the day at the end of the most pronounced decrease in P4. The PCL mares were subgrouped into those with an abrupt but incomplete P4 decrease (partial luteolysis; n = 5) at the expected time and those without partial luteolysis (n = 6). There were no significant differences between the 2 subgroups in concentrations of PGFM and prolactin, but on a tentative basis (P < 0.10), the concentration of PGFM seemed more focused on the day of the most pronounced decrease in P4 in the subgroup with partial luteolysis. Results for PCL compared with IOI indicated (1) postovulatory LH and prolactin were lower, (2) treatment to reduce postovulatory LH did not increase the incidence

  7. Blunted Sleep-Related Luteinizing Hormone Rise in Healthy Premenarcheal Pubertal Girls with Elevated Body Mass Index

    PubMed Central

    Bordini, Brian; Littlejohn, Elizabeth; Rosenfield, Robert L.

    2009-01-01

    Objective: Our objective was to determine whether excessive adiposity is associated with alteration of the normal hormonal changes of early pubertal girls. Design and Participants: Healthy 6.4- to 9.5-yr-old, prepubertal (PRE, n = 20) and 9.4- to 13.0-yr-old pubertal premenarcheal volunteers (PUB, n = 20) were divided into excessive-weight (EW) or normal-weight (NW) groups according to the 85th percentile body mass index. Interventions and Setting: Overnight blood sampling; GnRH agonist (GnRHag), low-dose ACTH, oral glucose tolerance tests, and pelvic ultrasonograms were performed in our Clinical Research Center. Results: EW girls were similar in age and baseline and ACTH- and GnRHag-stimulated androgen levels to stage-matched NW girls. However, the sleep-related LH rise was blunted in EW-PUB girls compared with NW-PUB girls. The sleep-related rise of mean LH in EW-PUB [0.68 ± 0.35 (sem) U/liter] was insignificant, less than that of NW-PUB (2.1 ± 0.45, P < 0.05) and not significantly different from that of PRE girls (0.08±0.03). EW-PUB had slower LH pulse frequency and a lower rise in LH pulse amplitude during sleep than NW-PUB girls (both P < 0.05). Overnight FSH patterns paralleled LH patterns, whereas estradiol levels were similar in stage-matched NW and EW groups, differing between stages as expected. Early morning and peak LH, FSH, and estradiol responses to GnRHag were similar in EW-PUB and NW-PUB and significantly greater than those of PRE girls. Conclusions: Healthy EW-PUB girls have significantly blunted sleep-related LH production. These data suggest that excess adiposity, in the absence of sex steroid excess, may subtly suppress hypothalamic-pituitary-gonadal function in premenarcheal pubertal girls. PMID:19190110

  8. Serum copper, follicular stimulating hormone, luteinizing hormone, prolactin, spermatic count, viability, progression and seminal zinc correlations in a human (male) infertility study

    SciTech Connect

    Sella, G.E.; Cunnane, S.C.; McInnes, R.A.

    1981-06-01

    The role of copper and its correlations to other parameters has been investigated in a male-fertility pilot study at a University infertility clinic in Montreal. Serum and semen Cu concentrations were determined in 100 men (age 25 to 54 years) referred to the clinic for infertility evaluation. The results of the significant correlations between serum Cu concentrations and male fertility parameters such as (1) the serum concentrations of the hormones FSH, LH and prolactin; (2) spermatozoal count, viability and progression and (3) seminal zinc concentrations are reported.

  9. Stability of cytotoxic luteinizing hormone-releasing hormone conjugate (AN-152) containing doxorubicin 14-O-hemiglutarate in mouse and human serum in vitro: implications for the design of preclinical studies.

    PubMed

    Nagy, A; Plonowski, A; Schally, A V

    2000-01-18

    Recently, we developed a series of cytotoxic peptide conjugates containing 14-O-glutaryl esters of doxorubicin (DOX) or 2-pyrrolino-DOX (AN-201). Serum carboxylesterase enzymes (CE) can partially hydrolyze these conjugates in the circulation, releasing the cytotoxic radical, before the targeting is complete. CE activity in serum of nude mice is about 10 times higher than in human serum. Thus, we found that the t(1/2) of AN-152, an analog of luteinizing hormone-releasing hormone (LH-RH) containing DOX, at 0.3 mg/ml is 19. 49 +/- 0.74 min in mouse serum and 126.06 +/- 3.03 min in human serum in vitro. The addition of a CE inhibitor, diisopropyl fluorophosphate (DFP), to mouse serum in vitro significantly (P < 0. 01) prolongs the t(1/2) of AN-152 to 69.63 +/- 4.44 min. When DFP is used in vivo, 400 nmol/kg cytotoxic somatostatin analog AN-238 containing AN-201 is well tolerated by mice, whereas all animals die after the same dose without DFP. In contrast, DFP has no effect on the tolerance of AN-201. A better tolerance to AN-238 after DFP treatment is due to the selective uptake of AN-238 by somatostatin receptor-positive tissues. Our results demonstrate that the suppression of the CE activity in nude mice greatly decreases the toxicity of cytotoxic hybrids containing 2-pyrrolino-DOX 14-O-hemiglutarate and brings this animal model closer to the conditions that exist in humans. The use of DFP together with these peptide conjugates in nude mice permits a better understanding of their mechanism of action and improves the clinical predictability of the oncological and toxicological results. PMID:10639165

  10. Relationships between Serum Luteinizing Hormone Level, Endometrial Thickness and Body Mass Index in Polycystic Ovary Syndrome Patients with and without Endometrial Hyperplasia

    PubMed Central

    Ramezanali, Fariba; Khalili, Gholamreza; Arabipoor, Arezoo; Bagheri Lankarani, Narges; Moini, Ashraf

    2016-01-01

    Background The endometrial hyperplasia measured by ultrasound in polycystic ovary syndrome (PCOS) women is strongly related to pathologic endometrial thickness, but there is no consensus on the relation between serum luteinizing hormone (LH) and either of these factors: pathologic endometrial hyperplasia and body mass index (BMI). Materials and Methods In this observational cross-sectional study, three hundred fifty infertile PCOS women were involved in this research. An endometrial biopsy was taken by using a pipelle instrument, regardless of menstrual cycle’s day and all samples were reported by the same pathologist. Basal serum LH level was compared between two subgroups (hyperplasia and non-hyperplasia). The intended population was divided into three groups according to BMI and basal serum LH, later on the comparison was made in three groups. Chi-square test was applied to compare nominal variables between groups. Mann-Whitney U, and one way ANOVA tests were used to compare means on the basis of the result of normality test. Results The frequency of endometrial hyperplasia was 2.6%. Endometrial thickness in the patients with endometrial hyperplasia was significantly higher than that of a normal endometrium (10.78 ± 3.70 vs. 7.90 ± 2.86 respectively, P=0.020). There was no relation between endometrial hyperplasia and serum LH (P=0.600). The ANOVA test showed serum LH levels were not the same among three BMI groups (P=0.007). Post hoc test was also performed. It showed that the LH level in normal BMI group was significantly higher than those of other groups (P=0.005 and P=0.004), but there was no statistical difference between overweight and obese groups (P=0.8). We found no relationship between BMI and endometrial thickness in PCOS patients (P=0.6). Conclusion Sonographic endometrial stripe thickness is predictive for endometrial hyperplasia in PCOS women. We could not find out any relationship between serum LH level and BMI with endometrial thickness in

  11. Utrogestan as an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization.

    PubMed

    Zhu, Xiuxian; Zhang, Xiaole; Fu, Yonglun

    2015-05-01

    A major cause of cycle cancellation during controlled ovarian hyperstimulation (COH) in women undergoing in vitro fertilization (IVF) is the occurrence of premature luteinizing hormone (LH) surges. Steroidal preparations can modulate the secretion of gonadotropins (Gn); however, few studies using progesterone to inhibit the premature LH surges in COH have been published. The purpose of the study was to evaluate the oral delivery of progesterone soft capsules (Utrogestan) to prevent LH surges from the follicular phase and to compare cycle characteristics as well as to evaluate pregnancy outcomes in subsequent frozen-thawed embryo transfer (FET) cycles. A total of 374 patients were enrolled in this retrospective study, among which 187 patients were simultaneously administered Utrogestan and human menopausal gonadotrophin (hMG) from cycle day 3 until the trigger day. A short protocol including 187 controls with comparable age, body mass index (BMI), infertility duration, and antral follicle count was also used. GnRH agonist (0.1 mg) or hCG (3000 IU) was used for a trigger when the dominant follicles matured. Viable embryos were cryopreserved for later transfer in both groups. The primary outcome was the number of oocytes retrieved. The secondary outcomes included the number of mature oocytes, incidence of premature LH surge, and clinical pregnancy outcomes from FET cycles. Consistent LH suppression was achieved during COH, with a range of 0.07 to 8.9 IU/L, and no premature LH surge was detected. The number of oocytes retrieved in the Utrogestan and hMG protocol was comparable with that in the short protocol (10.92 ± 5.74 vs 10.6 ± 6.22, P > 0.05), and the dose of hMG was higher than that used in the short protocol (1884.22 ± 439.47 IU vs 1446.26 ± 550.48 IU, P < 0.05). No significant between-group difference was observed in the mature oocyte rate (88.88% vs 90.12%), cleavage rate (96.58% vs 96.58%), clinical pregnancy rate (54.27% vs

  12. Lutein and Brain Function

    PubMed Central

    Erdman, John W.; Smith, Joshua W.; Kuchan, Matthew J.; Mohn, Emily S.; Johnson, Elizabeth J.; Rubakhin, Stanislav S.; Wang, Lin; Sweedler, Jonathan V.; Neuringer, Martha

    2015-01-01

    Lutein is one of the most prevalent carotenoids in nature and in the human diet. Together with zeaxanthin, it is highly concentrated as macular pigment in the foveal retina of primates, attenuating blue light exposure, providing protection from photo-oxidation and enhancing visual performance. Recently, interest in lutein has expanded beyond the retina to its possible contributions to brain development and function. Only primates accumulate lutein within the brain, but little is known about its distribution or physiological role. Our team has begun to utilize the rhesus macaque (Macaca mulatta) model to study the uptake and bio-localization of lutein in the brain. Our overall goal has been to assess the association of lutein localization with brain function. In this review, we will first cover the evolution of the non-human primate model for lutein and brain studies, discuss prior association studies of lutein with retina and brain function, and review approaches that can be used to localize brain lutein. We also describe our approach to the biosynthesis of 13C-lutein, which will allow investigation of lutein flux, localization, metabolism and pharmacokinetics. Lastly, we describe potential future research opportunities. PMID:26566524

  13. Time dependent impact of perinatal hypoxia on growth hormone, insulin-like growth factor 1 and insulin-like growth factor binding protein-3.

