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Sample records for bovine pituitary secretory

  1. Primary structure of bovine pituitary secretory protein I (chromogranin A) deduced from the cDNA sequence

    SciTech Connect

    Ahn, T.G.; Cohn, D.V.; Gorr, S.U.; Ornstein, D.L.; Kashdan, M.A.; Levine, M.A.

    1987-07-01

    Secretory protein I (SP-I), also referred to as chromogranin A, is an acidic glycoprotein that has been found in every tissue of endocrine and neuroendocrine origin examined but never in exocrine or epithelial cells. Its co-storage and co-secretion with peptide hormones and neurotransmitters suggest that it has an important endocrine or secretory function. The authors have isolated cDNA clones from a bovine pituitary lambdagt11 expression library using an antiserum to parathyroid SP-I. The largest clone (SP4B) hybridized to a transcript of 2.1 kilobases in RNA from parathyroid, pituitary, and adrenal medulla. Immunoblots of bacterial lysates derived from SP4B lysognes demonstrated specific antibody binding to an SP4B/..beta..-galactosidase fusion protein (160 kDa) with a cDNA-derived component of 46 kDa. Radioimmunoassay of the bacterial lystates with SP-I antiserum yielded parallel displacement curves of /sup 125/I-labeled SP-I by the SP4B lysate and authentic SP-I. SP4B contains a cDNA of 1614 nucleotides that encodes a 449-amino acid protein (calculated mass, 50 kDa). The nucleotide sequences of the pituitary SP-I cDNA and adrenal medullary SP-I cDNAs are nearly identical. Analysis of genomic DNA suggests that pituitary, adrenal, and parathyroid SP-I are products of the same gene.

  2. Pituitary: Non-Secretory Tumors

    MedlinePlus

    ... categories—tumor mass effects and hyposecretion effects. Tumor mass effects Visual field disturbances, most commonly loss of ... surgery. The goal is to completely remove the mass or cyst and preserve normal pituitary, brain, and ...

  3. Characterization of GnRH receptors in bovine pituitary membranes.

    PubMed

    Hazum, E; Keinan, D

    1984-05-01

    Bovine pituitary gonadotropin-releasing hormone (GnRH) receptors were characterized and identified utilizing a superactive GnRH analog, Buserelin [( D-Ser(t-Bu)6, des-Gly10-ethylamide]-GnRH), and a photoreactive GnRH analog, [azidobenzoyl-D- Lys6 ]-GnRH. Both analogs bind with high affinity to a single class of receptors, with apparent IC50 values of 0.5 nM and 1 nM, respectively. The binding of 125I-labeled Buserelin to pituitary membranes was inhibited, in a dose-responsive manner, by both trypsin and chymotrypsin, with the former being less effective. Neuraminidase at a concentration up to 100 micrograms/ml did not affect the binding. Lectins, such as concanavalin A and wheat-germ agglutinin, at a concentration range of 20-200 micrograms/ml had no effect on the binding, whereas soybean agglutinin at high concentrations (150 and 200 micrograms/ml) slightly inhibited the specific binding. Photoaffinity labeling of the bovine pituitary GnRH receptors resulted in the identification of two specific bands with apparent molecular weights of 60 K and 30 K daltons. The latter probably represents very low affinity binding sites. Both specific bands were sensitive to trypsin and chymotrypsin treatment but were not affected by neuraminidase treatment. These results suggest a slight difference between rat and bovine pituitary GnRH receptors. PMID:6329848

  4. Prolactin kinase activity in bovine anterior pituitary sub-cellular fractions.

    PubMed

    Wicks, J R; Brooks, C L

    1999-01-25

    Bovine anterior pituitary cells phosphorylate prolactin (PRL). We describe the phosphorylation of endogenous and exogenous bPRL in highly enriched subcellular fractions of bovine anterior pituitary using [gamma-32P]-ATP. 32P-labeling of endogenous and exogenous bPRL occurred in all subcellular membrane fractions, but most significantly in the fraction enriched for secretory granules. Zn2+ (0.8 mM), Cu2+ (0.8 mM), and Mn2+ (9.8 mM) increased bPRL phosphorylation by 268, 214, and 154%, respectively, relative to basal phosphorylation with no added cations. Neither Mg2+ (10 mM) nor Ca2+ (0.9 mM) increased bPRL phosphorylation above basal levels. Phosphorylation was dependent on the concentration of Zn2+ with an apparent Km of 570 microM. bPRL phosphorylation occurred over a wide pH range of 5.9-8.3, with the greatest activity at pH of 6.7 or greater. Phosphorylation of bPRL was time-dependent. The apparent Kms of the bPRL kinase for exogenous bPRL and ATP were 15.3 and 267 microM, respectively. bPRL incorporation of 32P was unaffected by the presence of calcium and calmodulin, cAMP, phosphotidylserine and diolein, or spermine. From these results we conclude that in vitro phosphorylation of bPRL occurs under physiological conditions that would be found in pituitary cells. PMID:10195699

  5. Kinetics of the secretory response in bovine chromaffin cells following flash photolysis of caged Ca2+.

    PubMed Central

    Heinemann, C; Chow, R H; Neher, E; Zucker, R S

    1994-01-01

    The kinetics of the secretory response in bovine chromaffin cells following flash photolysis of caged Ca2+ were studied by capacitance (Cm) measurements with millisecond time resolution. After elevation of the internal Ca2+ concentration ([Ca2+]i), Cm rises rapidly with one or more exponentials. The time constant of the fastest component decreases for higher [Ca2+]i (range 3-600 microM) over three orders of magnitude before it saturates at approximately 1 ms. The corresponding maximal rates of secretion can be as fast as 100,000 fF/s or 40,000 vesicles/s. There is a Ca(2+)-dependent delay before Cm rises, which may reflect the kinetics of multiple Ca2+ ions binding to the secretory apparatus. The initial rise in Cm is described by models containing a sequence of two to four single Ca(2+)-binding steps followed by a rate-limiting exocytosis step. The predicted Ca2+ dissociation constant (Kd) of a single Ca(2+)-binding site is between 7 and 21 microM. At [Ca2+]i > 30 microM clear indications of a fast endocytotic process complicate the analysis of the secretory response. PMID:7696493

  6. Immunocytochemical localization of secretory phospholipase A(2)-like protein in the pituitary gland and surrounding tissue of the bullfrog, Rana catesbeiana.

    PubMed

    Yaoi, Y; Kikuyama, S; Hayashi, H; Hanaoka, Y; Sakai, M; Tanaka, S

    2001-05-01

    Previously, we obtained a protein that has considerable amino acid sequence homology with secretory phospholipase A(2) (PLA(2)) from a bullfrog pituitary fraction obtained during the purification of thyrotropin (TSH). Subsequently, partial amino acid sequence (N-terminal 45 amino acid residues) analysis revealed this protein to be identical to the N-terminal amino acid sequence of otoconin-22, the major protein of aragonitic otoconia in the Xenopus saccule. In this study we developed an antibody against the N-terminal peptide of the bullfrog protein and applied it for immunocytochemical study of the pituitary and its surrounding tissue. Western blotting analysis showed that this antibody recognizes a 20.4-kD protein that has a molecular mass close to that of otoconin-22. Immunohistochemical reaction with the antibody was not found in any anterior pituitary cells but was intense in the monolayer epithelial cells of the endolymphatic sac surrounding the pituitary gland, which is a major storage site of calcium carbonate in amphibians. An electron microscopic study revealed that the cuboidal cells in the endolymphatic sac contained large, polymorphic secretory granules in their apical cytoplasm. Immunogold particles indicating the presence of a PLA(2)-like protein were observed predominately in these secretory granules. These findings support the view that this PLA(2)-like protein obtained during purification of TSH was derived from the endolymphatic sac adhering to the pituitary and that this protein is a bullfrog otoconin. (J Histochem Cytochem 49:631-637, 2001) PMID:11304801

  7. Prolactinomas, Cushing's disease and acromegaly: debating the role of medical therapy for secretory pituitary adenomas

    PubMed Central

    2010-01-01

    Pituitary adenomas are associated with a variety of clinical manifestations resulting from excessive hormone secretion and tumor mass effects, and require a multidisciplinary management approach. This article discusses the treatment modalities for the management of patients with a prolactinoma, Cushing's disease and acromegaly, and summarizes the options for medical therapy in these patients. First-line treatment of prolactinomas is pharmacotherapy with dopamine agonists; recent reports of cardiac valve abnormalities associated with this class of medication in Parkinson's disease has prompted study in hyperprolactinemic populations. Patients with resistance to dopamine agonists may require other treatment. First-line treatment of Cushing's disease is pituitary surgery by a surgeon with experience in this condition. Current medical options for Cushing's disease block adrenal cortisol production, but do not treat the underlying disease. Pituitary-directed medical therapies are now being explored. In several small studies, the dopamine agonist cabergoline normalized urinary free cortisol in some patients. The multi-receptor targeted somatostatin analogue pasireotide (SOM230) shows promise as a pituitary-directed medical therapy in Cushing's disease; further studies will determine its efficacy and safety. Radiation therapy, with medical adrenal blockade while awaiting the effects of radiation, and bilateral adrenalectomy remain standard treatment options for patients not cured with pituitary surgery. In patients with acromegaly, surgery remains the first-line treatment option when the tumor is likely to be completely resected, or for debulking, especially when the tumor is compressing neurovisual structures. Primary therapy with somatostatin analogues has been used in some patients with large extrasellar tumors not amenable to surgical cure, patients at high surgical risk and patients who decline surgery. Pegvisomant is indicated in patients who have not responded to

  8. A comparison between the equine and bovine hypothalamus-pituitary-adrenocortical axis.

    PubMed

    van der Kolk, J H; Fouché, N; Gross, J J; Gerber, V; Bruckmaier, R M

    2016-07-01

    In this review, we address the function of the hypothalamus-pituitary-adrenocortical (HPA) axis with special emphasis on the comparison between the bovine and equine species. The pars intermedia of the pituitary gland is particularly well developed in horses and cattle. However, its function is not well appreciated in cattle yet. The Wulzen's cone of the adenohypophysis is a special feature of ruminants. Total basal cortisol concentration is much higher in horses than that in cows with similar free cortisol fractions. Corticotropin-releasing factor (CRF) concentrations in equine pituitary venous blood are lower compared with other species, whereas plasma ACTH concentrations in cows are higher than those in horses. A CRF challenge test induced a more pronounced cortisol response in horses compared with cattle, whereas regarding ACTH challenge testing, the opposite seems true. Based on data from literature, the bovine species is characterized by relatively high basal blood CRF and ACTH and low cortisol and glucose concentrations. Obviously, further lowering of blood cortisol in cattle is easily prevented by the high sensitivity to ACTH, and as a consequence, subsequent increased gluconeogenesis prevents imminent hypoglycemia. Hypoglycemia is less likely in horses given their high muscle glycogen content and their relatively high cortisol concentration. When assessing HPA axis reactivity, response patterns to exogenous ACTH or CRH might be used as a reliable indicator of animal welfare status in cows and horses, respectively, although it is emphasized that considerable caution should be exercised in using measures of HPA activity solely to assess animal welfare. PMID:27345307

  9. Effects of low-dose cranial radiation on growth hormone secretory dynamics and hypothalamic-pituitary function

    SciTech Connect

    Costin, G.

    1988-08-01

    Spontaneous growth hormone (GH) secretory dynamics and hypothalamic-pituitary function were studied in 16 long-term survivors of acute lymphoblastic leukemia who were aged 9 to 15 1/2 years and had been treated with prophylactic central nervous system radiation and combined chemotherapy. At the time of study, the mean height was -1.5 SD score below the mean, less than genetic potential, and significantly less than the mean pretreatment height of -0.25 SD score. Height velocity was subnormal for age and sexual stage in all patients. Two patients had compensated hypothyroidism, and four had evidence of gonadal failure. In 11 patients, the peak GH level after two provocative tests was below 10 micrograms/L, which was consistent with GH deficiency. In ten of 13 patients tested, spontaneous GH secretion determined by a 24-hour GH concentration (GHC), GH pulse amplitude, frequency of GH pulses greater than or equal to 5 micrograms/L, and GH peak during wake and sleep hours was significantly less than in normal height controls. Although in three pubertal patients the 24-hour GHC was within normal limits, the GHC during sleep hours, GH pulse amplitude during 24 hours and sleep hours, and peak GH during wake hours were significantly less than in normal height controls. In all pubertal and in two of the prepubertal patients, the somatomedin C (SmC) level was significantly less than in controls. The 24-hour GHC correlated well with the GHC during sleep, peak-stimulated GH level, gonadal steroid level, and the SmC level, but not with height velocity, dose of radiation, or age at radiation. A significant increase in height velocity and the SmC level was noted in all patients treated with GH. These results indicate that GH deficiency occurs after 18 to 24 Gy of cranial radiation and that the puberty-associated growth spurt may mask the decline in height velocity owing to GH deficiency.

  10. Bovine parotid secretory protein: structure, expression and relatedness to other BPI (bactericidal/permeability-increasing protein)-like proteins.

    PubMed

    Wheeler, T T; Hood, K; Oden, K; McCracken, J; Morris, C A

    2003-08-01

    Members of the family of BPI (bactericidal/permeability-increasing protein)-like proteins are as yet incompletely characterized, particularly in cattle, where full-length sequence information is available for only three of the 13 family members known from other species. Structural bioinformatic analyses incorporating bovine homologues of several members of the BPI-like protein family, including two forms of bovine parotid secretory protein (PSP), showed that this family is also present in cattle. Expression analyses of several members of the BPI-like protein family in cattle, including PSP (Bsp30), von Ebner's minor salivary gland protein (VEMSGP) and lung-specific X protein (LUNX), showed a restricted pattern of expression, consistent with earlier hypotheses that these proteins function in the innate immune response to bacteria. The possible role of bovine PSP in susceptibility to pasture bloat in cattle is discussed. PMID:12887305

  11. Pituitary: Secretory Tumors

    MedlinePlus

    ... too much prolactin, the hormone that causes milk production. Prolactinomas affect both men and women. While excess ... acting somatostatin analogue, a drug that suppresses GH production. Somatostatin analogues are given by a monthly injection ...

  12. Differential localization of prohormone convertases PC1 and PC2 in two distinct types of secretory granules in rat pituitary gonadotrophs.

    PubMed

    Uehara, M; Yaoi, Y; Suzuki, M; Takata, K; Tanaka, S

    2001-04-01

    Prohormone convertases PC1 and PC2 are endoproteases involved in prohormone cleavage at pairs of basic amino acids. There is a report that prohormone convertase exists in the rat anterior pituitary gonadotrophs, where it had previously been considered that proprotein processing does not take place. In addition to luteinizing hormone and follicle-stimulating hormone, rat pituitary gonadotrophs contain chromogranin A (CgA) and secretogranin II (SgII), two members of the family of granin proteins, which have proteolytic sites in their molecules. In the present study we examined whether there is a close correlation between subcellular localization of prohormone convertases and granin proteins. Ultrathin sections of rat anterior pituitary were immunolabeled with anti-PC1 or -PC2 antisera and then stained with immunogold. Immunogold particles for PC1 were exclusively found in large, lucent secretory granules, whereas those for PC2 were seen in both large, lucent and small, dense granules. The double-immunolabeling also demonstrated colocalization of PC2 and SgII in small, dense granules and of PC1, PC2, and CgA in large, lucent granules. These immunocytochemical results suggest that PC2 may be involved in the proteolytic processing of SgII and that both PC1 and PC2 may be necessary to process CgA. PMID:11383885

  13. Single Nucleotide Polymorphism Discovery in Bovine Pituitary Gland Using RNA-Seq Technology.

    PubMed

    Pareek, Chandra Shekhar; Smoczyński, Rafał; Kadarmideen, Haja N; Dziuba, Piotr; Błaszczyk, Paweł; Sikora, Marcin; Walendzik, Paulina; Grzybowski, Tomasz; Pierzchała, Mariusz; Horbańczuk, Jarosław; Szostak, Agnieszka; Ogluszka, Magdalena; Zwierzchowski, Lech; Czarnik, Urszula; Fraser, Leyland; Sobiech, Przemysław; Wąsowicz, Krzysztof; Gelfand, Brian; Feng, Yaping; Kumar, Dibyendu

    2016-01-01

    Examination of bovine pituitary gland transcriptome by strand-specific RNA-seq allows detection of putative single nucleotide polymorphisms (SNPs) within potential candidate genes (CGs) or QTLs regions as well as to understand the genomics variations that contribute to economic trait. Here we report a breed-specific model to successfully perform the detection of SNPs in the pituitary gland of young growing bulls representing Polish Holstein-Friesian (HF), Polish Red, and Hereford breeds at three developmental ages viz., six months, nine months, and twelve months. A total of 18 bovine pituitary gland polyA transcriptome libraries were prepared and sequenced using the Illumina NextSeq 500 platform. Sequenced FastQ databases of all 18 young bulls were submitted to NCBI-SRA database with NCBI-SRA accession numbers SRS1296732. For the investigated young bulls, a total of 113,882,3098 raw paired-end reads with a length of 156 bases were obtained, resulting in an approximately 63 million paired-end reads per library. Breed-wise, a total of 515.38, 215.39, and 408.04 million paired-end reads were obtained for Polish HF, Polish Red, and Hereford breeds, respectively. Burrows-Wheeler Aligner (BWA) read alignments showed 93.04%, 94.39%, and 83.46% of the mapped sequencing reads were properly paired to the Polish HF, Polish Red, and Hereford breeds, respectively. Constructed breed-specific SNP-db of three cattle breeds yielded at 13,775,885 SNPs. On an average 765,326 breed-specific SNPs per young bull were identified. Using two stringent filtering parameters, i.e., a minimum 10 SNP reads per base with an accuracy ≥ 90% and a minimum 10 SNP reads per base with an accuracy = 100%, SNP-db records were trimmed to construct a highly reliable SNP-db. This resulted in a reduction of 95,7% and 96,4% cut-off mark of constructed raw SNP-db. Finally, SNP discoveries using RNA-Seq data were validated by KASP™ SNP genotyping assay. The comprehensive QTLs/CGs analysis of 76 QTLs

  14. Formation of secretory vesicles in permeabilized cells: a salt extract from yeast membranes promotes budding of nascent secretory vesicles from the trans-Golgi network of endocrine cells.

    PubMed Central

    Ling, W L; Shields, D

    1996-01-01

    The mechanism of secretory-vesicle formation from the trans-Golgi network (TGN) of endocrine cells is poorly understood. To identify cytosolic activities that facilitate the formation and fission of nascent secretory vesicles, we treated permeabilized pituitary GH3 cells with high salt to remove endogenous budding factors. Using this cell preparation, secretory-vesicle budding from the TGN required addition of exogenous cytosol and energy. Mammalian cytosols (GH3 cells and bovine brain) promoted post-TGN vesicle formation. Most significantly, a salt extract of membranes from the yeast Saccharomyces cerevisiae, a cell lacking a regulated secretory pathway, stimulated secretory vesicle budding in the absence of mammalian cytosolic factors. These results demonstrate that the factors which promote secretory-vesicle release from the TGN are conserved between yeast and mammalian cells. PMID:8615761

  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. cap alpha. -transforming growth factor secreted by untransformed bovine anterior pituitary cells in culture. I. Purification from conditioned medium

    SciTech Connect

    Samsoondar, J.; Kobrin, M.S.; Kudlow, J.E.

    1986-11-05

    A 6-kDa ..cap alpha..-transforming growth factor (TGF) was purified 100,000-fold to homogeneity from the culture fluid conditioned by normal bovine anterior pituitary-derived cells. Initial purification of the acid-soluble TGF from concentrated conditioned medium was achieved by Bio-Gel P-60 gel filtration (apparent molecular mass of 9 kDa). After the Bio-Gel step, three different steps of reverse-phase fast-protein liquid chromatography on the same Pharmacia C/sub 18/ column, using linear acetonitrile gradients, gave complete purification. The ion-pairing agents used in the three consecutive steps were: 0.1% trifluoroacetic acid, 0.13% heptafluorobutyric acid, and again, 0.1% trifluoroacetic acid at a shallower gradient. Homogeneity was confirmed by reverse-phase high performance liquid chromatography, and by polyacrylamide gel electrophoresis, where TGF visualization was facilitated by autoradiography of /sup 125/I-TGF. The /sup 125/I-TGF bound to epidermal growth factor (EGF) receptors and after elution ran identically to the starting material. The molecular mass of TGF is 6 kDa by polyacrylamide gel electrophoresis and 6.6 kDa by amino acid analysis. The amino acid composition of bovine TGF is similar to that of rat or human ..cap alpha..TGF and distinct from epidermal growth factor. Colony-stimulating activity was lost after purification, but the TGF retained its ability to stimulate thymidine uptake by quiescent cells. This mitogenic activity could be blocked completely by anti-EGF-receptor monoclonal antibodies, indicating that the activity was mediated through the EGF-receptor.

  17. cap alpha. -transforming growth factor secreted by untransformed bovine anterior pituitary cells in culture. II. Identification using a sequence-specific monoclonal antibody

    SciTech Connect

    Kobrin, M.S.; Samsoondar, J.; Kudlow, J.E.

    1986-11-05

    Untransformed bovine anterior pituitary cells cultured in serum-free defined medium secrete an epidermal growth factor (EGF)-like peptide with an amino acid composition similar to rat or human ..cap alpha..-transforming growth factor (..cap alpha..TGF). To further characterize the bovine pituitary ..cap alpha..TGF, it was compared to a human ..cap alpha..TGF partially purified from the conditioned medium of a human melanoma cell line. An anti-..cap alpha..TGF monoclonal antibody, MF9, was produced from hybridomas derived from mice immunized with a 17-residue synthetic peptide corresponding to the carboxyl-terminal sequence of rat ..cap alpha..TGF. The hybridoma supernatants were initially screened for the ability to immunoprecipitate /sup 125/I-peptide and then tested for recognition of human ..cap alpha..TGF. Only 2 of 36 antipeptide antibodies recognized the native ..cap alpha..TGF. The binding of /sup 125/I-peptide to MF9 was displaced by human ..cap alpha..TGF but not by EGF. Bovine pituitary ..cap alpha..TGF also displaced the binding of /sup 125/I-peptide to MF9 in a similar manner to human ..cap alpha..TGF. Both iodinated human and bovine pituitary ..cap alpha..TGF were immunoprecipitated by MF9 whereas /sup 125/I-EGF was not. Tryptic digests of both /sup 125/I-..cap alpha..TGFs chromatographed to give a single, indistinguishable peak of iodinated material on a reverse-phase C/sub 18/ high performance liquid chromatography column when eluted with two different solvent systems, suggesting the generation of a single and identical tyrosine-containing tryptic peptide from both ..cap alpha..TGFs. The comparisons of the bovine pituitary and human melanoma ..cap alpha..TGF using a sequence-specific monoclonal antibody and peptide mapping suggest that these ..cap alpha..TGFs are related and that ..cap alpha..TGF production is not limited to transformed or fetal sources.

  18. Functional characteristics of the bovine hypothalamic-pituitary-adrenal axis vary with temperament.

    PubMed

    Curley, Kevin O; Neuendorff, Don A; Lewis, Andrew W; Cleere, Jason J; Welsh, Thomas H; Randel, Ronald D

    2008-01-01

    Hypothalamic-pituitary-adrenal (HPA) axis function, in Brahman heifers of differing temperament, was evaluated using separate challenges with CRH and ACTH. Exit velocity (EV) measurement was used to classify heifer temperament as calm [C; consisted of 6 slowest heifers (EV=1.05+/-0.05 m/s)] or temperamental [T; 6 fastest heifers (EV=3.14+/-0.22 m/s)]. During the 6 h prior to CRH challenge, areas under the ACTH (P=0.025) and cortisol (P<0.001) curves were greater in the temperamental heifers. Baseline cortisol (P<0.001) but not ACTH (P=0.10) differed between temperament groups. Following CRH challenge, areas under the ACTH (P=0.057) and cortisol (P<0.01) response curves were greater in the calm animals. The same animals were subjected to an ACTH challenge 14 d following their utilization in the CRH stimulation experiment. Prior to ACTH challenge, baseline cortisol concentrations were higher (P<0.001) in the temperamental heifers (T=18+/-2.6, C=4.3+/-0.6 ng/mL). Following ACTH administration, area under the cortisol response curve was greater (P=0.07) in the calm heifers. After declining below baseline concentrations during the post-challenge recovery period, cortisol in temperamental animals was again greater (P=0.02) than in the calm heifers. These data demonstrate that cattle with an excitable temperament exhibit increased stress responsiveness to handling, increased baseline adrenal function but not increased basal pituitary function, and a muted responsiveness to pharmacological stimulus. Thus, functional characteristics of the HPA axis vary with animal temperament. PMID:17916358

  19. Asparagine-linked oligosaccharides on lutropin, follitropin, and thyrotropin: structural elucidation of the sulfated and sialylated oligosaccharides on bovine, ovine, and human pituitary glycoprotein hormones

    SciTech Connect

    Green, E.D.; Baenziger, J.U.

    1988-01-05

    The authors have elucidated the structures of the anionic asparagine-linked oligosaccharides present on the glycoprotein hormones lutropin (luteinizing hormone), follitropin (follicle-stimulating hormone), and thyrotropin (thyroid-stimulating hormone). Purified hormones, isolated from bovine, ovine, and human pituitaries, were digested with N-glycanase, and the released oligosaccharides were reduced with NaB(/sup 3/H)/sub 4/. The /sup 3/H-labeled oligosaccharides from each hormone were then fractionated by anion-exchange high performance liquid chromatography (HPLC) into populations differing in the number of sulfate and/or sialic acid moieties. The sulfated, sialylated, and sulfated/sialylated structures, which together comprised 67-90% of the asparagine-linked oligosaccharides on the pituitary glycoprotein hormones, were highly heterogeneous and displayed hormone- as well as animal species-specific features. A previously uncharacterized dibranched oligosaccharide, bearing one residue each of sulfate and sialic acid, was found on all of the hormones except bovine lutropin. In this study, they describe the purification and detailed structural characterizations of the sulfated, sialylated, and sulfated/sialylated oligosaccharides found on lutropin, follitropin, and thyrotropin from several animal species.

  20. The adverse effects of aldrin and dieldrin on both myometrial contractions and the secretory functions of bovine ovaries and uterus in vitro

    SciTech Connect

    Wrobel, Michał H. Grzeszczyk, Marlena; Mlynarczuk, Jaroslaw; Kotwica, Jan

    2015-05-15

    Aldrin and dieldrin are chloroorganic insecticides which are recognised as endocrine disruptors. The aim of the study was to investigate their effect on the secretory functions of the uterus and ovary and on myometrial contractions. Myometrial strips and uterine and ovarian cells from nonpregnant cows were incubated with the xenobiotics (0.1, 1 or 10 ng/ml) for 24 or 72 h. Next, their effect on viability of myometrial, endometrial, granulosa and luteal cells, myometrial strip contractions, the synthesis and secretion of prostaglandins (PGs: PGF2α and PGE2) from uterine cells, the secretion of oestradiol (E2), testosterone (T) and oxytocin (OT) from granulosa cells and the secretion of progesterone (P4) and OT from luteal cells were determined. Neither of the xenobiotics (10 ng/ml) affected (P > 0.05) the viability of the ovarian and uterine cells, while both (0.1–10 ng/ml) decreased (P < 0.05) the basal and OT-stimulated myometrial contractions. In spite of these effects, neither of the insecticides affected (P > 0.05) the synthesis and the secretion of PGs from the myometrial cells. Although they also did not impair the secretion of the PGs from the endometrial cells, they abolished (P < 0.05) the stimulatory effect of OT (P < 0.05) on the secretion of the PGs and stimulated (P < 0.05) the secretion of OT from the granulosa and luteal cells. Moreover, aldrin and dieldrin stimulated secretion of E2 and T from the granulosa cells, while only dieldrin increased (P < 0.05) the secretion of P4 from luteal cells. The data show that aldrin and dieldrin stimulated the secretory function of the cultured granulosa and luteal cells and inhibited the myometrial contractions of cows in vitro, which may affect on natural parturition. - Highlights: • Aldrin and dieldrin inhibited bovine myometrial contractions. • The studied xenobiotics stimulated steroids and oxytocin secretion from ovaries. • Prostaglandins are not involved in adverse effect of the xenobiotics on

  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. 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

  3. The nonsteroidal mycoestrogen zearalenone and its five metabolites suppress LH secretion from the bovine anterior pituitary cells via the estradiol receptor GPR30 in vitro.

    PubMed

    Nakamura, Urara; Kadokawa, Hiroya

    2015-11-01

    Picomolar concentrations of estradiol produce nongenomic suppression of GnRH-induced LH secretion from the anterior pituitary (AP) of cattle via G-protein-coupled receptor 30 (GPR30). Zearalenone (ZEN) is the nonsteroidal mycoestrogen produced by Fusarium fungi and has been detected in cereal grains, animal feed, and ruminant urine worldwide. Zearalenone has a prolonged blood half-life that results from enterohepatic cycling. There are five metabolites of ZEN: α-zearalanol (α-ZAL), β-zearalanol (β-ZAL), α-zearalenol (α-ZOL), β-zearalenol (β-ZOL), and zearalanone, which may persist for long periods in animals and humans after consumption of ZEN-contaminated feed. We recently reported that GPR30 bound with α-ZAL decreases cytoplasmic cAMP but not gene expression of LHα and LHβ subunits, and GPR30 bound with α-ZAL suppresses GnRH-induced LH release in bovine AP cells in vitro. We tested the hypothesis that GPR30 bound with ZEN or one of the four previously untested metabolites suppresses GnRH-induced LH release from the bovine AP cells in vitro. Anterior pituitary cells were cultured for 3 days under steroid-free conditions and were then incubated with various concentrations (0.001-10 nM) of estradiol or one of the ZEN analogs for 5 minutes before GnRH stimulation. Gonadotropin-releasing hormone-stimulated LH secretion from AP cells was inhibited by all of the test concentrations of ZEN, 0.001 to 1 nM of α-ZAL, and 0.001 to 0.1 nM of the remaining four analogs. Pretreatment for 5 minutes with a GPR30-specific antagonist, G36, inhibited estradiol- and the ZEN analog-induced suppression of LH secretion from cultured AP cells. G36 alone had no significant effect on LH secretion. The estimated order of the nongenomic inhibiting effect was ZEN, α-ZAL, zearalanone, α-ZOL, β-ZOL, and β-ZAL, which is quite different from the reported order for their genomic effects. Therefore, ZEN and all of its metabolites suppress LH secretion from the bovine AP

  4. Secretory autophagy.

    PubMed

    Ponpuak, Marisa; Mandell, Michael A; Kimura, Tomonori; Chauhan, Santosh; Cleyrat, Cédric; Deretic, Vojo

    2015-08-01

    Autophagy, once viewed exclusively as a cytoplasmic auto-digestive process, has its less intuitive but biologically distinct non-degradative roles. One manifestation of these functions of the autophagic machinery is the process termed secretory autophagy. Secretory autophagy facilitates unconventional secretion of the cytosolic cargo such as leaderless cytosolic proteins, which unlike proteins endowed with the leader (N-terminal signal) peptides cannot enter the conventional secretory pathway normally operating via the endoplasmic reticulum and the Golgi apparatus. Secretory autophagy may also export more complex cytoplasmic cargo and help excrete particulate substrates. Autophagic machinery and autophagy as a process also affect conventional secretory pathways, including the constitutive and regulated secretion, as well as promote alternative routes for trafficking of integral membrane proteins to the plasma membrane. Thus, autophagy and autophagic factors are intimately intertwined at many levels with secretion and polarized sorting in eukaryotic cells. PMID:25988755

  5. Effects of 31 kDa bovine inhibin on FSH and LH in rat pituitary cells in vitro: antagonism of gonadotrophin-releasing hormone agonists.

    PubMed

    Farnworth, P G; Robertson, D M; de Kretser, D M; Burger, H G

    1988-11-01

    The effects of 31 kDa bovine inhibin on the release of FSH and LH stimulated by gonadotrophin-releasing hormone (GnRH) or its agonist analogue buserelin have been studied using 5-day-old cultures of pituitary cells prepared from adult male Sprague-Dawley rats. Exposure of cultures to increasing concentrations of inhibin for 3 days before and during a 4-h stimulation with GnRH resulted in the progressive suppression of both basal and stimulated gonadotrophin release. At the highest inhibin concentrations FSH release was abolished (inhibin median inhibitory concentration (IC50) = 0.15 U/ml) whereas LH release was suppressed by 75% (IC50 = 0.93 U/ml). To correct for the reduced size of the FSH pool resulting from inhibin pretreatment, the amount of FSH or LH released by an agonist was expressed as a proportion of the total hormone available for release in each case. Following this adjustment, concentrations of inhibin producing maximal effects increased the GnRH median effective concentration for FSH release 4.1-fold and that for LH release 2.2-fold, with inhibin IC50 values of 0.45 and 0.32 U/ml respectively. Inhibin also suppressed the maximum proportion of both FSH and LH that excess GnRH released in 4 h by 36%, with IC50 values of 0.53 and 0.76 U/ml respectively. These effects were not changed by reduction of the inhibin pretreatment period from 3 days to 1 day or by exclusion of inhibin during the stimulation period. After a 3-day pretreatment, inhibin inhibited gonadotrophin release by buserelin less effectively than that by GnRH, but the pattern of antagonism was the same.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3143796

  6. Pituitary abscess.

    PubMed

    Rudwan, M A

    1977-05-28

    Three cases of pituitary abscess are presented. The history of recurrent attacks of aseptic meningitis, together with radiological and clinical features suggestive of pituitary tumor, appear to form a fairly typical picture of the condition. Long follow-up was possible in two of the cases. There are no radiological features which distinguish the lesion from pituitary tumor, hence the importance of recognizing the significance of such a clinical presentation with radiological evidence of sellar enlargement. Pituitary abscesses seem to occur in preexisting pituitary tumors. The possible relationship with pituitary infarction is discussed. PMID:865667

  7. Pituitary gland

    MedlinePlus Videos and Cool Tools

    ... gland is the hypothalamus. The hypothalamus decides which hormones the pituitary should release by sending it either ... the hypothalamus, the pituitary gland releases the following hormones: GH (growth hormone) – increases size of muscle and ...

  8. Inhibitory effect of pure 31-kilodalton bovine inhibin on gonadotropin-releasing hormone (GnRH)-induced up-regulation of GnRH binding sites in cultured rat anterior pituitary cells.

    PubMed

    Wang, Q F; Farnworth, P G; Findlay, J K; Burger, H G

    1989-01-01

    Primary cultures of enzymatically dispersed rat anterior pituitary cells were used to examine the effect of pure 31 kilodalton bovine inhibin on GnRH-induced up-regulation of GnRH binding sites. After 2 days in culture, the cells were exposed to stimuli with or without test substances for 10 h, followed by evaluation of GnRH binding sites using iodinated GnRH-A (Buserelin) as tracer. Inhibin suppressed GnRH-induced up-regulation of GnRH binding sites in a dose-dependent manner with an IC50 of 0.13 U/ml (5.5 pM). The inhibin-related peptides transforming growth factor-beta, and Müllerian inhibitory substance had no detectable effect (stimulatory or inhibitory), suggesting that the action is specific to inhibin. In addition, inhibin inhibited the calcium ionophore A23187-induced up-regulation of GnRH binding sites, indicating that this effect of inhibin can occur, at least in part, at a stage subsequent to Ca2+ mobilization. Inhibin did not compete with iodinated GnRH-A for GnRH binding sites. In conclusion, pure 31 kilodalton bovine inhibin suppressed GnRH-induced up-regulation of GnRH binding sites in cultured rat anterior pituitary cells, providing direct evidence that inhibin modulates delayed actions of GnRH. PMID:2535810

  9. The adverse effects of aldrin and dieldrin on both myometrial contractions and the secretory functions of bovine ovaries and uterus in vitro.

    PubMed

    Wrobel, Michał H; Grzeszczyk, Marlena; Mlynarczuk, Jaroslaw; Kotwica, Jan

    2015-05-15

    Aldrin and dieldrin are chloroorganic insecticides which are recognised as endocrine disruptors. The aim of the study was to investigate their effect on the secretory functions of the uterus and ovary and on myometrial contractions. Myometrial strips and uterine and ovarian cells from nonpregnant cows were incubated with the xenobiotics (0.1, 1 or 10 ng/ml) for 24 or 72 h. Next, their effect on viability of myometrial, endometrial, granulosa and luteal cells, myometrial strip contractions, the synthesis and secretion of prostaglandins (PGs: PGF2α and PGE2) from uterine cells, the secretion of oestradiol (E2), testosterone (T) and oxytocin (OT) from granulosa cells and the secretion of progesterone (P4) and OT from luteal cells were determined. Neither of the xenobiotics (10 ng/ml) affected (P>0.05) the viability of the ovarian and uterine cells, while both (0.1-10 ng/ml) decreased (P<0.05) the basal and OT-stimulated myometrial contractions. In spite of these effects, neither of the insecticides affected (P>0.05) the synthesis and the secretion of PGs from the myometrial cells. Although they also did not impair the secretion of the PGs from the endometrial cells, they abolished (P<0.05) the stimulatory effect of OT (P<0.05) on the secretion of the PGs and stimulated (P<0.05) the secretion of OT from the granulosa and luteal cells. Moreover, aldrin and dieldrin stimulated secretion of E2 and T from the granulosa cells, while only dieldrin increased (P<0.05) the secretion of P4 from luteal cells. The data show that aldrin and dieldrin stimulated the secretory function of the cultured granulosa and luteal cells and inhibited the myometrial contractions of cows in vitro, which may affect on natural parturition. PMID:25771128

  10. Electrophoretic separation of kidney and pituitary cells on STS-8

    NASA Technical Reports Server (NTRS)

    Morrison, D. R.; Nachtwey, D. S.; Barlow, G. H.; Cleveland, C.; Lanham, J. W.; Farrington, M. A.; Hatfield, J. M.; Hymer, W. C.; Grindeland, R.; Lewis, M. L.

    1984-01-01

    Specific secretory cells were separated from suspensions of cultured primary human embryonic cells and rat pituitary cells in microgravity conditions, with an objective of isolating the subfractions of kidney cells that produce the largest amount of urakinase, and the subfractions of rat pituitary cells that secrete growth hormones (GH), prolactin (PRL), and other hormones. It is inferred from the experimental observations that the surface charge distributions of the GH-containing cells differ from those of the PRL-containing cells, which is explained by the presence of secretory products on the surface of pituitary cells. For kidney cells, the electrophoretic mobility distributions in flight experiments were spread more than the ground controls.

  11. Pituitary tumor

    MedlinePlus

    ... The pituitary is a small gland at the base of the brain. It regulates the body's balance of many hormones. ... cause symptoms and are never diagnosed during the person's lifetime. ... at the base of the brain. The pituitary helps control the ...

  12. Pituitary Tumors

    MedlinePlus

    ... or milk production), sex hormones (control the menstrual cycle and other sexual functions), thyroid gland hormones (control the thyroid gland), adrenal gland hormones, and vasopressin (a hormone involved in water and electrolyte balance). Symptoms of pituitary adenoma and ...