    PubMed

    Kartal, Ömer; Aydınöz, Seçil; Kartal, Ayşe Tuğba; Kelestemur, Taha; Caglayan, Ahmet Burak; Beker, Mustafa Caglar; Karademir, Ferhan; Süleymanoğlu, Selami; Kul, Mustafa; Yulug, Burak; Kilic, Ertugrul

    2016-08-01

    Hypoxic-ischemia (HI) is a widely used animal model to mimic the preterm or perinatal sublethal hypoxia, including hypoxic-ischemic encephalopathy. It causes diffuse neurodegeneration in the brain and results in mental retardation, hyperactivity, cerebral palsy, epilepsy and neuroendocrine disturbances. Herein, we examined acute and subacute correlations between neuronal degeneration and serum growth factor changes, including growth hormone (GH), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) after hypoxic-ischemia (HI) in neonatal rats. In the acute phase of hypoxia, brain volume was increased significantly as compared with control animals, which was associated with reduced GH and IGF-1 secretions. Reduced neuronal survival and increased DNA fragmentation were also noticed in these animals. However, in the subacute phase of hypoxia, neuronal survival and brain volume were significantly decreased, accompanied by increased apoptotic cell death in the hippocampus and cortex. Serum GH, IGF-1, and IGFBP-3 levels were significantly reduced in the subacute phase of HI. Significant retardation in the brain and body development were noted in the subacute phase of hypoxia. Here, we provide evidence that serum levels of growth-hormone and factors were decreased in the acute and subacute phase of hypoxia, which was associated with increased DNA fragmentation and decreased neuronal survival. PMID:26943480

  14. Circannual changes in progesterone secretion in intact ewes, luteinizing hormone secretion in ovariectomized estradiol-implanted ewes, and prolactin secretion in three sheep breeds anticipated to differ in seasonality of reproduction.

    PubMed

    Goff, Katherine J; Knight, James W; Pelzer, Kevin D; Akers, R Michael; Notter, David R

    2013-05-01

    Changes in progesterone secretion in intact ewes (7 or 9 per breed) and luteinizing hormone secretion in ovariectomized, estradiol-implanted ewes (9 or 10 per breed) were monitored for 12 mo in Suffolk, tropically adapted St. Croix, and OOS ewes. The OOS line is a composite population of 50% Dorset, 25% Rambouillet, and 25% Finnish Landrace breeding that was selected for 10 yr for ability to lamb in October and early November. Ewes were isolated from rams, and blood samples were collected twice weekly. Circulating prolactin concentrations were also determined from blood samples collected near the summer and winter solstice and vernal and autumnal equinox. Intact OOS ewes entered anestrus later, began the subsequent breeding season sooner, and had a shorter seasonal anestrus than Suffolk and St. Croix ewes (P ≤ 0.005). St. Croix ewes did not differ from Suffolk ewes in date of onset or cessation of breeding or duration of anestrus (P ≥ 0.06). Breed differences in duration of luteinizing hormone inhibition in ovariectomized ewes were essentially identical to those observed for duration of anestrous. Prolactin concentrations varied during the year: annual changes were larger in relatively seasonal Suffolk ewes than in tropically-derived St. Croix ewes (P<0.01), and OOS ewes were intermediate to, and tended to differ from (P<0.10), the other two breeds. We conclude that OOS ewes developed by selection for fertility in spring matings had an abbreviated seasonal anestrus that is one of the shortest ever reported for temperate breeds, and that tropical St. Croix sheep did not have a shorter seasonal anestrus than Suffolk sheep under temperate conditions and ram isolation. PMID:23528712

  15. The non-steroidal mycoestrogen zeranol suppresses luteinizing hormone secretion from the anterior pituitary of cattle via the estradiol receptor GPR30 in a rapid, non-genomic manner.

    PubMed

    Nakamura, Urara; Rudolf, Faidiban O; Pandey, Kiran; Kadokawa, Hiroya

    2015-05-01

    Picomolar concentrations of estradiol produce rapid suppression of GnRH-induced luteinizing hormone (LH) secretion from the anterior pituitary (AP) of cattle via G-protein-coupled receptor 30 (GPR30). Zeranol is a strong estrogenic metabolite derived from zearalenone, a non-steroidal mycoestrogen produced by Fusarium that induces reproductive disorders in domestic animals. The hypothesis was tested that zeranol suppresses GnRH-induced LH release from the AP of cattle via GPR30 in a rapid, non-genomic manner. The AP cells (n=15) were cultured for 3 days in steroid-free conditions and then treated them with estradiol (0.001-10nM) or zeranol (0.001-100nM) for 5min before GnRH stimulation. Pre-treatment with 0.001-0.1nM estradiol suppressed GnRH-stimulated LH secretion. Pre-treatment with zeranol at concentrations of 0.001nM (P<0.01), 0.01nM (P<0.01), 0.1nM (P<0.05), and 1nM (P<0.05), but not at concentrations of 10 and 100nM, also inhibited GnRH-stimulated LH secretion from AP cells. Pre-treatment for 5min with a GPR30-specific antagonist, G36, inhibited estradiol or zeranol suppression of LH secretion from cultured AP cells. Cyclic AMP measurements and quantitative PCR analyses revealed that pre-treatment with small amounts of estradiol (P<0.05) or zeranol (P<0.01) decreased cAMP, but not gene expressions of the LHα, LHβ, or FSHβ subunits in the AP cells. Hence, zeranol may suppress luteinizing hormone secretion from the AP of cattle via GPR30 in a rapid, non-genomic manner. PMID:25824341

  16. Changes in brain mRNA levels of gonadotropin-releasing hormone, pituitary adenylate cyclase activating polypeptide, and somatostatin during ovulatory luteinizing hormone and growth hormone surges in goldfish.

    PubMed

    Canosa, Luis Fabián; Stacey, Norm; Peter, Richard Ector

    2008-12-01

    In goldfish, circulating LH and growth hormone (GH) levels surge at the time of ovulation. In the present study, changes in gene expression of salmon gonadotropin-releasing hormone (sGnRH), chicken GnRH-II (cGnRH-II), somatostatin (SS) and pituitary adenylate cyclase activating polypeptide (PACAP) were analyzed during temperature- and spawning substrate-induced ovulation in goldfish. The results demonstrated that increases in PACAP gene expression during ovulation are best correlated with the GH secretion profile. These results suggest that PACAP, instead of GnRH, is involved in the control of GH secretion during ovulation. Increases of two of the SS transcripts during ovulation are interpreted as the activation of a negative feedback mechanism triggered by high GH levels. The results showed a differential regulation of sGnRH and cGnRH-II gene expression during ovulation, suggesting that sGnRH controls LH secretion, whereas cGnRH-II correlates best with spawning behavior. This conclusion is further supported by the finding that nonovulated fish induced to perform spawning behavior by prostaglandin F2alpha treatment increased cGnRH-II expression in both forebrain and midbrain, but decreased sGnRH expression in the forebrain. PMID:18815210

  17. A high response to controlled ovarian stimulation induces premature luteinization with a negative impact on pregnancy outcomes in a gonadotropin-releasing hormone antagonist cycle

    PubMed Central

    Koo, Hwa Seon; Cha, Sun Hwa; Kim, Hye Ok; Song, In Ok; Min, Eung Gi; Yang, Kwang Moon

    2015-01-01

    Objective The goal of this study was to investigate the relationship between serum progesterone (P4) levels on the day of human chorionic gonadotropin (hCG) administration and the pregnancy rate among women undergoing controlled ovarian stimulation for in vitro fertilization (IVF) or intracytoplasmic sperm injection-embryo transfer (ICSI-ET) using a flexible antagonist protocol. Methods This prospective study included 200 IVF and ICSI-ET cycles in which a flexible antagonist protocol was used. The patients were divided into five distinct groups according to their serum P4 levels at the time of hCG administration (0.80, 0.85, 0.90, 0.95, and 1.00 ng/mL). The clinical pregnancy rate (CPR) was calculated for each P4 interval. Statistically significant differences were observed at a serum P4 level of 0.9 ng/mL. These data suggest that a serum P4 concentration of 0.9 ng/mL may represent the optimal threshold level for defining premature luteinization (PL) based on the presence of a significant negative impact on the CPR. Results The CPR for each round of ET was significantly lower in the PL group defined using this threshold (25.8% vs. 41.8%; p=0.019), and the number of oocytes retrieved was significantly higher than in the non-PL group (17.3±7.2 vs. 11.0±7.2; p=0.001). Elevated serum P4 levels on the day of hCG administration were associated with a reduced CPR, despite the retrieval of many oocytes. Conclusion Measuring serum P4 values at the time of hCG administration is necessary in order to determine the optimal strategy for embryo transfer. PMID:26816874

  18. Luteinizing Hormone Receptor-Stimulated Progesterone Production by Preovulatory Granulosa Cells Requires Protein Kinase A-Dependent Activation/Dephosphorylation of the Actin Dynamizing Protein Cofilin

    PubMed Central

    Karlsson, Amelia B.; Maizels, Evelyn T.; Flynn, Maxfield P.; Jones, Jonathan C.; Shelden, Eric A.; Bamburg, James R.; Hunzicker-Dunn, Mary

    2010-01-01

    Activation of the LH receptor (LHR) on preovulatory granulosa cells stimulates the cAMP/protein kinase A (PKA) pathway to regulate expression of genes required for ovulation and luteinization. LHR signaling also initiates rearrangement of the actin cytoskeleton. Because disruption of the actin cytoskeleton has been causally linked to steroidogenesis in various cell models, we sought to identify the cellular mechanisms that may modulate reorganization of the actin cytoskeleton and to determine whether cytoskeletal reorganization is required for steroidogenesis. Herein we report that LHR signaling in preovulatory granulosa cells promotes rapid dephosphorylation of the actin-depolymerizing factor cofilin at Ser3 that is dependent on PKA. The LHR-stimulated dephosphorylation of cofilin(Ser3) switches on cofilin activity to bind actin filaments and enhance their dynamics. Basal phosphorylation of cofilin(Ser3) is mediated by active/GTP-bound Rho and downstream protein kinases; LHR signaling promotes a decrease in active/GTP-bound Rho by a PKA-dependent mechanism. LHR-dependent Rho inactivation and subsequent activation of cofilin does not involve ERK, epidermal growth factor receptor, or phosphatidylinositol 3-kinase pathways downstream of PKA. To understand the biological significance of cofilin activation, preovulatory granulosa cells were transduced with a mutant cofilin adenoviral vector in which Ser3 was mutated to Glu (S-E cofilin). Inactive S-E cofilin abolished LHR-mediated reorganization of the actin cytoskeleton and caused a 70% decrease in LHR-stimulated progesterone that is obligatory for ovulation. Taken together, these results show that LHR signaling via PKA activates a cofilin-regulated rearrangement of the actin cytoskeleton and that active cofilin is required to initiate progesterone secretion by preovulatory granulosa cells. PMID:20610540

  19. MicroRNA miR-513a-3p acts as a co-regulator of luteinizing hormone/chorionic gonadotropin receptor gene expression in human granulosa cells.

    PubMed

    Troppmann, B; Kossack, N; Nordhoff, V; Schüring, A N; Gromoll, J

    2014-06-01

    The luteinizing hormone/chorionic gonadotropin receptor (LHCGR) is essential for normal male and female reproductive processes. The spatial and temporal LHCGR gene expression is controlled by a complex system of regulatory mechanisms which are crucial for normal physiological function, especially during the female cycle. In this study, we aimed to elucidate whether microRNAs are involved in this network and play a role in regulating LHCGR expression. Computational analysis predicted that miR-513a-3p interacts with the LHCGR mRNA via three binding sites located in the 3'UTR region, enabling a synergistic action. Moreover, using a luciferase-based reporter assay we found that miR-513a-3p targets the LHCGR, resulting in a significant down-regulation of its expression. In human primary granulosa cell cultures we detected a dynamic, inversely associated expression pattern of miR-513a-3p and the LHCGR. In addition, transfection with miR-513a-3p or its specific inhibitor led to a down- or up-regulation at the LHCGR mRNA level, respectively. An increased amount of miR-513a-3p resulted in the down-regulation of the LHCGR mRNA, reflected by the attenuation of cAMP synthesis after hormonal stimulation. In conclusion, these data demonstrate that miR-513a-3p is involved in the control of the LHCGR expression by an inversely regulated mechanism at the post-transcriptional level and show for the first time that this kind of post-transcriptional process contributes to the multifaceted system of the human LHCGR regulation. PMID:24747085

  20. Stability of lutein in wholegrain bakery products naturally high in lutein or fortified with free lutein.

    PubMed

    Abdel-Aal, El-Sayed M; Young, J Christopher; Akhtar, Humayoun; Rabalski, Iwona

    2010-09-22

    Lutein is a yellow pigment found in common foods that promotes the health of eyes and skin and is associated with reduced risk of age-related macular degeneration and cataracts. In the present study, selected high-lutein wheat and corn were milled into wholegrain flours by two mills to improve flour uniformity. The high-lutein and lutein-fortified wholegrain flours were processed into breads, cookies, and muffins to study lutein stability during baking and subsequent storage. Lutein and its isomers were separated, identified, and quantified by LC-UV/vis and LC-MS following extraction with water-saturated 1-butanol. Baking resulted in a significant reduction in all-trans-lutein and the formation of cis-lutein and cis-zeaxanthin isomers. Subsequent storage at ambient temperature had a slight impact on the content of all-trans-lutein. Effects of processing were more pronounced in lutein-fortified products, and the degradation rate of lutein was influenced by concentration and baking recipe. Fortified cookies and muffins showed greater lutein reduction compared with bread. Despite the significant reduction in lutein, the fortified bakery products still possessed reasonable amounts per serving that would enhance daily intake and consumption of wholegrain foods. PMID:20734986

  1. Lutein and brain function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lutein is one of the most prevalent carotenoids in nature and in the human diet. Together with zeaxanthin, it is highly concentrated in macular pigment in the foveal retina of primates, attenuating blue light exposure, providing protection from photo-oxidation and enhancing visual performance. Rece...

  2. Luteinizing Hormone Causes Phosphorylation and Activation of the cGMP Phosphodiesterase PDE5 in Rat Ovarian Follicles, Contributing, Together with PDE1 Activity, to the Resumption of Meiosis.

    PubMed

    Egbert, Jeremy R; Uliasz, Tracy F; Shuhaibar, Leia C; Geerts, Andreas; Wunder, Frank; Kleiman, Robin J; Humphrey, John M; Lampe, Paul D; Artemyev, Nikolai O; Rybalkin, Sergei D; Beavo, Joseph A; Movsesian, Matthew A; Jaffe, Laurinda A

    2016-05-01

    The meiotic cell cycle of mammalian oocytes in preovulatory follicles is held in prophase arrest by diffusion of cGMP from the surrounding granulosa cells into the oocyte. Luteinizing hormone (LH) then releases meiotic arrest by lowering cGMP in the granulosa cells. The LH-induced reduction of cGMP is caused in part by a decrease in guanylyl cyclase activity, but the observation that the cGMP phosphodiesterase PDE5 is phosphorylated during LH signaling suggests that an increase in PDE5 activity could also contribute. To investigate this idea, we measured cGMP-hydrolytic activity in rat ovarian follicles. Basal activity was due primarily to PDE1A and PDE5, and LH increased PDE5 activity. The increase in PDE5 activity was accompanied by phosphorylation of PDE5 at serine 92, a protein kinase A/G consensus site. Both the phosphorylation and the increase in activity were promoted by elevating cAMP and opposed by inhibiting protein kinase A, supporting the hypothesis that LH activates PDE5 by stimulating its phosphorylation by protein kinase A. Inhibition of PDE5 activity partially suppressed LH-induced meiotic resumption as indicated by nuclear envelope breakdown, but inhibition of both PDE5 and PDE1 activities was needed to completely inhibit this response. These results show that activities of both PDE5 and PDE1 contribute to the LH-induced resumption of meiosis in rat oocytes, and that phosphorylation and activation of PDE5 is a regulatory mechanism. PMID:27009040

  3. Relationships Between the Appearances and Changes of Estrous Signs and the Estradiol-17β Peak, Luteinizing Hormone Surge and Ovulation During the Periovulatory Period in Lactating Dairy Cows Kept in Tie-stalls

    PubMed Central

    SUMIYOSHI, Toshiaki; TANAKA, Tomomi; KAMOMAE, Hideo

    2014-01-01

    Lactating Holstein-Friesian cows kept in tie-stall barn were used as subjects in this study. Rectal examination, ultrasonography and blood sampling were conducted every other day and then daily after the day on which diameter of the corpus luteum decreased. After the luteal diameter decreased for 2 consecutive days, rectal and ultrasound examinations, blood sampling, and observation of estrous signs were conducted at 6-h intervals. Most of the estrous signs became obvious with the increase in estradiol-17β (E2) and became most remarkable 24 to 30 hours before ovulation, at which point the E2 peak and luteinizing hormone (LH) surge were achieved, and then weakened which progression to ovulation. The correlation between the intensity of four estrous signs (hyperemia and swelling of the intravaginal part of the uterus, opening of the external uterine orifice and viscosity of the cervical mucus) and the plasma E2 concentration was higher than that of three estrous signs (swelling of the vulva, contraction of the uterus, diameter of uterine horn) and the plasma E2 concentration. The relaxation of the intravaginal part of the uterus showed a unique change compared with the other estrous signs, and it became most obvious 6, 12 and 18 h before ovulation; this obviously relaxed period was consistent with the generally accepted theoretical optimal time for artificial insemination (AI), i.e., 6 to 24 h after initiation of estrus. These results suggest that observation of estrous signs by vaginoscopic examination gave useful information for detection of the optimal timing of AI in the periovulatory period in lactating dairy cows kept in a tie-stall barn. PMID:24492642

  4. Comparison between lactating and non-lactating dairy cows on follicular growth and corpus luteum development, and endocrine patterns of ovarian steroids and luteinizing hormone in the estrous cycles.

    PubMed

    Endo, Natsumi; Nagai, Kiyosuke; Tanaka, Tomomi; Kamomae, Hideo

    2012-10-01

    The dynamics of ovarian follicle, corpus luteum (CL), and peripheral plasma ovarian steroids were compared between lactating and non-lactating cows, and a possible association of pulsatile luteinizing hormone (LH) secretion with the dynamics was examined. Lactating (n=5) and non-lactating (n=5) cows were monitored daily for follicle and CL throughout two consecutive estrous cycles (Day 0: day of ovulation). Blood samples were collected daily and at 15 min intervals for 8h on Days 2, 4, 6, 8, and 14 of the second cycle. Lactating cows had larger CL (25.4 ± 1.8mm vs. 23.5 ± 1.5mm, P<0.01) and greater progesterone concentrations (4.6 ± 1.0ng/ml vs. 3.9 ± 0.9 ng/ml, P<0.01) during mid-luteal phase compared with non-lactating cows. Maximal diameters of the first wave dominant follicle (17.2 ± 1.8mm vs. 15.5 ± 0.8mm) and the ovulatory follicle (17.9 ± 1.2mm vs. 15.2 ± 0.8mm) were greater (P<0.05) in lactating cows than in non-lactating cows during the estrous cycles with two follicular waves, but no significant differences were detected between the groups during the estrous cycles with three follicular waves. Plasma estradiol concentrations did not differ between the groups throughout the experiment. Lactating cows had more LH pulses from Days 2 to 14 than non-lactating cows. These results imply that differences in ovarian dynamics may exist between lactating and non-lactating cows, for which the increased number of LH pulses observed in lactating cows may have responsibility. PMID:22951117

  5. Circadian Clock genes Per2 and clock regulate steroid production, cell proliferation, and luteinizing hormone receptor transcription in ovarian granulosa cells

    SciTech Connect

    Shimizu, Takashi; Hirai, Yuko; Murayama, Chiaki; Miyamoto, Akio; Miyazaki, Hitoshi; Miyazaki, Koyomi

    2011-08-19

    Highlights: {yields} Treatment with Per2 and Clock siRNAs decreased the number of granulosa cells and LHr expression. {yields}Per2 siRNA treatment did not stimulate the production of estradiol and expression of P450arom. {yields} Clock siRNA treatment inhibited the production of estradiol and expression of P450arom mRNA. {yields}Per2 and Clock siRNA treatment increased and unchanged, respectively, progesterone production in FSH-treated granulosa cells. {yields} The expression of StAR mRNA was increased by Per2 siRNA and unchanged by Clock siRNA. -- Abstract: Circadian Clock genes are associated with the estrous cycle in female animals. Treatment with Per2 and Clock siRNAs decreased the number of granulosa cells and LHr expression in follicle-stimulating hormone FSH-treated granulosa cells. Per2 siRNA treatment did not stimulate the production of estradiol and expression of P450arom, whereas Clock siRNA treatment inhibited the production of estradiol and expression of P450arom mRNA. Per2 and Clock siRNA treatment increased and unchanged, respectively, progesterone production in FSH-treated granulosa cells. Similarly, expression of StAR mRNA was increased by Per2 siRNA and unchanged by Clock siRNA. Our data provide a new insight that Per2 and Clock have different action on ovarian granulosa cell functions.

  6. Hormones

    MedlinePlus

    Hormones are your body's chemical messengers. They travel in your bloodstream to tissues or organs. They work ... glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, ...

  7. Luteal expression of cytochrome P450 side-chain cleavage, steroidogenic acute regulatory protein, 3beta-hydroxysteroid dehydrogenase, and 20alpha-hydroxysteroid dehydrogenase genes in late pregnant rats: effect of luteinizing hormone and RU486.