  13. Asparagine-linked oligosaccharides on lutropin, follitropin, and thyrotropin: distributions of sulfated and sialylated oligosaccharides on bovine, ovine, and human pituitary glycoprotein hormones

    SciTech Connect

    Green, E.D.; Baenziger, J.U.

    1988-01-05

    The asparagine-linked oligosaccharides on the pituitary glycoprotein hormones lutropin (LH), follitropin (FSH), and thyrotropin (TSH) consist of a heterogeneous array of neutral, sulfated, sialylated, and sulfated/sialylated structures. In this study, the authors determined the relative quantities of the various asparagine-linked oligosaccharides on LH, FSH, and TSH from these three animal species. The proportions of sulfated versus sialylated oligosaccharides varied markedly among the different hormones. Both hormone- and animal species-specific differences in the types and distributions of sulfated, sialylated, and sulfated/sialylated structures were evident. In particular, LH and FSH, which are synthesized in the same pituitary cell and bear ..cap alpha..-subunits with the identical amino acid sequence, contained significantly different distributions of sulfated and sialylated oligosaccharides. For all three animal species, the ratio of sialylated to sulfated oligosaccharides differed by >10-fold for LH and FSH, with sulfated structures dominating on LH and sialylated structures on FSH. Sialylated oligosaccharides were also heterogeneous with respect to sialic acid linkage (..cap alpha..2,3 versus ..cap alpha..2,6). The differences in oligosaccharide structures among the various pituitary glycoprotein hormones as well as among the various glycosylation sites within a single hormone support the hypothesis that glycosylation may serve important functional roles in the expression and/or regulation of hormone bioactivity.

  14. Effects of pergolide on diethylstilbestrol-induced rat pituitary hyperplasia.

    PubMed Central

    Lloyd, R. V.; Schmidt, K.; Nath, V.

    1985-01-01

    Hyperplastic anterior pituitary glands were produced in female rats by treatment with 10 mg of diethylstilbestrol in Silastic tubing. This led to increased numbers of immunoreactive prolactin cells and increased serum prolactin levels. After 6 weeks of diethylstilbestrol treatment, one group of rats was treated with daily injections of pergolide for 3 weeks. Pergolide produced a significant decrease in pituitary gland weight and in serum prolactin levels but did not change the percentage of prolactin cells significantly, compared with that of control rats. Ultrastructural studies showed a significant increase in the numbers of prolactin secretory granules and numerous large intracellular bodies with associated secretory granules in pituitaries from rats treated with pergolide. In one group of rats in which the diethylstilbestrol was discontinued for 3 weeks after 6 weeks of treatment there was a significant decrease in pituitary gland weight and serum prolactin and a significant decrease in the percentage of prolactin cells, compared with values in the rats treated with diethylstilbestrol for 9 weeks. These results indicate that pergolide causes decreased release of prolactin from secretory granules in anterior pituitary prolactin cells and an increase in the numbers of PRL secretory granules per cell but does not change the percentage of prolactin-producing pituitary cells after 3 weeks of treatment. Images Figure 3 Figure 4 Figure 1 p489-a Figure 2 Figure 5 Figure 6 PMID:4073221

  15. Pituitary Apoplexy.

    PubMed

    Briet, Claire; Salenave, Sylvie; Bonneville, Jean-François; Laws, Edward R; Chanson, Philippe

    2015-12-01

    Pituitary apoplexy, a rare clinical syndrome secondary to abrupt hemorrhage or infarction, complicates 2%-12% of pituitary adenomas, especially nonfunctioning tumors. Headache of sudden and severe onset is the main symptom, sometimes associated with visual disturbances or ocular palsy. Signs of meningeal irritation or altered consciousness may complicate the diagnosis. Precipitating factors (increase in intracranial pressure, arterial hypertension, major surgery, anticoagulant therapy or dynamic testing, etc) may be identified. Corticotropic deficiency with adrenal insufficiency may be life threatening if left untreated. Computed tomography or magnetic resonance imaging confirms the diagnosis by revealing a pituitary tumor with hemorrhagic and/or necrotic components. Formerly considered a neurosurgical emergency, pituitary apoplexy always used to be treated surgically. Nowadays, conservative management is increasingly used in selected patients (those without important visual acuity or field defects and with normal consciousness), because successive publications give converging evidence that a wait-and-see approach may also provide excellent outcomes in terms of oculomotor palsy, pituitary function and subsequent tumor growth. However, it must be kept in mind that studies comparing surgical approach and conservative management were retrospective and not controlled. PMID:26414232

  16. 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

  17. Pituitary Tumors

    MedlinePlus

    ... org Tel: 773-577-8750; 800-886-2282 Fax: 847-827-9918 National Brain Tumor Society 55Chapel ... http://www.braintumor.org Tel: 866-455-3214 Fax: 617-924-9998 Pituitary Network Association P.O. ...

  18. Outcomes of endoscopic transsphenoidal pituitary surgery.

    PubMed

    Dallapiazza, Robert F; Jane, John A

    2015-03-01

    Since the 1990s, endoscopic transsphenoidal surgery for pituitary adenomas has increased in popularity. Outcomes of endoscopic surgery for clinically secretory adenomas are favorable, and results for nonfunctional tumors reveal high rates of complete resection, improvements in vision, and low rates of complications. This article discusses some of the recent studies reporting outcomes from endoscopic series for Cushing disease, acromegaly, prolactin-secreting tumors, and nonfunctioning macroadenomas. PMID:25732647

  19. Stages of Pituitary Tumors

    MedlinePlus

    ... tumors that may spread to bones of the skull or the sinus cavity below the pituitary gland. ... sella (the bone at the base of the skull , where the pituitary gland sits). Recurrent Pituitary Tumors ...

  20. Gonadotropin-releasing hormone agonist-induced pituitary apoplexy

    PubMed Central

    Keane, Fergus; Navin, Patrick; Brett, Francesca; Dennedy, Michael C

    2016-01-01

    Summary Pituitary apoplexy represents an uncommon endocrine emergency with potentially life-threatening consequences. Drug-induced pituitary apoplexy is a rare but important consideration when evaluating patients with this presentation. We describe an unusual case of a patient with a known pituitary macroadenoma presenting with acute-onset third nerve palsy and headache secondary to tumour enlargement and apoplexy. This followed gonadotropin-releasing hormone (GNRH) agonist therapy used to treat metastatic prostate carcinoma. Following acute management, the patient underwent transphenoidal debulking of his pituitary gland with resolution of his third nerve palsy. Subsequent retrospective data interpretation revealed that this had been a secretory gonadotropinoma and GNRH agonist therapy resulted in raised gonadotropins and testosterone. Hence, further management of his prostate carcinoma required GNRH antagonist therapy and external beam radiotherapy. This case demonstrates an uncommon complication of GNRH agonist therapy in the setting of a pituitary macroadenoma. It also highlights the importance of careful, serial data interpretation in patients with pituitary adenomas. Finally, this case presents a unique insight into the challenges of managing a hormonal-dependent prostate cancer in a patient with a secretory pituitary tumour. Learning points While non-functioning gonadotropinomas represent the most common form of pituitary macroadenoma, functioning gonadotropinomas are exceedingly rare. Acute tumour enlargement, with potential pituitary apoplexy, is a rare but important adverse effect arising from GNRH agonist therapy in the presence of both functioning and non-functioning pituitary gonadotropinomas. GNRH antagonist therapy represents an alternative treatment option for patients with hormonal therapy-requiring prostate cancer, who also have diagnosed with a pituitary gonadotropinoma. PMID:27284452

  1. The pituitary growth hormone cell in space

    NASA Technical Reports Server (NTRS)

    Hymer, Wesley C.; Grindeland, R.

    1989-01-01

    Growth hormone (GH), produced and secreted from specialized cells in the pituitary gland, controls the metabolism of protein, fat, and carbohydrate. It is also probably involved in the regulation of proper function of bone, muscle and immune systems. The behavior of the GH cell system was studied by flying either isolated pituitary cells or live rats. In the latter case, pituitary GH cells are prepared on return to earth and then either transplanted into hypophysectomized rats or placed into cell culture so that function of GH cells in-vivo vs. in-vitro can be compared. The results from three flights to date (STS-8, 1983; SL-3, 1985; Cosmos 1887, 1987) established that the ability of GH cells to release hormone, on return to earth, is compromised. The mechanism(s) responsible for this attenuation response is unknown. However, the data are sufficiently positive to indicate that the nature of the secretory defect resides directly within the GH cells.

  2. Pathogenesis of pituitary tumors.

    PubMed

    Yu, Run; Melmed, Shlomo

    2010-01-01

    Pituitary tumors are common and mostly benign neoplasia which cause excess or deficiency of pituitary hormones and compressive damage to adjacent organs. Oncogene activation [e.g. PTTG (pituitary tumor-transforming gene) and HMGA2], tumor suppressor gene inactivation (e.g. MEN1 and PRKAR1A), epigenetic changes (e.g. methylation) and humoral factors (e.g. ectopic production of stimulating hormones) are all possible pituitary tumor initiators; the micro-environment of pituitary tumors including steroid milieu, angiogenesis and abnormal cell adhesion further promote tumor growth. Senescence, a cellular defence mechanism against malignant transformation, may explain the benign nature of at least some pituitary tumors. We suggest that future research on pituitary tumor pathogenesis should incorporate systems approaches, and address regulatory mechanisms for pituitary cell proliferation, development of new animal models of pituitary tumor and isolation of functional human pituitary tumor cell lines. PMID:20541667

  3. Purinergic Regulation of Hypothalamo-Pituitary Functions

    PubMed Central

    Stojilkovic, Stanko S.

    2009-01-01

    The hypothalamus controls the release of hormones by the pituitary and is involved in control of food and water intake, sexual behavior, reproduction, and daily cycles in physiological state and behavior, temperature regulation, and emotional responses. Adenosine-5′-triphosphate (ATP) and its metabolic products contribute to these functions, acting as agonists for adenosine and P2Y receptors and two-transmembrane domain P2X receptor channels. This review summarizes the recent findings on purinergic receptor expression and their roles in signaling and cellular function in secretory and supporting cells of the hypothalamo-pituitary system. ATP secretion by these tissues, the enzymes involved in ATP hydrolysis, and the relevance of this pathway for sequential activation of receptors and termination of signaling is also discussed. PMID:19800813

  4. Pregnancy and pituitary adenomas.

    PubMed

    Glezer, Andrea; Jallad, Raquel S; Machado, Marcio C; Fragoso, Maria C; Bronstein, Marcello D

    2016-09-01

    Infertility is frequent in patients harboring pituitary adenomas. The mechanisms involved include hypogonadism secondary to hormonal hypersecretion (prolactin, growth hormone and cortisol), stalk disconnection and pituitary damage. With the improvement of clinical and surgical treatment, pregnancy in women harboring pituitary adenomas turned into a reality. Pituitary hormonal hyper- and hyposecretion influences pregnancy outcomes, as well as pregnancy can interfere on pituitary tumors, especially in prolactinomas. We review literature about specific follow-up and management in pregnant women harboring prolactinomas, acromegaly, or Cushings disease and the impact of clinical and surgical treatment on each condition. PMID:26977888

  5. General Information about Pituitary Tumors

    MedlinePlus

    ... tumors that may spread to bones of the skull or the sinus cavity below the pituitary gland. ... sella (the bone at the base of the skull , where the pituitary gland sits). Recurrent Pituitary Tumors ...

  6. Treatment Option Overview (Pituitary Tumors)

    MedlinePlus

    ... tumors that may spread to bones of the skull or the sinus cavity below the pituitary gland. ... sella (the bone at the base of the skull , where the pituitary gland sits). Recurrent Pituitary Tumors ...

  7. Familial pituitary tumors.

    PubMed

    Alband, Neda; Korbonits, Márta

    2014-01-01

    Pituitary adenomas are benign intracranial neoplasms that present a major clinical concern due to hormone overproduction and/or tumor mass effects. The majority of pituitary adenomas occur sporadically; however, familial cases are increasingly being recognized, such as multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC), and familial isolated pituitary adenoma (FIPA). Familial pituitary tumors appear to differ from their sporadic counterparts both in their genetic basis and in clinical characteristics. Evidence suggests that, especially in MEN1 and FIPA, tumors are more aggressive and affect patients at a younger age, therefore justifying the importance of early diagnosis, while in Carney complex pituitary hyperplasia is common. The genetic alterations responsible for the formation of familial pituitary syndromes include the MEN1 gene, responsible for about 80% of MEN1 cases, the regulatory subunit of the protein kinase A, PRKAR1A, responsible for about 70% of Carney complex cases, and AIP, the gene coding the aryl hydrocarbon receptor interacting protein, responsible for about 20% of FIPA cases. Rarely other genes have also been found responsible for familial pituitary adenoma cases. McCune-Albright syndrome (MAS) also has a genetic origin due to mosaic mutations in the G protein-coupled α subunit coded by the GNAS1 gene. In this chapter, we summarize the genetic and clinical characteristics of these familial pituitary syndromes and MAS. PMID:25248598

  8. Electrophoretic separation of cells and particles from rat pituitary and rat spleen

    NASA Technical Reports Server (NTRS)

    Hymer, Wesley C.

    1993-01-01

    There are 3 parts to the IML-2 TX-101 experiment. Part 1 is a pituitary cell culture experiment. Part 2 is a pituitary cell separation experiment using the Japanese free flow electrophoresis unit (FFEU). Part 3 is a pituitary secretory granule separation experiment using the FFEU. The objectives of this three part experiment are: (1) to determine the kinetics of production of biologically active growth hormone (GH) and prolactin (PRL) in rat pituitary GH and PRL cells in microgravity (micro-g); (2) to investigate three mechanisms by which a micro-g-induced lesion in hormone production may occur; and (3) to determine the quality of separations of pituitary cells and organelles by continuous flow electrophoresis (CFE) in micro-g under conditions where buoyancy-induced convection is eliminated.

  9. Double pituitary adenomas.

    PubMed

    Iacovazzo, D; Bianchi, A; Lugli, F; Milardi, D; Giampietro, A; Lucci-Cordisco, E; Doglietto, F; Lauriola, L; De Marinis, L

    2013-04-01

    Double pituitary adenomas represent up to 2.6 % of pituitary adenomas in large surgical series and up to 3.3 % of patients with Cushing's disease have been found to have double or multiple pituitary adenomas. We report the case of a 60-year-old male patient whose medical history began in 2002 with erectile dysfunction; hyperprolactinemia was found and MRI showed a 6-mm area of delayed enhancement in the lateral portion of the right pituitary lobe. Treatment with cabergoline was started with normalization of prolactin levels; the following MRI, performed in 2005 and 2008, showed shrinkage of the pituitary lesion. In 2005, the patient began to manifest weight gain, hypertension, and facial plethora, but no further evaluations were done. In January 2010, the patient came to our attention and underwent multiple tests that suggested Cushing's disease. A new MRI was negative. Bilateral inferior petrosal sinus sampling showed significant pituitary-to-peripheral ratio and, in May 2010, the patient underwent exploratory pituitary surgery with evidence of a 1-2-mm white-coloured midline area compatible with pituitary adenoma that was surgically removed. Post-operatively, the patient's clinical conditions improved with onset of secondary hypoadrenalism. The histologic examination confirmed a pituitary adenoma (immunostaining was found to be positive for ACTH and negative for prolactin). We report the case of an ACTH-producing microadenoma metachronous to a prolactin secreting microadenoma although not confirmed histologically, shrunk by medical treatment. A review of data in the literature regarding double or multiple pituitary adenomas has also been done. PMID:23325364

  10. Protein mobility within secretory granules.

    PubMed

    Weiss, Annita Ngatchou; Bittner, Mary A; Holz, Ronald W; Axelrod, Daniel

    2014-07-01

    We investigated the basis for previous observations that fluorescent-labeled neuropeptide Y (NPY) is usually released within 200 ms after fusion, whereas labeled tissue plasminogen activator (tPA) is often discharged over many seconds. We found that tPA and NPY are endogenously expressed in small and different subpopulations of bovine chromaffin cells in culture. We measured the mobility of these proteins (tagged with fluorophore) within the lumen of individual secretory granules in living chromaffin cells, and related their mobilities to postfusion release kinetics. A method was developed that is not limited by standard optical resolution, in which a bright flash of strongly decaying evanescent field (∼64 nm exponential decay constant) produced by total internal reflection (TIR) selectively bleaches cerulean-labeled protein proximal to the glass coverslip within individual granules. Fluorescence recovery occurred as unbleached protein from distal regions within the 300 nm granule diffused into the bleached proximal regions. The fractional bleaching of tPA-cerulean (tPA-cer) was greater when subsequently probed with TIR excitation than with epifluorescence, indicating that tPA-cer mobility was low. The almost equal NPY-cer bleaching when probed with TIR and epifluorescence indicated that NPY-cer equilibrated within the 300 ms bleach pulse, and therefore had a greater mobility than tPA-cer. TIR-fluorescence recovery after photobleaching revealed a significant recovery of tPA-cer (but not NPY-cer) fluorescence within several hundred milliseconds after bleaching. Numerical simulations, which take into account bleach duration, granule diameter, and the limited number of fluorophores in a granule, are consistent with tPA-cer being 100% mobile, with a diffusion coefficient of 2 × 10(-10) cm(2)/s (∼1/3000 of that for a protein of similar size in aqueous solution). However, the low diffusive mobility of tPA cannot alone explain its slow postfusion release. In the

  11. Pituitary Tumors: Condition Information

    MedlinePlus

    ... stress. Growth hormone helps control body growth and metabolism. Thyroid-stimulating hormone is involved in growth, body temperature, and heart rate. Nonfunctioning pituitary tumors (also called nonsecretory tumors) do ...

  12. What Are Pituitary Tumors?

    MedlinePlus

    ... too little makes you sluggish. If a pituitary tumor makes too much TSH, it can cause hyperthyroidism (an overactive thyroid gland). Adrenocorticotropic hormone (ACTH, also known as corticotropin ) causes ...

  13. Mapping organelle motion reveals a vesicular conveyor belt spatially replenishing secretory vesicles in stimulated chromaffin cells.

    PubMed

    Maucort, Guillaume; Kasula, Ravikiran; Papadopulos, Andreas; Nieminen, Timo A; Rubinsztein-Dunlop, Halina; Meunier, Frederic A

    2014-01-01

    How neurosecretory cells spatially adjust their secretory vesicle pools to replenish those that have fused and released their hormonal content is currently unknown. Here we designed a novel set of image analyses to map the probability of tracked organelles undergoing a specific type of movement (free, caged or directed). We then applied our analysis to time-lapse z-stack confocal imaging of secretory vesicles from bovine Chromaffin cells to map the global changes in vesicle motion and directionality occurring upon secretagogue stimulation. We report a defined region abutting the cortical actin network that actively transports secretory vesicles and is dissipated by actin and microtubule depolymerizing drugs. The directionality of this "conveyor belt" towards the cell surface is activated by stimulation. Actin and microtubule networks therefore cooperatively probe the microenvironment to transport secretory vesicles to the periphery, providing a mechanism whereby cells globally adjust their vesicle pools in response to secretagogue stimulation. PMID:24489879

  14. Amyloid formation of growth hormone in presence of zinc: Relevance to its storage in secretory granules.

    PubMed

    Jacob, Reeba S; Das, Subhadeep; Ghosh, Saikat; Anoop, Arunagiri; Jha, Narendra Nath; Khan, Tuhin; Singru, Praful; Kumar, Ashutosh; Maji, Samir K

    2016-01-01

    Amyloids are cross-β-sheet fibrillar aggregates, associated with various human diseases and native functions such as protein/peptide hormone storage inside secretory granules of neuroendocrine cells. In the current study, using amyloid detecting agents, we show that growth hormone (GH) could be stored as amyloid in the pituitary of rat. Moreover, to demonstrate the formation of GH amyloid in vitro, we studied various conditions (solvents, glycosaminoglycans, salts and metal ions) and found that in presence of zinc metal ions (Zn(II)), GH formed short curvy fibrils. The amyloidogenic nature of these fibrils was examined by Thioflavin T binding, Congo Red binding, transmission electron microscopy and X-ray diffraction. Our biophysical studies also suggest that Zn(II) initiates the early oligomerization of GH that eventually facilitates the fibrillation process. Furthermore, using immunofluorescence study of pituitary tissue, we show that GH in pituitary significantly co-localizes with Zn(II), suggesting the probable role of zinc in GH aggregation within secretory granules. We also found that GH amyloid formed in vitro is capable of releasing monomers. The study will help to understand the possible mechanism of GH storage, its regulation and monomer release from the somatotrophs of anterior pituitary. PMID:27004850

  15. Amyloid formation of growth hormone in presence of zinc: Relevance to its storage in secretory granules

    PubMed Central

    Jacob, Reeba S.; Das, Subhadeep; Ghosh, Saikat; Anoop, Arunagiri; Jha, Narendra Nath; Khan, Tuhin; Singru, Praful; Kumar, Ashutosh; Maji, Samir K.

    2016-01-01

    Amyloids are cross-β-sheet fibrillar aggregates, associated with various human diseases and native functions such as protein/peptide hormone storage inside secretory granules of neuroendocrine cells. In the current study, using amyloid detecting agents, we show that growth hormone (GH) could be stored as amyloid in the pituitary of rat. Moreover, to demonstrate the formation of GH amyloid in vitro, we studied various conditions (solvents, glycosaminoglycans, salts and metal ions) and found that in presence of zinc metal ions (Zn(II)), GH formed short curvy fibrils. The amyloidogenic nature of these fibrils was examined by Thioflavin T binding, Congo Red binding, transmission electron microscopy and X-ray diffraction. Our biophysical studies also suggest that Zn(II) initiates the early oligomerization of GH that eventually facilitates the fibrillation process. Furthermore, using immunofluorescence study of pituitary tissue, we show that GH in pituitary significantly co-localizes with Zn(II), suggesting the probable role of zinc in GH aggregation within secretory granules. We also found that GH amyloid formed in vitro is capable of releasing monomers. The study will help to understand the possible mechanism of GH storage, its regulation and monomer release from the somatotrophs of anterior pituitary. PMID:27004850

  16. Treatment Options for Pituitary Tumors

    MedlinePlus

    ... brain, including the sella (the bone at the base of the skull , where the pituitary gland sits). ... sphenoid bone (a butterfly-shaped bone at the base of the skull ) to reach the pituitary gland . ...

  17. Changes in Pituitary Function with Aging and Implications for Patient Care

    PubMed Central

    Veldhuis, Johannes D.

    2014-01-01

    The pituitary gland has a role in puberty, reproduction, stress-adaptive responses, sodium and water balance, uterine contractions, lactation, thyroid function, growth, body composition and skin pigmentation. Ageing is marked by initially subtle erosion of physiological signalling mechanisms, resulting in lower incremental secretory-burst amplitude, more disorderly patterns of pituitary hormone release and blunted 24 h rhythmic secretion. Almost all pituitary hormones are altered by ageing in humans, often in a manner dependent upon sex, body composition, stress, comorbidity, intercurrent illness, medication use, physical frailty, caloric intake, immune status, level of exercise, and neurocognitive decline. The aim of this article is to critically discuss the mechanisms mediating clinical facets of changes in the hypothalamic–pituitary axis during ageing, and the extent to which confounding factors operate to obscure ageing effects. PMID:23438832

  18. [Treatment of pituitary adenomas].

    PubMed

    Mezosi, Emese; Nemes, Orsolya

    2009-09-27

    According to epidemiological studies, the prevalence of pituitary adenomas is 16.5% and the majority of them are "incidentalomas". The symptoms of pituitary disorders are often non-specific; disturbances of pituitary function, compression symptoms, hypophysis apoplexy or accidental findings may help the diagnosis. The hormonal evaluation of pituitary adenomas is different from the algorithm used in the disorders of peripheral endocrine organs. The first-line therapy of prolactinomas are the dopamine agonists, and the aims of the treatment are to normalize the prolactin level, restore fertility in child-bearing age, decrease tumor mass, save or improve the residual pituitary function and inhibit the relapse of the disease. The available dopamine agonists in Hungary are bromocriptine and quinagolide. In case of tumors with good therapeutic response, medical therapy can be withdrawn after 3-5 years; hyperprolactinemia will not recur in 2/3 of these patients. Neurosurgery is the primary therapy of GH-, ACTH-, TSH-producing and inactive adenomas. In the last decades, significant improvement has been reached in surgical procedures, resulting in low mortality rates. Acromegalic patients with unresectable tumors have a great benefit from somatostatin analog treatment. The growth hormone receptor antagonist pegvisomant is the newest modality for the treatment of acromegaly. The medical therapy of Cushing's disease is still based on the inhibition of steroid production. A new, promising somatostatin analog, pasireotide is evaluated in clinical trials. The rare TSH-producing tumor can respond to both dopamine agonist and somatostatin analog therapy. The application of conventional radiotherapy has decreased; radiotherapy is mainly used in the treatment of invasive, incurable or malignant tumors. Further studies are needed to elucidate the exact role of radiosurgery and fractionated stereotaxic irradiation in the treatment of pituitary tumors. PMID:19758960

  19. Pituitary abscess: an unexpected diagnosis.

    PubMed

    Shuster, Anatoly; Gunnarsson, Thorsteinn; Sommer, Doron; Miller, Elka

    2010-02-01

    The pituitary gland can demonstrate a variety of pathologies with different clinical presentations. Amongst them, pituitary abscess is a rare infectious disease for which contrast-enhanced MRI aids the diagnostic pathway. We present a 16-year-old girl with imaging and surgical findings consistent with primary pituitary abscess. PMID:19937240

  20. Prokaryotic adenylate cyclase toxin stimulates anterior pituitary cells in culture

    SciTech Connect

    Cronin, M.J.; Evans, W.S.; Rogol, A.D.; Weiss, A.A.; Thorner, M.O.; Orth, D.N.; Nicholson, W.E.; Yasumoto, T.; Hewlett, E.L.

    1986-08-01

    Bordetella pertussis synthesis a variety of virulence factors including a calmodulin-dependent adenylate cyclase (AC) toxin. Treatment of anterior pituitary cells with this AC toxin resulted in an increase in cellular cAMP levels that was associated with accelerated exocytosis of growth hormone (GH), prolactin, adrenocorticotropic hormone (ACTH), and luteinizing hormone (LH). The kinetics of release of these hormones, however, were markedly different; GH and prolactin were rapidly released, while LH and ACTH secretion was more gradually elevated. Neither dopamine agonists nor somatostatin changes the ability of AC toxin to generate cAMP (up to 2 h). Low concentrations of AC toxin amplified the secretory response to hypophysiotrophic hormones. The authors conclude that bacterial AC toxin can rapidly elevate cAMP levels in anterior pituitary cells and that it is the response that explains the subsequent acceleration of hormone release.

  1. Three-dimensional reconstruction and morphological characterization of pituitary macroadenomas

    PubMed Central

    Wei, Lin; Jing, Jun-Jie; Zhang, Shang-Ming

    2016-01-01

    Introduction The aim was to investigate the relationship between the tumor (clinicopathologic and radiological) characteristics and the morphological parameters of pituitary macroadenoma or giant adenoma patients using a three-dimensional (3D) reconstructed model. Material and methods Magnetic resoanance imaging (MRI) was performed preoperatively; tumor grade was determined by the Knosp-Steiner classification and tumor morphology by the SIPAP classification. Pituitary adenomas and adjacent structures were reconstructed three-dimensionally by volume rendering. Results Fifty-two and 6 patients underwent surgery via the transnasal transsphenoidal or pterional approach, respectively. Knosp-Steiner grades I to IV adenomas were observed in 5.2%, 25.9%, 22.4% and 46.6% of the patients, respectively. The 3D model was reconstructed in all cases with superb delineation of tumor morphology and the spatial relationship between the tumor and adjacent tissues. Pituitary adenomas were categorized into intrasellar (13.8%), suprasellar (20.7%), infrasellar (17.2%), and lobulated adenomas (48.3%). Suprasellar adenomas had the smallest (2.27 ±3.22 cm3) and lobulated adenomas the largest volume (24.61 ±30.50 cm3). Intrasellar adenomas were all functioning, while 75%, 60% and 60.7%, respectively, of suprasellar, infrasellar and lobulated adenomas were nonfunctioning, with a significant association between tumor morphology and secretory function (p = 0.005). Conclusions Three-dimensional reconstruction of pituitary macroadenomas offers a simplified morphological classification of pituitary adenomas and may be helpful for neurosurgeons to categorize and characterize pituitary adenomas. PMID:27279851

  2. Proteolysis in the secretory pathway

    SciTech Connect

    Guzowski, D.E.; Bienkowski, R.S.

    1987-05-01

    Many secretory proteins are degraded intracellularly rather than secreted, however the location of this catabolic process is not known. The authors have tested the hypothesis that the degradation occurs in the organelles of the secretory pathway. Slices of rat liver were incubated with (/sup 14/C)leucine for 3 h and then incubated under chase conditions for 30 min. The tissue was homogenized and the Golgi apparatus, smooth endoplasmic reticulum (sER) and rough endoplasmic reticulum (rER) were isolated by ultracentrifugation on a discontinuous sucrose gradient. The organelles were incubated in 0.3M sucrose-50 mM citrate (pH 4) for 8-12 h at 37 C; control samples were incubated at 4 C. Percent degradation was calculated as the amount of acid soluble radioactivity released relative to total radioactivity in the sample. Proteolysis in the organelles incubated at 37 C was as follows: Golgi: 15-25%; sER: 10-20%; rER: 10-20%. Proteolysis at 4 C was negligible in all cases. These results support the hypothesis that the compartments of the secretory pathway are capable of degrading newly synthesized secretory proteins.

  3. Molecular Imaging of Pituitary Pathology.

    PubMed

    de Herder, Wouter W

    2016-01-01

    The presence of large numbers and/or the high affinity of dopamine D2 and/or somatostatin receptors on pituitary adenomas may enable their visualization with radionuclide-coupled receptor agonists or antagonists. However, the role of these imaging modalities in the differential diagnosis of or therapeutic purposes for pituitary lesions is very limited. Only in very specific cases might these molecular imaging techniques become helpful. These include the differential diagnosis of pituitary lesions, ectopic production of pituitary hormones, such as adrenocorticotrophic hormone, growth hormone (GH) or their releasing hormones (corticotropin-releasing hormone and GH-releasing hormone), and the localization of metastases from pituitary carcinomas. PMID:27002335

  4. Pituitary cells in space

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.; Shellenberger, K.; Grindeland, R.

    1994-01-01

    Cells of the mammalian pituitary gland synthesize and secrete several protein hormones which regulate a number of organ systems throughout the body. These include the musculoskeletal, immune, vascular and endocrine systems. Since changes occur in these tissues as a result of spaceflight, and since pituitary growth hormone (GH) and prolactin (PRL) play a role in the control of these systems on earth, we have focused attention over the last 10 years on GH and PRL cell function during and after spaceflight. The cumulative results of 4 spaceflight missions and several mimicked microgravity experiments establish 1) that production and release of biologically active GH and PRL is repeatedly and significantly attenuated (usually >50%) and 2) that changes in cell morphology also occur. In this paper we describe our results within the framework of methodologies and approaches frequently used to study pituitary cell function on earth. In so doing we hope to develop future flight experiments aimed at uncovering possible microgravity 'sensing systems' within the pituitary cell.

  5. Pituitary aspergillus infection.

    PubMed

    Moore, Lauren A; Erstine, Emily M; Prayson, Richard A

    2016-07-01

    Fungal infection should be considered in the differential diagnosis of a pituitary or sellar mass, albeit fungal infections involving the pituitary gland and sella are a rare occurrence. We report a case of Aspergillus infection involving the pituitary gland and sellar region discovered in a 74-year-old man. The patient had a history of hypertension, chronic renal disease, autoimmune hemolytic anemia and presented with right eye pain, headaches and worsening hemiparesis. Imaging studies revealed a right internal carotid artery occlusion and an acute right pontine stroke along with smaller infarcts in the right middle cerebral artery distribution. Clinically, the patient was thought to have vasculitis. An infectious etiology was not identified. He developed respiratory distress and died. At autopsy, necrotizing meningitis was discovered. A predominantly chronic inflammatory cell infiltrate consisting of benign-appearing lymphocytes, plasma cells and macrophages was accompanied by acute angle branching, angioinvasive hyphae which were highlighted on Gomori methenamine silver staining and were morphologically consistent with Aspergillus species. In previously reported cases of Aspergillus infection involving the pituitary or sella, most presented with headaches or impaired vision and were not immunocompromised. A transsphenoidal surgical approach is recommended in suspected cases in order to minimize the risk of dissemination of the infection. Some patients have responded well to antifungal medications once diagnosed. PMID:26896907

  6. Pituitary Disorders and Osteoporosis

    PubMed Central

    Jawiarczyk-Przybyłowska, Aleksandra

    2015-01-01

    Various hormonal disorders can influence bone metabolism and cause secondary osteoporosis. The consequence of this is a significant increase of fracture risk. Among pituitary disorders such effects are observed in patients with Cushing's disease, hyperprolactinemia, acromegaly, and hypopituitarism. Severe osteoporosis is the result of the coexistence of some of these disorders and hypogonadism at the same time, which is quite often. PMID:25873948

  7. Pituitary cells in space

    NASA Astrophysics Data System (ADS)

    Hymer, W. C.; Shellenberger, K.; Grindeland, R.

    1994-08-01

    Cells of the mammalian pituitary gland synthesize and secrete several protein hormones which regulate a number of organ systems throughout the body. These include the musculoskeletal, immune, vascular and endocrine systems. Since changes occur in these tissues as a result of spaceflight, and since pituitary growth hormone (GH) and prolactin (PRL) play a role in the control of these systems on earth, we have focused attention over the last 10 years on GH and PRL cell function during and after spaceflight. The cumulative results of 4 spaceflight missions and several mimicked microgravity (μG) experiments establish 1) that production and release of biologically active GH and PRL is repeatedly and significantly attenuated (usually > 50%) and 2) that changes in cell morphology also occur. In this paper we describe our results within the framework of methodologies and approaches frequently used to study pituitary cell function on earth. In so doing we hope to develop future flight experiments aimed at uncovering possible μG ``sensing systems'' within the pituitary cell.

  8. Secretory Pathway of Trypanosomatid Parasites

    PubMed Central

    McConville, Malcolm J.; Mullin, Kylie A.; Ilgoutz, Steven C.; Teasdale, Rohan D.

    2002-01-01

    The Trypanosomatidae comprise a large group of parasitic protozoa, some of which cause important diseases in humans. These include Trypanosoma brucei (the causative agent of African sleeping sickness and nagana in cattle), Trypanosoma cruzi (the causative agent of Chagas' disease in Central and South America), and Leishmania spp. (the causative agent of visceral and [muco]cutaneous leishmaniasis throughout the tropics and subtropics). The cell surfaces of these parasites are covered in complex protein- or carbohydrate-rich coats that are required for parasite survival and infectivity in their respective insect vectors and mammalian hosts. These molecules are assembled in the secretory pathway. Recent advances in the genetic manipulation of these parasites as well as progress with the parasite genome projects has greatly advanced our understanding of processes that underlie secretory transport in trypanosomatids. This article provides an overview of the organization of the trypanosomatid secretory pathway and connections that exist with endocytic organelles and multiple lytic and storage vacuoles. A number of the molecular components that are required for vesicular transport have been identified, as have some of the sorting signals that direct proteins to the cell surface or organelles in the endosome-vacuole system. Finally, the subcellular organization of the major glycosylation pathways in these parasites is reviewed. Studies on these highly divergent eukaryotes provide important insights into the molecular processes underlying secretory transport that arose very early in eukaryotic evolution. They also reveal unusual or novel aspects of secretory transport and protein glycosylation that may be exploited in developing new antiparasite drugs. PMID:11875130

  9. The organization of the secretory machinery in chromaffin cells as a major factor in modeling exocytosis

    PubMed Central

    Villanueva, José; Torregrosa-Hetland, Cristina J.; Gil, Amparo; González-Vélez, Virginia; Segura, Javier; Viniegra, Salvador; Gutiérrez, Luis M.