    PubMed

    Stocco, C O; Chedrese, J; Deis, R P

    2001-10-01

    A decrease in serum progesterone at the end of pregnancy is essential for the induction of parturition in rats. We have previously demonstrated that LH participates in this process through: 1) inhibiting 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity and 2) stimulating progesterone catabolism by inducing 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) activity. The objective of this investigation was to determine the effect of LH and progesterone on the luteal expression of the steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage (P450(scc)), 3beta-HSD, and 20alpha-HSD genes. Gene expression was analyzed by Northern blot analysis 24 and 48 h after administration of LH or vehicle on Day 19 of pregnancy. StAR and 3beta-HSD mRNA levels were lower in LH-treated rats than in rats administered with vehicle at both time points studied. P450(scc) mRNA levels were unaffected by LH. The 20alpha-HSD mRNA levels were not different between LH and control rats 24 h after treatment; however, greater expression of 20alpha-HSD, with respect to controls, was observed in LH-treated rats 48 h after treatment. Luteal progesterone content dropped in LH-treated rats at both time points studied, whereas serum progesterone decreased after 48 h only. In a second set of experiments, the anti-progesterone RU486 was injected intrabursally on Day 20 of pregnancy. RU486 had no effect on 3beta-HSD or P450(scc) expression but increased 20alpha-HSD mRNA levels after 8 h treatment. In conclusion, the luteolytic effect of LH is mediated by a drop in StAR and 3beta-HSD expression without effect on P450(scc) expression. We also provide the first in vivo evidence indicating that a decrease in luteal progesterone content may be an essential step toward the induction of 20alpha-HSD expression at the end of pregnancy in rats. PMID:11566732

  8. Ovarian hemangioma associated with concomitant stromal luteinization and ascites.

    PubMed

    Yamawaki, T; Hirai, Y; Takeshima, N; Hasumi, K

    1996-06-01

    A 62-year-old female presented with a pelvic mass and ascites. The Papanicolaou vaginal smear showed an unusual maturation, maturation index being 0/80/20. The serum level of estradiol was 48.7 pg/ml. The preoperative checkup suggested a pelvic malignancy with a differential diagnosis of hormone-secreting ovarian tumor. On surgical exploration, she had a hemangioma of the ovary without malignant cytology in the ascitic fluid. Histologically, this tumor was associated with stromal luteinization. This is the first case, reported in the literature, possessing ovarian hemangioma with stromal luteinization accompanying massive ascites. It should be noted that an ovarian hemangioma can be associated with stromal luteinization and ascites, and that MR imaging is sometimes of value for making a preoperative diagnosis of ovarian hemangioma. PMID:8641629

  9. Bioavailability and biodistribution of nanodelivered lutein

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The aim of the study was to evaluate the ability of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) to enhance lutein bioavailability. The bioavailability of free lutein and PLGA-NP lutein in rats was assessed by determining plasma pharmacokinetics and deposition in selected tissues. Lutein ...

  10. Long [R3] insulin-like growth factor-I reduces growth, plasma growth hormone, IGF binding protein-3 and endogenous IGF-I concentrations in pigs.

    PubMed

    Dunaiski, V; Dunshea, F R; Walton, P E; Goddard, C

    1997-12-01

    Growth hormone (GH) improves growth performance in the pig. Analogues of insulin-like growth factor-I (IGF-I) that bind poorly to IGF binding proteins (IGFBP) stimulate growth in the rat but, in contrast, inhibit growth in the pig. This study was designed to determine the effect of IGF peptides alone or in combination with porcine GH (pGH) on growth characteristics and plasma hormone concentrations in finisher pigs. A four-day infusion of Long [R3] IGF-I (LR3IGF-I; 180 micrograms/kg/day) decreased the average daily gain, food intake, and plasma IGFBP-3, IGF-I and insulin concentrations. The mean plasma GH concentration was decreased by 23% and the area under the GH peaks was reduced by 60%. Co-administration of pGH (30 micrograms/kg/day) with LR3IGF-I had no interactive effect on growth performance, and plasma insulin, IGFBP-3 and IGF-I concentrations remained suppressed. The area under the GH peaks was not restored with this combination treatment although mean plasma GH concentrations were elevated in all animals receiving pGH. Infusion of IGF-I (180 micrograms/kg/day) decreased plasma insulin and mean GH concentrations but had no significant effect on IGFBP-3 concentrations. Average daily gain and feed intake were not changed by IGF-I treatment. A combination of IGF-I and pGH injection (30 micrograms/kg/day) increased plasma IGFBP-3 concentrations but plasma insulin levels remained suppressed. Plasma glucose levels were unaffected by any treatment. The study demonstrates that both IGF-I and LR3IGF-I suppress plasma GH concentrations in finisher pigs. This, in turn, may be responsible for the reduction in the plasma concentration of IGF-I, IGFBP-3 and insulin seen in LR3IGF-I-treated animals. The decrease in these parameters may contribute to the inhibitory effect of LR3IGF-I on growth performance in the pig. PMID:9488001

  11. Hormones

    MedlinePlus

    ... the foods you eat Sexual function Reproduction Mood Endocrine glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, thymus, thyroid, adrenal ...

  12. Hormone Therapy for Prostate Cancer

    MedlinePlus

    ... agonists , which are sometimes called LHRH analogs, are synthetic proteins that are structurally similar to LHRH and ... gland to stop producing luteinizing hormone, which prevents testosterone from being produced. Treatment with an LHRH agonist ...

  13. Induction of follicular luteinization by equine chorionic gonadotropin in cyclic guinea pigs*

    PubMed Central

    Li, Jun-rong; Wang, Wei; Shi, Fang-xiong

    2015-01-01

    The effects of equine chorionic gonadotropin (eCG) on follicular development and ovulation in cyclic guinea pigs were investigated by histological and immunohistochemical analyses. Three groups of guinea pigs (n=12) were administrated subcutaneously with saline, 20 or 50 IU of eCG, respectively, on cyclic Day 12 (Day 1=vaginal openings). Ovaries were collected at 4 and 8 d after administration (6 animals per group each time). The eCG administration induced significant and distinct morphological changes in the ovaries, as it promoted the luteinization of granulosa cells, but not follicular development. In addition, proliferating cell nuclear antigen (PCNA) and steroidogenic acute regulatory protein (StAR) were immunolocalized specifically in luteinized follicles. Our experiments together indicate that eCG administration can induce follicular luteinization but not superovulation in guinea pigs. The eCG in cyclic guinea pigs functions similar to that of luteinizing hormone (LH), but not follicle-stimulating hormone (FSH). PMID:26642181

  14. Effects of acute feed restriction combined with targeted use of increasing luteinizing hormone content of follicle-stimulating hormone preparations on ovarian superstimulation, fertilization, and embryo quality in lactating dairy cows.

    PubMed

    Bender, R W; Hackbart, K S; Dresch, A R; Carvalho, P D; Vieira, L M; Crump, P M; Guenther, J N; Fricke, P M; Shaver, R D; Combs, D K; Wiltbank, M C

    2014-02-01

    Multiple metabolic and hormonal factors can affect the success of protocols for ovarian superstimulation. In this study, the effect of acute feed restriction and increased LH content in the superstimulatory FSH preparation on numbers of ovulations, fertilization, and embryo quality in lactating dairy cows was evaluated. Two experiments were performed using a Latin square design with treatments arranged as a 2 × 2 factorial: feed restriction (FR; 25% reduction in dry matter intake) compared with ad libitum (AL) feeding, combined with high (H) versus low (L) LH in the last 4 injections of the superstimulatory protocol. As expected, FR decreased circulating insulin concentrations (26.7 vs. 46.0 μU/mL). Two analyses were performed: one that evaluated the complete Latin square in experiment 2 and a second that evaluated only the first periods of experiments 1 and 2. For both analyses, follicle numbers, ovulation rates, and corpora lutea on d 7 were not different. In the first period analysis of experiments 1 and 2, we observed an interaction between feed allowance and amount of LH on fertilization rates, percentage of embryos or oocytes that were quality 1 and 2 embryos, and number of embryos or oocytes that were degenerate. Fertilization rates were greater for the AL-L (89.4%) and FR-H (80.1%) treatments compared with the AL-H (47.9%) and FR-L (59.9%) treatments. Similarly, the proportion of total embryos or oocytes designated as quality 1 and 2 embryos was greater for AL-L (76.7%) and FR-H (73.4%) treatments compared with AL-H (35.6%) and FR-L (47.3%) treatments. In addition, the number of degenerate embryos was decreased for AL-L (1.3) and FR-H (0.4) treatments compared with the AL-H (2.6) and FR-L (2.3) treatments. Thus, cows with either too low (FR-L) or too high (AL-H) insulin and LH stimulation had lesser embryo production after superstimulation because of reduced fertilization rate and increased percentage of degenerate embryos. Therefore, interaction of the

  15. Effect of Chlorotriazine Pesticides on Gonadotrophin Releasing Hormone in the Neuronal GT1-7 Cell Line and Hypothalamic Explants

    EPA Science Inventory

    Gonadotrophin releasing hormone (GnRH) stimulates the release of pituitary luteinizing hormone (LH) and follicle stimulating hormone. These pituitary hormones are necessary for normal reproductive function in both males and females. It is well recognized that disruption of nor...

  16. Bioavailability and biodistribution of nanodelivered lutein.

    PubMed

    Kamil, Alison; Smith, Donald E; Blumberg, Jeffrey B; Astete, Carlos; Sabliov, Cristina; Oliver Chen, C-Y

    2016-02-01

    The aim of the study was to evaluate the ability of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) to enhance lutein bioavailability. The bioavailability of free lutein and PLGA-NP lutein in rats was assessed by determining plasma pharmacokinetics and deposition in selected tissues. Lutein uptake and secretion was also assessed in Caco-2 cells. Compared to free lutein, PLGA-NP increased the maximal plasma concentration (Cmax) and area under the time-concentration curve in rats by 54.5- and 77.6-fold, respectively, while promoting tissue accumulation in the mesenteric fat and spleen. In comparison with micellized lutein, PLGA-NP lutein improved the Cmax in rat plasma by 15.6-fold and in selected tissues by ⩾ 3.8-fold. In contrast, PLGA-NP lutein had a lower uptake and secretion of lutein in Caco-2 cells by 10.0- and 50.5-fold, respectively, compared to micellized lutein. In conclusion, delivery of lutein with polymeric NP may be an approach to improve the bioavailability of lutein in vivo. PMID:26304429

  17. Characterization of milk proteins-lutein complexes and the impact on lutein chemical stability.

    PubMed

    Yi, Jiang; Fan, Yuting; Yokoyama, Wallace; Zhang, Yuzhu; Zhao, Liqing

    2016-06-01

    In this study, the interaction of WPI (whey protein isolate) and SC (sodium caseinate) with hydrophobic lutein was investigated through UV-vis spectroscopy and circular dichroism (CD) as well as fluorescence. The effects on lutein's chemical stability were also examined. The decrease of turbidity of lutein suggested that lutein's aqueous solubility was improved after binding with milk proteins. CD analysis indicated lutein had little impact on the secondary structures of both proteins. Different preparation methods have significant impacts on the binding constant. Fluorescence results indicated that WPI and SC interact with lutein by hydrophobic contacts. Milk proteins have protective effects on lutein against oxidation and decomposition, and SC showed better capability in protecting lutein from oxidation than WPI during 16 days storage. The lutein's chemical stability was increased with increasing of proteins concentration. The results indicated that milk proteins may act as effective carriers for lipophilic nutraceuticals. PMID:26830565

  18. Low reversibility of intracellular cAMP accumulation in mouse Leydig tumor cells (MLTC-1) stimulated by human Luteinizing Hormone (hLH) and Chorionic Gonadotropin (hCG).