    2010-01-01

    The organization of cytoplasm in excitable cells was a largely ignored factor when mathematical models were developed to understand intracellular calcium and secretory behavior. Here we employed a combination of fluorescent evanescent and transmitted light microscopy to explore the F-actin cytoskeletal organization in the vicinity of secretory sites in cultured bovine chromaffin cells. This technique and confocal fluorescent microscopy show chromaffin granules associated with the borders of cortical cytoskeletal cages forming an intricate tridimensional network. Furthermore, the overexpression of SNAP-25 in these cells also reveals the association of secretory machinery clusters with the borders of these cytoskeletal cages. The importance of these F-actin cage borders is stressed when granules appear to interact and remain associated during exocytosis visualized in acridin orange loaded vesicles. These results will prompt us to propose a model of cytoskeletal cages, where the secretory machinery is associated with its borders. Both the calcium level and the secretory response are enhanced in this geometrical arrangement when compared with a random distribution of the secretory machinery that is not restricted to the borders of the cage. PMID:20885775

  10. Molecular Mechanisms Underlying Pituitary Pathogenesis.

    PubMed

    Sapochnik, Melanie; Nieto, Leandro Eduardo; Fuertes, Mariana; Arzt, Eduardo

    2016-04-01

    During the last years, progress has been made on the identification of mechanisms involved in anterior pituitary cell transformation and tumorigenesis. Oncogene activation, tumor suppressor gene inactivation, epigenetic changes, and microRNAs deregulation contribute to the initiation of pituitary tumors. Despite the high prevalence of pituitary adenomas, they are mostly benign, indicating that intrinsic mechanisms may regulate pituitary cell expansion. Senescence is characterized by an irreversible cell cycle arrest and represents an important protective mechanism against malignancy. Pituitary tumor transforming gene (PTTG) is an oncogene involved in early stages of pituitary tumor development, and also triggers a senescence response by activating DNA-damage signaling pathway. Cytokines, as well as many other factors, play an important role in pituitary physiology, affecting not only cell proliferation but also hormone secretion. Special interest is focused on interleukin-6 (IL-6) because its dual function of stimulating pituitary tumor cell growth but inhibiting normal pituitary cells proliferation. It has been demonstrated that IL-6 has a key role in promoting and maintenance of the senescence program in tumors. Senescence, triggered by PTTG activation and mediated by IL-6, may be a mechanism for explaining the benign nature of pituitary tumors. PMID:26718581

  11. Pituitary stalk tuberculoma.

    PubMed

    Stalldecker, Graciela; Diez, Sabrina; Carabelli, Alejandra; Reynoso, Roxana; Rey, Raul; Hofmann, Nestor; Beresñak, Alejandro

    2002-01-01

    Pituitary tuberculomas are exceptionally rare. Even with no evidence of systemic tuberculosis, it is important to recognize these lesions in the differential diagnosis of the intrasuprasellar tumors because they are curable. At present, in developed countries the frequency of intracranial tuberculomas of nervous system tumors is around 0.5-4%, whereas in under developed countries is 15-30%. It mainly affects children and young adults. In some cases, an accurate diagnosis may lead to an efficient medical therapy on the basis of biological, hormonal and imaging scans examinations. The case we studied shows the difficulties encountered in the diagnosis of a thickened stalk having normal pituitary image. It is to be highlighted the usage of the Polymerase Chain Reaction (PCR) technique. PMID:12812306

  12. Familial pituitary adenomas.

    PubMed

    Vandeva, S; Vasilev, V; Vroonen, L; Naves, L; Jaffrain-Rea, M-L; Daly, A F; Zacharieva, S; Beckers, A

    2010-12-01

    Pituitary adenomas are benign intracranial neoplasms that present a major clinical concern because of hormonal overproduction or compression symptoms of adjacent structures. Most arise in a sporadic setting with a small percentage developing as a part of familial syndromes such as multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC), and the recently described familial isolated pituitary adenomas (FIPA) and MEN-4. While the genetic alterations responsible for the formation of sporadic adenomas remain largely unknown, considerable advances have been made in defining culprit genes in these familial syndromes. Mutations in MEN1 and PRKAR1A genes are found in the majority of MEN1 and CNC patients, respectively. About 15% of FIPA kindreds present with mutations of the aryl hydrocarbon receptor-interacting protein (AIP) gene. Mutations in the CDKN1B gene, encoding p27(Kip)¹ were identified in MEN4 cases. Familial tumours appear to differ from their sporadic counterparts not only in genetic basis but also in clinical characteristics. Evidence suggests that, especially in MEN1 and FIPA, they are more aggressive and affect patients at younger age, therefore justifying the importance of early diagnosis. In this review, we summarize the genetic and clinical characteristics of these familial pituitary adenomas. PMID:20961530

  13. Synchronous pituitary adenoma and pituicytoma.

    PubMed

    Neidert, Marian C; Leske, Henning; Burkhardt, Jan-Karl; Kollias, Spyros S; Capper, David; Schrimpf, Daniel; Regli, Luca; Rushing, Elisabeth J

    2016-01-01

    Pituicytoma is a rare benign neoplasm arising in the sellar region, usually found in the posterior lobe and/or pituitary stalk. Here, we report the case of a 67-year-old woman who presented with bitemporal hemianopsia and visual impairment accompanied by mildly elevated prolactin. Pathologic and molecular examination of the tissue removed transsphenoidally revealed 2 distinct tumors: pituitary adenoma and pituicytoma. To the best of our knowledge, histologically proven pituicytoma and pituitary adenoma have never been reported together. PMID:26476569

  14. A signal sequence is sufficient for green fluorescent protein to be routed to regulated secretory granules.

    PubMed

    El Meskini, R; Jin, L; Marx, R; Bruzzaniti, A; Lee, J; Emeson, R; Mains, R

    2001-02-01

    To investigate trafficking in neuroendocrine cells, green fluorescent protein (GFP) tags were fused to various portions of the preproneuropeptide Y (NPY) precursor. Two neuroendocrine cell lines, AtT-20 corticotrope tumor cells and PC-12 pheochromocytoma cells, along with primary anterior pituitary cells, were examined. Expression of chimeric constructs did not disrupt trafficking or regulated secretion of endogenous ACTH and prohormone convertase 1 in AtT-20 cells. Western blot and immunocytochemical analyses demonstrated that the chimeric constructs remained intact, as long as the Lys-Arg cleavage site within preproNPY was deleted. GFP was stored in, and released from, regulated granules in cells expressing half of the NPY precursor fused to GFP, and also in cells in which only the signal sequence of preproNPY was fused to GFP. Thus, in neuroendocrine cells, entering the lumen of the secretory pathway is sufficient to target GFP to regulated secretory granules. PMID:11159860

  15. Clinical Impact of the Current WHO Classification of Pituitary Adenomas.

    PubMed

    Saeger, W; Honegger, J; Theodoropoulou, M; Knappe, U J; Schöfl, C; Petersenn, S; Buslei, R

    2016-06-01

    WHO classifications should be used for comparing the results from different groups of pathologist and clinicians by standardized histopathological methods. Our present report describes the important parameters of pituitary adenoma pathology as demand of the WHO classification for correlation to endocrine data and prognosis. The combination of HE stain based structures with immunostainings for pituitary hormones allows subclassification of adenomas as the best method not only for correlations to clinical hyperfunctions but also for statements to the sensitivity of drug therapies (somatostatin analogs, dopamine agonists). GH-, PRL- and ACTH-secreting pituitary adenomas are further classified based on the size and number of their secretory granules by electron microscopy, or as is mostly the case nowadays by cytokeratin staining pattern, into densely and sparsely granulated. Granulation pattern may be considered for the prediction of treatment response in patients with GH-secreting adenomas, since the sparsely granulated subtype was shown to be less responsive to somatostatin analog treatment. For prognosis, it is important to identify aggressive adenomas by measurements of the Ki-67 index, of the number of mitoses, and of nuclear expression of p53. Among the criteria for atypical adenomas, high Ki-67 labeling index and invasive character are the most important adverse prognostic factors. Promising molecular markers have been identified that might supplement the currently used proliferation parameters. For defining atypical adenomas in a future histopathological classification system, we propose to provide the proliferative potential and the invasive character separately. PMID:26860936

  16. Electrophoretic separation of kidney and pituitary cells on STS-8

    NASA Astrophysics Data System (ADS)

    Morrison, D. R.; Nachtwey, D. S.; Barlow, G. H.; Cleveland, C.; Lanham, J. W.; Farrington, M. A.; Hatfield, J. M.; Hymer, W. C.; Todd, P.; Wilfinger, W.; Grindeland, R.; Lewis, M. L.

    A Continuous Flow Electrophoresis System (CFES) was used on Space Shuttle flight STS-8 to separate specific secretory cells from suspensions of cultured primary human embryonic kidney cells and rat pituitary cells. The objectives were to isolate the subfractions of kidney cells that produce the largest amounts of urokinase (plasminogen activator), and to isolate the subfractions of rat pituitary cells that secrete growth hormone, prolactin, and other hormones. Kidney cells were separated into more than 32 fractions in each of two electrophoretic runs. Electrophoretic mobility distributions in flight experiments were spread more than the ground controls. Multiple assay methods confirmed that all cultured kidney cell fractions produced some urokinase, and five to six fractions produced significantly more urokinase than the other fractions. Several fractions also produced tissue plasminogen activator. The pituitary cells were separated into 48 fractions in each of the two electrophoretic runs, and the amounts of growth hormone (GH) and prolactin (PRL) released into the medium for each cell fraction were determined. Cell fractions were grouped into eight mobility classes and immunocytochemically assayed for the presence of GH, PRL, ACTH, LH, TSH, and FSH. The patterns of hormone distribution indicate that the specialized cells producing GH and PRL are isolatable due to the differences in electrophoretic mobilities.

  17. Stress modulates intestinal secretory immunoglobulin A

    PubMed Central

    Campos-Rodríguez, Rafael; Godínez-Victoria, Marycarmen; Abarca-Rojano, Edgar; Pacheco-Yépez, Judith; Reyna-Garfias, Humberto; Barbosa-Cabrera, Reyna Elizabeth; Drago-Serrano, Maria Elisa

    2013-01-01

    Stress is a response of the central nervous system to environmental stimuli perceived as a threat to homeostasis. The stress response triggers the generation of neurotransmitters and hormones from the hypothalamus pituitary adrenal axis, sympathetic axis and brain gut axis, and in this way modulates the intestinal immune system. The effects of psychological stress on intestinal immunity have been investigated mostly with the restraint/immobilization rodent model, resulting in an up or down modulation of SIgA levels depending on the intensity and time of exposure to stress. SIgA is a protein complex formed by dimeric (dIgA) or polymeric IgA (pIgA) and the secretory component (SC), a peptide derived from the polymeric immunoglobulin receptor (pIgR). The latter receptor is a transmembrane protein expressed on the basolateral side of gut epithelial cells, where it uptakes dIgA or pIgA released by plasma cells in the lamina propria. As a result, the IgA-pIgR complex is formed and transported by vesicles to the apical side of epithelial cells. pIgR is then cleaved to release SIgA into the luminal secretions of gut. Down modulation of SIgA associated with stress can have negative repercussions on intestinal function and integrity. This can take the form of increased adhesion of pathogenic agents to the intestinal epithelium and/or an altered balance of inflammation leading to greater intestinal permeability. Most studies on the molecular and biochemical mechanisms involved in the stress response have focused on systemic immunity. The present review analyzes the impact of stress (mostly by restraint/immobilization, but also with mention of other models) on the generation of SIgA, pIgR and other humoral and cellular components involved in the intestinal immune response. Insights into these mechanisms could lead to better therapies for protecting against pathogenic agents and avoiding epithelial tissue damage by modulating intestinal inflammation. PMID:24348350

  18. Imaging of pediatric pituitary endocrinopathies

    PubMed Central

    Chaudhary, Vikas; Bano, Shahina

    2012-01-01

    Accurate investigation of the hypothalamic-pituitary area is required in pediatric patients for diagnosis of endocrine-related disorders. These disorders include hypopituitarism, growth failure, diencephalic syndrome, delayed puberty, precocious puberty, diabetes insipidus, syndrome of inappropriate antidiuretic hormone (SIADH) secretion, and hyperpituitarism. Magnetic resonance imaging (MRI) is the modality of choice to visualize hypothalamic-pituitary axis and associated endocrinopathies. Neuroimaging can be normal or disclose abnormalities related to pituitary-hypothalamic axis like (i) congenital and developmental malformations; (ii) tumors; (iii) cystic lesions; and (iv) infectious and inflammatory conditions. Classical midline anomalies like septo-optic dysplasias or corpus callosum agenesis are commonly associated with pituitary endocrinopathies and also need careful evaluation. In this radiological review, we will discuss neuroendocrine disorders related to hypothalamic pituitary-axis. PMID:23087850

  19. Cell-specific analysis of tracheobronchial secretory cells and secretions

    SciTech Connect

    Finkbeiner, W.E.

    1989-01-01

    In these studies, two methods (cell culture and monoclonal antibody production) that allowed cell-specific analysis of tracheobronchial secretion were used. Bovine tracheal submucosal gland cells were isolated, placed into culture and serially propagated. In culture, the cells maintained features of serous cells. The cells incorporated {sup 35}S into high molecular weight molecules. {beta}-adrenergic agonists stimulated release of radiolabeled molecules and elevations in intracellular cAMP levels, responses that could be blocked by the {beta}-adrenergic antagonist propranolol. Cyclic AMP appeared to be involved in the stimulus-secretion coupling events in serous cells since the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine potentiated the effects of isoproterenol on the secretory response and the elevation of intracellular cAMP levels. Furthermore, cAMP analogues elicited a secretory response in the absence of cAMP. The phosphorylation state of several cytosolic and particulate phosphoproteins was altered by cAMP-activated kinase activity. Monoclonal antibodies were produced against human airway secretions.

  20. Endoscopic pituitary surgery.

    PubMed

    Cappabianca, Paolo; Cavallo, Luigi Maria; de Divitiis, Oreste; Solari, Domenico; Esposito, Felice; Colao, Annamaria

    2008-01-01

    Pituitary surgery is a continuous evolving speciality of the neurosurgeons' armamentarium, which requires precise anatomical knowledge, technical skills and integrated appreciation of the pituitary pathophysiology. What we consider "pure" endoscopic transsphenoidal surgery is a procedure performed through the nose and the sphenoid bone, with the endoscope alone throughout the whole approach to visualize the surgical target area and without the use of any transsphenoidal retractor. It offers some advantages due to the endoscope itself: a superior close-up view of the relevant anatomy and an enlarged working angle are provided with an increased panoramic vision inside the surgical area. Concerning results in terms of mass removal, relief of clinical symptoms, cure of the underlying disease and complication rate, they are, at least, similar to those reported in the major microsurgical series, but patient compliance is by far better. Furthermore transsphenoidal endoscopy brings advantages to the patient (less nasal traumatism, no nasal packing, less post-op pain and usually quick recovery), to the surgeon (wider and closer view of the surgical target area, increase of the scientific activity as from the peer-reviewed literature on the topic in the last 10 years, smoothing of interdisciplinary cooperation), to the institution (shorter post-op hospital stay, increase of the case load). Besides, further progress and technological advance are expected from the close cooperation between different technologies and industries. Continuing works in such field of "minimalism" will offer further possibilities to provide the surgeon with even more effectiveness and safety, and, on the other hand, the patient with improvement of results. PMID:18286374

  1. Corticotropin-releasing factor (CRF) receptors in intermediate lobe of the pituitary: Biochemical characterization and autoradiographic localization

    SciTech Connect

    Grigoriadis, D.E.; De Souza, E.B.

    1989-01-01

    CRF receptors were characterized using radioligand binding and chemical affinity cross-linking techniques and localized using autoradiographic techniques in porcine, bovine and rat pituitaries. The binding of 125I-(Tyr0)-ovine CRF (125I-oCRF) to porcine anterior and neurointermediate lobe membranes was saturable and of high affinity with comparable KD values (200-600 pM) and receptor densities (100-200 fmoles/mg protein). The pharmacological rank order of potencies for various analogs and fragments of CRF in inhibiting 125I-oCRF binding in neurointermediate lobe was characteristic of the well-established CRF receptor in anterior pituitary. Furthermore, the binding of 125I-oCRF to both anterior and neurointermediate lobes of the pituitary was guanine nucleotide-sensitive. Affinity cross-linking studies revealed that the molecular weight of the CRF binding protein in rat intermediate lobe was identical to that in rat anterior lobe (Mr = 75,000). While the CRF binding protein in the anterior lobes of porcine and bovine pituitaries had identical molecular weights to CRF receptors in rat pituitary (Mr = 75,000), the molecular weight of the CRF binding protein in porcine and bovine intermediate lobe was slightly higher (Mr = 78,000). Pituitary autoradiograms from the three species showed specific binding sites for 125I-oCRF in anterior and intermediate lobes, with none being apparent in the posterior pituitary. The identification of CRF receptors in the intermediate lobe with comparable characteristics to those previously identified in the anterior pituitary substantiate further the physiological role of CRF in regulating intermediate lobe hormone secretion.

  2. Animal models of pituitary neoplasia

    PubMed Central

    Lines, K.E.; Stevenson, M.; Thakker, R.V.

    2016-01-01

    Pituitary neoplasias can occur as part of a complex inherited disorder, or more commonly as sporadic (non-familial) disease. Studies of the molecular and genetic mechanisms causing such pituitary tumours have identified dysregulation of >35 genes, with many revealed by studies in mice, rats and zebrafish. Strategies used to generate these animal models have included gene knockout, gene knockin and transgenic over-expression, as well as chemical mutagenesis and drug induction. These animal models provide an important resource for investigation of tissue-specific tumourigenic mechanisms, and evaluations of novel therapies, illustrated by studies into multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome in which ∼30% of patients develop pituitary adenomas. This review describes animal models of pituitary neoplasia that have been generated, together with some recent advances in gene editing technologies, and an illustration of the use of the Men1 mouse as a pre clinical model for evaluating novel therapies. PMID:26320859

  3. Secretory diarrhoea: mechanisms and emerging therapies

    PubMed Central

    Thiagarajah, Jay R.; Donowitz, Mark; Verkman, Alan S.

    2016-01-01

    Diarrhoeal disease remains a major health burden worldwide. Secretory diarrhoeas are caused by certain bacterial and viral infections, inflammatory processes, drugs and genetic disorders. Fluid secretion across the intestinal epithelium in secretory diarrhoeas involves multiple ion and solute transporters, as well as activation of cyclic nucleotide and Ca2+ signalling pathways. In many secretory diarrhoeas, activation of Cl− channels in the apical membrane of enterocytes, including the cystic fibrosis transmembrane conductance regulator and Ca2+-activated Cl− channels, increases fluid secretion, while inhibition of Na+ transport reduces fluid absorption. Current treatment of diarrhoea includes replacement of fluid and electrolyte losses using oral rehydration solutions, and drugs targeting intestinal motility or fluid secretion. Therapeutics in the development pipeline target intestinal ion channels and transporters, regulatory proteins and cell surface receptors. This Review describes pathogenic mechanisms of secretory diarrhoea, current and emerging therapeutics, and the challenges in developing antidiarrhoeal therapeutics. PMID:26122478

  4. Pituitary function following treatment with reproductive toxins

    SciTech Connect

    Cooper, R.L.; Goldman, J.M.; Rehnberg, G.L.

    1986-12-01

    Appropriate regulation of reproductive processes are dependent upon the integrity of pituitary function. In this selected review, the authors evaluate the evidence that certain environmental compounds exert their effect on reproductive function via a direct action on the pituitary gland. They also discuss examples of changes in pituitary hormone secretion that occur in response to changes in neuronal or gonadal control of the pituitary. A limited number of studies suggest that measures of pituitary hormone secretion provide an early and sensitive measure of a compound's potential effects on the reproductive system. However, the most striking aspect of this area is the sparse and inconsistent information describing pituitary function following exposure to environmental pollutants.

  5. Quantitative determination of the intracellular fate of internalized plasma membrane in dissociated pituitary prolactin cells utilizing a radioiodinated cationic ferritin probe (CFI) and electron microscopic autoradiography

    SciTech Connect

    Rosenzweig, L.J.; Kanwar, Y.S.

    1984-02-01

    Dissociated anterior pituitary cells derived from estrogen-treated female rats were incubated with radioiodinated cationic ferritin (CFI) for 2 min and subsequently in the absence of CFI for varying periods of time up to 3 hr in order to quantitate, using electron microscopic autoradiography, the distribution of retrieved plasma membrane in these cells. Following a 2-min incubation with CFI, autoradiographic grains were found to be associated almost exclusively with the plasma membrane. With increasing periods of incubation in the absence of CFI, grain-density analysis revealed increasing levels of CFI in multiple intracellular organelles. The levels of CFI were greatest for the lysosomes, intermediate for the mature secretory granules, and least for the Golgi cisternae and immature secretory granules. These findings are consistent with the idea that a portion of the retrieved plasma membrane is degraded in lysosomes and that the remainder is recycled to organelles comprising the secretory pathway to be reutilized in successive waves of the secretory cycle.

  6. Delayed sequelae of pituitary irradiation

    SciTech Connect

    Woodruff, K.H.; Lyman, J.T.; Lawrence, J.H.; Tobias, C.A.; Born, J.L.; Fabrikant, J.I.

    1984-01-01

    Since 1958, 781 patients at Lawrence Berkeley Laboratory have received helium-particle stereotactic radiosurgery to the adenohypophysis. Autopsy findings in 15 of these patients are reported. Ten patients received pituitary radiation (average dose, 116 Gy in six fractions) for progressive neovascularization retinopathy due to diabetes mellitus. Evidence of a time-dependent course of progressive fibrosis in their pituitary glands was found. Five patients were treated for eosinophilic adenomas. Although they had lower average doses of radiation (56 Gy in six fractions), their pituitary glands showed cystic cavitation of the adenomas. The adenomas thus appeared more radiosensitive than the normal pars anterior, which, in turn, was more radiosensitive than the adjacent neurohypophysis. No significant radiation changes were found in the surrounding brain or cranial nerves. The endocrine organs under pituitary control showed varying degrees of atrophy, and clinical tests revealed progressive hypofunction. It was concluded that charged-particle therapy produced a sharply delineated focal ral tests revealed progressive hypofunction. It was concluded that charged-particle therapy produced a sharply delineated focal radiation lesion confined to the pituitary gland but did not cause injury to the critical structures of the surrounding central nervous system.

  7. Porosome: The Universal Secretory Portal in Cells

    NASA Astrophysics Data System (ADS)

    Jena, Bhanu

    2012-10-01

    In the past 50 years it was believed that during cell secretion, membrane-bound secretory vesicles completely merge at the cell plasma membrane resulting in the diffusion of intra-vesicular contents to the cell exterior and the compensatory retrieval of the excess membrane by endocytosis. This explanation made no sense or logic, since following cell secretion partially empty vesicles accumulate as demonstrated in electron micrographs. Furthermore, with the ``all or none'' mechanism of cell secretion by complete merger of secretory vesicle membrane at the cell plasma membrane, the cell is left with little regulation and control of the amount of content release. Moreover, it makes no sense for mammalian cells to possess such `all or none' mechanism of cell secretion, when even single-cell organisms have developed specialized and sophisticated secretory machinery, such as the secretion apparatus of Toxoplasma gondii, the contractile vacuoles in paramecium, or the various types of secretory structures in bacteria. Therefore, in 1993 in a News and Views article in Nature, E. Neher wrote ``It seems terribly wasteful that, during the release of hormones and neurotransmitters from a cell, the membrane of a vesicle should merge with the plasma membrane to be retrieved for recycling only seconds or minutes later.'' This conundrum in the molecular mechanism of cell secretion was finally resolved in 1997 following discovery of the ``Porosome,'' the universal secretory machinery in cells. Porosomes are supramolecular lipoprotein structures at the cell plasma membrane, where membrane-bound secretory vesicles transiently dock and fuse to release inravesicular contents to the outside during cell secretion. In the past decade, the composition of the porosome, its structure and dynamics at nm resolution and in real time, and its functional reconstitution into artificial lipid membrane, have all been elucidated. Since porosomes in exocrine and neuroendocrine cells measure 100-180 nm

  8. The genetics of pituitary adenomas.

    PubMed

    Vandeva, Silvia; Jaffrain-Rea, Marie-Lise; Daly, Adrian F; Tichomirowa, Maria; Zacharieva, Sabina; Beckers, Albert

    2010-06-01

    Pituitary adenomas are one of the most frequent intracranial tumors with a prevalence of clinically-apparent tumors close to 1:1000 of the general population. They are clinically significant because of hormone overproduction and/or tumor mass effects in addition to the need for neurosurgery, medical therapies and radiotherapy. The majority of pituitary adenomas have a sporadic origin with recognized genetic mutations seldom being found; somatotropinomas are an exception, presenting frequent somatic GNAS mutations. In this and other phenotypes, tumorigenesis could possibly be explained by altered function of genes implicated in cell cycle regulation, growth factors or their receptors, cell-signaling pathways, specific hormonal factors or other molecules with still unclear mechanisms of action. Genetic changes, such as allelic loss or gene amplification, and epigenetic changes, usually by promoter methylation, have been implicated in abnormal gene expression, but alternative mechanisms may be present. Familial cases of pituitary adenomas represent 5% of all pituitary tumors. MEN1 mutations cause multiple endocrine neoplasia type 1 (MEN1), while the Carney complex (CNC) is characterized by mutations in the protein kinase A regulatory subunit-1alpha (PRKAR1A) gene or changes in a locus at 2p16. Recently, a MEN1-like condition, MEN4, was found to be related to mutations in the CDKN1B gene. The clinical entity of familial isolated pituitary adenomas (FIPA) is characterized by genetic defects in the aryl hydrocarbon receptor interacting protein (AIP) gene in about 15% of all kindreds and 50% of homogenous somatotropinoma families. Identification of familial cases of pituitary adenomas is important as these tumors may be more aggressive than their sporadic counterparts. PMID:20833337

  9. Secretory function of adipose tissue.

    PubMed

    Kuryszko, J; Sławuta, P; Sapikowski, G

    2016-01-01

    There are two kinds of adipose tissue in mammals: white adipose tissue - WAT and brown adipose tissue - BAT. The main function of WAT is accumulation of triacylglycerols whereas the function of BAT is heat generation. At present, WAT is also considered to be an endocrine gland that produces bioactive adipokines, which take part in glucose and lipid metabolism. Considering its endocrine function, the adipose tissue is not a homogeneous gland but a group of a few glands which act differently. Studies on the secretory function of WAT began in 1994 after discovery of leptin known as the satiation hormone, which regulates body energy homeostasis and maintainence of body mass. Apart from leptin, the following belong to adipokines: adiponectin, resistin, apelin, visfatin and cytokines: TNF and IL 6. Adiponectin is a polypeptide hormone of antidiabetic, anti-inflammatory and anti-atherogenic activity. It plays a key role in carbohydrate and fat metabolism. Resistin exerts a counter effect compared to adiponectin and its physiological role is to maintain fasting glycaemia. Visfatin stimulates insulin secretion and increases insulin sensitivity and glucose uptake by muscle cells and adipocytes. Apelin probably increases the insulin sensitivity of tissues. TNF evokes insulin resistance by blocking insulin receptors and inhibits insulin secretion. Approximately 30% of circulating IL 6 comes from adipose tissue. It causes insulin resistance by decreasing the expression of insulin receptors, decreases adipogenesis and adiponectin and visfatin secretion, and stimulates hepatic gluconeogenesis. In 2004, Bays introduced the notion of adiposopathy, defined as dysfunction of the adipose tissue, whose main feature is insulin and leptin resistance as well as the production of inflammatory cytokines: TNF and IL 6 and monocyte chemoattractant protein. This means that excess of adipose tissue, especially visceral adipose tissue, leads to the development of a chronic subclinical

  10. Changes in pituitary growth hormone cells prepared from rats flown on Spacelab 3

    NASA Technical Reports Server (NTRS)

    Grindeland, R.; Hymer, W. C.; Farrington, M.; Fast, T.; Hayes, C.; Motter, K.; Patil, L.; Vasques, M.

    1987-01-01

    The effect of exposure to microgravity on pituitary gland was investigated by examining cells isolated from anterior pituitaries of rats flown on the 7-day Spacelab 3 mission and, subsequently, cultured for 6 days. Compared with ground controls, flight cells contained more intracellular growth hormone (GH); however, the flight cells released less GH over the 6-day culture period and after implantation into hypophysectomized rats than did the control cells. Compared with control rats, glands from large rats (400 g) contained more somatotrophs (44 percent compared with 37 percent in control rats); small rats (200 g) showed no difference. No major differences were found in the somatotroph ultrastructure (by TEM) or in the pattern of the immunoactive GH variants. However, high-performance liquid chromatography fractionation of culture media indicated that flight cells released much less of a biologically active high-molecular weight GH variant, suggesting that space flight may lead to secretory dysfunction.

  11. Inhibition of the pituitary-adrenal response to stress during deprivation-induced feeding

    NASA Technical Reports Server (NTRS)

    Heybach, J. P.; Vernikos-Danellis, J.

    1979-01-01

    Plasma corticosterone and plasma and pituitary ACTH concentrations were determined during feeding and after application of an acute stress at various times after food and water presentation to male rats maintained on a restricted feeding and watering schedule. Both plasma corticosterone and ACTH concentrations fell after the presentation of food and water, and this fall was accompanied by increased levels of ACTH in the pituitary gland. In addition, a rise in plasma levels of ACTH was inhibited in response to an acute stress applied at 0-5 min after presentation of food and water, but ACTH synthesis was not. This inhibition of ACTH and corticosterone secretion in response to stress was transient and dissipated as a relatively linear function of the interval between food presentation and application of the stress. The results suggest that this feeding-induced, corticosteroid-independent inhibition of pituitary-adrenal activity involves active inhibitory mechanisms operating initially on ACTH secretory processes of the pituitary and later on the synthesis of ACTH or on the secretion of hypothalamic corticotropin-releasing factor.

  12. Characterization of pituitary growth hormone and its receptor in the green iguana (Iguana iguana).

    PubMed

    Ávila-Mendoza, José; Carranza, Martha; Pérez-Rueda, Ernesto; Luna, Maricela; Arámburo, Carlos

    2014-07-01

    Pituitary growth hormone (GH) has been studied in most vertebrate groups; however, only a few studies have been carried out in reptiles. Little is known about pituitary hormones in the order Squamata, to which the green iguana (gi) belongs. In this work, we characterized the hypophysis of Iguana iguana morphologically. The somatotrophs (round cells of 7.6-10 μm containing 250- to 300-nm secretory granules where the giGH is stored) were found, by immunohistochemistry and in situ hybridization, exclusively in the caudal lobe of the pars distalis, whereas the lactotrophs were distributed only in the rostral lobe. A pituitary giGH-like protein was obtained by immuno-affinity chromatography employing a heterologous antibody against chicken GH. giGH showed molecular heterogeneity (22, 44, and 88 kDa by SDS-PAGE/Western blot under non-reducing conditions and at least four charge variants (pIs 6.2, 6.5, 6.9, 7.4) by isoelectric focusing. The pituitary giGH cDNA (1016 bp), amplified by PCR and RACE, encodes a pre-hormone of 218 aa, of which 190 aa correspond to the mature protein and 28 aa to the signal peptide. The giGH receptor cDNA was also partially sequenced. Phylogenetic analyses of the amino acid sequences of giGH and giGHR homologs in vertebrates suggest a parallel evolution and functional relationship between the GH and its receptor. PMID:24769041

  13. [Pituitary apoplexy in a young woman.

    PubMed

    Lewis, Anna; Jarløv, Anne Elisabeth; Holm, Kirsten; Cleemann, Line

    2014-04-22

    Pituitary apoplexy occurs when a preexisting pituitary adenoma undergoes acute haemorrhage, infarct or both. The patho-genesis is not fully understood but macroadenomas and prolactinomas have been reported as being predisposed to apoplexy. Only a few cases are described in the paediatric population. We present a 17-year-old woman with secondary amenorrhoea, headache and blurred vision. An MRI showed a pituitary apoplexy in a preexisting macroadenoma. The majority of milder cases resolve spontaneously. Close monitoring of the pituitary function is important to detect pituitary insufficiency witch may need long-term hormone replacement therapy. PMID:25351468

  14. Toxoplasma secretory granules: one population or more?

    PubMed

    Mercier, Corinne; Cesbron-Delauw, Marie-France

    2015-02-01

    In Toxoplasma gondii, dense granules are known as the storage secretory organelles of the so-called GRA proteins (for dense granule proteins), which are destined to the parasitophorous vacuole (PV) and the PV-derived cyst wall. Recently, newly annotated GRA proteins targeted to the host cell nucleus have enlarged this view. Here we provide an update on the latest developments on the Toxoplasma secreted proteins, which to date have been mainly studied at both the tachyzoite and bradyzoite stages, and we point out that recent discoveries could open the issue of a possible, yet uncharacterized, distinct secretory pathway in Toxoplasma. PMID:25599584

  15. Quality control in the secretory assembly line.

    PubMed Central

    Helenius, A

    2001-01-01

    As a rule, only proteins that have reached a native, folded and assembled structure are transported to their target organelles and compartments within the cell. In the secretory pathway of eukaryotic cells, this type of sorting is particularly important. A variety of molecular mechanisms are involved that distinguish between folded and unfolded proteins, modulate their intracellular transport, and induce degradation if they fail to fold. This phenomenon, called quality control, occurs at several levels and involves different types of folding sensors. The quality control system provides a stringent and versatile molecular sorting system that guaranties fidelity of protein expression in the secretory pathway. PMID:11260794

  16. Management of nonfunctioning pituitary incidentaloma.

    PubMed

    Galland, Françoise; Vantyghem, Marie-Christine; Cazabat, Laure; Boulin, Anne; Cotton, François; Bonneville, Jean-François; Jouanneau, Emmanuel; Vidal-Trécan, Gwénaelle; Chanson, Philippe

    2015-07-01

    Prevalence of pituitary incidentaloma is variable: between 1.4% and 27% at autopsy, and between 3.7% and 37% on imaging. Pituitary microincidentalomas (serendipitously discovered adenoma <1cm in diameter) may increase in size, but only 5% exceed 10mm. Pituitary macroincidentalomas (serendipitously discovered adenoma>1cm in diameter) show increased size in 20-24% and 34-40% of cases at respectively 4 and 8years' follow-up. Radiologic differential diagnosis requires MRI centered on the pituitary gland. Initial assessment of nonfunctioning (NF) microincidentaloma is firstly clinical, the endocrinologist looking for signs of hypersecretion (signs of hyperprolactinemia, acromegaly or Cushing's syndrome), followed up by systematic prolactin and IGF-1 assay. Initial assessment of NF macroincidentaloma is clinical, the endocrinologist looking for signs of hormonal hypersecretion or hypopituitarism, followed up by hormonal assay to screen for hypersecretion or hormonal deficiency and by ophthalmologic assessment (visual acuity and visual field) if and only if the lesion is near the optic chiasm (OC). NF microincidentaloma of less than 5mm requires no surveillance; those of≥5mm are not operated on but rather monitored on MRI at 6months and then 2years. Macroincidentaloma remote from the OC is monitored on MRI at 1year, with hormonal exploration (for anterior pituitary deficiency), then every 2years. When macroincidentaloma located near the OC is managed by surveillance rather than surgery, MRI is recommended at 6months, with hormonal and visual exploration, then annual MRI and hormonal and visual assessment every 6months. Surgery is indicated in the following cases: evolutive NF microincidentaloma, NF macroincidentaloma associated with hypopituitarism or showing progression, incidentaloma compressing the OC, possible malignancy, non-compliant patient, pregnancy desired in the short-term, or context at risk of apoplexy. PMID:26054868

  17. Advanced virtual endoscopic pituitary surgery.

    PubMed

    Neubauer, André; Wolfsberger, Stefan; Forster, Marie-Thérèse; Mroz, Lukas; Wegenkittl, Rainer; Bühler, Katja

    2005-01-01

    Endoscopy has recently been introduced to endonasal transsphenoidal pituitary surgery as a minimally invasive procedure for the removal of various kinds of pituitary tumors. To reduce morbidity and mortality with this new technique, the surgeon must be well-trained and well-prepared. Virtual endoscopy can be beneficial as a tool for training, preoperative planning, and intraoperative support. This paper introduces STEPS, a virtual endoscopy system designed to aid surgeons in getting acquainted with the endoscopic view of the anatomy, the handling of instruments, the transsphenoidal approach, and challenges associated with the procedure. STEPS also assists experienced surgeons in planning a real endoscopic intervention by getting familiar with the individual patient anatomy, identifying landmarks, planning the approach, and deciding upon the ideal target position of the actual surgical activity. The application provides interactive visualization, navigation, and perception aids and the possibility of simulating the procedure, including haptic feedback and simulation of surgical instruments. PMID:16144247

  18. Hypothalamic-pituitary thyroid axis alterations in female mice with deletion of the neuromedin B receptor gene.

    PubMed

    Oliveira, Karen J; Paula, Gabriela S M; Império, Guinever E; Bressane, Nina O; Magalhães, Carolina M A; Miranda-Alves, Leandro; Ortiga-Carvalho, Tania M; Pazos-Moura, Carmen C

    2014-11-01

    Neuromedin B, a peptide highly expressed at the pituitary, has been shown to act as autocrine/paracrine inhibitor of thyrotropin (TSH) release. Here we studied the thyroid axis of adult female mice lacking neuromedin B receptor (NBR-KO), compared to wild type (WT) littermates. They exhibited slight increase in serum TSH (18%), with normal pituitary expression of mRNA coding for α-glycoprotein subunit (Cga), but reduced TSH β-subunit mRNA (Tshb, 41%), lower intra-pituitary TSH content (24%) and increased thyroid hormone transporter MCT-8 (Slc16a2, 44%) and thyroid hormone receptor β mRNA expression (Thrb, 39%). NBR-KO mice exhibited normal thyroxine (T4) and reduced triiodothyronine (T3) (30%), with no alterations in the intra-thyroidal content of T4 and T3 or thyroid morphological changes. Hypothalamic thyrotropin-releasing hormone (TRH) mRNA (Trh) was increased (68%), concomitant with a reduction in type 2 deiodinase mRNA (Dio2, 30%) and no changes in MCT-8 and thyroid hormone receptor mRNA expression. NBR-KO mice exhibited a 56% higher increase in serum TSH in response to an acute single intraperitoneal injection of TRH concomitant with a non-significant increase in pituitary TRH receptor (Trhr) mRNA at basal state. The phenotype of female NBR-KO mice at the hypothalamus-pituitary axis revealed alterations in pituitary and hypothalamic gene expression, associated with reduced serum T3, and higher TSH response to TRH, with apparently normal thyroid morphology and hormonal production. Thus, results confirm that neuromedin B pathways are importantly involved in secretory pathways of TSH and revealed its participation in the in vivo regulation of gene expression of TSH β-subunit and pituitary MCT8 and Thrb and hypothalamic TRH and type 2 deiodinase. PMID:25454367

  19. Gamma knife radiosurgery for pituitary adenomas.

    PubMed

    Ježková, Jana; Marek, Josef

    2016-09-01

    Pituitary adenomas are frequently occurring intracranial neoplasms. The aim of the treatment of pituitary adenomas is to normalize hormonal hypersecretion, to preserve the normal pituitary function, to reserve or treat impaired pituitary function and to control tumor growth and its mechanical effects on the surrounding structures. Treatment modalities include surgical, medical and radiation therapy. Radiosurgery is mainly used as a secondary line treatment after surgery for residual or recurrent tumors. The antiproliferative effect is achieved by LKG irradiation in more than 90% of patients. Regarding the functioning pituitary adenomas, the manifestation of the treatment effect is slow and depends mainly on the type of adenoma. Gamma knife irradiation is safe when the maximal doses to pituitary and infundibulum are respected. PMID:26899535

  20. Pituitary function following treatment with reproductive toxins.

    PubMed Central

    Cooper, R L; Goldman, J M; Rehnberg, G L

    1986-01-01

    Appropriate regulation of reproductive processes are dependent upon the integrity of pituitary function. In this selected review, we evaluate the evidence that certain environmental compounds exert their effect on reproductive function via a direct action on the pituitary gland. We also discuss examples of changes in pituitary hormone secretion that occur in response to changes in neuronal or gonadal control of the pituitary. A limited number of studies suggest that measures of pituitary hormone secretion provide an early and sensitive measure of a compound's potential effects on the reproductive system. However, the most striking aspect of this area is the sparse and inconsistent information describing pituitary function following exposure to environmental pollutants. PMID:3830104

  1. Ultrastructural autoradiographic localization of somatostatin-28 in the rat pituitary gland

    SciTech Connect

    Morel, G.; Leroux, P.; Pelletier, G.

    1985-04-01

    To identify the anterior pituitary cell type(s) containing somatostatin-28 (SS-28)-binding sites and to study the internalization processes of this peptide by the target cells, autoradiography was performed on rat anterior pituitaries removed at specific intervals (2-60 min) after iv injection of the (/sup 125/I)iodo-SS-28 agonist (Leu8,D-Trp22,Tyr25)SS-28 into intact, adrenalectomized, or castrated male rats. At the light microscopic level, the silver grains were found in 75% of cells. Concomitant injection of an excess of unlabeled peptide prevented the binding of label, verifying the specificity of binding. No specific labeling could be detected in the adrenocorticotrophs of adrenalectomized rats or gonadotrophs (castration cells) of castrated rats. At the electron microscopic level, three cell types (somatotrophs, thyrotrophs, and mammotrophs) appear to contain radiolabeled SS-28. The time-course study in somatotrophs of intact animals showed that 2 min after injection, most silver grains were associated with the plasma membrane. Five to 15 min after injection, label was found over both the plasma membrane and cytoplasmic organelles, especially the Golgi apparatus, lysosomes, and secretory granules. At the longest time interval (60 min), labeling was mostly associated with the cytoplasmic organelles. These results indicate that SS-28-binding sites are present only in those cell types in which somatostatin is known to regulate secretory functions. The present data also show that a rapid internalization of the radiolabeled peptide occurs.

  2. Hormone Secretion by Pituitary Adenomas Is Characterized by Increased Disorderliness and Spikiness but More Regular Pulsing

    PubMed Central

    Pereira, Alberto M.; Biermasz, Nienke R.; Veldhuis, Johannes D.

    2014-01-01

    Context: Hormone secretion by functioning pituitary tumors is characterized by increased basal (nonpulsatile) secretion, enhanced pulse frequency, amplified pulse mass, and increased disorderliness. Objective: The objective of the study was to quantify (subtle) abnormalities of hormone secretion by pituitary adenomas and the influence of selective pituitary surgery and suppressive medications on these parameters. Methods: Approximate entropy (ApEn) was quantified with a refined algorithm, spikiness by a new method to evaluate sudden short-lived increases in hormone levels, and pulsing regularity, determined with a fully automated deconvolution program. These 3 distinct measures of secretory disruption were compared in untreated and treated patients with acromegaly, prolactinoma, and Cushing's disease together with matching profiles in healthy controls. Results: ApEn and spikiness were markedly increased in all untreated patient groups and normalized after pituitary surgery in acromegaly and hypercortisolism. In contrast, hormone-suppressive medical treatment in acromegaly and prolactinoma did not normalize ApEn. Spikiness normalized in acromegalic patients but not in prolactinoma. GH and cortisol pulsing regularity was elevated in acromegaly and Cushing's disease, respectively, and normalized after surgery. Medical treatment caused normalization of pulsing regularity in acromegaly but not in prolactinoma patients. Conclusion: This study extends the understanding of disorganized hormone secretion by hyperfunctioning pituitary adenomas. The new findings are increased spikiness in all 3 tumor groups and increased pulsing regularity in GH- and ACTH-secreting adenomas. The mechanisms behind the marked pattern irregularity and the selective normalization by surgical and medical therapies are not established yet but may include diminished feedback signaling in addition to the anatomical and functional disorganization of intrapituitary cell networks. PMID:25014002

  3. Stimulation of secretion from bovine adrenal chromaffin cells by microsecond bursts of therapeutic levels of ultrasound.

    PubMed Central

    Robinson, I M; Kinnick, R R; Greenleaf, J F; Fernandez, J M

    1996-01-01

    1. In this study the secretory response of individual bovine adrenal chromaffin cells was monitored using amperometric carbon-fibre microelectrodes. Cells were stimulated to secrete by exposure to 20-100 microseconds long tonebursts of ultrasound (2-4 x 10(5) Pa; peak pressure at 1 MHz). 2. Three types of secretory responses were observed: an almost instantaneous response, a delayed release of catecholamines, or a series of 'burst-like' secretory bouts. 3. Fura-2 measurements of intracellular Ca2+ concentrations showed that the release of catecholamines was accompanied by an increase in the intracellular Ca2+ concentration. In the absence of extracellular Ca2+, secretory responses were not evoked showing that Ca2+ entry was necessary to elicit catecholamine release. Images Figure 1 PMID:8730600

  4. What Are the Key Statistics about Pituitary Tumors?

    MedlinePlus

    ... factors for pituitary tumors? What are the key statistics about pituitary tumors? About 10,000 pituitary tumors ... Symptoms of Cancer Treatments & Side Effects Cancer Facts & Statistics News About Cancer Expert Voices Blog Programs & Services ...

  5. Docking of Secretory Vesicles Is Syntaxin Dependent

    PubMed Central

    de Wit, Heidi; Cornelisse, L. Niels; Toonen, Ruud F.G.; Verhage, Matthijs

    2006-01-01

    Secretory vesicles dock at the plasma membrane before they undergo fusion. Molecular docking mechanisms are poorly defined but believed to be independent of SNARE proteins. Here, we challenged this hypothesis by acute deletion of the target SNARE, syntaxin, in vertebrate neurons and neuroendocrine cells. Deletion resulted in fusion arrest in both systems. No docking defects were observed in synapses, in line with previous observations. However, a drastic reduction in morphologically docked secretory vesicles was observed in chromaffin cells. Syntaxin-deficient chromaffin cells showed a small reduction in total and plasma membrane staining for the docking factor Munc18-1, which appears insufficient to explain the drastic reduction in docking. The sub-membrane cortical actin network was unaffected by syntaxin deletion. These observations expose a docking role for syntaxin in the neuroendocrine system. Additional layers of regulation may have evolved to make syntaxin redundant for docking in highly specialized systems like synaptic active zones. PMID:17205130

  6. Mast cell secretory granules: armed for battle.

    PubMed

    Wernersson, Sara; Pejler, Gunnar

    2014-07-01

    Mast cells are important effector cells of the immune system and recent studies show that they have immunomodulatory roles in diverse processes in both health and disease. Mast cells are distinguished by their high content of electron-dense secretory granules, which are filled with large amounts of preformed and pre-activated immunomodulatory compounds. When appropriately activated, mast cells undergo degranulation, a process by which these preformed granule compounds are rapidly released into the surroundings. In many cases, the effects that mast cells have on an immune response are closely associated with the biological actions of the granule compounds that they release, as exemplified by the recent studies showing that mast cell granule proteases account for many of the protective and detrimental effects of mast cells in various inflammatory settings. In this Review, we discuss the current knowledge of mast cell secretory granules. PMID:24903914

  7. Yeast secretory expression of insulin precursors.

    PubMed

    Kjeldsen, T

    2000-09-01

    Since the 1980s, recombinant human insulin for the treatment of diabetes mellitus has been produced using either the yeast Saccharomyces cerevisiae or the prokaryote Escherichia coli. Here, development of the insulin secretory expression system in S. cerevisiae and its subsequent optimisation is described. Expression of proinsulin in S. cerevisiae does not result in efficient secretion of proinsulin or insulin. However, expression of a cDNA encoding a proinsulin-like molecule with deletion of threonine(B30) as a fusion protein with the S. cerevisiae alpha-factor prepro-peptide (leader), followed either by replacement of the human proinsulin C-peptide with a small C-peptide (e.g. AAK), or by direct fusion of lysine(B29) to glycine(A1), results in the efficient secretion of folded single-chain proinsulin-like molecules to the culture supernatant. The secreted single-chain insulin precursor can then be purified and subsequently converted to human insulin by tryptic transpeptidation in organic aqueous medium in the presence of a threonine ester. The leader confers secretory competence to the insulin precursor, and constructed (synthetic) leaders have been developed for efficient secretory expression of the insulin precursor in the yeasts S. cerevisiae and Pichia pastories. The Kex2 endoprotease, specific for dibasic sites, cleaves the leader-insulin precursor fusion protein in the late secretory pathway and the folded insulin precursor is secreted to the culture supernatant. However, the Kex2 endoprotease processing of the pro-peptide-insulin precursor fusion protein is incomplete and a significant part of the pro-peptide-insulin precursor fusion protein is secreted to the culture supernatant in a hyperglycosylated form. A spacer peptide localised between the leader and the insulin precursor has been developed to optimise Kex2 endoprotease processing and insulin precursor fermentation yield. PMID:11030562

  8. RFP tags for labeling secretory pathway proteins

    SciTech Connect

    Han, Liyang; Zhao, Yanhua; Xu, Pingyong; Huan, Shuangyan

    2014-05-09

    Highlights: • Membrane protein Orai1 can be used to report the fusion properties of RFPs. • Artificial puncta are affected by dissociation constant as well as pKa of RFPs. • Among tested RFPs mOrange2 is the best choice for secretory protein labeling. - Abstract: Red fluorescent proteins (RFPs) are useful tools for live cell and multi-color imaging in biological studies. However, when labeling proteins in secretory pathway, many RFPs are prone to form artificial puncta, which may severely impede their further uses. Here we report a fast and easy method to evaluate RFPs fusion properties by attaching RFPs to an environment sensitive membrane protein Orai1. In addition, we revealed that intracellular artificial puncta are actually colocalized with lysosome, thus besides monomeric properties, pKa value of RFPs is also a key factor for forming intracellular artificial puncta. In summary, our current study provides a useful guide for choosing appropriate RFP for labeling secretory membrane proteins. Among RFPs tested, mOrange2 is highly recommended based on excellent monomeric property, appropriate pKa and high brightness.

  9. Anatomy, Physiology, and Laboratory Evaluation of the Pituitary Gland.

    PubMed

    Hong, Gregory K; Payne, Spencer C; Jane, John A

    2016-02-01

    The pituitary gland functions prominently in the control of most endocrine systems in the body. Diverse processes such as metabolism, growth, reproduction, and water balance are tightly regulated by the pituitary in conjunction with the hypothalamus and various downstream endocrine organs. Benign tumors of the pituitary gland are the primary cause of pituitary pathology and can result in inappropriate secretion of pituitary hormones or loss of pituitary function. First-line management of clinically significant tumors often involves surgical resection. Understanding of normal pituitary physiology and basic testing strategies to assess for pituitary dysfunction should be familiar to any skull base surgeon. PMID:26614827

  10. Cytological study on the anterior pituitary of senile untreated beagle bitches with spontaneous mammary tumours.

    PubMed

    Attia, M A

    1982-05-01

    Pituitaries were obtained from senile untreated Beagle bitches of comparable age (7-9 years) and genital status. The animals were divided into three groups; one was normal (without mammary lesions), one had benign tumours and one had mammary adenocarcinomas. PRL-, STH-, ACTH- and gonadotrophin-producing cells are studied and counted in serial paraffin sections stained with histochemical techniques. The animals with mammary malignancy displayed a marked increase in the relative number of PRL and ACTH cells with morphological signs of higher secretory activity in most cells, compared with that in normal bitches or bitches with benign tumours. STH cells in bitches with adenocarcinomas were reduced in number; however the secretory activity in these animals was the same as that observed in the normal bitches. In the animals with benign mammary tumours, STH cells showed morphological indication of higher secretory activity than in the other groups. PRL and ACTH cells were slightly increased in number and had slightly higher activity than that in normal bitches. These findings may suggest a role for hypophyseal hormones in mammary neoplasias. PMID:6287969

  11. Localization of p24 putative cargo receptors in the early secretory pathway depends on the biosynthetic activity of the cell.

    PubMed Central

    Kuiper, R P; Bouw, G; Janssen, K P; Rötter, J; van Herp, F; Martens, G J

    2001-01-01

    Members of the p24 family of putative cargo receptors (subdivided into p24-alpha, -beta, -gamma and -delta) are localized in the intermediate-and cis-Golgi compartments of the early secretory pathway, and are thought to play an important role in protein transport. In the present study, we wondered what effect increased biosynthetic cell activity with resulting high levels of protein transport would have on the subcellular localization of p24. We examined p24 localization in Xenopus intermediate pituitary melanotrope cells, which in black- and white-adapted animals are biosynthetically highly active and virtually inactive respectively. In addition, p24 localization was studied in Xenopus anterior pituitary cells whose activity is not changed during background adaptation. Using organelle fractionation, we found that in the inactive melanotropes and moderately active anterior pituitary cells of white-adapted animals, the p24-alpha, -beta, -gamma and -delta proteins are all located in the Golgi compartment. In the highly active melanotropes, but not in the anterior cells of black-adapted animals, the steady-state distribution of all four p24 members changed towards the intermediate compartment and subdomains of the endoplasmic reticulum (ER), most probably the ER exit sites. In the active melanotropes, the major cargo protein pro-opiomelanocortin was mostly localized to ER subdomains and partially co-localized with the p24 proteins. Furthermore, in the active cells, in vitro blocking of protein biosynthesis by cycloheximide or dispersion of the Golgi complex by brefeldin A led to a redistribution of the p24 proteins, indicating their involvement in ER-to-Golgi protein transport and extensive cycling in the early secretory pathway. We conclude that the subcellular localization of p24 proteins is dynamic and depends on the biosynthetic activity of the cell. PMID:11716771

  12. The effect of endotoxin administration on the secretory dynamics of oxytocin in follicular phase mares: relationship to stress axis hormones.

    PubMed

    Alexander, S L; Irvine, C H G

    2002-07-01

    The primary aim of this study was to define the secretory dynamics of oxytocin and vasopressin in pituitary venous effluent from ambulatory horses during acute endotoxaemia, a stimulus that may release both hormones. Our secondary aim was to investigate the role of oxytocin in regulating adrenocorticotropic hormone (ACTH) secretion by comparing oxytocin, vasopressin, corticotropin-releasing hormone (CRH) and ACTH secretory profiles during endotoxaemia and by monitoring the ACTH response to oxytocin administration. Pituitary venous blood was collected nonsurgically continuously and divided into 1-min segments from eight follicular phase mares. Four mares were sampled for 30 min before and 3.5 h after receiving an i.v. infusion of bacterial endotoxin (TOX). Four control mares were sampled for 2.5 h without infusion of TOX. Another three follicular phase mares were given 5 U of oxytocin to replicate the peak response to TOX and pituitary blood collected every 1 min for 10 min before and 15 min after injection. Endotoxin raised the secretion rates of all hormones measured. All hormones were released episodically throughout the experiment, with TOX increasing the amplitude of peaks in each hormone. Peaks in oxytocin and vasopressin were coincident in each treated mare. Similarly, ACTH peaks were coincident with peaks of oxytocin and vasopressin in each treated mare, and with peaks of CRH in three mares. However, oxytocin administration did not affect ACTH secretion. We conclude that during endotoxaemia in horses: (i) oxytocin and vasopressin are secreted synchronously; (ii) oxytocin is unlikely to be acting as an ACTH secretagogue since inducing peak oxytocin concentrations observed during TOX does not raise ACTH; and therefore (iii) the close relationship between oxytocin and ACTH secretion is circumstantial and due to the fact that oxytocin secretion is concurrent with that of vasopressin, a proven ACTH secretagogue in horses. PMID:12121490

  13. Intensity-modulated radiotherapy for pituitary adenomas: The preliminary report of Cleveland Clinic experience

    SciTech Connect

    Mackley, Heath B. . E-mail: hmackley@alumni.upenn.edu; Reddy, Chandana A. M.S.; Lee, S.-Y.; Harnisch, Gayle A.; Mayberg, Marc R.; Hamrahian, Amir H.; Suh, John H.

    2007-01-01

    Purpose: Intensity-modulated radiotherapy (IMRT) is being increasingly used for the treatment of pituitary adenomas. However, there have been few published data on the short- and long-term outcomes of this treatment. This is the initial report of Cleveland Clinic's experience. Methods and Materials: Between February 1998 and December 2003, 34 patients with pituitary adenomas were treated with IMRT. A retrospective chart review was conducted for data analysis. Results: With a median follow-up of 42.5 months, the treatment has proven to be well tolerated, with performance status remaining stable in 90% of patients. Radiographic local control was 89%, and among patients with secretory tumors, 100% had a biochemical response. Only 1 patient required salvage surgery for progressive disease, giving a clinical progression free survival of 97%. The only patient who received more than 46 Gy experienced optic neuropathy 8 months after radiation. Smaller tumor volume significantly correlated with subjective improvements in nonvisual neurologic complaints (p = 0.03), and larger tumor volume significantly correlated with subjective worsening of visual symptoms (p = 0.05). New hormonal supplementation was required for 40% of patients. Younger patients were significantly more likely to require hormonal supplementation (p 0.03). Conclusions: Intensity-modulated radiation therapy is a safe and effective treatment for pituitary adenomas over the short term. Longer follow-up is necessary to determine if IMRT confers any advantage with respect to either tumor control or toxicity over conventional radiation modalities.

  14. 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

  15. Cerebrospinal fluid rhinorrhoea in pituitary tumours1

    PubMed Central

    Cole, I E; Keene, Malcolm

    1980-01-01

    Three cases of CSF rhinorrhoea due to pituitary tumours are reported and the literature reviewed. The treatment of choice appears to be trans-sphenoidal exploration of the pituitary fossa with insertion of a free muscle graft followed by radiotherapy. The probability of the tumour being a prolactin-secreting adenoma is discussed. PMID:7017123

  16. The Enigma behind Pituitary and Sella Turcica

    PubMed Central

    Gopalakrishnan, Umarevathi; Mahendra, Lodd; Rangarajan, Sumanth; Madasamy, Ramasamy; Ibrahim, Mohammad

    2015-01-01

    The pituitary gland's role as a functional matrix for sella turcica has not been suggested in orthodontic literature. This paper is an attempt to correlate the role of pituitary gland in the development of sella turcica. A case report of dwarfism associated with hypopituitarism is presented to highlight the above hypothesis. PMID:26199763

  17. Reversible suprasellar pituitary mass secondary to hypothyroidism

    SciTech Connect

    Atchison, J.A.; Lee, P.A.; Albright, A.L. Children's Hospital of Pittsburgh, PA )

    1989-12-08

    Sellar enlargement and suprasellar extension of a pituitary mass, demonstrated by magnetic resonance imaging or computed tomographic scanning in three children with primary hypothyroidism, resolved after treatment with levothyroxine sodium. This condition, a logical consequence of the pathogenesis of primary hypothyroidism, must be considered in patients with pituitary and suprasellar masses.

  18. A case of pituitary abscess presenting without a source of infection or prior pituitary pathology

    PubMed Central

    Kern, Philip A

    2016-01-01

    Summary Pituitary abscess is a relatively uncommon cause of pituitary hormone deficiencies and/or a suprasellar mass. Risk factors for pituitary abscess include prior surgery, irradiation and/or pathology of the suprasellar region as well as underlying infections. We present the case of a 22-year-old female presenting with a spontaneous pituitary abscess in the absence of risk factors described previously. Her initial presentation included headache, bitemporal hemianopia, polyuria, polydipsia and amenorrhoea. Magnetic resonance imaging (MRI) of her pituitary showed a suprasellar mass. As the patient did not have any risk factors for pituitary abscess or symptoms of infection, the diagnosis was not suspected preoperatively. She underwent transsphenoidal resection and purulent material was seen intraoperatively. Culture of the surgical specimen showed two species of alpha hemolytic Streptococcus, Staphylococcus capitis and Prevotella melaninogenica. Urine and blood cultures, dental radiographs and transthoracic echocardiogram failed to show any source of infection that could have caused the pituitary abscess. The patient was treated with 6weeks of oral metronidazole and intravenous vancomycin. After 6weeks of transsphenoidal resection and just after completion of antibiotic therapy, her headache and bitemporal hemianopsia resolved. However, nocturia and polydipsia from central diabetes insipidus and amenorrhoea from hypogonadotrophic hypogonadism persisted. Learning points Pituitary abscesses typically develop in patients who have other sources of infection or disruption of the normal suprasellar anatomy by either surgery, irradiation or pre-existing pathology; however, they can develop in the absence of known risk factors. Patients with pituitary abscesses typically complain of headache, visual changes and symptoms of pituitary hormone deficiencies. As other pituitary neoplasms present with similar clinical findings, the diagnosis of pituitary abscess is often not

  19. Pituitary Involvement in Granulomatosis With Polyangiitis

    PubMed Central

    De Parisot, Audrey; Puéchal, Xavier; Langrand, Corinne; Raverot, Gerald; Gil, Helder; Perard, Laurent; Le Guenno, Guillaume; Berthier, Sabine; Tschirret, Olivier; Eschard, Jean Paul; Vinzio, Stephane; Guillevin, Loïc; Sève, Pascal

    2015-01-01

    Abstract Pituitary dysfunction is a rare manifestation of granulomatosis with polyangiitis (GPA) (Wegener). The main aim of this multicenter retrospective study was to describe the characteristics and outcomes of pituitary manifestations in patients with GPA included in the French Vasculitis Study Group database. Among the 819 GPA patients included in the database, 9 (1.1%) had pituitary involvement. The median age at diagnosis of GPA and pituitary involvement was 46 and 50.8 years, respectively. Pituitary involvement was present at onset of GPA in 1 case and occurred later in 8 patients after a median follow up of 58.5 months. When pituitary dysfunction occurred, 8 patients had active disease at other sites including ENT (n = 6), eye (n = 4), or central nervous system (n = 3) involvement. The most common hormonal dysfunctions were diabetes insipidus (n = 7) and hypogonadism (n = 7). Magnetic resonance imaging was abnormal in 7 patients. The most common lesions were an enlargement of the pituitary gland, thickening of the pituitary stalk, and loss of posterior hypersignal on T1-weighed images. All patients were treated with corticosteroid therapy and 8 patients received immunosuppressive agents for the pituitary involvement, including cyclophosphamide (n = 3), rituximab (n = 2), and methotrexate (n = 3). After a median follow-up of 9.2 years, GPA was in complete remission in 7 patients, but 8 patients were still under hormone replacement therapy. Among the 5 patients who had a subsequent MRI, 2 had complete resolution of pituitary lesions.By combining our study and the literature review, the frequency of hypogonadism and diabetes insipidus, among the patients with pituitary dysfunction, can be estimated at 78% and 71% respectively. Despite a high rate of systemic disease remission on maintenance therapy, 86% of the patients had persistent pituitary dysfunction. The patients who recovered from pituitary dysfunction had all been

  20. Pituitary stem cells: candidates and implications.

    PubMed

    Nassiri, Farshad; Cusimano, Michael; Zuccato, Jeff A; Mohammed, Safraz; Rotondo, Fabio; Horvath, Eva; Syro, Luis V; Kovacs, Kalman; Lloyd, Ricardo V

    2013-09-01

    The pituitary is the master endocrine gland of the body. It undergoes many changes after birth, and these changes may be mediated by the differentiation of pituitary stem cells. Stem cells in any tissue source must display (1) pluripotent capacity, (2) capacity for indefinite self-renewal, and (3) a lack of specialization. Unlike neural stem cells identified in the hippocampus and subventricular zone, pituitary stem cells are not associated with one specific cell type. There are many major candidates that are thought to be potential pituitary stem cell sources. This article reviews the evidence for each of the major cell types and discuss the implications of identifying a definitive pituitary stem cell type. PMID:23423660

  1. Somatotroph pituitary tumors in budgerigars (Melopsittacus undulatus).

    PubMed

    Langohr, I M; Garner, M M; Kiupel, M

    2012-05-01

    A series of 11 pituitary tumors in budgerigars were classified on the basis of their clinical, gross, microscopic, and immunohistochemical characteristics. Affected birds were young to middle-aged. Clinically, neurologic signs--including difficulties flying, ataxia, and blindness--were most commonly reported. Additional clinical signs included weight loss, abnormal feathers or molting, increased respiratory efforts, and exophthalmos. Nine birds were diagnosed with chromophobic pituitary adenomas, and 2 birds had chromophobic pituitary carcinomas. Only 1 tumor was delimited to the pituitary gland; the other 10 variably invaded the brain, skull, and retrobulbar space. Distant metastases were identified in 2 birds. All tumors were immunohistochemically strongly positive for growth hormone, consistent with the diagnosis of somatotroph tumors. The common occurrence and early onset may suggest a genetic predisposition of budgerigars to develop somatotroph pituitary tumors with a high incidence of local invasion and with metastatic potential. PMID:21900544

  2. The inhibition of bovine and rat parotid deoxyribonuclease I by skeletal muscle actin. A biochemical and immunocytochemical study.

    PubMed Central

    Mannherz, H G; Kreuder, V; Koch, J; Dieckhoff, J; Drenckhahn, D

    1982-01-01

    Rat and bovine parotid gland and pancreas contain deoxyribonuclease I (DNAase I) activities in different amounts. The DNAase I activity in tissue homogenates of bovine and rat parotid gland can be inhibited by addition of monomeric actin, as with the enzyme of bovine pancreas. The isolated DNAase I species from bovine and rat parotid gland differ in their molecular weights and also in their affinities for monomeric actin, being lowest for rat parotid DNAase I (5 X 10(6)M(-1). Antibodies raised against rat and bovine parotid and bovine pancreatic DNAase I can be used to study the subcellular localization of DNAase I in these tissues by indirect immunofluorescence. DNAase I was found to be confined solely to the secretory granules of the tissue from which it was isolated. Images Fig. 3. PLATE 1 Fig. 7. PMID:6297457

  3. Insulin-like growth factor-I mRNA and peptide in the human anterior pituitary.

    PubMed

    Jevdjovic, T; Bernays, R L; Eppler, E

    2007-05-01

    The pituitary is the central organ regulating virtually all endocrine processes, and pathologies of the pituitary cause manifold adverse effects. Because insulin-like growth factor (IGF)-I appears to be involved in tumour pathogenesis, progression, and persistence, and only few data exist on the cellular synthesis sites of IGF-I, the present study aims to create a basis for further research on pituitary adenomas by investigating the presence of IGF-I in the human pituitary using reverse transcriptase-polymerase chain reaction, in situ hybridisation, immunohistochemistry and immunocytochemistry. IGF-I was expressed in the pituitary, and gene sequence analysis revealed a sequence identical to that found in human liver. The distribution pattern of IGF-I mRNA found by in situ hybridisation corresponded to that of IGF-I peptide in immunohistochemistry. In all pituitary samples investigated, IGF-I-immunoreactivity occurred in almost all adrenocorticotrophic hormone (ACTH)-immunoreactive cells. Occasionally, an interindividually varying number of growth hormone (GH) and, infrequently, follicle-stimulating hormone and luteinising hormone cells contained IGF-I-immunoreactivity but none was detected in supporting cells. At the ultrastructural level, IGF-I-immunoreactivity was confined to secretory granules in coexistence with ACTH- or GH-immunoreactivity, respectively, indicating a concomitant release of the hormones. Thus, in humans, IGF-I appears to be a constituent in ACTH cells whereas its production in GH-producing and gonadotrophic cells may depend on the physiological status (e.g. serum IGF-I level, age or reproductive phase). It is assumed that locally produced IGF-I plays a crucial role in the regulation of endocrine cells by autocrine/paracrine mechanisms in addition to the endocrine route. PMID:17425608

  4. Influence of experimental hypokinesia on gastric secretory function

    NASA Technical Reports Server (NTRS)

    Markova, O. O.; Vavryshchuk, V. I.; Rozvodovskyy, V. I.; Proshcheruk, V. A.

    1980-01-01

    The gastric secretory function of rats was studied in 4, 8, 16 and 30 day hypokinesia. Inhibition of both the gastric juice secretory and acid producing functions was found. The greatest inhibition was observed on day 8 of limited mobility. By days 16 and 30 of the experiment, a tendency of the gastric secretory activity to return to normal was observed, although it remained reduced.

  5. Isotonic water transport in secretory epithelia.

    PubMed

    Swanson, C H

    1977-01-01

    The model proposed by Diamond and Bossert [1] for isotonic water transport has received wide acceptance in recent years. It assumes that the local driving force for water transport is a standing osmotic gradient produced in the lateral intercellular spaces of the epithelial cell layer by active solute transport. While this model is based on work done in absorptive epithelia where the closed to open direction of the lateral space and the direction of net transport are the same, it has been proposed that the lateral spaces could also serve as the site of the local osmotic gradients for water transport in secretory epithelia, where the closed to open direction of the lateral space and net transport are opposed, by actively transporting solute out of the space rather than into it. Operation in the backward direction, however, requires a lower than ambient hydrostatic pressure within the lateral space which would seem more likely to cause the space to collapse with loss of function. On the other hand, most secretory epithelia are characterized by transport into a restricted ductal system which is similar to the lateral intercellular space in the absorptive epithelia in that its closed to open direction is the same as that of net transport. In vitro micropuncture studies on the exocrine pancreas of the rabbit indicate the presence of a small but statistically significant increase in juice osmolality, 6 mOsm/kg H(2)O, at the site of electrolyte and water secretion in the smallest extralobular ducts with secretin stimulation which suggests that the ductal system in the secretory epithelia rather than the lateral intercellular space is the site of the local osmotic gradients responsible for isotonic water transport. PMID:331693

  6. Psychological distress and salivary secretory immunity.

    PubMed

    Engeland, C G; Hugo, F N; Hilgert, J B; Nascimento, G G; Junges, R; Lim, H-J; Marucha, P T; Bosch, J A

    2016-02-01

    Stress-induced impairments of mucosal immunity may increase susceptibility to infectious diseases. The present study investigated the association of perceived stress, depressive symptoms, and loneliness with salivary levels of secretory immunoglobulin A (S-IgA), the subclasses S-IgA1, S-IgA2, and their transporter molecule Secretory Component (SC). S-IgA/SC, IgA1/SC and IgA2/SC ratios were calculated to assess the differential effects of stress on immunoglobulin transport versus availability. This study involved 113 university students, in part selected on high scores on the UCLA Loneliness Scale and/or the Beck Depression Inventory. Stress levels were assessed using the Perceived Stress Scale. Unstimulated saliva was collected and analysed for total S-IgA and its subclasses, as well as SC and total salivary protein. Multiple linear regression analyses, adjusted for gender, age, health behaviours, and concentration effects (total protein) revealed that higher perceived stress was associated with lower levels of IgA1 but not IgA2. Perceived stress, loneliness and depressive symptoms were all associated with lower IgA1/SC ratios. Surprisingly, higher SC levels were associated with loneliness and depressive symptoms, indicative of enhanced transport activity, which explained a lower IgA1/SC ratio (loneliness and depression) and IgA2/SC ratio (depression). This is the first study to investigate the effects of protracted psychological stress across S-IgA subclasses and its transporter SC. Psychological stress was negatively associated with secretory immunity, specifically IgA1. The lower immunoglobulin/transporter ratio that was associated with higher loneliness and depression suggested a relative immunoglobulin depletion, whereby availability was not keeping up with enhanced transport demand. PMID:26318411

  7. "Secretory" Carcinoma of the Skin Mimicking Secretory Carcinoma of the Breast: Case Report and Literature Review.

    PubMed

    Huang, Sixia; Liu, Yan; Su, Jing; Liu, Jianying; Guo, Xiaoning; Mei, Fang; Zheng, Jie; Liao, Songlin

    2016-09-01

    Secretory carcinoma is a unique kind of adenocarcinoma. It has distinct histological features and a special genetic change, that is, t (12; 15) (p13; q25) translocation which leads to the expression of the ETV6-NTRK3 fusion gene. Secretory carcinoma has been found to occur both in the breast and salivary gland. Here the authors present a case of 22-year-old woman with a unique cutaneous neoplasm located at the axilla. The tumor was characterized histologically with the formation of round to ovoid microcysts and papillary structure, which was similar to the secretory carcinoma of the breast and salivary gland. Furthermore, the gene sequence analysis of reverse-transcription polymerase chain reaction products demonstrated the expression of the ETV6-NTRK3 fusion gene. To the authors' knowledge, this is the first case of secretory carcinoma from the skin which has the same genetic change as those from the breast and salivary gland. Local excision was performed on this patient. She had been followed up for nearly 1 year. No recurrence or metastasis was found yet. PMID:26981741

  8. Pituitary abscess: an unusual presentation of "aseptic meningitis".

    PubMed

    Schwartz, I D; Zalles, M C; Foster, J L; Burry, V F

    1995-01-01

    Granulomatous inflammation of the pituitary and pituitary abscesses are rare entities. These conditions are found even more rarely in the pediatric aged population. We report a case of a radiographic and clinical, sterile pituitary abscess with non-caseating granulomatous inflammation in a girl who presented with hypopituitarism, meningeal irritation, and symptoms of pituitary apoplexy. PMID:7584709

  9. Membrane retrieval in the guinea-pig neurohypophysis. Isolation and characterization of secretory vesicles and coated microvesicles after radiolabel incorporation in vivo.

    PubMed

    Saermark, T; Jones, P M; Robinson, I C

    1984-03-01

    We have developed small-scale methods for the isolation and biochemical characterization of subcellular fractions from single guinea-pig posterior-pituitary glands. Secretory vesicles and coated microvesicles produced in this way were of similar purity to those isolated from large amounts of tissue by conventional ultracentrifugation. [35S]Cysteine injected into the hypothalamus was found in the soluble contents of secretory vesicles isolated from the neural lobes 24 h later. High-pressure liquid-chromatographic analysis revealed that the radiolabel was incorporated into the expected neurosecretory products (oxytocin, vasopressin and neurophysin) and also into a biosynthetic intermediate in the vasopressin system. The membranes of secretory vesicles were labelled with [3H]choline 24 h after its hypothalamic injection. Little or no [3H]choline could be demonstrated in coated microvesicles at this time, although these structures were labelled 5 days after injection. Stimulating hormone secretion by chronic dehydration produced a significant fall in [3H]choline content of the secretory-vesicle membranes without any transfer of label into coated microvesicles, suggesting that coated microvesicles are not involved in membrane retrieval in the neurohypophysis. PMID:6712633

  10. Membrane retrieval in the guinea-pig neurohypophysis. Isolation and characterization of secretory vesicles and coated microvesicles after radiolabel incorporation in vivo.

    PubMed Central

    Saermark, T; Jones, P M; Robinson, I C

    1984-01-01

    We have developed small-scale methods for the isolation and biochemical characterization of subcellular fractions from single guinea-pig posterior-pituitary glands. Secretory vesicles and coated microvesicles produced in this way were of similar purity to those isolated from large amounts of tissue by conventional ultracentrifugation. [35S]Cysteine injected into the hypothalamus was found in the soluble contents of secretory vesicles isolated from the neural lobes 24 h later. High-pressure liquid-chromatographic analysis revealed that the radiolabel was incorporated into the expected neurosecretory products (oxytocin, vasopressin and neurophysin) and also into a biosynthetic intermediate in the vasopressin system. The membranes of secretory vesicles were labelled with [3H]choline 24 h after its hypothalamic injection. Little or no [3H]choline could be demonstrated in coated microvesicles at this time, although these structures were labelled 5 days after injection. Stimulating hormone secretion by chronic dehydration produced a significant fall in [3H]choline content of the secretory-vesicle membranes without any transfer of label into coated microvesicles, suggesting that coated microvesicles are not involved in membrane retrieval in the neurohypophysis. Images Fig. 1. PMID:6712633

  11. Pituitary carcinoma with endolymphatic sac metastasis.

    PubMed

    Balili, Irida; Sullivan, Steven; Mckeever, Paul; Barkan, Ariel

    2014-06-01

    Pituitary carcinoma is characterized by the presence of a metastatic lesion(s) in a location non-contiguous with the original pituitary tumor. The mechanism(s) of malignant transformation are not known. A 15 year-old male was diagnosed in 1982 with a pituitary macroadenoma and acromegaly (random GH 67 ng/ml and no suppression by oral glucose). His prolactin was normal between 18 and 23 ng/ml. Transcranial resection in July 1983 was followed by radiation therapy. The tumor was immunopositive for GH and prolactin. The proliferation MIB-1 index was 0-1%. With aqueous Octreotide 100 mcg 4× daily both GH and IGF-1 became normal. The patient was lost to follow-up and was treated by his local physician. In 2001, his IGF-1 level was 1271 ng/ml, and his random GH was 1.8-2.4 ng/ml by ILMA despite progressive increase in the dose of Sandostatin LAR to 140 mg/month in divided doses. Prolactin remained normal or minimally increased between 15 and 25 ng/ml. In 2009 he was diagnosed with the tumor in the location of left endolymphatic sac. Histological examination showed low grade pituitary carcinoma strongly immunopositive for prolactin but negative for GH. MIB-1 antibody labeled 0-5% cells. In 2012 endoscopic resection of the pituitary tumor remnant was attempted. Immunohistochemical stains were strongly immunopositive for both prolactin and GH, similar to his original pituitary tumor. The MIB-1 proliferation index was low from 0 to 1%. To our knowledge this is the first case of pituitary carcinoma in the endolymphatic sac region. The dichotomy between the cell population of the pituitary lesion (GH/prolactin producing) and the metastasis (purely prolactin-producing) may suggest that the metastatic pituitary lesion derived from a clone distinct from the original one. PMID:23645293

  12. Subcellular localization of pituitary enzymes

    NASA Technical Reports Server (NTRS)

    Smith, R. E.

    1970-01-01

    A cytochemical procedure is reported for identifying subcellular sites of enzymes hydrolyzing beta-naphthylamine substrates, and to study the sites of reaction product localization in cells of various tissues. Investigations using the substrate Leu 4-methoxy-8-naphthylamine, a capture with hexonium pararosaniline, and the final chelation of osmium have identified the hydrolyzing enzyme of rat liver cells; this enzyme localized on cell membranes with intense deposition in the areas of the parcanaliculi. The study of cells in the anterior pituitary of the rat showed the deposition of reaction product on cell membrane; and on the membranes of secretion granules contained within the cell. The deposition of reaction product on the cell membrane however showed no increase or decrease with changes in the physiological state of the gland and release of secretion granules from specific cells.

  13. Hypothalamus-Pituitary-Thyroid Axis.

    PubMed

    Ortiga-Carvalho, Tania M; Chiamolera, Maria I; Pazos-Moura, Carmen C; Wondisford, Fredic E

    2016-01-01

    The hypothalamus-pituitary-thyroid (HPT) axis determines the set point of thyroid hormone (TH) production. Hypothalamic thyrotropin-releasing hormone (TRH) stimulates the synthesis and secretion of pituitary thyrotropin (thyroid-stimulating hormone, TSH), which acts at the thyroid to stimulate all steps of TH biosynthesis and secretion. The THs thyroxine (T4) and triiodothyronine (T3) control the secretion of TRH and TSH by negative feedback to maintain physiological levels of the main hormones of the HPT axis. Reduction of circulating TH levels due to primary thyroid failure results in increased TRH and TSH production, whereas the opposite occurs when circulating THs are in excess. Other neural, humoral, and local factors modulate the HPT axis and, in specific situations, determine alterations in the physiological function of the axis. The roles of THs are vital to nervous system development, linear growth, energetic metabolism, and thermogenesis. THs also regulate the hepatic metabolism of nutrients, fluid balance and the cardiovascular system. In cells, TH actions are mediated mainly by nuclear TH receptors (210), which modify gene expression. T3 is the preferred ligand of THR, whereas T4, the serum concentration of which is 100-fold higher than that of T3, undergoes extra-thyroidal conversion to T3. This conversion is catalyzed by 5'-deiodinases (D1 and D2), which are TH-activating enzymes. T4 can also be inactivated by conversion to reverse T3, which has very low affinity for THR, by 5-deiodinase (D3). The regulation of deiodinases, particularly D2, and TH transporters at the cell membrane control T3 availability, which is fundamental for TH action. © 2016 American Physiological Society. Compr Physiol 6:1387-1428, 2016. PMID:27347897

  14. ATP: The crucial component of secretory vesicles.

    PubMed

    Estévez-Herrera, Judith; Domínguez, Natalia; Pardo, Marta R; González-Santana, Ayoze; Westhead, Edward W; Borges, Ricardo; Machado, José David

    2016-07-12

    The colligative properties of ATP and catecholamines demonstrated in vitro are thought to be responsible for the extraordinary accumulation of solutes inside chromaffin cell secretory vesicles, although this has yet to be demonstrated in living cells. Because functional cells cannot be deprived of ATP, we have knocked down the expression of the vesicular nucleotide carrier, the VNUT, to show that a reduction in vesicular ATP is accompanied by a drastic fall in the quantal release of catecholamines. This phenomenon is particularly evident in newly synthesized vesicles, which we show are the first to be released. Surprisingly, we find that inhibiting VNUT expression also reduces the frequency of exocytosis, whereas the overexpression of VNUT drastically increases the quantal size of exocytotic events. To our knowledge, our data provide the first demonstration that ATP, in addition to serving as an energy source and purinergic transmitter, is an essential element in the concentration of catecholamines in secretory vesicles. In this way, cells can use ATP to accumulate neurotransmitters and other secreted substances at high concentrations, supporting quantal transmission. PMID:27342860

  15. Secretory pattern of canine growth hormone

    SciTech Connect

    French, M.B.; Vaitkus, P.; Cukerman, E.; Sirek, A.; Sirek, O.V.