    PubMed

    Klett, Danièle; Meslin, Philippine; Relav, Lauriane; Nguyen, Thi Mong Diep; Mariot, Julie; Jégot, Gwenhaël; Cahoreau, Claire; Combarnous, Yves

    2016-10-15

    In order to study the intracellular cAMP response kinetics of Leydig cells to hormones with LH activity, we used MLTC-1 cells transiently expressing a chimeric cAMP-responsive luciferase so that real-time variations of intracellular cAMP concentration could be followed using oxiluciferin luminescence produced from catalyzed luciferin oxidation. The potencies of the different LHs and CGs were evaluated using areas under the curves (AUC) of their kinetics over 60 min stimulation. All mammalian LHs and CGs tested were found to stimulate cAMP accumulation in these cells. The reversibility of this stimulation was studied by removing the hormone from the culture medium after 10 min of incubation. The ratios of kinetics AUC after removing or not the hormone were used to evaluate the stimulation reversibility of each hormone. Natural and recombinant hLHs and hCGs were found to exhibit slowly reversible activation compared to pituitary rat, ovine, porcine, camel and equine LHs, serum-derived eCG (PMSG) and recombinant eLH/CGs. Carbohydrate side chains are not involved in this phenomenon since natural and recombinant homologous hormones exhibit the same reversibility rates. It is still unknown whether only one human subunit, α or β, is responsible for this behaviour or whether it is due to a particular feature of the hLH and hCG quaternary structure. PMID:27373440

  19. Environmental Effects on Lutein Concent and Relationship of Lutein and Other Seed Components in Soybean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lutein is a major carotenoid in soybean [Glycine max (L.) Merr. ] seed, and has been shown to be beneficial for eye health in humans. Development of soybeans high in lutein is a goal of some breeding programs. Little is known about how different growing environments affect lutein concentration. Obje...

  20. The Tissue Distribution of Lutein in Laying Hens Fed Lutein Fortified Chlorella and Production of Chicken Eggs Enriched with Lutein.

    PubMed

    An, Byoung-Ki; Jeon, Jin-Young; Kang, Chang-Won; Kim, Jin-Man; Hwang, Jae-Kwan

    2014-01-01

    Two experiments were conducted to investigate the dietary effects of conventional or lutein fortified chlorella on lutein absorptions, the tissue distributions and the changes in lutein content of eggs in laying hens. In Exp 1, a total of one hundred and fifty, 70 wk-old Hy-Line brown layers were divided into three groups with five replicates and fed with each experiment diet (control diet, diet with 1% conventional chlorella or lutein fortified chlorella) for 2 wk, respectively. The egg production in groups fed diets containing both chlorella powders were higher than that of the control group (p<0.01). With chlorella supplementations, the yolk color significantly increased, although there were no significant differences in the eggshell qualities. The lutein contents of serum, liver and growing oocytes were greatly increased by feeding conventional or lutein fortified chlorella (p<0.01). In Exp. 2, a total of ninety 60 wk-old Hy-Line brown layers were assigned into three groups with three replicates per group (10 birds per replicate). The birds were fed with one of three experimental diets (0, 0.1 or 0.2% lutein fortified chlorella) for 2 wk, respectively. The egg production was not affected by dietary treatments. The egg weight in the group fed with diet containing 0.2% of lutein fortified chlorella was higher than that of the control (p<0.05). As the dietary chlorella levels increased, the daily egg mass linearly increased, although not significantly. The yolk colors in groups fed diets containing lutein fortified chlorella were dramatically increased as compared to the control (p<0.001). The lutein in chicken eggs significantly increased when fed with 0.2% of lutein fortified chlorella (p<0.01). These results suggested that the dietary lutein derived from chlorella was readily absorbed into the serum and absorbed by the liver with growing oocyte for commercial laying hens. Particularly, the lutein fortified chlorella was a valuable natural source for the

  1. Absorption and ocular deposition of dietary lutein in marine mammals.

    PubMed

    Koutsos, Elizabeth A; Schmitt, Todd; Colitz, Carmen M H; Mazzaro, Lisa

    2013-01-01

    Cataracts and ocular disease are common lesions of marine mammals in zoological collections. Lutein, an oxygenated carotenoid, may have therapeutic or prophylactic effects on ocular disorder. Therefore, this study examined the ability of marine mammals to absorb dietary lutein. Two preliminary trials examined lutein in two forms (beadlet or ester) in a small sample size of marine mammals representing pinnipeds and cetaceans. Lutein was fed daily in tablets providing 0.89-3.6 mg lutein/kg body weight(0.75) per day for 15 days to 2 years. A third study was conducted using lutein beadlet fed at 3.6 mg lutein/kg body weight(0.75) per day for 15-21 days. Blood was analyzed for lutein pre- and postsupplementation. In the preliminary trials, lutein beadlet was observed to result in greater blood lutein levels than lutein esters, and cetaceans had more noticeable responses than pinnipeds. In Study 3, serum lutein and zeaxanthin increased postsupplementation in beluga whales (P < 0.05), and serum lutein tended to increase postsupplementation in dolphins (P < 0.10), but little change was seen in serum lutein in pinnipeds or manatee. Opportunistic retinal samples demonstrated some detectable lutein in the retina of a dolphin and several harp seals. The lutein levels in dolphins after supplementation are similar to those reported in free-ranging animals. Ocular lutein in harp seals demonstrates that ocular deposition occurs despite low circulating lutein levels. PMID:22753123

  2. Structure of the lutein-binding domain of human StARD3 at 1.74 Å resolution and model of a complex with lutein.

    PubMed

    Horvath, Martin P; George, Evan W; Tran, Quang T; Baumgardner, Kody; Zharov, Gabe; Lee, Sarah; Sharifzadeh, Hassan; Shihab, Saeed; Mattinson, Ty; Li, Binxing; Bernstein, Paul S

    2016-08-01

    A crystal structure of the lutein-binding domain of human StARD3 (StAR-related lipid-transfer protein 3; also known as MLN64) has been refined to 1.74 Å resolution. A previous structure of the same protein determined to 2.2 Å resolution highlighted homology with StARD1 and shared cholesterol-binding character. StARD3 has since been recognized as a carotenoid-binding protein in the primate retina, where its biochemical function of binding lutein with specificity appears to be well suited to recruit this photoprotective molecule. The current and previous structures correspond closely to each other (r.m.s.d. of 0.25 Å), especially in terms of the helix-grip fold constructed around a solvent-filled cavity. Regions of interest were defined with alternate conformations in the current higher-resolution structure, including Arg351 found within the cavity and Ω1, a loop of four residues found just outside the cavity entrance. Models of the complex with lutein generated by rigid-body docking indicate that one of the ionone rings must protrude outside the cavity, and this insight has implications for molecular interactions with transport proteins and enzymes that act on lutein. Interestingly, models with the ℇ-ionone ring characteristic of lutein pointing towards the bottom of the cavity were associated with fewer steric clashes, suggesting that steric complementarity and ligand asymmetry may play a role in discriminating lutein from the other ocular carotenoids zeaxanthin and meso-zeaxanthin, which only have β-ionone rings. PMID:27487925

  3. Structure of the lutein-binding domain of human StARD3 at 1.74 Å resolution and model of a complex with lutein

    PubMed Central

    Horvath, Martin P.; George, Evan W.; Tran, Quang T.; Baumgardner, Kody; Zharov, Gabe; Lee, Sarah; Sharifzadeh, Hassan; Shihab, Saeed; Mattinson, Ty; Li, Binxing; Bernstein, Paul S.

    2016-01-01

    A crystal structure of the lutein-binding domain of human StARD3 (StAR-related lipid-transfer protein 3; also known as MLN64) has been refined to 1.74 Å resolution. A previous structure of the same protein determined to 2.2 Å resolution highlighted homology with StARD1 and shared cholesterol-binding character. StARD3 has since been recognized as a carotenoid-binding protein in the primate retina, where its biochemical function of binding lutein with specificity appears to be well suited to recruit this photoprotective molecule. The current and previous structures correspond closely to each other (r.m.s.d. of 0.25 Å), especially in terms of the helix-grip fold constructed around a solvent-filled cavity. Regions of interest were defined with alternate conformations in the current higher-resolution structure, including Arg351 found within the cavity and Ω1, a loop of four residues found just outside the cavity entrance. Models of the complex with lutein generated by rigid-body docking indicate that one of the ionone rings must protrude outside the cavity, and this insight has implications for molecular interactions with transport proteins and enzymes that act on lutein. Interestingly, models with the ∊-ionone ring characteristic of lutein pointing towards the bottom of the cavity were associated with fewer steric clashes, suggesting that steric complementarity and ligand asymmetry may play a role in discriminating lutein from the other ocular carotenoids zeaxanthin and meso-zeaxanthin, which only have β-ionone rings. PMID:27487925

  4. MULTIPLE STABLE PERIODIC SOLUTIONS IN A MODEL FOR THE HORMONAL REGULATION OF THE MENSTRUAL CYCLE

    EPA Science Inventory

    ABSTRACT

    The pituitary hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and the ovarian hormones, estradiol (E2), progesterone (P4), and inhibin (Ih), are five hormones important for the regulation and maintenance of the human menstrual cycle. The...

  5. Plasma steroid hormone concentrations and blood flow of the ovarian structures of the female dromedary (Camelus dromedarius) during growth, dominance, spontaneous ovulation, luteinization and regression of the follicular wave.