    1987-02-01

    The aim of this paper was to define the secretory pattern of growth hormone (GH) under basal conditions in fasted, conscious, male dogs accustomed to handling. Blood samples were withdrawn from a cephalic vein at 15-min intervals. In this way, any ultradian rhythms, if present, could be detected within the frequency range of 0.042-2 cycles/h. In addition, samples were drawn at either 1- or 2.5-min intervals for 2.5 or 5 h to determine whether frequency components greater than 2 cycles/h were present. GH was measured by radioimmunoassay and the raw data were submitted to time series analysis employing power spectral estimation by means of fast Fourier transformation techniques. Peak plasma levels were up to 12 times higher than the baseline concentration of approx. 1 ng/ml. Spectral analysis revealed an endogenous frequency of 0.22 cycles/h, i.e., a periodicity of 4.5 h/cycle. The results indicate that under basal conditions the secretory bursts of canine GH are limited to one peak every 4.5 h.

  16. Evidence for a nonprolactin, non-growth-hormone mammary mitogen in the human pituitary gland.

    PubMed Central

    Newman, C B; Cosby, H; Friesen, H G; Feldman, M; Cooper, P; De Crescito, V; Pilon, M; Kleinberg, D L

    1987-01-01

    To determine whether the human pituitary contains a previously unidentified, nonprolactin (non-hPRL), non-growth-hormone (non-hGH) factor capable of stimulating mammary development, we tested the effects of whole human pituitary extract (hPE) and pituitary extracts depleted of hPRL and hGH ("stripped hPE") in hypophysectomized, castrated estradiol (E2)-treated male rats and rhesus monkeys. Both whole and stripped hPE significantly stimulated rat mammary development (mean scores = 3.3 and 2.0, respectively, on a scale ranging from 0 to 4) in comparison with controls (mean score = 1.0). Mammary development was not due to minute concentrations of hGH or hPRL remaining in stripped hPE because 30- to 100-fold higher concentrations of hGH (Genentech) and 1000-fold higher concentrations of hPRL were required to stimulate significant mammary development. Non-pituitary extracts of human ovary, muscle, and serum, and bovine serum albumin did not stimulate rat mammary gland growth. Trypsin destroyed the mammary mitogenic activity of whole hPE, indicating that the unidentified factor is likely a protein. Mammary growth and development were also stimulated in hypophysectomized, E2-treated monkeys by stripped hPE (mean histological score = 3.25 vs. 1.35 in control animals). Monkeys receiving stripped hPE had undetectable levels of hGH and hPRL in serum sampled over a 24-hr period. These findings suggest that the human pituitary contains a non-hPRL, non-hGH factor that stimulates mammary growth and may be important in normal mammary growth and development and perhaps in breast cancer. Images PMID:3479780

  17. Receptors for vasoactive intestinal peptide in rat anterior pituitary glands: Localization of binding to lactotropes

    SciTech Connect

    Wanke, I.E.; Rorstad, O.P. )

    1990-04-01

    Vasoactive intestinal peptide (VIP) has been implicated as a physiological PRL-releasing factor; however, characterization of VIP receptors on normal pituitaries using radioligand-binding methods has been problematic. In this study we demonstrated specific receptors for VIP in anterior pituitary glands of female rats using HPLC-purified monoiodinated (Tyr(125I)10)VIP. Binding of VIP was reversible, saturable to receptor and radioligand, regulated by guanine nucleotides, and dependent on time and temperature. Scatchard analysis of competitive binding studies indicated high and low affinity binding sites, with equilibrium dissociation constants (Kd) of 0.19 +/- 0.03 and 28 +/- 16 nM, respectively. The corresponding maximum numbers of binding sites were 158 +/- 34 fmol/mg and 11.7 +/- 6.9 pmol/mg. Binding was specific, as peptides with structural homology to VIP were less than 100th as potent as VIP. The rank order of potency of the peptides tested was VIP greater than rat (r) peptide histidine isoleucine = human (h) PHI greater than rGRF greater than bovine GRF = porcine PHI = VIP-(10-28) greater than hGRF greater than secretin greater than apamin greater than glucagon. Radioligand binding was associated primarily with lactotrope-enriched fractions prepared by unit gravity sedimentation of dispersed anterior pituitary cells. VIP stimulated PRL release from cultured rat anterior pituitary cells, with an ED50 of 1 nM. These results, comprising the first identification of specific VIP receptors in normal rat anterior pituitary tissue using radioligand-binding methods, provide additional support for a biological role of VIP in lactotrope function.

  18. Ameloblast transcriptome changes from secretory to maturation stages

    PubMed Central

    Simmer, James P.; Richardson, Amelia S.; Wang, Shih-Kai; Reid, Bryan M.; Bai, Yongsheng; Hu, Yuanyuan; Hu, Jan C.-C.

    2014-01-01

    The purpose of this study was to identify the major molecular components in the secretory and maturation stages of amelogenesis through transcriptome analyses. Ameloblasts (40 sections per age group) were laser micro-dissected from Day 5 (secretory stage) and Days 11–12 (maturation stage) first molars. PolyA+ RNA was isolated from the lysed cells, converted to cDNA, and amplified to generate a cDNA library. DNA sequences were obtained using next generation sequencing and analyzed to identify genes whose expression had increased or decreased at least 1.5-fold in maturation stage relative to secretory stage ameloblasts. Among the 9198 genes that surpassed the quality threshold, 373 showed higher expression in secretory stage, while 614 genes increased in maturation stage ameloblasts. The results were crosschecked against a previously published transcriptome generated from tissues overlying secretory and maturation stage mouse incisor enamel and 34 increasing and 26 decreasing expressers common to the two studies were identified. Expression of F2r, which encodes protease activated receptor 1 (PAR1) that showed 10-fold higher expression during the secretory stage in our transcriptome analysis, was characterized in mouse incisors by immunohistochemistry. PAR1 was detected in secretory, but not maturation stage ameloblasts. We conclude that transcriptome analyses are a good starting point for identifying genes/proteins that are critical for proper dental enamel formation and that PAR1 is specifically expressed by secretory stage ameloblasts. PMID:25158176

  19. Genetics Home Reference: familial isolated pituitary adenoma

    MedlinePlus

    ... 1,000 people. FIPA, though, is quite rare, accounting for approximately 2 percent of pituitary adenomas. More ... be inherited? More about Inheriting Genetic Conditions Diagnosis & Management These resources address the diagnosis or management of ...

  20. [Pituitary abscess. A case report (author's transl)].

    PubMed

    Guy, G; Jallet, G; Bigorgne, J C

    The case of a patient with apparently primitive pituitary abscess is presented along with a review of the current literature on the subject. Pituitary abscess is rare and should be suspected in patients with hypopituitarism or a febrile chiasma syndrome as well as in the presence of acute or chronic relapsing aseptic meningitis. Diagnosis is based upon radiologic examination particularly tomography of the sella turcica and computerized axial tomography. With early surgical treatment the prognosis is favourable resulting at times in partial or total correction of pituitary function. Twenty-six patients were studied. In twelve of these patients no origin of the abscess was found. Pituitary tumor was found in eight patients and sphenoidal sinusitis in six patients. PMID:6261360

  1. Making a Pituitary Gland in a Dish

    PubMed Central

    Tabar, Viviane

    2016-01-01

    The adenohypophysis secretes multiple hormones that control vital physiological functions. A recent article in Nature (Suga et al., 2011) describes a 3D protocol for the derivation of several endocrine pituitary cell types from mouse ESCs. PMID:22136918

  2. Genetics Home Reference: combined pituitary hormone deficiency

    MedlinePlus

    ... People with combined pituitary hormone deficiency may have hypothyroidism, which is underactivity of the butterfly-shaped thyroid gland in the lower neck. Hypothyroidism can cause many symptoms, including weight gain and ...

  3. Primary immune thrombocytopenia accompanied by pituitary apoplexy.

    PubMed

    Tsuji, Takahiro; Mochinaga, Hiromi; Yamasaki, Hiroshi; Tsuda, Hiroyuki

    2016-07-01

    An 83-year-old woman was admitted to our hospital with a severe headache and purpura. She had previously been diagnosed with idiopathic thrombocytopenia purpura (ITP) and achieved complete remission with steroid therapy. Steroid therapy had been completed one week prior to the current admission. The recurrence of severe thrombocytopenia (<1.0×10(4) platelets/μl) was detected and a CT scan revealed pituitary hemorrhage without pituitary adenoma. She received steroid therapy combined with intravenous immunoglobulin, which resulted in the amelioration of ITP and improvements in the pituitary hemorrhage. Intracranial hemorrhage, which is the most serious bleeding manifestation in ITP, is relatively uncommon. Pituitary apoplexy in ITP is extremely rare. PMID:27498733

  4. ISOLATED NERVE ENDINGS (NEUROSECRETOSOMES) FROM THE POSTERIOR PITUITARY

    PubMed Central

    Bindler, Elliot; Labella, Frank S.; Sanwal, Madhu

    1967-01-01

    Subcellular fractions of the bovine posterior pituitary, including one composed almost exclusively of pinched-off nerve endings (neurosecretosomes), were characterized electron microscopically, hormonally, and enzymically. 15% of the nerve terminals in the gland were isolated as neurosecretosomes, as estimated from determinations of lactic dehydrogenase, a soluble, cytoplasmic enzyme. Neurosecretosomes were subdivided into three fractions by density-gradient centrifugation. The three subfractions, each shown to be nearly homogeneous populations of neurosecretosomes by means of electron microscopic and enzymic criteria, differed from each other in their vasopressin/oxytocin (VP/OT) ratios. The VP/OT ratio increased from the lightest to the densest fraction, indicating that VP is localized to denser and OT to lighter neurosecretosomes; similar results have been obtained previously for subfractions of neurosecretory granules (NSG). No morphological differences were apparent in neurosecretosomes among the three subfractions. Although complete separation of VP and OT was not achieved, the findings suggest that VP and OT are each stored in a different species of nerve ending and support the hypothesis that a given neurosecretory cell synthesizes, stores, and secretes only one of the peptide hormones. Microvesicles, 40–80 mµ diameter and contained in typical neurosecretory cell terminals, are believed to be degradation products of membrane ghosts of depleted NSG; electron micrographs indicative of this transformation are presented. A fraction rich in microvesicles, but containing some NSG membranes, was prepared by density-gradient centrifugation of an osmolysate of neurosecretosomes. Smaller, apparently nonneurosecretory nerve endings, lacking NSG but filled with small vesicles, are occasionally seen in sections from whole gland. The vesicles in these atypical posterior pituitary nerve endings may be true neurohumor-containing, "synaptic" vesicles. PMID:6040535

  5. The pituitary gland: a brief history.

    PubMed

    Kaplan, Solomon Alexander

    2007-01-01

    The functions of the pituitary gland as an important constituent of the endocrine system were not understood until the latter part of the nineteenth century and the first half of the 20th century. At one time, the pituitary was deemed to be the "leader of the endocrine orchestra," but more recent studies have shown that its secretions are influenced by external stimuli and that it is largely under the control of the hypothalamus. PMID:17690988

  6. Genetic regulation of murine pituitary development

    PubMed Central

    Rizzoti, Karine

    2015-01-01

    Significant progress has been made recently in unravelling the embryonic events leading to pituitary morphogenesis, both in vivo and in vitro. This includes dissection of the molecular mechanisms controlling patterning of the ventral diencephalon that regulate formation of the pituitary anlagen or Rathke's pouch. There is also a better characterisation of processes that underlie maintenance of pituitary progenitors, specification of endocrine lineages and the three-dimensional organisation of newly differentiated endocrine cells. Furthermore, a population of adult pituitary stem cells (SCs), originating from embryonic progenitors, have been described and shown to have not only regenerative potential, but also the capacity to induce tumour formation. Finally, the successful recapitulation in vitro of embryonic events leading to generation of endocrine cells from embryonic SCs, and their subsequent transplantation, represents exciting advances towards the use of regenerative medicine to treat endocrine deficits. In this review, an up-to-date description of pituitary morphogenesis will be provided and discussed with particular reference to pituitary SC studies. PMID:25587054

  7. 21 CFR 866.5380 - Free secretory component immuno-logical test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... immunochemical techniques free secretory component (normally a portion of the secretory IgA antibody molecule) in... repetitive lung infections and other hypogammaglobulinemic conditions (low antibody levels)....

  8. Alterations in hypothalamic-pituitary-adrenal function associated with captivity in Gambel's white-crowned sparrows (Zonotrichia leucophrys gambelii).

    PubMed

    Romero, L M; Wingfield, J C

    1999-01-01

    Gambel's white-crowned sparrows were captured and brought into captivity in order to study seasonal changes in the function of the hypothalamic-pituitary-adrenal (HPA) axis in captive birds. 30 min of restraint elicited a rise in corticosterone titers that varied depending upon the season and physiological state of the birds. Restraint elevated corticosterone titers significantly more during the fall (within 2 weeks of capture from the wild) than during either the winter or during a prealternate or prebasic molt. We also examined what changes in the HPA axis could account for altered corticosterone levels. Exogenous ACTH significantly elevated corticosterone levels beyond the response to restraint during the fall, indicating a dramatic enhancement of the adrenal's ability to secrete corticosterone. Exogenous ACTH was ineffective at other times, suggesting that the adrenal's ability to release corticosterone often limits circulating levels. We further inferred the pituitary's ACTH secretory ability by injecting exogenous corticotrophin-releasing factor, arginine vasotocin, and mesotocin and measuring corticosterone release. Pituitaries failed to respond to any exogenous releasing factor during the fall, suggesting that the pituitary may be the site in the HPA axis regulating corticosterone release at this time. When compared to wild-caught birds, these results suggest that captivity alters both adrenal and pituitary function during restraint in white-crowned sparrows, and that this change depends upon the season and/or physiological state of the animal. Captivity thus appears to have a profound affect on the function of the HPA axis, and these results reiterate the caution that must be used to extrapolate laboratory data to field conditions. PMID:10327590

  9. Identification of aromatase activity in rodent pituitary cell strains.

    PubMed

    Callard, G V; Petro, Z; Tashjian, A H

    1983-07-01

    To date, biochemical evidence has been presented for hypophysial aromatization in only one species, a teleost fish, although the pituitary glands of several mammals have been reported to be aromatase negative. To reinvestigate this problem, established clonal strains of rodent pituitary cells (GH3, GH4C1, and AtT20/D16) were incubated at 37 C for 6-48 h in serum-less medium containing [7-3H]androstenedione. Radiolabeled metabolites were isolated by solvent extraction, thin layer chromatography, and phenolic partition. The authenticity of the estrogenic products in both cells and incubation medium was verified by methylation and recrystallization to constant specific activity. Measurement of androgen metabolites was also validated by recrystallization of selected samples. Authentic estrone and 17 beta-estradiol were identified in cultures of the two PRL- and GH-secreting clones, and there were strain differences in the quantity of estrogen produced (GH3 greater than GH4C1). Under the same conditions, aromatization was not detectable in the ACTH-secreting line (AtT20/D16). A time-yield analysis of androgen metabolism in GH4C1 cells showed that aromatization was linear for 12 h after labeling, but that substrate was diverted mainly to 5 alpha-reducing pathways. Large amounts of highly polar metabolites accumulated 24 and 48 h after the addition of [3H]androgen, and subsequent hydrolysis revealed that these were sulfo- and glucuronoconjugates. The metabolic fate of estrogen in GH4C1 cultures was investigated indirectly by adding a radioinert estrone trap together with the radiolabeled androgen substrate and was also tested in separate cultures by adding [3H]estrone and [3H]estradiol directly. Although the two estrogens were interconverted, there was no evidence that formed or added estrogen was extensively metabolized or conjugated. We conclude that the expression of aromatase activity in hypophysial cells is not a property of all transformed lines but may be dictated

  10. Presence of secretory IgA in human periapical lesions.

    PubMed

    Torres, J O; Torabinejad, M; Matiz, R A; Mantilla, E G

    1994-02-01

    The concentration of secretory IgA in fluids present in the canals of 33 teeth was determined by the rocket immunoelectrophoresis technique. Except for the presence or absence of communication between the oral cavity and the root canals of the affected teeth, no other clinical finding showed significant statistical correlation with the presence of secretory IgA. The canals which were open to the oral flora had significantly higher concentrations of secretory IgA. Leaving canals open to the oral cavity may result in formation of periapical cysts. PMID:8006572

  11. Idiopathic Granulomatous Hypophysitis Mimicking Pituitary Abscess

    PubMed Central

    Kong, Xiangyi; Wang, Renzhi; Yang, Yi; Wu, Huanwen; Su, Changbao; Ma, Wenbin; Li, Yongning; Xing, Bing; Lian, Wei; Xu, Zhiqin; Yao, Yong; Ren, Zuyuan

    2015-01-01

    Abstract Idiopathic granulomatous hypophysitis (IGH) is a rare inflammatory disease of the pituitary that commonly presents with enlargement of the pituitary gland. Clinically and radiologically, IGH is a rare sellar entity easily to be misdiagnosed as a pituitary adenoma. Through such a case, we aim to present this rarity and emphasize the importance to correctly diagnose confusing pituitary lesions comprehensively by clinical presentations, radiological signs, and biopsy. We present an uncommon case of IGH in a 19-year-old man. The patient was admitted to the hospital with severe headache, vomiting, and vision's sharp decline. Magnetic resonance imaging showed a sellar lesion with obvious cystic change and ring enhancement. The disease course including diagnosis and treatment was presented and analyzed in detail. The pertinent literature is reviewed regarding this uncommon entity. The patient underwent surgical exploration and partial resection via the transsphenoidal approach. The pathologic findings suggested IGH giving no significant evidences of systemic granulomatous disease and venereal disease. Large dose methylprednisolone was then used. The pituitary function recovered, but there was no apparent improvement of his vision. IGH is a rarely occurred inflammatory disease of unknown etiology. It is difficult to diagnose preoperatively and is often misdiagnosed. Although rare, IGH should be kept in mind in terms of differential diagnosis of sellar region lesions. PMID:26181544

  12. The retinoblastoma gene in human pituitary tumors

    SciTech Connect

    Cryns, V.L.; Arnold, A.; Alexander, J.M.; Klibanski, A. )

    1993-09-01

    Functional inactivation of the retinoblastoma (RB) tumor suppressor gene is important in the pathogenesis of many human tumors. Recently, the frequent occurrence of pituitary tumors was reported in mice genetically engineered to have one defective RB allele, a genetic background analogous to that of patients with familial retinoblastoma. The molecular pathogenesis of human pituitary tumors is largely unknown, and the potential role of RB gene inactivation in these neoplasms has not been examined. Consequently, the authors studied 20 human pituitary tumors (12 clinically nonfunctioning tumors, 4 somatotroph adenomas, 2 prolactinomas, and 2 corticotrophy adenomas) for tumor-specific allelic loss of the RB gene using a highly informative polymorphic locus within the gene. Control leukocyte DNA samples from 18 of these 20 patients were heterozygous at this locus, permitting genetic evaluation of their paired tumor specimens. In contrast to the pituitary tumors in the mouse model, none of these 18 human tumors exhibited RB allelic loss. These findings indicate that RB gene inactivation probably does not play an important role in the pathogenesis of common types of human pituitary tumors. 24 refs., 1 fig.

  13. Stellate Cell Networks in the Teleost Pituitary

    PubMed Central

    Golan, Matan; Hollander-Cohen, Lian; Levavi-Sivan, Berta

    2016-01-01

    The folliculostellate cells of the mammalian pituitary are non-endocrine cells that are implicated in long-distance communication and paracrine signaling, but to date, these cells have yet to be characterized in teleosts. We found that the stellate cells of the teleost pituitary share many common attributes with mammalian folliculostellate cells. By labeling of stellate cells in live preparations of tilapia pituitaries we investigated their distribution, association with other endocrine cells and their anatomical and functional coupling. In the pars intermedia, stellate cells were arranged around neuronal bundles and their processes extended into the pars distalis. Within the pars distalis, stellate cells formed close associations with FSH cells and, to a lesser degree, with GH and LH cells, suggesting differential paracrine regulation of the two gonadotrope populations. The production of follistatin by stellate cells further corroborates the notion of a paracrine role on FSH release. We also found stellate cells to form gap junctions that enabled dye transfer to neighboring stellate cells, implicating that these cells form a large-scale network that connects distant parts of the pituitary. Our findings represent the first wide-scale study of stellate cells in teleosts and provide valuable information regarding their functional roles in pituitary function. PMID:27086978

  14. Paediatric pituitary adenomas: a decade of change.

    PubMed

    Guaraldi, Federica; Storr, Helen L; Ghizzoni, Lucia; Ghigo, Ezio; Savage, Martin O

    2014-01-01

    Pituitary adenomas, although rare in the paediatric age range and mostly benign, represent very challenging disorders for diagnosis and management. The recent identification of genetic alterations in young individuals with pituitary adenomas has broadened the scope of molecular investigations and contributed to the understanding of mechanisms of tumorigenesis. Recent identification of causative mutations of genes such as GNAS, PRKAR1A, MEN1 and AIP has introduced the concept of molecular screening of young apparently healthy family members. Population-based studies have reported a significantly higher number of affected subjects and genetic variations than expected. Radiological techniques have advanced, yet many microadenomas remain undetectable on scanning. However, experience with transsphenoidal and endoscopic pituitary surgery has led to higher rates of cure. Prolactinomas, corticotroph and somatotroph adenomas remain the most prevalent, with each diagnosis presenting its own challenges. As paediatric pituitary adenomas occur very infrequently within the paediatric age range, paediatric endocrine units cannot provide expert management in isolation. Consequently, close co-operation with adult endocrinology colleagues with experience of pituitary disease is strongly recommended. PMID:24525527

  15. Bovine Leukemia Virus DNA in Human Breast Tissue

    PubMed Central

    Shen, Hua Min; Jensen, Hanne M.; Choi, K. Yeon; Sun, Dejun; Nuovo, Gerard

    2014-01-01

    Bovine leukemia virus (BLV), a deltaretrovirus, causes B-cell leukemia/lymphoma in cattle and is prevalent in herds globally. A previous finding of antibodies against BLV in humans led us to examine the possibility of human infection with BLV. We focused on breast tissue because, in cattle, BLV DNA and protein have been found to be more abundant in mammary epithelium than in lymphocytes. In human breast tissue specimens, we identified BLV DNA by using nested liquid-phase PCR and DNA sequencing. Variations from the bovine reference sequence were infrequent and limited to base substitutions. In situ PCR and immunohistochemical testing localized BLV to the secretory epithelium of the breast. Our finding of BLV in human tissues indicates a risk for the acquisition and proliferation of this virus in humans. Further research is needed to determine whether BLV may play a direct role in human disease. PMID:24750974

  16. Identification of stimulatory and inhibitory inputs to the hypothalamic-pituitary-adrenal axis during hypoglycaemia or transport in ewes.

    PubMed

    Smith, R F; French, N P; Saphier, P W; Lowry, P J; Veldhuis, J D; Dobson, H

    2003-06-01

    This study used the novel approach of statistical modelling to investigate the control of hypothalamic-pituitary-adrenal (HPA) axis and quantify temporal relationships between hormones. Two experimental paradigms were chosen, insulin-induced hypoglycaemia and 2 h transport, to assess differences in control between noncognitive and cognitive stimuli. Vasopressin and corticotropin-releasing hormone (CRH) were measured in hypophysial portal plasma, and adrenocorticotropin hormone (ACTH) and cortisol in jugular plasma of conscious sheep, and deconvolution analysis was used to calculate secretory rates, before modelling. During hypoglycaemia, the relationship between plasma glucose and vasopressin or CRH was best described by log10 transforming variables (i.e. a positive power-curve relationship). A negative-feedback relationship with log10 cortisol concentration 2 h previously was detected. Analysis of the "transport" stimulus suggested that the strength of the perceived stimulus decreased over time after accounting for cortisol facilitation and negative-feedback. The time course of vasopressin and CRH responses to each stimulus were different However, at the pituitary level, the data suggested that log10 ACTH secretion rate was related to log10 vasopressin and CRH concentrations with very similar regression coefficients and an identical ratio of actions (2.3 : 1) for both stimuli. Similar magnitude negative-feedback effects of log10 cortisol at -110 min (hypoglycaemia) or -40 min (transport) were detected, and both models contained a stimulatory relationship with cortisol at 0 min (facilitation). At adrenal gland level, cortisol secretory rates were related to simultaneously measured untransformed ACTH concentration but the regression coefficient for the hypoglycaemia model was 2.5-fold greater than for transport. No individual sustained maximum cortisol secretion for longer than 20 min during hypoglycaemia and 40 min during transport. These unique models demonstrate

  17. 77 FR 20319 - Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-04

    ...; ] DEPARTMENT OF AGRICULTURE Animal and Plant Health Inspection Service 9 CFR Part 93 RIN 0579-AC68 Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products Correction In proposed rule...

  18. 78 FR 73993 - Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-10

    ... Health Inspection Service 9 CFR Parts 92, 93, 94, 95, 96, and 98 RIN 0579-AC68 Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products Corrections In rule document 2013-28228 appearing...

  19. Methylmercury inhibits prolactin release in a cell line of pituitary origin

    PubMed Central

    Maués, L.A.L.; Macchi, B.M.; Crespo-López, M.E.; Nasciutti, L.E.; Picanço-Diniz, D.L.W.; Antunes-Rodrigues, J.; do Nascimento, J.L.M.

    2015-01-01

    Heavy metals, such as methylmercury, are key environmental pollutants that easily reach human beings by bioaccumulation through the food chain. Several reports have demonstrated that endocrine organs, and especially the pituitary gland, are potential targets for mercury accumulation; however, the effects on the regulation of hormonal release are unclear. It has been suggested that serum prolactin could represent a biomarker of heavy metal exposure. The aim of this study was to evaluate the effect of methylmercury on prolactin release and the role of the nitrergic system using prolactin secretory cells (the mammosomatotroph cell line, GH3B6). Exposure to methylmercury (0-100 μM) was cytotoxic in a time- and concentration-dependent manner, with an LC50 higher than described for cells of neuronal origin, suggesting GH3B6 cells have a relative resistance. Methylmercury (at exposures as low as 1 μM for 2 h) also decreased prolactin release. Interestingly, inhibition of nitric oxide synthase by N-nitro-L-arginine completely prevented the decrease in prolactin release without acute neurotoxic effects of methylmercury. These data indicate that the decrease in prolactin production occurs via activation of the nitrergic system and is an early effect of methylmercury in cells of pituitary origin. PMID:26108095

  20. Experimental Modification of Rat Pituitary Growth Hormone Cell Function During and After Spaceflight

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.; Salada, T.; Nye, P.; Grossman, E. J.; Lane, P. K.; Grindeland, R. E.

    1996-01-01

    Space-flown rats show a number of flight-induced changes in the structure and function of pituitary Growth Hormone (GH) cells after in vitro postflight testing. To evaluate the possible effects of microgravity on GH cells themselves, freshly dispersed rat anterior pituitary gland cells were seeded into vials containing serum +/- 1 micron HydroCortisone (HC) before flight. Five different cell preparations were used: the entire mixed-cell population of various hormone-producing cell types, cells of density less than 1.071 g/sq cm (band 1), cells of density greater than 1.071 g/sq cm (band 2), and cells prepared from either the dorsal or ventral part of the gland. Relative to ground control samples, bioactive GH released from dense cells during flight was reduced in HC-free medium but was increased in HC-containing medium. Band I and mixed cells usually showed opposite HC-dependent responses. Release of bioactive GH from ventral flight cells was lower; postflight responses to GH-releasing hormone challenge were reduced, and the cytoplasmic area occupied by GH in the dense cells was greater. Collectively, the data show that the chemistry and cellular makeup of the culture system modifies the response of GH cells to microgravity. As such, these cells offer a system to identify gravisensing mechanisms in secretory cells in future microgravity research.

  1. Effects of alcohol feeding on androgen receptors in the rat pituitary gland

    SciTech Connect

    Chung, K.W.

    1987-10-26

    Specific binding of testosterone-1..beta..,2..beta..-/sup 3/H by cytosol from anterior pituitary gland of ethanol-fed, isocaloric control, and castrated control and ethanol-fed rats with or without testosterone treatment has been investigated by charcoal assay. The number of androgen binding sites was significantly reduced in alcohol-fed rats when compared to the isocaloric control value, with no significant change in Kd. Castration significantly increased the number of receptor sites in control rats and when castrated control animals were treated with testosterone the binding sites were decreased to the intact control level. In contrast, castration or testosterone given to castrated alcohol-fed rats did not alter alcohol-induced reduction of the receptor sites. The binding affinity (Kd) is identical in all groups. The concentration of serum luteinizing hormone (LH) was significantly lower in alcohol-fed rats when compared to that of normal controls. An increased serum LH level with a decreased testosterone level was noted in castrated control rats. However, castration of alcohol-fed rats had little or no effects on the concentrations of LH and testosterone. Administration of testosterone suppressed castration-induced high LH in control rats but alcohol induced reduction of LH level was not altered by this treatment. These findings indicate that alcohol exerts a suppressive effect on the content of androgen receptors and secretory functions of gonadotropins in the pituitary gland. 23 references, 1 figure, 1 table.

  2. What's New in Pituitary Tumor Research and Treatment?

    MedlinePlus

    ... Next Topic Additional resources for pituitary tumors What’s new in pituitary tumor research and treatment? Research into ... of non-functioning adenomas, which may lead to new medical therapies for these tumors. Imaging tests such ...

  3. Polymicrobial Pituitary Abscess Predominately Involving Escherichia coli in the Setting of an Apoplectic Pituitary Prolactinoma.

    PubMed

    Beatty, Norman; Medina-Garcia, Luis; Al Mohajer, Mayar; Zangeneh, Tirdad T

    2016-01-01

    Pituitary abscess is a rare intracranial infection that can be life-threatening if not appropriately diagnosed and treated upon presentation. The most common presenting symptoms include headache, anterior pituitary hypofunction, and visual field disturbances. Brain imaging with either computed tomography or magnetic resonance imaging usually reveals intra- or suprasellar lesion(s). Diagnosis is typically confirmed intra- or postoperatively when pathological analysis is done. Clinicians should immediately start empiric antibiotics and request a neurosurgical consult when pituitary abscess is suspected. Escherichia coli (E. coli) causing intracranial infections are not well understood and are uncommon in adults. We present an interesting case of an immunocompetent male with a history of hypogonadism presenting with worsening headache and acute right eye vision loss. He was found to have a polymicrobial pituitary abscess predominantly involving E.   coli in addition to Actinomyces odontolyticus and Prevotella melaninogenica in the setting of an apoplectic pituitary prolactinoma. The definitive etiology of this infection was not determined but an odontogenic process was suspected. A chronic third molar eruption and impaction in close proximity to the pituitary gland likely led to contiguous spread of opportunistic oral microorganisms allowing for a polymicrobial pituitary abscess formation. PMID:27006841

  4. Polymicrobial Pituitary Abscess Predominately Involving Escherichia coli in the Setting of an Apoplectic Pituitary Prolactinoma

    PubMed Central

    Beatty, Norman; Medina-Garcia, Luis; Al Mohajer, Mayar; Zangeneh, Tirdad T.

    2016-01-01

    Pituitary abscess is a rare intracranial infection that can be life-threatening if not appropriately diagnosed and treated upon presentation. The most common presenting symptoms include headache, anterior pituitary hypofunction, and visual field disturbances. Brain imaging with either computed tomography or magnetic resonance imaging usually reveals intra- or suprasellar lesion(s). Diagnosis is typically confirmed intra- or postoperatively when pathological analysis is done. Clinicians should immediately start empiric antibiotics and request a neurosurgical consult when pituitary abscess is suspected. Escherichia coli (E. coli) causing intracranial infections are not well understood and are uncommon in adults. We present an interesting case of an immunocompetent male with a history of hypogonadism presenting with worsening headache and acute right eye vision loss. He was found to have a polymicrobial pituitary abscess predominantly involving E.   coli in addition to Actinomyces odontolyticus and Prevotella melaninogenica in the setting of an apoplectic pituitary prolactinoma. The definitive etiology of this infection was not determined but an odontogenic process was suspected. A chronic third molar eruption and impaction in close proximity to the pituitary gland likely led to contiguous spread of opportunistic oral microorganisms allowing for a polymicrobial pituitary abscess formation. PMID:27006841

  5. Cre-mediated recombination in pituitary somatotropes

    PubMed Central

    Nasonkin, Igor O.; Potok, Mary Anne; Camper, Sally A.

    2009-01-01

    We report a transgenic line with highly penetrant cre recombinase activity in the somatotrope cells of the anterior pituitary gland. Expression of the cre transgene is under the control of the locus control region of the human growth hormone gene cluster and the rat growth hormone promoter. Cre recombinase activity was assessed with two different lacZ reporter genes that require excision of a floxed stop sequence for expression: a chick β-actin promoter with the CMV enhancer transgene and a ROSA26 knock-in. Cre activity is detectable in the developing pituitary after initiation of Gh transcription and persists through adulthood with high penetrance in Gh expressing cells and lower penetrance in lactotropes, a cell type that shares a common origin with somatotropes. This Gh-cre transgenic line is suitable for efficient, cell-specific deletion of floxed regions of genomic DNA in differentiated somatotropes and a subset of lactotrope cells of the anterior pituitary gland. PMID:19039787

  6. Cre-mediated recombination in pituitary somatotropes.

    PubMed

    Nasonkin, Igor O; Potok, Mary Anne; Camper, Sally A

    2009-01-01

    We report a transgenic line with highly penetrant cre recombinase activity in the somatotrope cells of the anterior pituitary gland. Expression of the cre transgene is under the control of the locus control region of the human growth hormone gene cluster and the rat growth hormone promoter. Cre recombinase activity was assessed with two different lacZ reporter genes that require excision of a floxed stop sequence for expression: a chick beta-actin promoter with the CMV enhancer transgene and a ROSA26 knock-in. Cre activity is detectable in the developing pituitary after initiation of Gh transcription and persists through adulthood with high penetrance in Gh expressing cells and lower penetrance in lactotropes, a cell type that shares a common origin with somatotropes. This Gh-cre transgenic line is suitable for efficient, cell-specific deletion of floxed regions of genomic DNA in differentiated somatotropes and a subset of lactotrope cells of the anterior pituitary gland. PMID:19039787

  7. A Novel Mutation of DAX-1 Associated with Secretory Azoospermia

    PubMed Central

    Yang, Lihua; Liu, Yuchen; Diao, Ruiying; Cai, Zhiming; Li, Honggang; Gui, Yaoting

    2015-01-01

    Secretory azoospermia is a severe form of male infertility caused by unknown factors. DAX-1 is predominantly expressed in mammalian reproductive tissues and plays an important role in spermatogenesis because Dax-1 knockout male mice show spermatogenesis defects. To examine whether DAX-1 is involved in the pathogenesis of secretory azoospermia in humans, we sequenced all of the exons of DAX-1 in 776 patients diagnosed with secretory azoospermia and 709 proven fertile men. A number of coding mutations unique to the patient group, including two synonymous mutations and six missense mutations, were identified. Of the missense mutations, our functional assay demonstrated that the V385L mutation caused the reduced functioning of DAX-1. This novel mutation (p. V385L) of DAX-1 is the first to be identified in association with secretory azoospermia, thereby highlighting the important role of DAX-1 in spermatogenesis. PMID:26207377

  8. Contemporary issues in the evaluation and management of pituitary adenomas.

    PubMed

    Pekic, S; Stojanovic, M; Popovic, V

    2015-12-01

    Pituitary adenomas are common benign monoclonal neoplasms accounting for about 15% of intracranial neoplasms. Data from postmortem studies and imaging studies suggest that 1 of 5 individuals in the general population may have pituitary adenoma. Some pituitary adenomas (mainly microadenomas which have a diameter of less than 1 cm) are exceedingly common and are incidentally diagnosed on magnetic resonance imaging (MRI) performed for an unrelated reason (headache, vertigo, head trauma). Most microadenomas remain clinically occult and stable in size, without an increase in tumor cells and without local mass effects. However, some pituitary adenomas grow slowly, enlarge by expansion and become demarcated from normal pituitary (macroadenomas have a diameter greater than 1 cm). They may be clinically silent or secrete anterior pituitary hormones in excess such as prolactin, growth hormone (GH), or adrenocorticotropic hormone (ACTH) causing diseases like prolactinoma, acromegaly, Cushing's disease or rarely thyroid-stimulating hormone (TSH) or gonadotropins (LH, FSH). The incidence of the various subtypes of pituitary adenoma varies but the most common is prolactinoma. Clinically non-functioning pituitary adenomas (NFPAs), which do not secrete hormones often cause local mass symptoms and represent one-third of pituitary adenomas. Given the high prevalence of pituitary adenomas and their heterogeneity (different tumor subtypes), it is critical that clinicians have a thorough understanding of the potential abnormalities in pituitary function and prognostic factors for behavior of pituitary adenomas in order to timely implement specific treatment modalities. Regarding pathogenesis of these tumors genetics, epigenetics and signaling pathways are the focus of current research yet our understanding of pituitary tumorigenesis remains incomplete. Although several genes and signaling pathways have been identified as important factors in the development of pituitary tumors, current

  9. The clinical features and management of pituitary apoplexy.

    PubMed Central

    Lloyd, M. H.; Belchetz, P. E.