    PubMed

    Rawy, M S; Derar, R I; El-Sherry, T M; Megahed, G A

    2014-08-01

    The objectives of this study were to investigate the ovarian follicular waves and their corresponding hormonal changes in she-camels and to elucidate blood perfusion of the ovarian structures. Three reproductively sound, non-pregnant female camels were examined daily using B-mode and color Doppler to detect changes in their ovarian structures and blood vasculature for 22 follicular waves. Blood area (BA) and percentage (BA%) were determined for the ovarian structures. Three phases of follicular development, those of growth, maturation, and regression, were observed during each follicular wave. Deviation occurred on Day 6.1±1.08. Estradiol increased from basal levels of 27.4±0.4pg/ml to peak concentrations of 134.4±47.5pg/ml as the follicle reached a diameter of 13.2mm. Peripheral progesterone concentrations remained low (<0.4ng/ml) throughout the follicular waves. The blood flow to the dominant follicles increased gradually with follicular growth. The BA and BA% reached the maximum values of 18.4±11.6mm(2) and 6.04±2.03%, respectively, when the diameter of the dominant follicle was 17.5±3.4mm. The blood flow to the corpus luteum rose markedly after ovulation to reach a maximum BA% and BA at Days 5 and 7, respectively, post ovulation. In conclusion, the follicular wave pattern in dromedaries consists of individually variable periods of growth, maturation and regression. Deviation occurs 6.1±1.08d from emergence. Transrectal color-Doppler sonography is a useful technique for noninvasive evaluation of follicular vascularity in camels during various stages of the follicular wave. It provides additional information to assess the developmental stage and activity of the ovarian structures. PMID:24957969

  6. Functional lutein cyst in a postmenopausal woman.

    PubMed

    Stevens, M L; Plotka, E D

    1977-07-01

    A postmenopausal woman presented with enlarged breasts, increased vaginal mucus, and elevated serum estrogen and normal progesterone levels. A laparotomy was performed and revealed a cystic right ovary. Histologic examination of the ovary demonstrated a cyst lined by stratified lutein cells with abundant eosinophilic cytoplasm. The endometrium showed cystic and adenomatous hyperplasia. The diagnosis was functional lutein cyst. Removal of the cystic ovary reduced the estrogen levels, and the clinical picture reverted to that of a normal postmenopausal state. PMID:876536

  7. Lutein and cataract: from bench to bedside.

    PubMed

    Manayi, Azadeh; Abdollahi, Mohammad; Raman, Thiagarajan; Nabavi, Seyed Fazel; Habtemariam, Solomon; Daglia, Maria; Nabavi, Seyed Mohammad

    2016-10-01

    Cataract is one of the most important leading causes of blindness in the world. Extensive research showed that oxidative stress may play an important role in the initiation and progression of a cataract and other age-related eye diseases. Extra-generation of reactive oxygen and nitrogen species in the eye tissue has been shown as one of the most important risk factors for cataracts and other age-related eye diseases. With respect to this, it can be hypothesized that dietary antioxidants may be useful in the prevention and/or mitigation of cataract. Lutein is an important xanthophyll which is widely found in different vegetables such as spinach, kale and carrots as well as some other foods such as eggs. Lutein is concentrated in the macula and suppresses the oxidative stress in the eye tissues. A plethora of literature has shown that increased lutein consumption has a close correlation with reduction in the incidence of cataract. Despite this general information, there is a negligible number of review articles considering the beneficial effects of lutein on cataracts and age-related eye diseases. The present review is aimed at discussing the role of oxidative stress in the initiation and progression of a cataract and the possible beneficial effects of lutein in maintaining retinal health and fighting cataract. We also provide a perspective on the chemistry, sources, bioavailability and safety of lutein. PMID:26042352

  8. Lutein bioavailability from lutein ester-fortified fermented milk: in vivo and in vitro study.

    PubMed

    Granado-Lorencio, Fernando; Herrero-Barbudo, Carmer; Olmedilla-Alonso, Begoña; Blanco-Navarro, Inmaculada; Pérez-Sacristán, Belén

    2010-02-01

    We assessed the bioavailability of lutein from lutein-fortified fermented milk using in vivo and in vitro approaches. Twenty-four volunteers were randomized to take lutein-fortified fermented milk at two levels of fortification. Single-dose bioavailability study (2x100 ml, ca. 8 or 16 mg of lutein) was performed using a three-point approach (baseline, 3.5 and 6.5 h). Multiple-dose study consisted of consuming one serving/day (ca. 4 or 8 mg/100 ml) for 14 days. Blood samples for biochemical, hematological and lutein analysis were drawn at baseline, Day 7 and Day 14. In vitro bioaccessibility was assessed by a static gastrointestinal digestion model. Lutein content, in vitro ester hydrolysis and micellarization, and lutein concentrations achieved in serum were analyzed by HPLC. In vivo, post-prandial response was higher using the high content fermented milk, but the percentage of absorption was not different according to the dose consumed. Net increments at Day 7 and Day 14 were significantly higher on consuming the high-dose milk as well. In vitro, lutein ester hydrolysis was incomplete regardless of the amount initially present. Free lutein released was higher using the high-dose fermented milk, but the percentage of hydrolysis was similar at both levels of fortification. In the micellar phase, the percentage of free and total lutein was not different according to the dose. Our results support the suitability of the fermented milk as a carrier of lutein esters and an in vivo dose-dependent effect upon regular consumption and suggest the usefulness of in vitro models to provide relevant information to predict in vivo responses. PMID:19201183

  9. Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The xanthophyll pigments lutein and zeaxanthin cross the blood-retina barrier to preferentially accumulate in the macular region of the neural retina. There they form macular pigment, protecting the retina from blue light damage and oxidative stress. Lutein and zeaxanthin also accumulate in brain t...

  10. Nonparallel changes of growth hormone (GH) and insulin-like growth factor-I, insulin-like growth factor binding protein-3, and GH-binding protein, after craniospinal irradiation and chemotherapy

    SciTech Connect

    Nivot, S.; Adan, L.; Souberbielle, J.; Rappaport, R.; Brauner, R.; Benelli, C.; Clot, J.P.; Saucet, C.; Zucker, J.M.

    1994-03-01

    The authors studied the GH-insulin-like growth factor-I (IGF-I) axis serially over 24-36 months in six patients with medulloblastoma who underwent surgical removal of the tumor followed by craniospinal irradiation therapy for 6 weeks and then chemotherapy for 42 weeks. Eighteen and 24 months after beginning irradiation there was a decline in the peak GH secretory response to acute stimulation with arginine/insulin hypoglycemia. Six months after irradiation and during chemotherapy there was a transient decline in IGF-I, IGF binding protein-3 (IGFBP-3), and GH-BP values (respective mean values of 56.1 {+-} 9.0 ng/mL, 1.1 {+-} 0.2 {mu}g/mL, and 7.6 {+-} 3.3% of radioactivity as compared to time 0 values: 139 {+-} 15 ng/mL, 2.2 {+-} 0.2 {mu}g/mL, and 20.0 {+-} 4.0%, P < 0.001), although provoked GH secretion was normal at this time. The IGF-I, IGFBP-3, and GH-BP returned to pretreatment ranges by 12-36 months after initiation of the study. There was also a decline in body mass index and serum protein values at 6 months after irradiation in ligand and immunoblot analysis there was a decline in IGFBP-3 and an abnormal electrophoretic mobility of IGFBP-2 that were both normalized at 36 months. In one patient they observed a high level of IGFBP-3 proteolysis at this time. This study demonstrates that before the decrease of GH secretion in patients receiving cranial irradiation there is a transient phase of GH insensitivity that may be characteristic of the acute therapeutic phase including the chemotherapy. This partial insensitivity may explain the early growth retardation observed in these patients. 28 refs., 4 figs., 1 tab.

  11. Homeostasis, thymic hormones and aging.

    PubMed

    Goya, R G; Bolognani, F

    1999-01-01

    The thymic-pituitary axis constitutes a bidirectional circuit where the ascending feedback loop is effected by thymic factors of epithelial origin. The aim of the present article is, first, to introduce the idea of an immune-neuroendocrine homeostatic network in higher animals. Next, the relevance of the thymus in this network and the possible role of this gland in the neuroendocrine imbalances associated with aging are discussed. A number of studies are next reviewed which show that the endocrine thymus produces several bioactive molecules, generally called thymic hormones, which in addition to possessing immunoregulatory properties are also active on nervous and endocrine circuits. In particular, the reported activities of thymosin fraction five, thymosin alpha 1 and thymosin beta 4 on beta-endorphin, adrenocorticotropic hormone, glucocorticoids, luteinizing hormone-releasing hormone and luteinizing hormone secretion in different animal and cell models are reviewed. The known hypophysiotropic actions of other thymic hormones like thymulin, homeostatic thymus hormone and thymus factor are also summarized, and the impact of aging on pituitary responsiveness to thymic hormones is discussed. As a conclusion, it is proposed that in addition to its central role in the regulation of the immune function, the thymus gland may extend its influence to nonimmunologic components of the body, including the neuroendocrine system. The early onset of thymus involution might, therefore, act as a triggering event which would initiate the gradual decline in homeostatic potential that characterizes the aging process. PMID:10202264

  12. The Impact of Polymeric Nanoencapsulation on the Bioavailability of Lutein

    NASA Astrophysics Data System (ADS)

    Kamil, Alison

    Lutein, a fat-soluble xanthophyll, contributes partially to the health benefits from consuming plant foods. Like all dietary carotenoids, lutein has a low bioavailability. In addition to increasing the intake of lutein-rich foods to enhance lutein status, delivery of lutein in polymeric nanoparticles (NP) presents a novel approach to enhancing lutein bioavailability. The overall research objective of this project was to investigate, in rats, the impact of nanoencapsulation using poly(lactic-co-glycolic acid) (PLGA) on the pharmacokinetics of lutein. We also used an in vitro cell culture approach utilizing human epithelial colorectal adenocarcinoma (Caco-2) cells grown in both conventional (CONV) and permeable support (PS) systems to investigate the impact of PLGA-NP on the absorption of lutein in intestinal cells. In chapter one, we compared the efficacy of lutein absorption in vitro using Caco-2 cells grown in both CONV and PS systems. We further examined the role of the micelle, the physiological vehicle for lutein within the small intestine, on its intestinal absorption in vitro compared to an organic solvent, ethanol, which is safe and consumed by humans. The finding from this study demonstrated that the CONV system displayed a larger efficacy of lutein uptake by Caco-2 cells. Further, in the PS system, micelle components appeared to facilitate more effective intestinal secretion of lutein. These findings suggest that lutein uptake by Caco-2 cells is subject to the influence of culturing system (CONV vs. PS) and delivery vehicle (ethanol vs. micelle). Chapter two examined the impact of PLGA-NP in rats on lutein pharmacokinetics in plasma and distribution in selected tissues as compared to free lutein. We also investigated the effect of nanoencapsulation on the absorption of lutein in intestinal cells compared to a more physiological vehicle, the micelle, using the PS method. In addition, we explored the need of additional micelles for the ultimate absorption of

  13. Electronic spectra of structurally deformed lutein.

    PubMed

    Macernis, Mindaugas; Sulskus, Juozas; Duffy, Christopher D P; Ruban, Alexander V; Valkunas, Leonas

    2012-10-11

    Quantum chemical calculations have been employed for the investigation of the lowest excited electronic states of lutein, with particular reference to its function within light harvesting antenna complexes of higher plants. Through comparative analysis obtained by using different methods based on gas-phase calculations of the spectra, it was determined that variations in the lengths of the long C-C valence bonds and the dihedral angles of the polyene chain are the dominant factors in determining the spectral properties of Lut 1 and Lut 2 corresponding to the deformed lutein molecules taken from crystallographic data of the major pigment-protein complex of photosystem II. By MNDO-CAS-CI method, it was determined that the two singlet B(u) states of lutein (nominally 1B(u)(-)* and 1B(u)(+)) arise as a result of mixing of the canonical 1B(u)(-) and 1B(u)(+) states of the all-trans polyene due to the presence of the ending rings in lutein. The 1B(u)(-)* state of lutein is optically allowed, while the 1B(u)(-) of a pure all-trans polyene chain is optically forbidden. As demonstrated, the B(u) states are much more sensitive to minor distortions of the conjugated chain due to mixing of the canonical states, resulting in states of poorly defined particle-hole symmetry. Conversely, the A(g) states are relatively robust with respect to geometric distortion, and their respective inversion and particle-hole symmetries remain relatively well-defined. PMID:22974387

  14. Breeding success and lutein availability in great tit ( Parus major)

    NASA Astrophysics Data System (ADS)

    Sillanpää, Saila; Salminen, Juha-Pekka; Eeva, Tapio

    2009-11-01

    The relationship among temporal variation in the availability of carotenoid-rich food, tissue carotenoid levels and breeding success are poorly known. We studied how diet quality and quantity affect the carotenoid profile and fledging success of great tit ( Parus major) nestlings along a pollution gradient. We found declining seasonal trend in lutein concentration of caterpillars, which may be the explanation for the declining trend in nestlings' lutein concentration of plasma with season, despite the increase in caterpillar biomass. This may be because the biomass of most lutein-rich caterpillars (autumnal moths) decreased and less lutein-rich caterpillars (sawflies) increased during the breeding season. The temporal difference in occurrence of different caterpillar species means that peak lutein availability does not coincide with peak caterpillar abundance. However the positive association between total larval biomass and the number of great tit fledglings may suggest that fledging success depends more on total caterpillar availability than on lutein concentration of caterpillars.