    1977-01-01

    The clinical features and management of three patients presenting with pituitary apoplexy are described. They illustrate the difficulty of differentiating pituitary apoplexy from other acute neurologic conditions. One of the patients is the first reported case of pituitary apoplexy occurring in a histologically proved craniopharyngioma. Two of the cases reported were treated conservatively and recovered without seriouplexy as a neurosurgical emergency. The relationship between radiotherapy and pituitary apoplexy is discussed. PMID:876925

  10. Secretory protein trafficking in Giardia intestinalis.

    PubMed

    Hehl, Adrian B; Marti, Matthias

    2004-07-01

    Early diverged extant organisms, which may serve as convenient laboratory models to look for and study evolutionary ancient features of eukaryotic cell biology, are rare. The diplomonad Giardia intestinalis, a protozoan parasite known to cause diarrhoeal disease, has become an increasingly popular object of basic research in cell biology, not least because of a genome sequencing project nearing completion. Commensurate with its phylogenetic status, the Giardia trophozoite has a very basic secretory system and even lacks hallmark structures such as a morphologically identifiable Golgi apparatus. The cell's capacity for protein sorting is nevertheless unimpeded, exemplified by its ability to cope with massive amounts of newly synthesized cyst wall proteins and glycans, which are sorted to dedicated Golgi-like compartments termed encystation-specific vesicles (ESVs) generated from endoplasmic reticulum (ER)-derived transport intermediates. This soluble bulk cargo is kept strictly separate from constitutively transported variant surface proteins during export, a function that is dependent on the stage-specific recognition of trafficking signals. Encysting Giardia therefore provide a unique system for the study of unconventional, Golgi-independent protein trafficking mechanisms in the broader context of eukaryotic endomembrane organization and evolution. PMID:15225300

  11. Cell Type-Specific Sexual Dimorphism in Rat Pituitary Gene Expression During Maturation.

    PubMed

    Bjelobaba, Ivana; Janjic, Marija M; Kucka, Marek; Stojilkovic, Stanko S

    2015-07-01

    The most obvious functional differences between mammalian males and females are related to the control of reproductive physiology and include patterns of GnRH and gonadotropin release, the timing of puberty, sexual and social behavior, and the regulation of food intake and body weight. Using the rat as the best-studied mammalian model for maturation, we examined the expression of major anterior pituitary genes in five secretory cell types of developing males and females. Corticotrophs show comparable Pomc profiles in both sexes, with the highest expression occurring during the infantile period. Somatotrophs and lactotrophs also exhibit no difference in Gh1 and Prl profiles during embryonic to juvenile age but show the amplification of Prl expression in females and Gh1 expression in males during peripubertal and postpubertal ages. Gonadotrophs exhibit highly synchronized Lhb, Fshb, Cga, and Gnrhr expression in both sexes, but the peak of expression occurs during the infantile period in females and at the end of the juvenile period in males. Thyrotrophs also show different developmental Tshb profiles, which are synchronized with the expression of gonadotroph genes in males but not in females. These results indicate the lack of influence of sex on Pomc expression and the presence of two patterns of sexual dimorphism in the expression of other pituitary genes: a time shift in the peak expression during postnatal development, most likely reflecting the perinatal sex-specific brain differentiation, and modulation of the amplitude of expression during late development, which is secondary to the establishment of the hypothalamic-pituitary-gonadal and -thyroid axes. PMID:26063874

  12. Ultrastructural and neurochemical architecture of the pituitary neural lobe of Xenopus laevis.

    PubMed

    van Wijk, Diane C W A; Meijer, Kari H; Roubos, Eric W

    2010-09-01

    The melanotrope cell in the amphibian pituitary pars intermedia is a model to study fundamental aspects of neuroendocrine integration. They release alpha-melanophore-stimulating hormone (alphaMSH), under the control of a large number of neurochemical signals derived from various brain centers. In Xenopus laevis, most of these signals are produced in the hypothalamic magnocellular nucleus (Mg) and are probably released from neurohemal axon terminals in the pituitary neural lobe, to stimulate alphaMSH-release, causing skin darkening. The presence in the neural lobe of at least eight stimulatory factors implicated in melanotrope cell control has led us to investigate the ultrastructural architecture of this neurohemal organ, with particular attention to the diversity of neurohemal axon terminals and their neurochemical contents. Using regular electron microscopy, we here distinguish six types of neurohemal axon terminal, on the basis of the size, shape and electron-density of their secretory granule contents. Subsequently, we have identified the neurochemical contents of these terminal types by immuno-electron microscopy and antisera raised against not only the 'classical' neurohormones vasotocin and mesotocin but also brain-derived neurotrophic factor, cocaine- and amphetamine-regulated transcript peptide, corticotropin-releasing factor, metenkephalin, pituitary adenylyl cyclase-activating polypeptide, thyrotropin-releasing hormone and urocortin-1. This has revealed that each terminal type possesses a unique set of neurochemical messengers, containing at least four, but in some cases up to eight messengers. These results reveal the potential of the Mg/neural lobe system to release a wide variety of neurochemical messengers in a partly co-ordinated and partly differential way to control melanotrope cell activity as well as ion and water balance regulatory organs, in response to various, continuously changing, environmental stimuli. PMID:20067800

  13. Ectopic suprasellar pituitary adenoma. A case report.

    PubMed

    Caranci, F; Cirillo, L; Bartiromo, F; Ferraioli, M; Del Basso De Caro, M L; Esposito, F; Cappabianca, P; Brunetti, A; Elefante, R

    2007-01-31

    The occurrence of a pituitary adenoma located entirely outside the sella turcica, so-called ectopic adenoma, is extremely rare. We report a case of a non secreting-pituitary adenoma located above the diaphragma sellae, with no invasion into the sella turcica, confirmed at surgery. The tumor was initially treated unsuccessfully by operations via the transphenoidal route. After initial negative exploration by the transphenoidal route, the patient was successfully treated by an endoscopic endonasal transphenoidal approach extended to the tuberculum sellae and the posterior planum sphenoidale to access the suprasellar supraglandular region. A brief review of ectopic adenomas and a discussion of the preoperative diagnosis are presented. PMID:24351300

  14. The pituitary - Aging and spaceflown rats

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.; Grindeland, R. E.

    1991-01-01

    Decrements in growth hormone (GH) release we observed in two spaceflight experiments and four tail-suspended rat studies mimic age-associated changes in the mammalian pituitary GH system seen by Meites and others. The spaceflight data suggest that formation of high molecular weight bioactive disulfide-linked aggregates of the 20 and 22K monomeric GH forms may be reduced in microgravity, thereby, reducing target tissue activity. Correlative studies to confirm spaceflight as a model for pituitary GH system aging should include: (1) investigation of mechanisms of intracellular hormone packaging, (2) consequences to biological activity of the hormone molecule, and (3) study of intracellular microtubule dynamics.

  15. Brain serotonin and pituitary-adrenal functions

    NASA Technical Reports Server (NTRS)

    Vernikos-Danellis, J.; Berger, P.; Barchas, J. D.

    1973-01-01

    It had been concluded by Scapagnini et al. (1971) that brain serotonin (5-HT) was involved in the regulation of the diurnal rhythm of the pituitary-adrenal system but not in the stress response. A study was conducted to investigate these findings further by evaluating the effects of altering brain 5-HT levels on the daily fluctuation of plasma corticosterone and on the response of the pituitary-adrenal system to a stressful or noxious stimulus in the rat. In a number of experiments brain 5-HT synthesis was inhibited with parachlorophenylalanine. In other tests it was tried to raise the level of brain 5-HT with precursors.

  16. Serotonin involvement in pituitary-adrenal function

    NASA Technical Reports Server (NTRS)

    Vernikos-Danellis, J.; Kellar, K. J.; Kent, D.; Gonzales, C.; Berger, P. A.; Barchas, J. D.

    1977-01-01

    Experiments clarifying the effects of serotonin (5-HT) in the regulation of the hypothalamic-pituitary-adrenocortical system are surveyed. Lesion experiments which seek to determine functional maps of serotonergic input to areas involved in regulation are reported. Investigations of the effects of 5-HT levels on the plasma ACTH response to stress and the diurnal variation in basal plasma corticosterone are summarized, and the question of whether serotonergic transmission is involved in the regulation of all aspects of pituitary-adrenal function is considered with attention to the stimulatory and inhibitory action of 5-HT.

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. GIANT PITUITARY ADENOMA WITH NORMAL VISION AND MISLEADING RADIOLOGICAL FINDINGS.

    PubMed

    Khalid, Muhammad; Raina, Umer Farooq; uz Zaman, Khaleeq; Tahir, Muhammad

    2015-01-01

    Giant pituitary adenomas are rare and present with visual loss. Giant pituitary adenoma has rarely been reported presenting with normal vision. We report Giant pituitary adenoma with Normal vision in a 35 years old patient presenting with adult onset epilepsy and headache. PMID:26721053

  2. Pituitary abscess: a case report and review of the literature

    PubMed Central

    Karagiannis, Apostolos K A; Dimitropoulou, Fotini; Papatheodorou, Athanasios; Lyra, Stavroula; Seretis, Andreas

    2016-01-01

    Summary Pituitary abscess is a rare life-threating entity that is usually misdiagnosed as a pituitary tumor with a definite diagnosis only made postoperatively. Over the last several decades, advances in healthcare have led to a significant decrease in morbidity and mortality due to pituitary abscess. We report a case of a 34-year-old woman who was admitted to our department for investigation of a pituitary mass and with symptoms of pituitary dysfunction, headaches and impaired vision. During her admission, she developed meningitis-like symptoms and was treated with antibiotics. She eventually underwent transsphenoidal surgery for excision of the pituitary mass. A significant amount of pus was evident intraoperatively; however, no pathogen was isolated. Six months later, the patient was well and had full recovery of the anterior pituitary function. Her menses returned, and she was only on treatment with desmopressin for diabetes insipidus that developed postoperatively. Learning points Pituitary abscess is a rare disease and the reported clinical features vary mimicking other pituitary lesions. The diagnosis of pituitary abscess is often very difficult to make and rarely included in the differential. The histological findings of acute inflammatory infiltration confirm the diagnosis of pituitary abscess. Medical and surgical treatment is usually recommended upon diagnosis of a pituitary abscess. PMID:27274845

  3. Unlocking the bovine genome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The draft genome sequence of cattle (Bos taurus) has now been analyzed by the Bovine Genome Sequencing and Analysis Consortium and the Bovine HapMap Consortium, which together represent an extensive collaboration involving more than 300 scientists from 25 different countries. ...

  4. Bovine viral diarrhea viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infections with bovine viral diarrhea viruses (BVDV) result in significant economic losses for beef and dairy producers worldwide. BVDV is actually an umbrella term for two species of viruses, BVDV1 and BVDV2, within the Pestivirus genus of the Flavivirus family. While denoted as a bovine pathogen...

  5. Secretory pathway of cellulase: a mini-review

    PubMed Central

    2013-01-01

    Cellulase plays an important role in modern industry and holds great potential in biofuel production. Many different types of organisms produce cellulase, which go through secretory pathways to reach the extracellular space, where enzymatic reactions take place. Secretory pathways in various cells have been the focus of many research fields; however, there are few studies on secretory pathways of cellulases in the literature. It is therefore necessary and important to review the current knowledge on the secretory pathways of cellulases. In this mini-review, we address the subcellular locations of cellulases in different organisms, discuss the secretory pathways of cellulases in different organisms, and examine the secretory mechanisms of cellulases. These sections start with a description of general secreted proteins, advance to the situation of cellulases, and end with the knowledge of cellulases, as documented in UniProt Knowledgebase (UniProtKB). Finally, gaps in existing knowledge are highlighted, which may shed light on future studies for biofuel engineering. PMID:24295495

  6. Proteolysis sensitizes LDL particles to phospholipolysis by secretory phospholipase A2 group V and secretory sphingomyelinase

    PubMed Central

    Plihtari, Riia; Hurt-Camejo, Eva; Öörni, Katariina; Kovanen, Petri T.

    2010-01-01

    LDL particles that enter the arterial intima become exposed to proteolytic and lipolytic modifications. The extracellular hydrolases potentially involved in LDL modification include proteolytic enzymes, such as chymase, cathepsin S, and plasmin, and phospholipolytic enzymes, such as secretory phospholipases A2 (sPLA2-IIa and sPLA2-V) and secretory acid sphingomyelinase (sSMase). Here, LDL was first proteolyzed and then subjected to lipolysis, after which the effects of combined proteolysis and lipolysis on LDL fusion and on binding to human aortic proteoglycans (PG) were studied. Chymase and cathepsin S led to more extensive proteolysis and release of peptide fragments from LDL than did plasmin. sPLA2-IIa was not able to hydrolyze unmodified LDL, and even preproteolysis of LDL particles failed to enhance lipolysis by this enzyme. However, preproteolysis with chymase and cathepsin S accelerated lipolysis by sPLA2-V and sSMase, which resulted in enhanced fusion and proteoglycan binding of the preproteolyzed LDL particles. Taken together, the results revealed that proteolysis sensitizes the LDL particles to hydrolysis by sPLA2-V and sSMase. By promoting fusion and binding of LDL to human aortic proteoglycans, the combination of proteolysis and phospholipolysis of LDL particles potentially enhances extracellular accumulation of LDL-derived lipids during atherogenesis. PMID:20124257

  7. COMPARABLE OUTCOMES IN NON-SECRETORY AND SECRETORY MULTIPLE MYELOMA AFTER AUTOLOGOUS STEM CELL TRANSPLANTATION

    PubMed Central

    Kumar, Shaji; Pérez, Waleska S.; Zhang, Mei-Jie; Ballen, Karen; Bashey, Asad; To, L. Bik; Bredeson, Christopher N.; Cairo, Mitchell S.; Elfenbein, Gerald J.; Freytes, César O.; Gale, Robert Peter; Gibson, John; Kyle, Robert A.; Lacy, Martha Q.; Lazarus, Hillard M.; McCarthy, Philip L.; Milone, Gustavo A.; Moreb, Jan S.; Pavlovsky, Santiago; Reece, Donna E.; Vesole, David H.; Wiernik, Peter H.; Hari, Parameswaran

    2008-01-01

    Non-secretory myeloma (NSM) accounts for <5% of cases of multiple myeloma (MM). The outcome of these patients following autologous stem cell transplantation (ASCT) has not been evaluated in clinical trials. We compared the outcomes after ASCT for patients with NSM reported to the CIBMTR between 1989 and 2003, to a matched group of 438 patients (4 controls for each patient) with secretory myeloma (SM). The patients were matched using propensity scores calculated using age, Durie-Salmon stage, sensitivity to pre-transplant therapy, time from diagnosis to transplant and year of transplant. Disease characteristics were similar in both groups at diagnosis and at transplant except higher risk of anemia, hypoalbuminemia and marrow plasmacytosis (in SM) and plasmacytoma (more in NSM). Cumulative incidence of TRM, relapse, PFS and OS were similar between the groups. In multivariate analysis, based on a Cox model stratified on matched pairs and adjusted for covariates not considered in the propensity score, we found no difference in outcome between the NSM and SM groups. In this large cohort of patients undergoing ASCT, we found no difference in outcomes of patients with NSM compared to those with SM. PMID:18804043

  8. Progressive quality control of secretory proteins in the early secretory compartment by ERp44

    PubMed Central

    Sannino, Sara; Anelli, Tiziana; Cortini, Margherita; Masui, Shoji; Degano, Massimo; Fagioli, Claudio; Inaba, Kenji; Sitia, Roberto

    2014-01-01

    ERp44 is a pH-regulated chaperone of the secretory pathway. In the acidic milieu of the Golgi, its C-terminal tail changes conformation, simultaneously exposing the substrate-binding site for cargo capture and the RDEL motif for ER retrieval via interactions with cognate receptors. Protonation of cysteine 29 in the active site allows tail movements in vitro and in vivo. Here we show that also conserved histidines in the C-terminal tail regulate ERp44 in vivo. Mutants lacking these histidines are hyperactive in retaining substrates. Surprisingly, they are also O-glycosylated and partially secreted. Co-expression of client proteins prevents secretion of the histidine mutants, forcing tail opening and RDEL accessibility. Client-induced RDEL exposure allows retrieval of proteins from distinct stations along the secretory pathway, as indicated by the changes in O-glycosylation patterns upon over-expression of different partners. The ensuing gradients may help optimising folding and assembly of different cargoes. Endogenous ERp44 is O-glycosylated and secreted by human primary endometrial cells, suggesting possible pathophysiological roles of these processes. PMID:25097228

  9. Pituitary tuberculoma: A consideration in the differential diagnosis in a patient manifesting with pituitary apoplexy-like syndrome.

    PubMed

    Srisukh, Sasima; Tanpaibule, Tananun; Kiertiburanakul, Sasisopin; Boongird, Atthaporn; Wattanatranon, Duangkamon; Panyaping, Theerapol; Sriphrapradang, Chutintorn

    2016-01-01

    Pituitary tuberculoma is extremely rare, even in endemic regions of tuberculosis and much less frequently as a presentation of pituitary apoplexy. We describe a 25-year-old female presented with sudden onset of headache and vision loss of left eye which mimicking symptoms of pituitary apoplexy. MRI of the pituitary gland showed a rim-enhancing lesion at the intrasellar region extending into the suprasellar area, but absence of posterior bright spot with enhancement of the pituitary stalk. Pituitary hormonal evaluation revealed panhypopituitarism and diabetes insipidus. An urgent transphenoidal surgery of the pituitary gland was undertaken for which the histopathology showed necrotizing granulomatous inflammation with infarcted adjacent pituitary tissue. Despite negative fungal and AFB staining, pituitary tuberculoma was presumptively diagnosed based on imaging, pathology and the high incidence of tuberculosis in the country. After the course of anti-tuberculosis therapy, the clinical findings were dramatically improved, supporting the diagnosis. Pituitary tuberculoma is extremely rare in particular with an apoplexy-like presentation but should be one of the differential diagnosis list of intrasellar lesions in the patient presenting with sudden onset of headache and visual loss. The presence of diabetes insipidus and thickened with enhancement of pituitary stalk on MRI were very helpful in diagnosing pituitary tuberculosis. PMID:27516966

  10. Secretory sphingomyelinase in health and disease.

    PubMed

    Kornhuber, Johannes; Rhein, Cosima; Müller, Christian P; Mühle, Christiane

    2015-06-01

    Acid sphingomyelinase (ASM), a key enzyme in sphingolipid metabolism, hydrolyzes sphingomyelin to ceramide and phosphorylcholine. In mammals, the expression of a single gene, SMPD1, results in two forms of the enzyme that differ in several characteristics. Lysosomal ASM (L-ASM) is located within the lysosome, requires no additional Zn2+ ions for activation and is glycosylated mainly with high-mannose oligosaccharides. By contrast, the secretory ASM (S-ASM) is located extracellularly, requires Zn2+ ions for activation, has a complex glycosylation pattern and has a longer in vivo half-life. In this review, we summarize current knowledge regarding the physiology and pathophysiology of S-ASM, including its sources and distribution, molecular and cellular mechanisms of generation and regulation and relevant in vitro and in vivo studies. Polymorphisms or mutations of SMPD1 lead to decreased S-ASM activity, as detected in patients with Niemann-Pick disease B. Thus, lower serum/plasma activities of S-ASM are trait markers. No genetic causes of increased S-ASM activity have been identified. Instead, elevated activity is the result of enhanced release (e.g., induced by lipopolysaccharide and cytokine stimulation) or increased enzyme activation (e.g., induced by oxidative stress). Increased S-ASM activity in serum or plasma is a state marker of a wide range of diseases. In particular, high S-ASM activity occurs in inflammation of the endothelium and liver. Several studies have demonstrated a correlation between S-ASM activity and mortality induced by severe inflammatory diseases. Serial measurements of S-ASM reveal prolonged activation and, therefore, the measurement of this enzyme may also provide information on past inflammatory processes. Thus, S-ASM may be both a promising clinical chemistry marker and a therapeutic target. PMID:25803076

  11. An Indian family of hereditary pituitary dwarfism.

    PubMed

    Havaldar, P V

    1991-01-01

    Three girls and one boy out of six siblings born to parents of consanguineous marriage presented with pituitary dwarfism. Their parents were of normal height. All the affected children had features of classical isolated growth hormone deficiency. No hypoglycaemic attacks were noted. Three of them attained puberty at the age of 16 years. PMID:1721794

  12. Pituitary immunoexpression of ghrelin in anorexia nervosa.

    PubMed

    Rotondo, Fabio; Scheithauer, Bernd W; Syro, Luis V; Rotondo, Angelo; Kovacs, Kalman

    2012-12-01

    Ghrelin, an orexigenic hormone, is known to occur in the normal anterior pituitary where its physiologic role is uncertain but may include promotion of appetite. We sought to investigate anticipated differences in adenohypophysial and neurohypophysial ghrelin immunoexpression between normal subjects and patients with anorexia nervosa who had succumbed to complications of the disease. We hypothesized that the glands of anorexia nervosa patients would show relative diminished action in ghrelin content. The study included 12 autopsy-derived pituitaries of anorexia nervosa and 10 control glands. The streptavidin-biotin-peroxidase complex method and double immunohistochemical staining method were used to determine which cell types expressed both ghrelin and adenohypophysial hormones. Nontumorous control pituitaries were also obtained at autopsy. In anorexia nervosa and control adenohypophyses, ghrelin was mainly localized in somatotrophs and to a lesser extent in corticotrophs and gonadotrophs. Ghrelin accumulated within nerve fibers and Herring bodies in the neurohypophysis and pituitary stalk. In the controls, ghrelin expression was apparent in only a few cases. It was mild and only along few nerve fibers. In the adenohypophyses of anorexia nervosa patients, ghrelin was not depleted. It appears that in these patients, ghrelin is transported in excess from the hypothalamic neurohypophysial tract to the neurohypophysis. PMID:22081273

  13. Spinal metastases from pituitary hemangiopericytic meningioma

    SciTech Connect

    Kumar, P.P.; Good, R.R.; Skultety, F.M.; Masih, A.S.; McComb, R.D.

    1987-10-01

    A rare, previously irradiated, recurrent malignant angioblastic meningioma of the pituitary, hemangiopericytic type, was locally controlled by a new endocurietherapy technique that allows delivery of very high (10,000 cGy), sharply localized irradiation. Rather than succumbing to the local tumor recurrence, as would otherwise be expected, the patient developed distant spinal metastases several years later.

  14. Magnetic Resonance Imaging of Pituitary Tumors.

    PubMed

    Bonneville, Jean-François

    2016-01-01

    Magnetic Resonance Imaging (MRI) is currently considered a major keystone of the diagnosis of diseases of the hypothalamic-hypophyseal region. However, the relatively small size of the pituitary gland, its location deep at the skull base and the numerous physiological variants present in this area impede the precise assessment of the anatomical structures and, particularly, of the pituitary gland itself. The diagnosis of the often tiny lesions of this region--such as pituitary microadenomas--is then difficult if the MRI technology is not optimized and if potential artifacts and traps are not recognized. Advanced MRI technology can not only depict small lesions with greater reliability, but also help in the differential diagnosis of large tumors. In these, defining the presence or absence of invasion is a particularly important task. This review describes and illustrates the radiological diagnosis of the different tumors of the sellar region, from the common prolactinomas, nonfunctioning adenomas and Rathke's cleft cysts, to the less frequent and more difficult to detect corticotroph pituitary adenomas in Cushing's disease, and other neoplastic and nonneoplastic entities. Finally, some hints are given to facilitate the differential diagnosis of sellar lesions. PMID:27003878

  15. Pituitary Stone or Calcified Pituitary Tumor? Three Cases and Literature Review

    PubMed Central

    Chentli, Farida; Safer-Tabi, Amel

    2015-01-01

    Introduction: Pituitary stone or pituitary calculus is a scientific enigma characterized by a large calcification in the pituitary sella. It can be discovered incidentally or in a patient with endocrine and/or neurological problems. Its mechanism is not understood. In this article, we described three patients harboring a large pituitary calcification. Case Presentation: The first case was observed in a 27-year-old woman who consulted for secondary amenorrhea. The second case concerned a woman who consulted for infertility, and the third one was observed in an 11-year and nine-month-old girl who was sent to our department for short stature. Clinical examination was normal in both adults. The pediatric case had dwarfism with lack of pubertal development. Hormonal assessment showed hyperprolactinemia in both women and thyrotroph and somatotroph deficits in the child. Radiologic exploration discovered pituitary calcifications measuring 10, 11, and 45 mm without any cystic or solid mass. Conclusions: Radiological findings pleaded for a pituitary stone, but calcified adenomas in women, and calcified craniopharyngioma in the pediatric case could not be excluded, as our three patients were not operated on. PMID:26401144

  16. Ewes With Divergent Cortisol Responses to ACTH Exhibit Functional Differences in the Hypothalamo-Pituitary-Adrenal (HPA) Axis.

    PubMed

    Hewagalamulage, Sakda D; Clarke, Iain J; Rao, Alexandra; Henry, Belinda A

    2016-09-01

    Within any population, the cortisol response to ACTH covers a considerable range. High responders (HRs) exhibit a greater cortisol secretory response to stress or ACTH, compared with individuals classified as low cortisol responders (LRs). We administered ACTH (0.2 μg/kg, iv) to 160 female sheep and selected subpopulations of animals as LR and HR. In the present study, we aimed to characterize the hypothalamo-pituitary-adrenal axis in HR and LR and to identify factors that underlie the differing cortisol responses to ACTH. Hypothalami, pituitaries, and adrenals were collected from nonstressed HR and LR ewes. Expression of genes for CRH, arginine vasopressin (AVP), oxytocin, glucocorticoid receptor, and mineralocorticoid receptor were measured by in situ hybridization in the paraventricular nucleus of the hypothalamus, and proopiomelanocortin (POMC) gene expression was measured in the anterior pituitary. Expression of CRH, AVP, and POMC was higher in HR, with no differences in either glucocorticoid receptor or mineralocorticoid receptor expression. Oxytocin expression was greater in LR. In the adrenal gland, real-time PCR analysis indicated that expression of the ACTH receptor and a range of steroidogenic enzymes was similar in HR and LR. Adrenal weights, the cortex to medulla ratio and adrenal cortisol content were also similar in LR and HR. In conclusion, LR and HR display innate differences in the steady-state expression of CRH, AVP, oxytocin, and POMC, indicating that selection for cortisol responsiveness identifies distinct subpopulations that exhibit innate differences in the gene expression/function of hypothalamo-pituitary-adrenal axis markers. PMID:27414744

  17. Immortalized bovine mammary epithelial cells express stem cell markers and differentiate in vitro.

    PubMed

    Hu, Han; Zheng, Nan; Gao, Haina; Dai, Wenting; Zhang, Yangdong; Li, Songli; Wang, Jiaqi

    2016-08-01

    The bovine mammary epithelial cell is a secretory cell, and its cell number and secretory activity determine milk production. In this study, we immortalized a bovine mammary epithelial cell line by SV40 large T antigen gene using a retrovirus based on Chinese Holstein primary mammary epithelial cells (CMEC) cultured in vitro. An immortalized bovine mammary epithelial cell line surpassed the 50-passage mark and was designated the CMEC-H. The immortalized mammary epithelial cells grew in close contact with each other and exhibited the typical cobblestone morphology characteristic with obvious boundaries. The telomerase expression of CMEC-H has consistently demonstrated the presence of telomerase activity as an immortalized cell line, but the cell line never induced tumor formation in nude mice. CMEC-H expressed epithelial (cytokeratins CK7, CK8, CK18, and CK19), mesenchymal (vimentin), and stem/progenitor (CD44 and p63) cell markers. The induced expression of milk proteins, αS1 -casein, β-casein, κ-casein, and butyrophilin, indicated that CMEC-H maintained the synthesis function of the mammary epithelial cells. The established immortalized bovine mammary epithelial cell line CMEC-H is capable of self-renewal and differentiation and can serve as a valuable reagent for studying the physiological mechanism of the mammary gland. PMID:27189858

  18. A secretory kinase complex regulates extracellular protein phosphorylation.

    PubMed

    Cui, Jixin; Xiao, Junyu; Tagliabracci, Vincent S; Wen, Jianzhong; Rahdar, Meghdad; Dixon, Jack E

    2015-01-01

    Although numerous extracellular phosphoproteins have been identified, the protein kinases within the secretory pathway have only recently been discovered, and their regulation is virtually unexplored. Fam20C is the physiological Golgi casein kinase, which phosphorylates many secreted proteins and is critical for proper biomineralization. Fam20A, a Fam20C paralog, is essential for enamel formation, but the biochemical function of Fam20A is unknown. Here we show that Fam20A potentiates Fam20C kinase activity and promotes the phosphorylation of enamel matrix proteins in vitro and in cells. Mechanistically, Fam20A is a pseudokinase that forms a functional complex with Fam20C, and this complex enhances extracellular protein phosphorylation within the secretory pathway. Our findings shed light on the molecular mechanism by which Fam20C and Fam20A collaborate to control enamel formation, and provide the first insight into the regulation of secretory pathway phosphorylation. PMID:25789606

  19. Intestinal secretory mechanisms in irritable bowel syndrome-diarrhea.

    PubMed

    Camilleri, Michael

    2015-06-01

    Although diarrhea is the predominant bowel dysfunction in as many as one-third of patients with irritable bowel syndrome (IBS), it is unclear whether there is a specific disorder of intestinal fluid or electrolyte secretion in IBS. Diarrhea is generally considered a result of accelerated colonic transit in patients with IBS. Although a primary secretory diathesis has not been well-documented in patients with IBS with diarrhea (IBS-D), several mechanisms that could potentially contribute to intestinal secretion have been reported. Some of these mechanisms also influence motor and secretory dysfunctions that contribute to the pathophysiology of IBS-D. We review the evidence supporting secretion in IBS-D caused by peptides and amines produced by enteroendocrine cells or submucosal neurons, enterocyte secretory processes, and intraluminal factors (bile acids and short-chain fatty acids). Understanding these mechanisms and developing clinical methods for their identification could improve management of patients with IBS-D. PMID:25041862

  20. Control systems and coordination protocols of the secretory pathway.

    PubMed

    Luini, Alberto; Mavelli, Gabriella; Jung, Juan; Cancino, Jorge

    2014-01-01

    Like other cellular modules, the secretory pathway and the Golgi complex are likely to be supervised by control systems that support homeostasis and optimal functionality under all conditions, including external and internal perturbations. Moreover, the secretory apparatus must be functionally connected with other cellular modules, such as energy metabolism and protein degradation, via specific rules of interaction, or "coordination protocols". These regulatory devices are of fundamental importance for optimal function; however, they are generally "hidden" at steady state. The molecular components and the architecture of the control systems and coordination protocols of the secretory pathway are beginning to emerge through studies based on the use of controlled transport-specific perturbations aimed specifically at the detection and analysis of these internal regulatory devices. PMID:25374666

  1. [Physiology of secretory cells in the mouse mammary gland].

    PubMed

    Tolkunov, Iu A; Markov, A G

    2000-08-01

    Secretory cells' membrane potential and transepithelial potential difference in the mouse mammary gland diminish within 2.5 hours following breast-feeding of the litter. The transepithelial resistance for up to 20 hours after the feeding did not drop below 40-70 k omega. The secret pressure in the mammary gland does not grow during this period. Therefore an increase of interval between litter feeding up to 20 hours does not entail any mechanical lesion of the secretory epithelium. The latter's cells seem to secrete organic and inorganic substances in concentrations which do not change significantly during their transfer along the outgoing ducts. PMID:11059022

  2. Ultrastructural features of goat oviductal secretory cells at follicular and luteal phases of the oestrous cycle

    PubMed Central

    ABE, HIROYUKI; ONODERA, MASAKAZU; SUGAWARA, SHICHIRO; SATOH, TAKESHI; HOSHI, HIROYOSHI

    1999-01-01

    The aim of the present study was to investigate the ultrastructure of secretory cells in the various regions of the goat oviduct during the follicular and luteal phases of the oestrous cycle. During the follicular phase in the fimbriae, the secretory cells contained small secretory granules with electron-dense matrices. In the luteal phase, the secretory granules disappeared and cytoplasmic protrusions, extending beyond the luminal border of the ciliated cells and often containing the nucleus, were predominant. During the follicular phase in ampullary secretory cells, numerous secretory granules with moderately electron-dense matrices were present in the supranuclear cytoplasm and exocytosis of secretory granules was observed. The number of secretory granules was dramatically reduced in the ampullary secretory cells at the luteal phase. Conspicuous cytoplasmic protrusions of secretory cells were observed similar to those of the fimbrial epithelium. Isthmic cells were almost free of secretory granules and lysosome-like bodies were found both at the follicular and luteal phases. In conclusion, our ultrastructural observations of goat oviduct revealed marked cyclic changes in the ultrastructural features of secretory cells and the ultrastructural features and the numbers of secretory granules were distinctive for each particular segment. PMID:10634690

  3. Preoperative volume determination for pituitary adenoma

    NASA Astrophysics Data System (ADS)

    Zukic, Dženan; Egger, Jan; Bauer, Miriam H. A.; Kuhnt, Daniela; Carl, Barbara; Freisleben, Bernd; Kolb, Andreas; Nimsky, Christopher

    2011-03-01

    The most common sellar lesion is the pituitary adenoma, and sellar tumors are approximately 10-15% of all intracranial neoplasms. Manual slice-by-slice segmentation takes quite some time that can be reduced by using the appropriate algorithms. In this contribution, we present a segmentation method for pituitary adenoma. The method is based on an algorithm that we have applied recently to segmenting glioblastoma multiforme. A modification of this scheme is used for adenoma segmentation that is much harder to perform, due to lack of contrast-enhanced boundaries. In our experimental evaluation, neurosurgeons performed manual slice-by-slice segmentation of ten magnetic resonance imaging (MRI) cases. The segmentations were compared to the segmentation results of the proposed method using the Dice Similarity Coefficient (DSC). The average DSC for all datasets was 75.92%+/-7.24%. A manual segmentation took about four minutes and our algorithm required about one second.

  4. Localisation and semi-quantitative measurement of lipocortin 1 in rat anterior pituitary cells by fluorescence-activated cell analysis/sorting and electron microscopy.

    PubMed

    Christian, H C; Flower, R J; Morris, J F; Buckingham, J C

    1999-09-01

    Lipocortin 1 (LC1, also called annexin 1), a Ca2(+)- and phospholipid-binding protein, is an important mediator of glucocorticoid action in the anterior pituitary gland. Previous studies based on immunoprecipitation and Western blot analysis suggest that LC1 is found intracellularly both in the cytoplasm and in association with membranes and also on the cell surface where it attaches to the membrane by a Ca2(+)-dependent mechanism. However, as yet it is unclear which anterior pituitary cell types express the protein. Accordingly, we have developed a method based on a combination of fluorescence activated cell (FAC) analysis/sorting and electron microscopy to detect and quantify intracellular LC1 in rat anterior pituitary cells and to identify the cell types in which it is expressed. In addition, we have measured cell surface LC1 and examined the influence of glucocorticoids on the cellular disposition of the protein. Anterior pituitary cells were dispersed with collagenase. For experiments measuring intracellular LC1, three cell fixation/permeabilisation methods were examined initially, i.e. (1) Zamboni's fluid (30 min) and Triton-X-100 (0.12%, 1 or 12 h); (2) paraformaldehyde (2%, 1 h) and Triton-X-100 (0.2%, 10 min); and (3) paraformaldehyde (0.2%, 15 min) and saponin (0.1%, 5 min). The protocol using paraformaldehyde/Triton-X-100 provided optimal preservation of cell ultrastructure and of LC1 immunoreactivity (ir-LC1) while also effectively permeabilising the cells; it was therefore used in subsequent studies. Using an anti-LC1 monoclonal antibody as a probe, 82+/-5% of the secretory cells in the heterogeneous anterior pituitary cell preparation were shown by FAC analysis to display specific fluorescence for intracellular ir-LC1. Morphological analysis and immunogold-histochemistry of cells separated by FAC sorting identified corticotrophs, lactotrophs, somatotrophs and gonadotrophs in the population displaying LC1 immunofluorescence. LC1 was also detected on

  5. Advances in trans-sphenoidal pituitary surgery.

    PubMed

    Solari, D; Cavallo, L M; De Angelis, M; Villa, A; Somma, T; Esposito, F; Del Basso De Caro, M; Cappabianca, P

    2012-12-01

    Pituitary surgery is a continuous evolving speciality of the neurosurgeons' armamentarium, requiring precise anatomical knowledge, technical skills and integrated appreciation of the pituitary pathophysiology. Actually, it could be considered the result of a close cooperation between different specialists, i.e. the ophthalmologist, the neuroradiologist, the endocrinologist, the neurosurgeon, the pathologist, etc. In this teamwork environment each member plays his own role, offering his contribute to the final result; every effort is performed to provide patients with the best possible procedure, individually measured. The endoscopic pituitary surgery performed by means of a transsphenoidal approach perfectly fits this scenario, being though advocated as the result of an evolutionary process rather than a revolutionary one. The "pure" endoscopic transsphenoidal surgery - consisting of a whole procedure performed with the endoscope alone and without the use of any transsphenoidal retractor - offers some advantages due to the endoscope itself: a superior close-up view of the relevant anatomy, very important at the tumor/gland interface and an enlarged working angle are provided with an increased panoramic vision inside the surgical area. Results in terms of mass removal, relief of clinical symptoms, cure of the underlying disease and complication rate are similar to those reported in the major microsurgical series but patient compliance is by far better. PMID:23123578

  6. PITUITARY VOLUME IN SCHIZOPHRENIA SPECTRUM DISORDERS

    PubMed Central

    Romo-Nava, F.; Hoogenboom, W.S.; Pelavin, P. E.; Alvarado, J.L.; Bobrow, L.H.; MacMaster, F.P.; Keshavan, M.; McCarley, R.W.; Shenton, M.E.

    2013-01-01

    Introduction There is converging evidence supporting hyperactivity of the Hypothalamic-Pituitary-Adrenal (HPA) axis in schizophrenia spectrum disorders (SSD), such as schizotypal personality disorder (SPD), first-episode schizophrenia (FESZ) and chronic schizophrenia (CHSZ). Such an aberrant HPA activity might have volumetric consequences on the pituitary gland. However, previous magnetic resonance imaging (MRI) studies assessing pituitary volume (PV) in SSD are conflicting. The main objective of this study was to examine further PV in SSD. Methods PV were manually traced on structural MRIs in 137 subjects, including subjects with SPD (n=40), FESZ (n=15), CHSZ (n=15), and HC (n=67). We used an ANCOVA to test PV between groups and gender while controlling for inter-subject variability in age, years of education, socioeconomic status, and whole brain volume. Results Overall, women had larger PV than men, and within the male sample all SSD subjects had smaller PV than HC, statistically significant only for the SPD group. In addition, dose of medication, illness duration and age of onset were not associated with PV. Conclusion Chronic untreated HPA hyperactivity might account for smaller PV in SPD subjects, whereas the absence of PV changes in FESZ and CHSZ patients might be related to the normalizing effects of antipsychotics on PV. SPD studies offer a way to examine HPA related alterations in SSD without the potential confounds of medication effects. PMID:23522905

  7. Pituitary Adenoma Volumetry with 3D Slicer

    PubMed Central

    Nimsky, Christopher; Kikinis, Ron

    2012-01-01

    In this study, we present pituitary adenoma volumetry using the free and open source medical image computing platform for biomedical research: (3D) Slicer. Volumetric changes in cerebral pathologies like pituitary adenomas are a critical factor in treatment decisions by physicians and in general the volume is acquired manually. Therefore, manual slice-by-slice segmentations in magnetic resonance imaging (MRI) data, which have been obtained at regular intervals, are performed. In contrast to this manual time consuming slice-by-slice segmentation process Slicer is an alternative which can be significantly faster and less user intensive. In this contribution, we compare pure manual segmentations of ten pituitary adenomas with semi-automatic segmentations under Slicer. Thus, physicians drew the boundaries completely manually on a slice-by-slice basis and performed a Slicer-enhanced segmentation using the competitive region-growing based module of Slicer named GrowCut. Results showed that the time and user effort required for GrowCut-based segmentations were on average about thirty percent less than the pure manual segmentations. Furthermore, we calculated the Dice Similarity Coefficient (DSC) between the manual and the Slicer-based segmentations to proof that the two are comparable yielding an average DSC of 81.97±3.39%. PMID:23240062

  8. Case of pituitary stalk transection syndrome ascertained after breech delivery.

    PubMed

    Fukuta, Kaori; Hidaka, Takao; Ono, Yosuke; Kochi, Keiko; Yasoshima, Kuniaki; Arai, Takashi

    2016-02-01

    Pituitary stalk transection syndrome (PSTS) is a rare complication that can accompany breech delivery. Early diagnosis of this syndrome is difficult, and it may cause a serious delay in the diagnosis. We present a case of PSTS ascertained after breech delivery. A 20-year-old woman presented with primary amenorrhea. The patient was born by breech delivery and had a history of treatment for pituitary dwarfism. Her laboratory findings showed pituitary hypothyroidism, and hormone replacement therapy was initiated. At 28 years old, she became pregnant and had a normal delivery at 38 weeks' gestation. One year after delivery, her thyroid hormone level changed. Laboratory test showed adrenocortical insufficiency, and magnetic resonance imaging of the pituitary gland showed transection of the pituitary stalk and development of an ectopic posterior lobe. These findings were compatible with PSTS. When a patient who has been born by breech delivery presents with symptoms of pituitary deficiency, PSTS should be considered in the differential diagnosis. PMID:26631915

  9. Epistaxis and pituitary apoplexy due to ruptured internal carotid artery aneurysm embedded within pituitary adenoma

    PubMed Central

    Peng, Zesheng; Tian, Daofeng; Wang, Hongliu; Kong, Derek Kai; Zhang, Shenqi; Liu, Baohui; Deng, Gang; Xu, Zhou; Wu, Liquan; Ji, Baowei; Wang, Long; Cai, Qiang; Li, Mingchang; Wang, Junmin; Zhang, Aimin; Chen, Qianxue

    2015-01-01

    Epistaxis due to ruptured internal carotid artery (ICA) aneurysm embedded within a pituitary adenoma (PA) has seldom been reported in the literature. Here we want to elaborate the incidence, mechanisms, clinical manifestations, and treatment strategy for this condition. The first survived case of a patient with epistaxis and pituitary apoplexy due to ruptured aneurysm embedded within PA was reported and the literature was reviewed. A 53-year-old male patient presented to our institution with sudden onset epistaxis and progressive vision loss. Neurological examination revealed bilateral ptosis and dilated unresponsive pupils. A CT scan showed a large mass in the pituitary fossa with bony erosion. MRI revealed a large pituitary tumor and abnormal signal intensity in the tumor. No aneurysm was noted during the pre-operative MR angiography. Abundant arterial bleeding suddenly occurred during urgent transsphenoidal surgery. Digital subtraction angiography confirmed the presence of a 14 mm unexpected saccular aneurysm of right ICA in the cavernous sinus with the dome protruding into the sella turcica. Balloon test occlusion of the right ICA was undertaken and permanent occlusion was performed. The patient recovered well and received bromocriptine and thyroid hormone replacement therapy during the follow-up period. At 14-month followup, the patient had no neurological deficits, no features of ischaemia relating to the right ICA therapeutic occlusion. Our case indicated that epistaxis and pituitary apoplexy could be due to the rupture of an ICA aneurysm embedded in a PA. Clinical suspicion should remain high when evaluating any case of epistaxis and pituitary apoplexy. Optimal treatment should take into consideration individual features of the tumor, aneurysm, and patient. Making the correct diagnosis as well as identifying an appropriate management strategy is critical in the care of such patients. PMID:26823732

  10. Mycoplasma bovis MBOV_RS02825 Encodes a Secretory Nuclease Associated with Cytotoxicity.

    PubMed

    Zhang, Hui; Zhao, Gang; Guo, Yusi; Menghwar, Harish; Chen, Yingyu; Chen, Huanchun; Guo, Aizhen

    2016-01-01

    This study aimed to determine the activity of one Mycoplasma bovis nuclease encoded by MBOV_RS02825 and its association with cytotoxicity. The bioinformatics analysis predicted that it encodes a Ca(2+)-dependent nuclease based on existence of enzymatic sites in a TNASE_3 domain derived from a Staphylococcus aureus thermonuclease (SNc). We cloned and purified the recombinant MbovNase (rMbovNase), and demonstrated its nuclease activity by digesting bovine macrophage linear DNA and RNA, and closed circular plasmid DNA in the presence of 10 mM Ca(2+) at 22-65 °C. In addition, this MbovNase was localized in membrane and rMbovNase able to degrade DNA matrix of neutrophil extracellular traps (NETs). When incubated with macrophages, rMbovNase bound to and invaded the cells localizing to both the cytoplasm and nuclei. These cells experienced apoptosis and the viability was significantly reduced. The apoptosis was confirmed by activated expression of phosphorylated NF-κB p65 and Bax, and inhibition of Iκβα and Bcl-2. In contrast, rMbovNase(Δ181-342) without TNASE_3 domain exhibited deficiency in all the biological functions. Furthermore, rMbovNase was also demonstrated to be secreted. In conclusion, it is a first report that MbovNase is an active nuclease, both secretory and membrane protein with ability to degrade NETs and induce apoptosis. PMID:27136546

  11. Mycoplasma bovis MBOV_RS02825 Encodes a Secretory Nuclease Associated with Cytotoxicity

    PubMed Central

    Zhang, Hui; Zhao, Gang; Guo, Yusi; Menghwar, Harish; Chen, Yingyu; Chen, Huanchun; Guo, Aizhen

    2016-01-01

    This study aimed to determine the activity of one Mycoplasma bovis nuclease encoded by MBOV_RS02825 and its association with cytotoxicity. The bioinformatics analysis predicted that it encodes a Ca2+-dependent nuclease based on existence of enzymatic sites in a TNASE_3 domain derived from a Staphylococcus aureus thermonuclease (SNc). We cloned and purified the recombinant MbovNase (rMbovNase), and demonstrated its nuclease activity by digesting bovine macrophage linear DNA and RNA, and closed circular plasmid DNA in the presence of 10 mM Ca2+ at 22–65 °C. In addition, this MbovNase was localized in membrane and rMbovNase able to degrade DNA matrix of neutrophil extracellular traps (NETs). When incubated with macrophages, rMbovNase bound to and invaded the cells localizing to both the cytoplasm and nuclei. These cells experienced apoptosis and the viability was significantly reduced. The apoptosis was confirmed by activated expression of phosphorylated NF-κB p65 and Bax, and inhibition of Iκβα and Bcl-2. In contrast, rMbovNaseΔ181–342 without TNASE_3 domain exhibited deficiency in all the biological functions. Furthermore, rMbovNase was also demonstrated to be secreted. In conclusion, it is a first report that MbovNase is an active nuclease, both secretory and membrane protein with ability to degrade NETs and induce apoptosis. PMID:27136546

  12. 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

  13. PRKAR1A and the evolution of pituitary tumors.

    PubMed

    Kirschner, Lawrence S

    2010-09-15

    Carney complex (CNC) is an inherited tumor predisposition associated with pituitary tumors, including GH-producing pituitary adenomas and rare reports of prolactinomas. This disease is caused by mutations in PRKAR1A, which encodes the type 1A regulatory subunit of the cAMP-dependent protein kinase, PKA. Loss of PRKAR1A causes enhanced PKA signaling, which leads to pituitary tumorigenesis. Mutations in the gene have not been detected in sporadic pituitary tumors, but there is some data to suggest that non-genomic mechanisms may cause loss of protein expression. Unlike CNC patients, mice heterozygous for Prkar1a mutations do not develop pituitary tumors, although complete knockout of the gene in the Pit1 lineage of the pituitary produces GH-secreting pituitary adenomas. These data indicate that complete loss of Prkar1a/PRKAR1A is able to cause pituitary tumors in mice and men. The pattern of tumors is likely related to the signaling pathways employed in specific pituitary cell types. PMID:20451576

  14. [Leptomeningeal Dissemination in Patients with Pituitary Metastasis from Breast Cancer].

    PubMed

    Hayashi, Nakamasa; Mitsuya, Koichi; Harada, Hideyuki; Watanabe, Junichiro; Nishimura, Tetsuo; Nakasu, Yoko

    2016-05-01

    Pituitary metastases are uncommon complications of systemic cancer and account for only 1% of pituitary lesions. Breast cancer is one of the most common tumors to metastasize to the pituitary gland. A multidisciplinary approach that calls for close collaboration among oncologists, neurosurgeons, radiologists, and endocrinologists is mandatory for diagnosis and treatment of pituitary metastasis. From 2002 through 2013, 6 patients with pituitary metastases were treated at Shizuoka Cancer Center Hospital. The patients' age at presentation ranged from 45 to 75 years(average 59 years). Five of 6 patients had symptoms: anterior pituitary insufficiency in 4, diabetes insipidus in 3, and visual deficits in 2 patients. Five patients had other metastases at the time of presentation. Local irradiation to the metastatic lesion was adopted in 4, and whole brain irradiation was in 2 patients. In all cases, local control was achieved after irradiation, however, the pituitary insufficiency did not recover. Two of 4 patients treated with local irradiation suffered from meningeal dissemination within 5 months after treatment, and died at 8 and 11 months after diagnosis of pituitary metastasis, respectively. The patients treated with whole brain irradiation had longer survival periods. Early diagnosis, endocrinological management, and radiation therapy improve the quality of life in patients suffering from pituitary metastasis. Whole brain irradiation may be favorable in order to prevent meningeal dissemination. PMID:27166841

  15. Clinical applications of the radioimmunoassay of secretory tuberculoprotein.

    PubMed Central

    Straus, E; Wu, N; Quraishi, M A; Levine, S

    1981-01-01

    A radioimmunoassay that measures a specific secretory tuberculoprotein was used to detect Mycobacterium tuberculosis in 9 of 30 liquid cultures of sputum. The accumulation of immunoreactive material in liquid cultures containing isoniazid was shown to reflect in vitro susceptibility of mycobacteria to the antibiotic effects of the drug. PMID:6789332

  16. The transcriptional corepressor MTGR1 regulates intestinal secretory lineage allocation.

    PubMed

    Parang, Bobak; Rosenblatt, Daniel; Williams, Amanda D; Washington, Mary K; Revetta, Frank; Short, Sarah P; Reddy, Vishruth K; Hunt, Aubrey; Shroyer, Noah F; Engel, Michael E; Hiebert, Scott W; Williams, Christopher S

    2015-03-01

    Notch signaling largely determines intestinal epithelial cell fate. High Notch activity drives progenitors toward absorptive enterocytes by repressing secretory differentiation programs, whereas low Notch permits secretory cell assignment. Myeloid translocation gene-related 1 (MTGR1) is a transcriptional corepressor in the myeloid translocation gene/Eight-Twenty-One family. Given that Mtgr1(-/-) mice have a dramatic reduction of intestinal epithelial secretory cells, we hypothesized that MTGR1 is a key repressor of Notch signaling. In support of this, transcriptome analysis of laser capture microdissected Mtgr1(-/-) intestinal crypts revealed Notch activation, and secretory markers Mucin2, Chromogranin A, and Growth factor-independent 1 (Gfi1) were down-regulated in Mtgr1(-/-) whole intestines and Mtgr1(-/-) enteroids. We demonstrate that MTGR1 is in a complex with Suppressor of Hairless Homolog, a key Notch effector, and represses Notch-induced Hairy/Enhancer of Split 1 activity. Moreover, pharmacologic Notch inhibition using a γ-secretase inhibitor (GSI) rescued the hyperproliferative baseline phenotype in the Mtgr1(-/-) intestine and increased production of goblet and enteroendocrine lineages in Mtgr1(-/-) mice. GSI increased Paneth cell production in wild-type mice but failed to do so in Mtgr1(-/-) mice. We determined that MTGR1 can interact with GFI1, a transcriptional corepressor required for Paneth cell differentiation, and repress GFI1 targets. Overall, the data suggest that MTGR1, a transcriptional corepressor well characterized in hematopoiesis, plays a critical role in intestinal lineage allocation. PMID:25398765

  17. Porosome: the secretory NanoMachine in cells.

    PubMed

    Jena, Bhanu P

    2013-01-01

    Cells synthesize and store within membranous sacs products such as hormones, growth factors, neurotransmitters, or digestive enzymes, for release on demand. As recently as just 15 years ago, it was believed that during cell secretion, membrane-bound secretory vesicles completely merge at the cell plasma membrane resulting in the diffusion of intravesicular contents to the cell exterior and the compensatory retrieval of the excess membrane by endocytosis. This explanation, however, failed to explain the generation of partially empty vesicles observed in electron micrographs following secretion. Logically therefore, in a 1993 News and Views article in the journal Nature, Prof. Erwin Neher wrote "It seems terribly wasteful that, during the release of hormones and neurotransmitters from a cell, the membrane of a vesicle should merge with the plasma membrane to be retrieved for recycling only seconds or minutes later." The discovery of permanent secretory portals or nanomachines at the cell plasma membrane called POROSOMES, where membrane-bound secretory vesicles transiently dock and fuse to release intravesicular contents to the cell exterior, has finally resolved this conundrum. Following this discovery, the composition of the porosome, its structure and dynamics visualized with high-resolution imaging techniques atomic force and electron microscopy, and its functional reconstitution into artificial lipid membrane have provided a molecular understanding of cell secretion. In agreement, it has been demonstrated that "secretory granules are recaptured largely intact after stimulated exocytosis in cultured endocrine cells" (Proc Natl Acad Sci U S A 100:2070-2075, 2003); that "single synaptic vesicles fuse transiently and successively without loss of identity" (Nature 423:643-647, 2003); and that "zymogen granule exocytosis is characterized by long fusion pore openings and preservation of vesicle lipid identity" (Proc Natl Acad Sci U S A 101:6774-6779, 2004). It made no

  18. Isolated rat hepatocyte couplets: a primary secretory unit for electrophysiologic studies of bile secretory function.

    PubMed

    Graf, J; Gautam, A; Boyer, J L

    1984-10-01

    Hepatocyte couplets were isolated by collagenase perfusion from rat liver. Between adjacent cells, the bile canaliculus forms a closed space into which secretion occurs. As in intact liver, Mg2+-ATPase is localized at the canalicular lumen, the organic anion fluorescein is excreted, and secretion is modified by osmotic gradients. By passing a microelectrode through one cell into the canalicular vacuole, a transepithelial potential profile was obtained. In 27 cell couplets the steady-state intracellular (-26.3 +/- 5.3 mV) and intracanalicular (-5.9 +/- 3.3 mV) potentials were recorded at 37 degrees C with reference to the external medium. Input resistances were determined within the cell (86 +/- 23 M omega) and in the bile canalicular lumen (32 +/- 17 M omega) by passing current pulses through the microelectrode. These data define electrical driving forces for ion transport across the sinusoidal, canalicular, and paracellular barriers and indicate ion permeation across a leaky paracellular junctional pathway. These findings indicate that the isolated hepatocyte couplet is an effective model for electrophysiologic studies of bile secretory function. PMID:6149546

  19. Prosomatostatin processing in pituitary GH3 cells. Identification and secretion of the intact propeptide.

    PubMed

    Elgort, A; Shields, D

    1994-12-01

    Preprosomatostatin (preproSRIF) is a peptide hormone precursor that undergoes tissue-specific processing at either a single set of paired basic residues to yield SRIF-14 or, alternatively, at a monobasic site to produce SRIF-28, an NH2 terminally extended form of SRIF-14. Mammalian preproSRIFs are a family of precursors that are remarkably conserved from rat to humans. In five species, the signal peptide and propeptides are approximately 96% identical; this high degree of sequence identity may be indicative of functional conservation. Since the propeptide is approximately five times larger than SRIF-14, we hypothesized that it would be secreted as a separate polypeptide following proSRIF proteolytic processing. To test this idea, we raised polyclonal antibodies to the entire propeptide to follow its biosynthesis and secretion. Here we demonstrate that in transfected rat anterior pituitary GH3 cells both SRIF-14 and the intact 9.5-kDa propeptide were processed coordinately from proSRIF with identical kinetics. Treatment of the cells with chloroquine, a weak base which inhibits processing to mature SRIF-14, also inhibited the appearance of the 9.5-kDa propeptide. Approximately 40% of the propeptide was targeted to the regulated secretory pathway as determined by its quantitative secretion in response to secretagogues. We also examined the secretion of the SRIF propeptide independently of SRIF-14 by expressing a truncated "propeptide" in which SRIF-14 was deleted. Significantly, the SRIF propeptide was itself efficiently transported through the secretory pathway and secreted into the culture medium. This suggests that the propeptide possesses all the topogenic information necessary for intracellular transport. The coordinate secretion of the intact propeptide with mature SRIF-14 suggests that it might function as a novel bioactive peptide. PMID:7982986

  20. The transcriptional corepressor MTGR1 regulates intestinal secretory lineage allocation

    PubMed Central

    Parang, Bobak; Rosenblatt, Daniel; Williams, Amanda D.; Washington, Mary K.; Revetta, Frank; Short, Sarah P.; Reddy, Vishruth K.; Hunt, Aubrey; Shroyer, Noah F.; Engel, Michael E.; Hiebert, Scott W.; Williams, Christopher S.

    2015-01-01

    Notch signaling largely determines intestinal epithelial cell fate. High Notch activity drives progenitors toward absorptive enterocytes by repressing secretory differentiation programs, whereas low Notch permits secretory cell assignment. Myeloid translocation gene-related 1 (MTGR1) is a transcriptional corepressor in the myeloid translocation gene/Eight-Twenty-One family. Given that Mtgr1−/− mice have a dramatic reduction of intestinal epithelial secretory cells, we hypothesized that MTGR1 is a key repressor of Notch signaling. In support of this, transcriptome analysis of laser capture microdissected Mtgr1−/− intestinal crypts revealed Notch activation, and secretory markers Mucin2, Chromogranin A, and Growth factor-independent 1 (Gfi1) were down-regulated in Mtgr1−/− whole intestines and Mtgr1−/− enteroids. We demonstrate that MTGR1 is in a complex with Suppressor of Hairless Homolog, a key Notch effector, and represses Notch-induced Hairy/Enhancer of Split 1 activity. Moreover, pharmacologic Notch inhibition using a γ-secretase inhibitor (GSI) rescued the hyperproliferative baseline phenotype in the Mtgr1−/− intestine and increased production of goblet and enteroendocrine lineages in Mtgr1−/− mice. GSI increased Paneth cell production in wild-type mice but failed to do so in Mtgr1−/− mice. We determined that MTGR1 can interact with GFI1, a transcriptional corepressor required for Paneth cell differentiation, and repress GFI1 targets. Overall, the data suggest that MTGR1, a transcriptional corepressor well characterized in hematopoiesis, plays a critical role in intestinal lineage allocation.—Parang, B., Rosenblatt, D., Williams, A. D., Washington, M. K., Revetta, F., Short, S. P., Reddy, V. K., Hunt, A., Shroyer, N. F., Engel, M. E., Hiebert, S. W., Williams, C. S. The transcriptional corepressors MTGR1 regulates intestinal secretory lineage allocation. PMID:25398765

  1. Serum-free growth of human mammary epithelial cells: rapid clonal growth in defined medium and extended serial passage with pituitary extract

    SciTech Connect

    Hammond, S.L.; Ham, R.G.; Stampfer, M.R.

    1984-09-01

    A serum-free medium with bovine pituitary extract as the only undefined supplement has been developed for long-term culture of human mammary epithelial cells. This medium supports serial subculture of normal cells for 10-20 passages (1:10 splits) without conditioning or special substrates, and it supports rapid clonal growth with plating efficiencies up to 35%. It consists of an optimized basal nutrient medium, (MCDB 170, supplemented with insulin, hydrocortisone, epidermal growth factor, ethanolamine, phosphoethanolamine, and bovine pituitary extract. Replacement of pituitary extract with prostaglandin E/sub 1/ and ovine prolactin yields a defined medium that supports rapid clonal growth and serial subculture for three of four passages. Cultures initiated in these media from normal reduction mammoplasty tissue remain diploid and maintain normal epithelia morphology, distribution of cell-associated fibronectin, expression of keratin fibrils, and a low level of expression of milk fat globule antigen. Large cell populations can now be generated and stored frozen, permitting multiple experiments over a period of time with cells from a single donor. These media greatly extend the range of experiments that can be performed both conveniently and reproducibly with cultured normal and tumor-derived human mammary epithelial cells. 31 references, 3 figures, 4 tables.

  2. Dependence of spontaneous electrical activity and basal prolactin release on nonselective cation channels in pituitary lactotrophs.

    PubMed

    Kučka, M; Kretschmannová, K; Stojilkovic, S S; Zemková, H; Tomić, M

    2012-01-01

    All secretory anterior pituitary cells fire action potentials spontaneously and exhibit a high resting cation conductance, but the channels involved in the background permeability have not been identified. In cultured lactotrophs and immortalized GH(3) cells, replacement of extracellular Na(+) with large organic cations, but not blockade of voltage-gated Na(+) influx, led to an instantaneous hyperpolarization of cell membranes that was associated with a cessation of spontaneous firing. When cells were clamped at -50 mV, which was close to the resting membrane potential in these cells, replacement of bath Na(+) with organic cations resulted in an outward-like current, reflecting an inhibition of the inward holding membrane current and indicating loss of a background-depolarizing conductance. Quantitative RT-PCR analysis revealed the high expression of mRNA transcripts for TRPC1 and much lower expression of TRPC6 in both lactotrophs and GH(3) cells. Very low expression of TRPC3, TRPC4, and TRPC5 mRNA transcripts were also present in pituitary but not GH(3) cells. 2-APB and SKF-96365, relatively selective blockers of TRPC channels, inhibited electrical activity, Ca(2+) influx and prolactin release in a concentration-dependent manner. Gd(3+), a common Ca(2+) channel blocker, and flufenamic acid, an inhibitor of non-selective cation channels, also inhibited electrical activity, Ca(2+) influx and prolactin release. These results indicate that nonselective cation channels, presumably belonging to the TRPC family, contribute to the background depolarizing conductance and firing of action potentials with consequent contribution to Ca(2+) influx and hormone release in lactotrophs and GH(3) cells. PMID:22480423

  3. Gonadotropin-releasing hormone receptor mRNA expression by human pituitary tumors in vitro.

    PubMed Central

    Alexander, J M; Klibanski, A

    1994-01-01

    An important question in the pathogenesis and regulation of human gonadotroph adenomas is whether heterogeneous gonadotropin responses to gonadotropin-releasing hormone (GnRH) are due to dysregulation of GnRH receptor biosynthesis and/or cell-signaling pathways. We investigated gonadotropin responsiveness to pulsatile GnRH in 13 gonadotroph adenomas. All tumors had evidence of follicle-stimulating hormone (FSH) beta and alpha subunit biosynthesis using reverse transcriptase/polymerase chain reaction (RTPCR) techniques. Four tumors significantly increased gonadotropin and/or free subunit secretion during pulsatile 10(-8) M GnRH administration. The GnRH antagonist Antide (10(-6) to 10(-8) M) blocked secretory increases in all GnRH-responsive tumors. Gonadotropin and/or free subunit secretion increased after 60 mM KCl, confirming that GnRH nonresponsiveness was not due to intracellular gonadotropin depletion. We hypothesized that GnRH nonresponsiveness in these tumors may be due to GnRH receptor (GnRH-Rc) biosynthetic defects. RTPCR analyses detected GnRH-Rc transcripts only in responsive tumors and normal human pituitary. This is the first demonstration of a cell-surface receptor biosynthetic defect in human pituitary tumors. We conclude (a) one third of gonadotroph tumors respond to pulsatile GnRH in vitro, (b) GnRH-Rc mRNA is detected in human gonadotroph adenomas and predicts GnRH responsiveness, and (c) GnRH-Rc biosynthetic defects may underlie GnRH nonresponsiveness in gonadotroph tumors. Images PMID:8200967

  4. The solvent action of sodium hypochlorite on bovine tendon collagen, bovine pulp, and bovine gingiva.

    PubMed

    Nakamura, H; Asai, K; Fujita, H; Nakazato, H; Nishimura, Y; Furuse, Y; Sahashi, E

    1985-09-01

    The purpose of this study was to determine the optimum temperature and concentration of sodium hypochlorite solution required to dissolve bovine tendon collagen, pulp, and gingiva. The 10% concentration of sodium hypochlorite solution at 37 degrees C was found to be most effective in dissolving bovine tendon collagen, pulp, and gingiva. Sodium hypochlorite solution was more effective in dissolving bovine pulp or tendon collagen than in dissolving bovine gingiva. PMID:3862046

  5. Origin, Possible Function and Fate of “Follicular Cells” in the Anterior Lobe of the Human Pituitary

    PubMed Central

    Horvath, E.; Kovacs, K.; Penz, G.; Ezrin, C.

    1974-01-01

    In human anterior pituitaries, follicular structures were found to develop by transformation of various types of glandular cells around foci of ruptured granulated cells undergoing destruction. In phase I, junctional complexes between granulated cells, as well as microvilli at the luminal surfaces of cell membranes, are formed. In phase II, degranulation and dedifferentiation of cytoplasm dominate the picture. Phase III follicular cells are practically devoid of secretory granules and other ultrastructural features characteristic of granulated cells. The participation of cell types in follicle formation does not appear to be limited. The follicular content in phase I-II is clearly recognizable as cellular debris from adenohypophysiocytes. These findings indicate that neither follicles nor junctional complexes are necessarily permanent structures of the anterior pituitary. It can be assumed that substances escaping from ruptured granulated cells may induce the formation of junctional complexes between adjacent cells. ImagesFig 5Fig 6Fig 7Fig 8Fig 9Fig 1Fig 2Fig 10Fig 3Fig 4 PMID:4447128

  6. Multiple Pituitary Adenomas: A Systematic Review

    PubMed Central

    Budan, Renata M.; Georgescu, Carmen E.

    2016-01-01

    PubMed, Scopus, and Web of Science Core Collection databases were systematically searched for studies reporting synchronous double or multiple pituitary adenomas (MPA), a rare clinical condition, with a vague pathogenesis. Multiple adenomas of the pituitary gland are referred to as morphologically and/or immunocytochemically distinct tumors that are frequently small-sized and hormonally non-functional, to account for the low detection rate. There is no general agreement on how to classify MPA, various criteria, such as tumor contiguity, immunoreactivity, and clonality analysis are being used. Among the component tumors, prolactin (PRL)-immunopositive adenomas are highly prevalent, albeit mute in the majority of cases. The most frequent clinical presentation of MPA is Cushing’s syndrome, given the fact that in more than 50% of reported cases at least one lesion stains for adrenocorticotrophic hormone (ACTH). Plurihormonal hyperactivity may be diagnosed in a patient with MPA when more than one tumor is clinically active (e.g., ACTH and PRL) or in cases with at least one composite tumor (e.g., GH and PRL), to complicate the clinical scenario. Specific challenges associated with MPA include high surgical failure rates, enforcing second-look surgery in certain cases, and difficult preoperative neuroradiological imaging evaluation, with an overall sensitivity of only 25% for magnetic resonance imaging to detect distinct multiple tumors. Alternatively, minor pituitary imaging abnormalities may raise suspicion, as these are not uncommon. Postoperative immunohistochemistry is mandatory and in conjunction to electron microscopy scanning and testing for transcription factors (i.e., Pit-1, T-pit, and SF-1) accurately define and classify the distinct cytodifferentiation of MPA. PMID:26869991

  7. Nonfunctioning giant pituitary adenomas: Invasiveness and recurrence

    PubMed Central

    Landeiro, José Alberto; Fonseca, Elissa Oliveira; Monnerat, Andrea Lima Cruz; Taboada, Giselle Fernandes; Cabral, Gustavo Augusto Porto Sereno; Antunes, Felippe

    2015-01-01

    Background: We report our surgical series of 35 patients with giant nonfunctioning pituitary adenomas (GNFPA). We analyzed the rule of Ki-67 antigen expression in predicting recurrence. Methods: Thirty-five patients were operated between 2000 and 2010. Suprassellar extension of the tumors were classified according to Hardy and Mohr based on magnetic resonance (MR) studies. Pituitary endocrine function and MR scans were assessed preoperatively and at 1, 6, and 12 months postoperatively. Immunohistochemical studies were based in regard to the expression of the proliferative Ki-67 index and the hormonal receptor for luteinizing hormone, follicle stimulating hormone, growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, and prolactin. Tumors specimens were obtained from 35 patients with GNFPA. Endoscopic transsphenoidal surgery was the approach of choice. Results: Thirty-five patients were submitted to 49 surgeries, 44 (89.8%) were transsphenoidal and 5 (10.2%) were transcranial. The most frequent preoperative complaints were visual acuity impairment and visual field defect in 25 (71.2%) and 23 (65.7%) cases, respectively. Improvement of visual acuitiy and visual field deficit after surgery was seen in 20 (80%) and 17 (73.9%) patients, respectively. Endocrinological deficits were encountered in 20 patients (57.1%). After surgery, 18 patients (51.4%) required hormonal replacement. Three patients had visual symptoms related to pituitary apoplexy and recovered after surgery. The Ki-67 labeling index (LI) ranged from <1% to 4.8%. The rate of recurrence in tumors with Ki-67 <3% was 7.7% (2 patients), Ki-67 >3% was present in 5 patients and the recurrence committed 3 patients. Conclusion: In our series, regardless the improvement of visual function and compressing symptoms, 5 patients with expression of Ki-67 LI more than 3% experienced a recurrence. PMID:26674325

  8. Hemostatic Disorders in Hormonally Active Pituitary Tumors.

    PubMed

    Świątkowska-Stodulska, R; Babińska, A; Mital, A; Stodulski, D; Sworczak, K

    2015-10-01

    Endocrinopathies encompass heterogeneous diseases that can lead to hemostasis disorders at various stages over their clinical course. Normal hemostasis requires an equilibrium between the processes of coagulation and fibrinolysis, which depend on multiple activators and inhibitors. To date, the influence of various hormonal disorders on the hemostatic system has been assessed many times. The aim of this review was to analyze hemostasis abnormalities that occur in patients with hormonally active pituitary tumors: corticotropinoma, somatotropinoma, prolactinoma, gonadotropinoma and thyrotropinoma. Authors discuss studies that examined coagulation and hemostasis parameters among patients with these tumors, as well as analyze antithrombotic prophylaxis approach for endogenous hypercortisolemia subjects in particular. PMID:26285071

  9. Duplication of the pituitary gland - plus syndrome

    PubMed Central

    Sen, Debraj; Arora, Vijinder

    2016-01-01

    Duplication of the pituitary gland (DPG) is a very rare developmental anomaly that is often associated with other anomalies – the DPG-plus syndrome and occurs due to splitting of the rostral notochord and prechordal plate during blastogenesis. DPG with the constellation of associated anomalies as in our patient has not been reported previously. This article illustrates the importance of imaging the brain in all patients with obvious midline facial anomalies and the complementary role of MRI and CT in such cases. PMID:27081236

  10. Pituitary dysfunction in infective brain diseases

    PubMed Central

    Beatrice, Anne M.; Selvan, Chitra; Mukhopadhyay, Satinath

    2013-01-01

    Infectious diseases of the central nervous system (CNS) are increasingly being recognized as important causes of hypopituitarism. Although tuberculosis is the most common agent involved, non-mycobacterial agents like viruses, bacteria, fungus, and protozoa are important causes in our country. Involvement post infections could be due to a strategically located tuberculoma, or pituitary abscess, or meningoencephalitis. Although it might not be reasonable to screen all patients with CNS infections for hypopituitarism, awareness of the possibility and clinical follow-up for suggestive symptoms is required. PMID:24910821

  11. Pituitary-ovarian-splenic axis in ovulation

    PubMed Central

    Oakley, Oliver R.; Frazer, Michele L.; Ko, CheMyong

    2011-01-01

    Leukocytes are rapidly recruited to the preovulatory ovary and play a crucial role as facilitators of ovulation and luteal formation. In this article, recent findings on leukocyte trafficking to the ovary, as well as the physiological role of leukocytes in the ovary, will be summarized and discussed. We then explore the novel hypothesis that the hypothalamus-pituitary-ovarian (HPO) axis might include the spleen as a reservoir of leukocytes by summarizing recent reports on this topic, both in the fields of immunology and reproductive biology. PMID:21600783

  12. Dynamic computed tomography of the pituitary gland using a single slice scanner in dogs with pituitary-dependent hypercortisolism.

    PubMed

    Del Magno, Sara; Grinwis, Guy C M; Voorhout, George; Meij, Björn P

    2016-08-01

    Selective removal of the pituitary adenoma has not been advocated in dogs with pituitary-dependent hypercortisolism because the pituitary adenoma is usually not visualized on routine computed tomography (CT). Dynamic pituitary CT scanning is aimed at the detection of the pituitary flush and, indirectly, at the presence and position of the adenoma. The first aim of this retrospective study was to compare findings of a multiple slice dynamic scanning protocol with those of a single slice dynamic protocol using a single slice CT scanner. The second aim was to compare the CT findings with surgical findings, and surgical findings with histopathological findings. Computed tomography with single and multiple slice dynamic scanning protocols was performed in 86 dogs with pituitary-dependent hypercortisolism. Thirty dogs underwent transsphenoidal hypophysectomy and pituitary specimens were collected as tumor, normal, mixed and neurohypophyseal samples and processed for histology. The pituitary flush was not detected more frequent in multiple slice dynamic scanning series than in single slice dynamic scanning series. However, in non-enlarged pituitaries, the flush was seen significantly more frequently than in enlarged pituitaries. Prediction of the nature of the tissue during hypophysectomy by the surgeon was inconclusive. In conclusion, when using a single slice CT scanner, both single or multiple slice dynamic scanning protocols can be used for localization of the neurohypophyseal flush, and, indirectly, the adenoma. However, based on this study, the aim of surgery in dogs with pituitary-dependent hypercortisolism remains total adenohypophysectomy, and when the neurophypophysis is recognized, it may be left in situ. PMID:27473973

  13. Cushing's Syndrome From Pituitary Microadenoma and Pulmonary Nodules.

    PubMed

    Tating, Dan Louie Renz P; Montevirgen, Natasha Denise S; Cajucom, Loyda

    2016-03-01

    Cushing's syndrome is a state of cortisol excess, possibly from a tumor in the pituitary gland, the adrenal gland, or an ectopic nonpituitary ACTH-secreting source. The first form, pituitary in origin, was originally described by Harvey Cushing, MD, and was labeled as Cushing's disease. Long-term therapy with glucocorticoids also can lead to iatrogenic Cushing's syndrome. PMID:26906124

  14. Pituitary Volume Prospectively Predicts Internalizing Symptoms in Adolescence

    ERIC Educational Resources Information Center

    Zipursky, Amy R.; Whittle, Sarah; Yucel, Murat; Lorenzetti, Valentina; Wood, Stephen J.; Lubman, Dan I.; Simmons, Julian G.; Allen, Nicholas B.

    2011-01-01

    Background: Early adolescence is a critical time for the development of both internalizing and externalizing disorders. We aimed to investigate whether pituitary volume, an index of hypothalamic-pituitary-adrenal (HPA) axis function, represents a vulnerability factor for the emergence of internalizing and externalizing symptoms during adolescence…

  15. EFFECTS OF CAGING DENSITY ON PITUITARY AND TESTICLE RELATED RESPONSES

    EPA Science Inventory

    Effects of caging density on pituitary and testicle related responses

    A significant negative correlation between the incidence of testicular interstitial cell tumors (ICT) and of pituitary tumors (PT) in control male F344 rats is reported associated with the number of ani...

  16. TOXIC EFFECTS OF XENOBIOTICS ON THE PITUITARY GLAND

    EPA Science Inventory

    This overview provides a summary of adverse effects of xenobiotics upon the pituitary gland, an endocrine gland that plays an important role in the regulation of reproductive function. he most common histopathological pituitary lesions observed following exposure to drugs and che...

  17. Genetic Bases of Estrogen-Induced Pituitary Tumorigenesis

    PubMed Central

    Strecker, Tracy E.; Spady, Thomas J.; Schaffer, Beverly S.; Gould, Karen A.; Kaufman, Amy E.; Shen, Fangchen; McLaughlin, Mac T.; Pennington, Karen L.; Meza, Jane L.; Shull, James D.

    2005-01-01

    Estrogens stimulate proliferation and enhance survival of the prolactin (PRL)-producing lactotroph of the anterior pituitary gland and induce development of PRL-producing pituitary tumors in certain inbred rat strains but not others. The goal of this study was to elucidate the genetic bases of estrogen-induced pituitary tumorigenesis in reciprocal intercrosses between the genetically related ACI and Copenhagen (COP) rat strains. Following 12 weeks of treatment with the synthetic estrogen diethylstilbestrol (DES), pituitary mass, an accurate surrogate marker of absolute lactotroph number, was increased 10.6-fold in ACI rats and 4.5-fold in COP rats. Composite interval mapping analyses of the phenotypically defined F2 progeny from the reciprocal crosses identified six quantitative trait loci (QTL) that determine the pituitary growth response to DES. These loci reside on chromosome 6 [Estrogen-induced pituitary tumor (Ept)1], chromosome 3 (Ept2 and Ept6), chromosome 10 (Ept9), and chromosome 1 (Ept10 and Ept13). Together, these six Ept loci and one additional suggestive locus on chromosome 4 account for an estimated 40% of the phenotypic variance exhibited by the combined F2 population, while 34% of the phenotypic variance was estimated to result from environmental factors. These data indicate that DES-induced pituitary mass behaves as a quantitative trait and provide information that will facilitate identification of genes that determine the tumorigenic response of the pituitary gland to estrogens. PMID:15687265

  18. Expression studies of neuronatin in prenatal and postnatal rat pituitary.

    PubMed

    Kanno, Naoko; Higuchi, Masashi; Yoshida, Saishu; Yako, Hideji; Chen, Mo; Ueharu, Hiroki; Nishimura, Naoto; Kato, Takako; Kato, Yukio

    2016-05-01

    The pituitary gland, an indispensable endocrine organ that synthesizes and secretes pituitary hormones, develops with the support of many factors. Among them, neuronatin (NNAT), which was discovered in the neonatal mouse brain as a factor involved in neural development, has subsequently been revealed to be coded by an abundantly expressing gene in the pituitary gland but its role remains elusive. We analyze the expression profile of Nnat and the localization of its product during rat pituitary development. The level of Nnat expression was high during the embryonic period but remarkably decreased after birth. Immunohistochemistry demonstrated that NNAT appeared in the SOX2-positive stem/progenitor cells in the developing pituitary primordium on rat embryonic day 11.5 (E11.5) and later in the majority of SOX2/PROP1 double-positive cells on E13.5. Thereafter, during pituitary embryonic development, Nnat expression was observed in some stem/progenitor cells, proliferating cells and terminally differentiating cells. In postnatal pituitaries, NNAT-positive cells decreased in number, with most coexpressing Sox2 or Pit1, suggesting a similar role for NNAT to that during the embryonic period. NNAT was widely localized in mitochondria, peroxisomes and lysosomes, in addition to the endoplasmic reticulum but not in the Golgi. The present study thus demonstrated the variability in expression of NNAT-positive cells in rat embryonic and postnatal pituitaries and the intracellular localization of NNAT. Further investigations to obtain functional evidence for NNAT are a prerequisite. PMID:26613603

  19. Protein Crystal Bovine Insulin

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The comparison of protein crystal, Bovine Insulin space-grown (left) and earth-grown (right). Facilitates the incorporation of glucose into cells. In diabetics, there is either a decrease in or complete lack of insulin, thereby leading to several harmful complications. Principal Investigator is Larry DeLucas.