  15. hCG-dependent regulation of angiogenic factors in human granulosa lutein cells.

    PubMed

    Phan, B; Rakenius, A; Pietrowski, D; Bettendorf, H; Keck, C; Herr, D

    2006-07-01

    As prerequisite for development and maintenance of many diseases angiogenesis is of particular interest in medicine. Pathologic angiogenesis takes place in chronic arthritis, collagen diseases, arteriosclerosis, retinopathy associated with diabetes, and particularly in cancers. However, angiogenesis as a physiological process regularly occurs in the ovary. After ovulation the corpus luteum is formed by rapid vascularization of initially avascular granulosa lutein cell tissue. This process is regulated by gonadotropic hormones. In order to gain further insights in the regulatory mechanisms of angiogenesis in the ovary, we investigated these mechanisms in cell culture of human granulosa lutein cells. In particular, we determined the expression and production of several angiogenic factors including tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), Leptin, connective tissue growth factor (CTGF), meningioma-associated complimentary DNA (Mac25), basic fibroblast growth factor (bFGF), and Midkine. In addition, we showed that human chorionic gonadotropin (hCG) has distinct effects on their expression and production. hCG enhances the expression and production of TIMP-1, whereas it downregulates the expression of CTGF and Mac25. Furthermore it decreases the expression of Leptin. Our results provide evidence that hCG determines growth and development of the corpus luteum by mediating angiogenic pathways in human granulosa lutein cells. Hence we describe a further approach to understand the regulation of angiogenesis in the ovary. PMID:16596638

  16. Novel Lutein Loaded Lipid Nanoparticles on Porcine Corneal Distribution

    PubMed Central

    Liu, Chi-Hsien; Chiu, Hao-Che; Wu, Wei-Chi; Sahoo, Soubhagya Laxmi; Hsu, Ching-Yun

    2014-01-01

    Topical delivery has the advantages including being user friendly and cost effective. Development of topical delivery carriers for lutein is becoming an important issue for the ocular drug delivery. Quantification of the partition coefficient of drug in the ocular tissue is the first step for the evaluation of delivery efficacy. The objectives of this study were to evaluate the effects of lipid nanoparticles and cyclodextrin (CD) on the corneal lutein accumulation and to measure the partition coefficients in the porcine cornea. Lipid nanoparticles combined with 2% HPβCD could enhance lutein accumulation up to 209.2 ± 18 (μg/g) which is 4.9-fold higher than that of the nanoparticles. CD combined nanoparticles have 68% of drug loading efficiency and lower cytotoxicity in the bovine cornea cells. From the confocal images, this improvement is due to the increased partitioning of lutein to the corneal epithelium by CD in the lipid nanoparticles. The novel lipid nanoparticles could not only improve the stability and entrapment efficacy of lutein but also enhance the lutein accumulation and partition in the cornea. Additionally the corneal accumulation of lutein was further enhanced by increasing the lutein payload in the vehicles. PMID:25101172

  17. Is Lutein a Physiologically Important Ligand for Transthyretin in Humans?

    SciTech Connect

    Liwei Chen

    2003-05-31

    Lutein and zeaxanthin are the only carotenoids accumulated in the macula of the human retina and are known as the macular pigments (MP). These pigments account for the yellow color of the macula and appear to play an important role in protecting against age-related macular degeneration (AMD). The uptake of lutein and zeaxanthin in human eyes is remarkably specific. It is likely that specific transport or binding proteins are involved. The objective is to determine whether transthyretin (TTR) is a transport protein in human plasma and could thus deliver lutein from the blood to the retina. In this study, they used a biosynthetic {sup 13}C-lutein tracer and gas chromatography-combustion interfaced-isotope ratio mass spectrometry (GCC-IRMS) to gain the requisite sensitivity to detect the minute amounts of lutein expected as a physiological ligand for human transthyretin. The biosynthetic {sup 13}C-labeled lutein tracer was purified from algae. Healthy women (n = 4) each ingested 1 mg of {sup 13}C-labeled lutein daily for 3 days and a blood sample was collected 24 hours after the final dose. Plasma TTR was isolated by retinol-binding protein (RBP)-sepharose affinity chromatography and extracted with chloroform. The {sup 13}C/{sup 12}C ratio in the TTR extract was measured by GCC-IRMS. There was no {sup 13}C-lutein enrichment in the pure TTR extract. This result indicated that lutein is not associated with TTR in human plasma after ingestion in physiological amounts. Some hydrophobic compounds with yellow color may bind to human TTR in the plasma. However, this association needs to be further proved by showing specificity. The study provides a new approach for carotenoid-binding protein studies using a stable isotope tracer method combined with the high precision of GCC-IRMS. The mechanism of selective transport, uptake, and accumulation of lutein in human macula remain to be determined.

  18. Changes in Macular Pigment Optical Density and Serum Lutein Concentration in Japanese Subjects Taking Two Different Lutein Supplements

    PubMed Central

    Okazaki, Shigetoshi; Gellermann, Werner; Bernstein, Paul S.

    2015-01-01

    Purpose To investigate macular pigment optical density (MPOD) and serum concentration changes of lutein in Japanese subjects participating in a clinical trial in which two formulations of lutein and zeaxanthin supplements with different physiochemical properties are used. Methods Thirty-six healthy volunteers were recruited into this prospective, randomized, parallel-group, double-masked comparative study at a single institute. Two products were used, FloraGLO® (Kemin Japan) and XanMax® (Katra Phytochem). The lutein particle size and zeaxanthin concentrations differed between the formulations. The subjects consumed one of the two supplements for a duration of up to 6 months. MPOD levels were measured by resonance Raman spectrometry at baseline and once a month until the end of the study. Serum lutein concentration was measured at baseline, month 3, and month 6. The subjects were also tested for contrast sensitivity, glare sensitivity, visual acuity, and in addition had a focal electroretinogram measured. Results The mean serum lutein concentrations increased significantly after the first three months, but the mean MPOD levels in either supplement group did not show any statistically significant increase. A detailed analysis, however, revealed three response patterns in both groups for the increase of MPOD levels and serum lutein concentration, i.e. “retinal responders”, who had an increase of both MPOD levels and serum lutein concentrations (n = 13), “retinal non-responders”, who had only increased serum concentrations and no change in MPOD levels (n = 20), and “retinal and serum non-responders”, who had neither MPOD level nor plasma concentration increases (n = 3). The subjects with low MPOD levels at baseline appeared to show increased MPOD levels at the 6 month time point upon lutein supplementation (r = -0.4090, p = 0.0133). Glare sensitivity improved in retinal responders in both supplement groups, while there were no remarkable changes in

  19. Possible degradation/biotransformation of lutein in vitro and in vivo: isolation and structural elucidation of lutein metabolites by HPLC and LC-MS (atmospheric pressure chemical ionization).

    PubMed

    Lakshminarayana, Rangaswamy; Aruna, Gorusupudi; Sangeetha, Ravi Kumar; Bhaskar, Narayan; Divakar, Sounder; Baskaran, Vallikannan

    2008-10-01

    Metabolites of lutein are highly concentrated in the human macula and are known to provide protection against age-related macular degeneration. The aim of this investigation was to characterize the in vitro oxidation products of lutein obtained through photo-oxidation and to compare them with biologically transformed dietary lutein in intestine, plasma, liver, and eyes of rats. In vivo studies involved feeding rats a diet devoid of lutein for 2 weeks to induce deficiency. Rats were divided into two equal groups (n=6/group) and received either micellar lutein by gavage for 10 days or diet supplemented with fenugreek leaves as a lutein source for 4 weeks. Lutein metabolites/oxidation products obtained from in vivo and in vitro studies were characterized by HPLC and LC-MS (APCI) techniques to elucidate their structure. The characteristic fragmented ions resulting from photo-oxidation of lutein were identified as 523 (M(+)+H(+)-3CH(3)), 476 (M(+)+H(+)-6CH(3)), and 551 (M(+)+H(+)-H(2)O). In the eyes, the fragmented molecules resulting from lutein were 13-Z lutein, 13'-Z lutein, 13-Z zeaxanthin, all-E zeaxanthin, 9-Z lutein, 9'-Z lutein, and 3'-oxolutein. Epoxycarotenoids were identified in liver and plasma, whereas anhydrolutein was identified in intestine. This study emphasizes the essentiality of dietary lutein to maintain its status in the retina. PMID:18640265

  20. Hormones in Synergy: Regulation of the Pituitary Gonadotropin Genes

    PubMed Central

    Thackray, Varykina G.; Mellon, Pamela L.; Coss, Djurdjica

    2009-01-01

    The precise interplay of hormonal influences that governs gonadotropin hormone production by the pituitary includes endocrine, paracrine and autocrine actions of hypothalamic gonadotropin-releasing hormone (GnRH), activin and steroids. However, most studies of hormonal regulation of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the pituitary gonadotrope have been limited to analyses of the isolated actions of individual hormones. LHβ and FSHβ subunits have distinct patterns of expression during the menstrual/estrous cycle as a result of the integration of activin, GnRH, and steroid hormone action. In this review, we focus on studies that delineate the interplay among these hormones in the regulation of LHβ and FSHβ gene expression in gonadotrope cells and discuss how signaling cross-talk contributes to differential expression. We also discuss how recent technological advances will help identify additional factors involved in the differential hormonal regulation of LH and FSH. PMID:19747958

  1. Hormone levels

    MedlinePlus

    Blood or urine tests can determine the levels of various hormones in the body. This includes reproductive hormones, thyroid hormones, adrenal hormones, pituitary hormones, and many others. For more information, see: ...

  2. Lutein and lutein esters in whole grain flours made from 75 genotypes of 5 triticum species grown at multiple sites.

    PubMed

    Ziegler, Jochen U; Wahl, Sabine; Würschum, Tobias; Longin, C Friedrich H; Carle, Reinhold; Schweiggert, Ralf M

    2015-05-27

    Concentrations of lutein and lutein esters were determined in an ample collection of 75 wheat genotypes comprising bread wheat (Triticum aestivum L.), durum (Triticum durum Desf.), spelt (Triticum spelta L.), emmer (Triticum dicoccum Schrank), and einkorn (Triticum monococcum L.) grown in five different environments. Einkorn genotypes showed the highest total amounts of lutein (4.5-7.8 μg/g dry matter), followed by durum (2.0-4.6 μg/g), spelt (0.9-2.0 μg/g), emmer (0.8-1.9 μg/g), and bread wheat (0.7-2.0 μg/g). Due to the observed highly significant genetic variance and high heritability, lutein contents of wheat genotypes may be increased by future plant breeding. Detailed HPLC-DAD-APCI(±)-MS(n) data allowing the identification of six lutein monoesters and nine diesters are presented. Linoleic, palmitic, and oleic acids were the most abundant fatty acids in both the lutein esters and total free lipid fractions. Lutein esters were virtually absent in the tetraploid durum and emmer species, whereas their concentrations considerably differed among the genotypes belonging to the other species. PMID:25946219

  3. Luteinizing hormone-releasing hormone fusion protein vaccines block estrous cycle activity in beef heifers.

    PubMed

    Stevens, J D; Sosa, J M; deAvila, D M; Oatley, J M; Bertrand, K P; Gaskins, C T; Reeves, J J

    2005-01-01

    Two LHRH fusion proteins, thioredoxin and ovalbumin, each containing seven LHRH inserts were tested for their ability to inhibit estrous cycle activity. The objective was to evaluate immune and biological responses from alternating the two fusion proteins in an immunization schedule. One hundred ten heifers were divided equally into 11 groups. Two control groups consisted of either spayed or intact, untreated heifers. Heifers in the other nine groups were immunized on wk 0, 4, and 9. Treatments were immunizations of the same protein throughout or alternating the proteins in different booster sequences. Blood was collected weekly for 22 wk, and serum was assayed for concentrations of progesterone and titers of anti-LHRH. At slaughter, reproductive tracts were removed from each heifer and weighed. Heifers with >or=1 ng/mL of progesterone were considered to have a functional corpus luteum and thus to have estrous cycle activity. All LHRH-immunized groups of heifers had a smaller (P < 0.05) proportion of heifers showing estrous cycle activity after 6 wk than the intact, untreated control group. There was no difference in number of heifers cycling between the immunized groups and the spayed heifers during wk 9 to 22. Anti-LHRH did not differ among immunized groups during wk 1 to 9. Starting at wk 10 and continuing through the conclusion of the study, there was an overall difference among treatment groups for anti-LHRH (P < 0.05). Uterine weights differed among treatments (P < 0.05), with intact control animals having heavier uteri than all other groups (P < 0.05). Uterine weights were negatively correlated with maximum LHRH antibody binding (r = -0.44). In summary, the LHRH fusion proteins were as effective as surgical spaying in suppression of estrous cycle activity, but alternating the two proteins in an immunization schedule did not enhance the immunological or biological effectiveness of the vaccine. PMID:15583055

  4. Gonadotropin releasing hormone (GnRH) induced luteinizing hormone (LH) secretion from perifused equine pituitaries.

    PubMed

    Pinaud, M A; Roser, J F; Dybdal, N

    1991-07-01

    In vitro responsiveness of the horse anterior pituitary (AP) gonadotropes to single and multiple GnRH challenges was examined. The pituitaries were collected from reproductively sound mares in estrus (n = 5) and diestrus (n = 5). Uniform 0.5 mm AP slices were subdivided using a 3 mm biopsy punch and then bisected for use in the perifusion chamber. Four bisected sections per chamber were perifused at 0.5 ml/min at 37 C for 560 min in Medium 199 saturated with 95% 0(2)/5% CO2. Ten minute fractions were collected after an initial 2 hr equilibration period. Four different treatment regimes of GnRH (10(-10) M) were evaluated: (A) three consecutive 10 min GnRH pulses separated by 80 and 100 min, respectively; (B) a single 120 min GnRH infusion; (C) a 10 min GnRH pulse followed 80 min later by a 120 min GnRH infusion and (D) two 10 min GnRH pulses separated by 60 min followed 80 min later by a 120 min GnRH infusion. Estimated total pituitary LH content was higher in estrous than diestrus mares (p less than 0.05). The total amount of LH released in response to GnRH tended to be greater in estrus than diestrus (p less than 0.1), whereas the percentage of LH released in estrus and diestrus was similar. An increase in the area under the LH response curve was noted with each successive 10 min pulse of GnRH during both estrus and diestrus (p less than 0.05), demonstrating a self-priming effect of GnRH. In addition, a significant increase in the peak LH amplitude (p less than 0.05) and the slope to peak amplitude (p less than 0.05) were observed for the 120 min GnRH pulse in regime C and D indicating that prior exposure to short-term pulses of GnRH increased the acute LH secretory response. These results suggest that in the cycling mare (1) the responsiveness of the pituitary (amount of LH released as percent of total LH) is similar in both estrus and diestrus, however, the magnitude of the LH response (total microgram amount of LH released) differs with the stage of the estrous cycle, being highest in estrus, and appears to be related, in part, to pituitary LH content and (2) GnRH self-priming occurs independently of the stage of the estrous cycle. Furthermore, we have demonstrated that the pulsatile mode of GnRH can act directly on the anterior pituitary to dictate the pulsatile release pattern of LH in the cycling mare. PMID:1747998

  5. Luteinizing hormone-releasing immunization alters pituitary hormone synthesis and storage in bulls and steers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives of this study were (1) to determine if trenbolone acetate (TBA) co-administered with LHRH immunization would suppress reproductive function in beef bulls and (2) to examine the effects of LHRH immunization and TBA treatment on pituitary function. To address these objectives 44 Angus x He...

  6. A FEEDBACK MODEL FOR TESTICULAR-PITUITARY AXIS HORMONE KINETICS AND THEIR EFFECTS ON THE REGULATION OF THE PROSTATE IN ADULT MALE RATS

    EPA Science Inventory

    The testicular-hypothalamic-pituitary axis regulates male reproductive system functions. A model describing the kinetics and dynamics of testosterone (T), dihydrotestosterone (DHT) and luteinizing hormone (LH) was developed based on a model by Barton and Anderson (1997). The mode...

  7. EFFECTS OF METAL CATIONS ON PITUITARY HORMONE SECRETION IN VITRO (JOURNAL VERSION)

    EPA Science Inventory

    The purpose of the study was to determine, in vitro, the effects of nickel, cadmium, and zinc (50 microM) on both baseline and potassium chloride (KCl)-stimulated pituitary luteinizing hormone (LH), prolactin (Prl), and thyroid-stimulating hormone (TSH) release. Baseline and stim...

  8. Nutritional and clinical relevance of lutein in human health.

    PubMed

    Granado, F; Olmedilla, B; Blanco, I

    2003-09-01

    Lutein is one of the most widely found carotenoids distributed in fruits and vegetables frequently consumed. Its presence in human tissues is entirely of dietary origin. Distribution of lutein among tissues is similar to other carotenoids but, along with zeaxanthin, they are found selectively at the centre of the retina, being usually referred to as macular pigments. Lutein has no provitamin A activity in man but it displays biological activities that have attracted great attention in relation to human health. Epidemiological studies have shown inconsistent associations between high intake or serum levels of lutein and lower risk for developing cardiovascular disease, several types of cancer, cataracts and age-related maculopathy. Also, lutein supplementation has provided both null and positive results on different biomarkers of oxidative stress although it is effective in increasing macular pigment concentration and in improving visual function in some, but not all, subjects with different eye pathologies. Overall, data suggest that whereas serum levels of lutein have, at present, no predictive, diagnostic or prognostic value in clinical practice, its determination may be very helpful in assessing compliance and efficacy of intervention as well as potential toxicity. In addition, available evidence suggests that a serum lutein concentration between 0.6 and 1.05 micromol/l seems to be a safe, dietary achievable and desirable target potentially associated with beneficial impact on visual function and, possibly, on the development of other chronic diseases. The use of lutein as a biomarker of exposure in clinical practice may provide some rationale for assessing its relationship with human health as well as its potential use within the context of evidence-based medicine. PMID:14513828

  9. Human Ovarian Cancer Stroma Contains Luteinized Theca Cells Harboring Tumor Suppressor Gene GT198 Mutations*

    PubMed Central

    Peng, Min; Zhang, Hao; Jaafar, Lahcen; Risinger, John I.; Huang, Shuang; Mivechi, Nahid F.; Ko, Lan

    2013-01-01

    Ovarian cancer is a highly lethal gynecological cancer, and its causes remain to be understood. Using a recently identified tumor suppressor gene, GT198 (PSMC3IP), as a unique marker, we searched for the identity of GT198 mutant cells in ovarian cancer. GT198 has germ line mutations in familial and early onset breast and ovarian cancers and recurrent somatic mutations in sporadic fallopian tube cancers. GT198 protein has been shown as a steroid hormone receptor coregulator and also as a crucial factor in DNA repair. In this study, using GT198 as a marker for microdissection, we find that ovarian tumor stromal cells harboring GT198 mutations are present in various types of ovarian cancer including high and low grade serous, endometrioid, mucinous, clear cell, and granulosa cell carcinomas and in precursor lesions such as inclusion cysts. The mutant stromal cells consist of a luteinized theca cell lineage at various differentiation stages including CD133+, CD44+, and CD34+ cells, although the vast majority of them are differentiated overexpressing steroidogenic enzyme CYP17, a theca cell-specific marker. In addition, wild type GT198 suppresses whereas mutant GT198 protein stimulates CYP17 expression. The chromatin-bound GT198 on the human CYP17 promoter is decreased by overexpressing mutant GT198 protein, implicating the loss of wild type suppression in mutant cells. Together, our results suggest that GT198 mutant luteinized theca cells overexpressing CYP17 are common in ovarian cancer stroma. Because first hit cancer gene mutations would specifically mark cancer-inducing cells, the identification of mutant luteinized theca cells may add crucial evidence in understanding the cause of human ovarian cancer. PMID:24097974

  10. Composition of Lutein Ester Regioisomers in Marigold Flower, Dietary Supplement, and Herbal Tea.

    PubMed

    Abdel-Aal, El-Sayed M; Rabalski, Iwona

    2015-11-11

    Characterization of lutein and its esters in a health product is necessary for its efficacy. In the current study lutein ester regioisomers were quantified and identified in several dietary supplements and herbal teas in comparison with marigold flower, the commercial source of lutein. The products were extracted with three solvents and separated on a C30 column. The separated esters were identified/confirmed with LC-MS in APCI+ve mode with the use of synthetic lutein esters. The total content of lutein esters substantially varied among marigold flowers (167-5752 μg/g), supplements (88,000-110,700 μg/g), and herbal teas (12.4-91.3 μg/g). Lutein supplement had a lutein profile similar to that of marigold flower, whereas herbal tea showed an extremely different profile. Lutein dipalmitate was the dominant compound in supplements and marigold flowers followed by lutein 3'-O-myristate-3-O-palmitate and lutein 3'-O-palmitate-3-O-myristate. Lutein was the major compound in marigold herbal tea with small amounts of lutein mono- and diesters. Differences in the concentration and composition of lutein compounds among marigold products could indicate distinct product quality and lutein bioavailability. PMID:26496496