  20. Bovine Spongiform Encephalopathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine spongiform encephalopathy (BSE), also referred to as “mad cow disease” is a chronic, non-febrile, neuro-degenerative disease affecting the central nervous system. The transmissible spongiform encephalopathies (TSEs) of domestic animals, of which BSE is a member includes scrapie of sheep...

  1. [Bovine spongiform encephalopathy].

    PubMed

    Suárez Fernández, G

    2001-01-01

    An histórical and conceptual review is made about Bovine Spongiform Encephalopathy or mad cows disease and an epidemiological analysis as a present and future health problem. This analysis of BSE should not be negative, considering the truths that we know today. PMID:11783042

  2. BOVINE VIRAL DIARRHEA VIRUSES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea virus (BVDV) is an umbrella term for two species of viruses, BVDV1 and BVDV2, within the Pestivirus genus of the Flavivirus family. BVDV viruses are further subclassified as cytopathic and noncytopathic based on their activity in cultured epithelial cells. Noncytopathic BVDV p...

  3. Bovine milk exosome proteome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Exosomes are 40-100 nm membrane vesicles of endocytic origin and are found in blood, urine, amniotic fluid, bronchoalveolar lavage (BAL) fluid, as well as human and bovine milk. Exosomes are extracellular organelles important in intracellular communication/signaling, immune function, and biomarkers ...

  4. Genotyping bovine coronaviruses.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine coronaviruses (BoCV) are enveloped, single-stranded, positive-sense RNA viruses of the Coronaviridae family. Infection is associated with enteritis and pneumonia in calves and Winter Dysentery in adult cattle. Strains, isolated more than 50 years ago, are used in vaccines and as laboratory ...

  5. Insulin-like growth factor I (IGF-I) and its receptor (IGF-1R) in the rat anterior pituitary.

    PubMed

    Eppler, Elisabeth; Jevdjovic, Tanja; Maake, Caroline; Reinecke, Manfred

    2007-01-01

    Few and controversial results exist on the cellular sites of insulin-like growth factor (IGF)-I synthesis and the type 1 IGF receptor (IGF-1R) in mammalian anterior pituitary. Thus, the present study analysed IGF-I and the IGF-1R in rat pituitary. Reverse transcription-polymerase chain reaction revealed IGF-I and IGF-1R mRNA expression in pituitary. The sequences of both were identical to the corresponding sequences in other rat organs. In situ hybridization localized IGF-I mRNA in endocrine cells. The majority of the growth hormone (GH) cells and numerous adrenocorticotropic hormone (ACTH) cells exhibited IGF-1R-immunoreactivity at the cell membrane. At lower densities, IGF-1 receptors were also present at the other hormone-producing cell types, indicating a physiological impact of IGF-I for all endocrine cells. IGF-I-immunoreactivity was located constantly in almost all ACTH-immunoreactive cells. At the ultrastructural level, IGF-I-immunoreactivity was confined to secretory granules in co-existence with ACTH-immunoreactivity, indicating a concomitant release of both hormones. Occasionally, IGF-I-immunoreactivity was detected in an interindividually varying number of GH cells. In some individuals, weak IGF-I-immunoreactions were also detected also in follicle-stimulating hormone and luteinizing hormone cells. Thus, IGF-I seems to be produced as a constituent in ACTH cells, possibly indicating its particular importance in stress response. Generally, IGF-I from the endocrine cells may regulate synthesis and/or release of hormones in an autocrine/paracrine manner as well as prevent apoptosis and stimulate proliferation. Production of IGF-I in GH cells may depend on the physiological status, most likely the serum IGF-I level. IGF-I released from GH cells may suppress GH synthesis and/or release by an autocrine feedback mechanism in addition to the endocrine route. PMID:17241280

  6. Cytochemical calcium distribution in secretory ameloblasts of the rat in relation to enamel mineralization.

    PubMed

    Chen, S; Eisenmann, D R; Zaki, A E; Ashrafi, S H

    1986-01-01

    Calcium distribution in secretory ameloblasts was studied in rat incisor enamel in which mineralization was temporarily disturbed by injection of either fluoride or cobalt. Pyroantimonate precipitates of calcium were analysed morphometrically in regions of the cell membranes, mitochondria and secretory granules. The disturbances in mineralization were characterized by accumulations of unmineralized enamel matrix at the secretory regions of Tomes' process within 1 h after injection. Fluoride-induced disturbances in mineralization were not accompanied by marked changes in calcium concentration and distribution. It may be that fluoride causes alterations in the synthesis and secretion of the organic matrix which affects its ability to mineralize. Secretory ameloblasts treated with cobalt showed a broad basis for interference with calcium, in particular that which is associated with cell membranes and secretory granules. Secretory ameloblasts may be actively controlling the availability of calcium to enamel by mechanisms involving the cell membrane as well as the secretory granules. PMID:3739601

  7. Pituitary apoplexy presenting as diabetic ketoacidosis: A great simulator?

    PubMed

    Camara-Lemarroy, Carlos R; Infante-Valenzuela, Adrian; Rodriguez-Velver, Karla; Rodriguez-Gutierrez, Rene; Villareal-Velazquez, Hector J

    2016-01-01

    Pituitary apoplexy is a life-threatening illness due to acute infarction of the pituitary gland. The most common symptoms associated with pituitary apoplexy are headache, nausea, vomiting, visual impairment, hypopituitarism, and altered mental status. Diabetic ketoacidosis is a common acute complication of diabetes mellitus and is itself associated with similar symptoms. We present the case of a 38 year old woman, who presented with altered mental status and biochemical alterations suggestive of diabetic ketoacidosis who was found to have a pituitary apoplexy. The low frequency of this condition coupled with an acute and usually dramatic presentation that includes non-specific symptoms makes it a diagnostic challenge. Pituitary apoplexy can simulate a wide range of neurological conditions. PMID:26994379

  8. Diagnostic imaging of dopamine receptors in pituitary adenomas.

    PubMed

    de Herder, Wouter W; Reijs, Ambroos E M; Feelders, Richard A; van Aken, Maarten O; Krenning, Eric P; van der Lely, Aart-Jan; Kwekkeboom, Dik J

    2007-04-01

    Dopamine D2 receptor scintigraphy of pituitary adenomas is feasible by single-photon emission computed tomography using (123)I-S-(-)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-hydroxy-3-iodo-6-methoxybenzamide ((123)I-IBZM) and (123)I-epidepride. (123)I-epidepride is generally superior to (123)I-IBZM for the visualization of D2 receptors on pituitary macroadenomas. However, (123)I-IBZM and (123)I-epidepride scintigraphy are generally not useful to predict the response to dopaminergic treatment in pituitary tumour patients. These techniques might allow discrimination of non-functioning pituitary macroadenomas from other non-tumour pathologies in the sellar region. Dopamine D2 receptors on pituitary tumours can also be studied using positron emission tomography with (11)C-N-raclopride and (11)C-N-methylspiperone. PMID:17413189

  9. Research Advances in Pituitary Adenoma and DNA Methylation.

    PubMed

    Wei, Zhen-Qing; Li, Yang; Li, Wei-Hua; Lou, Jia-Cheng; Zhang, Bo

    2016-08-01

    DNA methylation is closely related to the genesis and development of pituitary adenoma. Studies have shown that high methylation in the promoter region of potassium voltage-gated chanel,shaker related subfamily,beta member 2,O-6-methylguanine-DNA methyltransferase,echinoderm microtubule associated protein like 2 ,ras homolog family member D ,homeobox B1 ,NNAT, and P16 inhibits the expression of these genes and regulates of the proliferation of pituitary adenoma. DNA methylation is also closely related to invasive pituitary adenoma. Therefore,further study on molecular mechanism of DNA methylation of pituitary adenoma will offer a new strategy for the diagnosis and treatment of pituitary adenoma. PMID:27594164

  10. Pituitary hyperplasia: an uncommon presentation of a common disease

    PubMed Central

    Massolt, E T; Peeters, R P; Neggers, S J; de Herder, W W

    2015-01-01

    Summary A 21-year-old woman presented with amenorrhea, bilateral galactorrhea and fatigue. Visual acuity and visual fields were normal. Laboratory examination demonstrated hyperprolactinemia. Magnetic resonance imaging (MRI) of the pituitary showed a 19×17×12-mm sellar mass with supra- and parasellar extension, causing compression of the pituitary stalk and optic chiasm. Further examinations confirmed mild hyperprolactinemia, strongly elevated TSH (>500 mU/l), low free thyroxine (FT4), hypogonadotropic hypogonadism and secondary adrenal insufficiency. Hydrocortisone and l-T4 replacement therapy was started. Three months later, the galactorrhea had disappeared, thyroid function was normalized and MRI revealed regression of the pituitary enlargement, confirming the diagnosis of pituitary hyperplasia (PH) due to primary hypothyroidism. Subsequently, the menstrual cycle returned and the hypocortisolism normalized. This case demonstrates that severe primary hypothyroidism may have an unusual presentation and should be considered in the differential diagnosis of pituitary enlargement associated with moderate hyperprolactinemia. Learning points One should always try to find one etiology as the common cause of all the clinical findings in a pathologic process.Amenorrhea, galactorrhea and fatigue may be the only presenting clinical manifestations of primary hypothyroidism.Not every patient with galactorrhea, hyperprolactinemia and a pituitary mass has a prolactinoma.Primary hypothyroidism should always be considered in the differential diagnosis of hyperprolactinemia associated with pituitary enlargement and pituitary hormone(s) deficiency(ies).When PH due to primary hypothyroidism is suspected, thyroid hormone replacement should be started and only regression of pituitary enlargement on MRI follow-up can confirm the diagnosis.Examination of thyroid function in patients with a pituitary mass may avoid unnecessary surgery. PMID:26279852

  11. Estradiol Upregulates c-FLIPlong Expression in Anterior Pituitary Cells.

    PubMed

    Jaita, G; Zárate, S; Ferraris, J; Gottardo, M F; Eijo, G; Magri, M L; Pisera, D; Seilicovich, A

    2016-04-01

    Anterior pituitary cell turnover depends on a tight balance between proliferation and apoptosis. We have previously shown that estrogens sensitize anterior pituitary cells to pro-apoptotic stimuli. c-FLIP (cellular-FLICE-inhibitory-protein) isoforms are regulatory proteins of apoptosis triggered by death receptors. c-FLIPshort isoform competes with procaspase-8 inhibiting its activation. However, c-FLIPlong isoform may have a pro- or anti-apoptotic function depending on its expression level. In the present study, we explored whether estrogens modulate c-FLIP expression in anterior pituitary cells from ovariectomized (OVX) rats and in GH3 cells, a somatolactotrope cell line. Acute administration of 17β-estradiol to OVX rats increased c-FLIPlong expression in the anterior pituitary gland without changing c-FLIPshort expression as assessed by Western blot. Estradiol in vitro also increased c-FLIPlong expression in anterior pituitary cells but not in GH3 cells. As determined by flow cytometry, the percentage of anterior pituitary cells expressing c-FLIP was higher than in GH3 cells. However, c-FLIP fluorescence intensity in GH3 cells was higher than in anterior pituitary cells. FasL increased the percentage of TUNEL-positive GH3 cells incubated either with or without estradiol suggesting that the pro-apoptotic action of Fas activation is estrogen-independent. Our results show that unlike what happens in nontumoral pituitary cells, estrogens do not modulate either c-FLIPlong expression or FasL-induced apoptosis in GH3 cells. The stimulatory effect of estradiol on c-FLIPlong expression could be involved in the sensitizing effect of this steroid to apoptosis in anterior pituitary cells. The absence of this estrogenic action in tumor pituitary cells could be involved in their tumor-like behavior. PMID:26566102

  12. Effect of Hypoxia on DDR1 Expression in Pituitary Adenomas

    PubMed Central

    Li, Shouchun; Zhang, Zhiwen; Xue, Jinghui; Guo, Xiaoming; Liang, Shuli; Liu, Aijun

    2015-01-01

    Background Pituitary adenoma is a common intracranial tumor in neurosurgery. Some pituitary adenomas have the characteristics of invasive growth make them unable to be removed completely by surgery leading to easy relapse. Discoidin domain receptor l (DDR1) is a new kind of tyrosine kinase receptor on the cell surface. DDR1 can be activated by tumor microenvironment signal in tumorigenesis, increasing MMP-2/9 expression and promoting the invasive ability of tumor cells. Anoxia can promote tumor growth and metastasis. This study investigated the impact of anoxic environment DDR1 expression in pituitary adenoma. Material/Methods A primary hypoxia pituitary adenoma cell model was established and treated with DDR1 inhibitor nilotinib. Real-time PCR and Western blot were used to detect DDR1 mRNA and protein expression. ELISA was used to detect MMP-2/9 changes. MTT method was used to detect pituitary adenoma cell proliferation. We used a transwell chamber to determine pituitary adenoma cell invasion ability. Results DDR1 mRNA and protein were significantly overexpressed under hypoxia (P<0.05). MMP-2 and MMP-9 expression was obviously increased in supernatant (P<0.05). Pituitary adenoma cell proliferation and invasive ability improved markedly under hypoxia (P<0.05). Nilotinib could reduce DDR1 expression, decrease MMP-2 and MMP-9 expression, and inhibit pituitary adenoma cells proliferation and invasion. Conclusions Hypoxia can increase DDR1 expression in pituitary adenoma cells, leading to improved MMP-2 and MMP-9 secretion, and promoting pituitary adenoma cell proliferation and invasion. PMID:26286316

  13. Charting the Secretory Pathway in a Simple Eukaryote

    PubMed Central

    2010-01-01

    George Palade, a founding father of cell biology and of the American Society for Cell Biology (ASCB), established the ultrastructural framework for an analysis of how proteins are secreted and membranes are assembled in eukaryotic cells. His vision inspired a generation of investigators to probe the molecular mechanisms of protein transport. My laboratory has dissected these pathways with complementary genetic and biochemical approaches. Peter Novick, one of my first graduate students, isolated secretion mutants of Saccharomyces cerevisiae, and through cytological analysis of single and double mutants and molecular cloning of the corresponding SEC genes, we established that yeast cells use a secretory pathway fundamentally conserved in all eukaryotes. A biochemical reaction that recapitulates the first half of the secretory pathway was used to characterize Sec proteins that comprise the polypeptide translocation channel in the endoplasmic reticulum (ER) membrane (Sec61) and the cytoplasmic coat protein complex (COPII) that captures cargo proteins into transport vesicles that bud from the ER. PMID:21079008

  14. Secretory function in subplate neurons during cortical development

    PubMed Central

    Kondo, Shinichi; Al-Hasani, Hannah; Hoerder-Suabedissen, Anna; Wang, Wei Zhi; Molnár, Zoltán

    2015-01-01

    Subplate cells are among the first generated neurons in the mammalian cerebral cortex and have been implicated in the establishment of cortical wiring. In rodents some subplate neurons persist into adulthood. Here we would like to highlight several converging findings which suggest a novel secretory function of subplate neurons during cortical development. Throughout the postnatal period in rodents, subplate neurons have highly developed rough endoplasmic reticulum (ER) and are under an ER stress condition. By comparing gene expression between subplate and layer 6, we found that several genes encoding secreted proteins are highly expressed in subplate neurons. One of these secreted proteins, neuroserpin, encoded by the serpini1 gene, is localized to the ER in subplate cells. We propose that subplate might influence cortical circuit formation through a transient secretory function. PMID:25859180

  15. Isolation of intact sub-dermal secretory cavities from Eucalyptus

    PubMed Central

    2010-01-01

    Background The biosynthesis of plant natural products in sub-dermal secretory cavities is poorly understood at the molecular level, largely due to the difficulty of physically isolating these structures for study. Our aim was to develop a protocol for isolating live and intact sub-dermal secretory cavities, and to do this, we used leaves from three species of Eucalyptus with cavities that are relatively large and rich in essential oils. Results Leaves were digested using a variety of commercially available enzymes. A pectinase from Aspergillus niger was found to allow isolation of intact cavities after a relatively short incubation (12 h), with no visible artifacts from digestion and no loss of cellular integrity or cavity contents. Several measurements indicated the potential of the isolated cavities for further functional studies. First, the cavities were found to consume oxygen at a rate that is comparable to that estimated from leaf respiratory rates. Second, mRNA was extracted from cavities, and it was used to amplify a cDNA fragment with high similarity to that of a monoterpene synthase. Third, the contents of the cavity lumen were extracted, showing an unexpectedly low abundance of volatile essential oils and a sizeable amount of non-volatile material, which is contrary to the widely accepted role of secretory cavities as predominantly essential oil repositories. Conclusions The protocol described herein is likely to be adaptable to a range of Eucalyptus species with sub-dermal secretory cavities, and should find wide application in studies of the developmental and functional biology of these structures, and the biosynthesis of the plant natural products they contain. PMID:20807444

  16. Neuroendocrine secretory protein 7B2: structure, expression and functions.

    PubMed Central

    Mbikay, M; Seidah, N G; Chrétien, M

    2001-01-01

    7B2 is an acidic protein residing in the secretory granules of neuroendocrine cells. Its sequence has been elucidated in many phyla and species. It shows high similarity among mammals. A Pro-Pro-Asn-Pro-Cys-Pro polyproline motif is its most conserved feature, being carried by both vertebrate and invertebrate sequences. It is biosynthesized as a precursor protein that is cleaved into an N-terminal fragment and a C-terminal peptide. In neuroendocrine cells, 7B2 functions as a specific chaperone for the proprotein convertase (PC) 2. Through the sequence around its Pro-Pro-Asn-Pro-Cys-Pro motif, it binds to an inactive proPC2 and facilitates its transport from the endoplasmic reticulum to later compartments of the secretory pathway where the zymogen is proteolytically matured and activated. Its C-terminal peptide can inhibit PC2 in vitro and may contribute to keep the enzyme transiently inactive in vivo. The PC2-7B2 model defines a new neuroendocrine paradigm whereby proteolytic activation of prohormones and proneuropeptides in the secretory pathway is spatially and temporally regulated by the dynamics of interactions between converting enzymes and their binding proteins. Interestingly, unlike PC2-null mice, which are viable, 7B2-null mutants die early in life from Cushing's disease due to corticotropin ('ACTH') hypersecretion by the neurointermediate lobe, suggesting a possible involvement of 7B2 in secretory granule formation and in secretion regulation. The mechanism of this regulation is yet to be elucidated. 7B2 has been shown to be a good marker of several neuroendocrine cell dysfunctions in humans. The possibility that anomalies in its structure and expression could be aetiological causes of some of these dysfunctions warrants investigation. PMID:11439082

  17. Secretory pattern and regulatory mechanism of growth hormone in cattle.

    PubMed

    Kasuya, Etsuko

    2016-02-01

    The ultradian rhythm of growth hormone (GH) secretion has been known in several animal species for years and has recently been observed in cattle. Although the physiological significance of the rhythm is not yet fully understood, it appears essential for normal growth. In this review, previous studies concerning the GH secretory pattern in cattle, including its ultradian rhythm, are introduced and the regulatory mechanism is discussed on the basis of recent findings. PMID:26260675

  18. Crush Cytology of Secretory Meningioma: A Case Report

    PubMed Central

    Kim, Na Rae; Yee, Gie-Taek

    2015-01-01

    Secretory meningioma, a histologic subtype of meningioma of World Health Organization grade 1, is clinically significant because it is frequently accompanied by peritumoral brain edema. The patient was a 53-year-old woman suffering from dysarthria and motor weakness of the right arm. Enhanced magnetic resonance images showed an enhancing mass measuring 2.5 cm in size located in the right parietal convexity. Intraoperative squash cytology showed moderately cellular smears composed mainly of clusters of ovoid cells with scattered whorl formations. The cells had round nuclei and a moderate amount of eosinophilic cytoplasm with ill-defined cell borders. Neither atypia nor mitosis was observed. Some scattered round shaped eosinophilic refractile hyaline globules, measuring from 5 to 25 µm, were observed, and a periglobular halo was occasionally observed. The diagnosis of secretory meningioma should be made as early as possible so that neurosurgeons can prevent postoperative aggravation of peritumoral edema. We emphasize that cytologic findings including eosinophilic, non-fibrillary cytoplasm with eosinophilic refractile hyaline globules are helpful in differentiating secretory meningioma from other subtypes of meningioma, primary and metastatic brain tumors. PMID:26605274

  19. Atomic force microscopy study of the secretory granule lumen.

    PubMed Central

    Parpura, V; Fernandez, J M

    1996-01-01

    We have used an atomic force microscope to study the mechanical properties of the matrix found in the lumen of secretory granules isolated from mast cells. The matrices were insoluble and had an average height of 474 +/- 197 nm. The volume of these matrices increased reversibly about tenfold by decreasing the valency of the bathing external cation (La3+ < Ca2+ < Na+). The elastic (Young's) modulus was found to decrease by about 100-fold (4.3 MPa in La3+ to 37 kPa in Na+) upon a tenfold increase in the matrix volume. A swollen granule matrix had an elastic modulus similar to that of gelatin in water. The elastic modulus was inversely related to the change in the volume of the matrix, following a relationship similar to that predicted for the elasticity of weakly cross-linked polymers. Our results show that the matrix of these secretory granules have the mechanical properties of weak ion exchange resins, lending strong support to an ion exchange mechanism for the storage and release of cationic secretory products. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 5 FIGURE 9 PMID:8913576

  20. A secretory kinase complex regulates extracellular protein phosphorylation

    PubMed Central

    Cui, Jixin; Xiao, Junyu; Tagliabracci, Vincent S; Wen, Jianzhong; Rahdar, Meghdad; Dixon, Jack E

    2015-01-01

    Although numerous extracellular phosphoproteins have been identified, the protein kinases within the secretory pathway have only recently been discovered, and their regulation is virtually unexplored. Fam20C is the physiological Golgi casein kinase, which phosphorylates many secreted proteins and is critical for proper biomineralization. Fam20A, a Fam20C paralog, is essential for enamel formation, but the biochemical function of Fam20A is unknown. Here we show that Fam20A potentiates Fam20C kinase activity and promotes the phosphorylation of enamel matrix proteins in vitro and in cells. Mechanistically, Fam20A is a pseudokinase that forms a functional complex with Fam20C, and this complex enhances extracellular protein phosphorylation within the secretory pathway. Our findings shed light on the molecular mechanism by which Fam20C and Fam20A collaborate to control enamel formation, and provide the first insight into the regulation of secretory pathway phosphorylation. DOI: http://dx.doi.org/10.7554/eLife.06120.001 PMID:25789606

  1. Menin immunoreactivity in secretory granules of human pancreatic islet cells.

    PubMed

    Debelenko, Larisa V; Agarwal, Sunita; Du, Qiang; Yan, Wusheng; Erickson, Heidi S; Abu-Asab, Mones; Raffeld, Mark A; Libutti, Steven K; Marx, Stephen J; Emmert-Buck, Michael R

    2014-01-01

    The protein product of the Multiple Endocrine Neoplasia Type I (MEN1) gene is thought to be involved in predominantly nuclear functions; however, immunohistochemical (IHC) analysis data on cellular localization are conflicting. To further investigate menin expression, we analyzed human pancreas (an MEN1 target organ) using IHC analyses and 6 antibodies raised against full-length menin or its peptides. In 10 normal pancreas specimens, 2 independently raised antibodies showed unexpected cytoplasmic immunoreactivity in peripheral cells in each islet examined (over 100 total across all 10 patients). The staining exhibited a distinct punctate pattern and subsequent immunoelectron microscopy indicated the target antigen was in secretory granules. Exocrine pancreas and pancreatic stroma were not immunoreactive. In MEN1 patients, unaffected islets stained similar to those in normal samples but with a more peripheral location of positive cells, whereas hyperplastic islets and tumorlets showed increased and diffuse cytoplasmic staining, respectively. Endocrine tumors from MEN1 patients were negative for menin, consistent with a 2-hit loss of a tumor suppressor gene. Secretory granule localization of menin in a subset of islet cells suggests a function of the protein unique to a target organ of familial endocrine neoplasia, although the IHC data must be interpreted with some caution because of the possibility of antibody cross-reaction. The identity, cellular trafficking, and role of this putative secretory granule-form of menin warrant additional investigation. PMID:25153502

  2. Souffle/Spastizin Controls Secretory Vesicle Maturation during Zebrafish Oogenesis

    PubMed Central

    Riedel, Dietmar; Schomburg, Christoph; Cerdà, Joan; Vollack, Nadine; Dosch, Roland

    2014-01-01

    During oogenesis, the egg prepares for fertilization and early embryogenesis. As a consequence, vesicle transport is very active during vitellogenesis, and oocytes are an outstanding system to study regulators of membrane trafficking. Here, we combine zebrafish genetics and the oocyte model to identify the molecular lesion underlying the zebrafish souffle (suf) mutation. We demonstrate that suf encodes the homolog of the Hereditary Spastic Paraplegia (HSP) gene SPASTIZIN (SPG15). We show that in zebrafish oocytes suf mutants accumulate Rab11b-positive vesicles, but trafficking of recycling endosomes is not affected. Instead, we detect Suf/Spastizin on cortical granules, which undergo regulated secretion. We demonstrate genetically that Suf is essential for granule maturation into secretion competent dense-core vesicles describing a novel role for Suf in vesicle maturation. Interestingly, in suf mutants immature, secretory precursors accumulate, because they fail to pinch-off Clathrin-coated buds. Moreover, pharmacological inhibition of the abscission regulator Dynamin leads to an accumulation of immature secretory granules and mimics the suf phenotype. Our results identify a novel regulator of secretory vesicle formation in the zebrafish oocyte. In addition, we describe an uncharacterized cellular mechanism for Suf/Spastizin activity during secretion, which raises the possibility of novel therapeutic avenues for HSP research. PMID:24967841

  3. Observations of Calcium Dynamics in Cortical Secretory Vesicles

    PubMed Central

    Raveh, Adi; Valitsky, Michael; Shani, Liora; Coorssen, Jens R.; Blank, Paul S.; Zimmerberg, Joshua; Rahamimoff, Rami

    2012-01-01

    SUMMARY Calcium (Ca2+) dynamics were evaluated in fluorescently labeled sea urchin secretory vesicles using confocal microscopy. 71% of the vesicles examined exhibited one or more transient increases in the fluorescence signal that was damped in time. The detection of transient increases in signal was dependent upon the affinity of the fluorescence indicator; the free Ca2+ concentration in the secretory vesicles was estimated to be in the range of ~10 – 100 μM. Non-linear stochastic analysis revealed the presence of extra variance in the Ca2+ dependent fluorescence signal. This noise process increased linearly with the amplitude of the Ca2+ signal. Both the magnitude and spatial properties of this noise process were dependent upon the activity of vesicle p-type (Cav2.1) Ca2+ channels. Blocking the p-type Ca2+ channels with ω-agatoxin decreased signal variance, and altered the spatial noise pattern within the vesicle. These fluorescence signal properties are consistent with vesicle Ca2+ dynamics and not simply due to obvious physical properties such as gross movement artifacts or pH driven changes in Ca2+ indicator fluorescence. The results suggest that the free Ca2+ content of cortical secretory vesicles is dynamic; this property may modulate the exocytotic fusion process. PMID:22831912

  4. Receptor-mediated binding and uptake of GnRH agonist and antagonist by pituitary cells

    SciTech Connect

    Jennes, L.; Stumpf, W.E.; Conn, P.M.

    1984-01-01

    The intracellular pathway of an enzyme resistant GnRH agonist (D- Lys6 -GnRH) conjugated to ferritin or to colloidal gold was followed in cultured pituitary cells. After an initial uniform distribution over the cell surface of gonadotropes, the electrondense marker was internalized, either individually or in small groups. After longer incubation times, the marker appeared in the lysosomal compartment and the Golgi apparatus, where it could be found in the vesicular as well as cisternal portion. In addition, the receptor-mediated endocytosis of the GnRH antagonist D-p-Glu1-D-Phe2-D-Trp3-D- Lys6 -GnRH was studied by light and electron microscopic autoradiography after 30 and 60 min of incubation to ensure uptake. At both time points, in in vitro as well as in vivo studies, silver grains were localized over cytoplasmic organelles of castration cells, including dilated endoplasmic reticulum, lysosomes, and clear vesicles. No consistent association with cell nuclei, mitochondria, or secretory vesicles could be observed. The results suggest that both agonist and antagonist are binding selectively to the plasma membrane of gonadotropes and subsequently are taken up via receptor-mediated endocytosis for degradation or possible action on synthetic processes.

  5. Impact of Sleep and Its Disturbances on Hypothalamo-Pituitary-Adrenal Axis Activity

    PubMed Central

    Balbo, Marcella; Leproult, Rachel; Van Cauter, Eve

    2010-01-01

    The daily rhythm of cortisol secretion is relatively stable and primarily under the influence of the circadian clock. Nevertheless, several other factors affect hypothalamo-pituitary-adrenal (HPA) axis activity. Sleep has modest but clearly detectable modulatory effects on HPA axis activity. Sleep onset exerts an inhibitory effect on cortisol secretion while awakenings and sleep offset are accompanied by cortisol stimulation. During waking, an association between cortisol secretory bursts and indices of central arousal has also been detected. Abrupt shifts of the sleep period induce a profound disruption in the daily cortisol rhythm, while sleep deprivation and/or reduced sleep quality seem to result in a modest but functionally important activation of the axis. HPA hyperactivity is clearly associated with metabolic, cognitive and psychiatric disorders and could be involved in the well-documented associations between sleep disturbances and the risk of obesity, diabetes and cognitive dysfunction. Several clinical syndromes, such as insomnia, depression, Cushing's syndrome, sleep disordered breathing (SDB) display HPA hyperactivity, disturbed sleep, psychiatric and metabolic impairments. Further research to delineate the functional links between sleep and HPA axis activity is needed to fully understand the pathophysiology of these syndromes and to develop adequate strategies of prevention and treatment. PMID:20628523

  6. Expression of the glycoprotein hormone alpha-subunit gene in the placenta requires a functional cyclic AMP response element, whereas a different cis-acting element mediates pituitary-specific expression.

    PubMed Central

    Bokar, J A; Keri, R A; Farmerie, T A; Fenstermaker, R A; Andersen, B; Hamernik, D L; Yun, J; Wagner, T; Nilson, J H

    1989-01-01

    The single-copy gene encoding the alpha subunit of glycoprotein hormones is expressed in the pituitaries of all mammals and in the placentas of only primates and horses. We have systematically analyzed the promoter-regulatory elements of the human and bovine alpha-subunit genes to elucidate the molecular mechanisms underlying their divergent patterns of tissue-specific expression. This analysis entailed the use of transient expression assays in a chorionic gonadotropin-secreting human choriocarcinoma cell line, protein-DNA binding assays, and expression of chimeric forms of human or bovine alpha subunit genes in transgenic mice. From the results, we conclude that placental expression of the human alpha-subunit gene requires a functional cyclic AMP response element (CRE) that is present as a tandem repeat in the promoter-regulatory region. In contrast, the promoter-regulatory region of the bovine alpha-subunit gene, as well as of the rat and mouse genes, was found to contain a single CRE homolog that differed from its human counterpart by a single nucleotide. This difference substantially reduced the binding affinity of the bovine CRE homolog for the nuclear protein that bound to the human alpha CRE and thereby rendered the bovine alpha-subunit promoter inactive in human choriocarcinoma cells. However, conversion of the bovine alpha CRE homolog to an authentic alpha CRE restored activity to the bovine alpha-subunit promoter in choriocarcinoma cells. Similarly, a human but not a bovine alpha transgene was expressed in placenta in transgenic mice. Thus, placenta-specific expression of the human alpha-subunit gene may be the consequence of the recent evolution of a functional CRE. Expression of the human alpha transgene in mouse placenta further suggests that evolution of placenta-specific trans-acting factors preceded the appearance of this element. Finally, in contrast to their divergent patterns of placental expression, both the human and bovine alpha

  7. Pituitary macroadenoma presenting with pituitary apoplexy, acromegaly and secondary diabetes mellitus - a case report

    PubMed Central

    Nganga, Hudson Kamau; Lubanga, Reuben Paul

    2013-01-01

    Pituitary adenomas are associated with significant morbidity. The usual symptoms on presentation are of endocrine dysfunction and mass effects. A 31-year-old African female presented with headache, irregular menses, blurring of vision in the right eye and complete loss of vision in the left eye for 1 year. She had coarse facial features, enlarged hands and feet. Her right eye had temporal hemianopia with decreased visual acuity and her left eye had no perception of light. Investigations revealed an elevated fasting blood sugar and an elevated prolactin and growth hormone level. A CT scan and MRI done showed a hemorrhagic pituitary macroadenoma. She was put on bromocriptine, ocreotide, analgesics and insulin. Thereafter, she underwent transphenoidal surgery, where near total resection of the tumor was achieved. Patient is doing well post-operatively. This case highlights the importance of the use of a high clinical index of suspicion and radiological findings in diagnosis. PMID:24062868

  8. Pituitary macroadenoma presenting with pituitary apoplexy, acromegaly and secondary diabetes mellitus - a case report.

    PubMed

    Nganga, Hudson Kamau; Lubanga, Reuben Paul

    2013-01-01

    Pituitary adenomas are associated with significant morbidity. The usual symptoms on presentation are of endocrine dysfunction and mass effects. A 31-year-old African female presented with headache, irregular menses, blurring of vision in the right eye and complete loss of vision in the left eye for 1 year. She had coarse facial features, enlarged hands and feet. Her right eye had temporal hemianopia with decreased visual acuity and her left eye had no perception of light. Investigations revealed an elevated fasting blood sugar and an elevated prolactin and growth hormone level. A CT scan and MRI done showed a hemorrhagic pituitary macroadenoma. She was put on bromocriptine, ocreotide, analgesics and insulin. Thereafter, she underwent transphenoidal surgery, where near total resection of the tumor was achieved. Patient is doing well post-operatively. This case highlights the importance of the use of a high clinical index of suspicion and radiological findings in diagnosis. PMID:24062868

  9. Pituitary volumes are changed in patients with conversion disorder.

    PubMed

    Atmaca, Murad; Baykara, Sema; Mermi, Osman; Yildirim, Hanefi; Akaslan, Unsal

    2016-03-01

    Our study group previously measured pituitary volumes and found a relationship between somatoform disoders and pituitary volumes. Therefore, in conversion disorder, another somatoform disorder, we hypothesized that pituitary gland volumes would be reduced. Twenty female patients and healthy controls were recruited to the present investigation. The volumes of the pituitary gland were determined by using a 1.5 Tesla magnetic resonance scanner. We found that the pituitary gland volumes of the patients with conversion disorder were significantly smaller than those of healthy control subjects. In the patients with conversion disorder but not in the healthy control group, a significant negative correlation between the duration of illness and pituitary gland volume was determined. In summary, in the present study, we suggest that the patients with conversion disorder have smaller pituitary volumes compared to those of healthy control subjects. Further studies should confirm our data and ascertain whether volumetric alterations determined in the patients with conversion disorder can be changed with treatment or if they change over time. PMID:25877743

  10. The prevalence of hyperprolactinemia in non-functioning pituitary macroadenomas

    PubMed Central

    Zhang, Fangfang; Huang, Yinxing; Ding, Chenyu; Huang, Guoliang; Wang, Shousen

    2015-01-01

    Objective: The prevalence of hyperprolactinemia in non-functioning pituitary macroadenomas (NFPMAs) is not well known, and hyperprolactinemia caused by a NFPMA is currently associated with diagnostic uncertainty. Thus, the aim of this study was to evaluate the prevalence of hyperprolactinemia in NFPMAs. Methods: A meta-analysis of all existing articles in PubMed was conducted. The search string was designed as “(non-functioning pituitary tumor OR non-functioning pituitary tumor OR non-functioning pituitary macroadenomas OR non-functioning pituitary macroadenomas OR non-functioning pituitary adenomas OR non-functioning pituitary adenomas) and hyperprolactinemia”. References of the articles found were also reviewed. Study selection and data extraction were performed independently by two reviewers. Data were analyzed with STATA 11.0 software (StataCorp LP, USA). The fixed effects model was used to evaluate these studies. Results: The search identified 57 published studies, seven of which were accepted for the final meta-analysis. The authors found an overall estimated 40.2% prevalence of (95% CI, 36.6%-43.7%) hyperprolactinemia in NFPMAs. Conclusions: Given the high frequency of hyperprolactinemia in NFPMAs, a diagnosis of NFPMA or prolactinoma should be made more carefully. PMID:26770524

  11. Pituitary Volumes Are Reduced in Patients with Somatization Disorder

    PubMed Central

    Yildirim, Hanefi; Sirlier, Burcu; Kayali, Alperen

    2012-01-01

    Objective Despite of the suggested physiological relationship between somatoform disorder and disturbances in HPA axis function no volumetric study of pituitary volumes in somatization disorder has been carried out. Therefore, we aimed to use structural MRI to evaluate the pituitary volumes of the patients with somatization disorder. Methods Eighteen female patients with somatization disorder according to DSM-IV and same number of healthy controls were included into the study. All subjects were scanned using a 1.5-T General Electric (GE; Milwaukee, USA) scanner. Pituitary volume measurements were determined by using manuallly tracings according to standard antomical atlases. Results It was found significantly smaller pituitary volumes of the whole group of somatization patients compared to healthy (t=-3.604, p=0.001). ANCOVA predicting pituitary volumes demonstrated a significant main effect of diagnostic group (F=13.530, p<0.001) but TBV (F=1.924, p>0.05) or age (F=1.159, p>0.05). It was determined that there was no significant correlation between smaller pituitary volumes and the duration of illness (r=0.16, p>0.05) in the patient group. Conclusion In conclusion, we suggest that the patients with somatization disorder might have significantly smaller pituitary volumes compared to healthy control subjects. PMID:22993528

  12. Development and sexual dimorphism of the pituitary gland

    PubMed Central

    MacMaster, Frank P.; Keshavan, Matcheri; Mirza, Yousha; Carrey, Normand; Upadhyaya, Ameet R.; El-Sheikh, Rhonda; Buhagiar, Christian J; Taormina, S. Preeya; Boyd, Courtney; Lynch, Michelle; Rose, Michelle; Ivey, Jennifer; Moore, Gregory J.; Rosenberg, David R.

    2007-01-01

    The pituitary gland plays a central role in sexual development and brain function. Therefore, we examined the effect of age and gender on pituitary volume in a large sample of healthy children and adults. Volumetric magnetic resonance imaging (MRI) was conducted in one hundred and fifty four (77 males and 77 females) healthy participants. Males were between the ages of 7 to 35 years (16.91 ± 5.89 years) and females were 7 to 35 years of age (16.75 ± 5.75 years). Subjects were divided into subgroups of age (7 to 9, 10 to 13, 14 to 17, 18 to 21, 22 and older) and sex (male/female). Pituitary gland volume differed between sexes when comparing the age groups (F = 3.55, df = 2, 143, p = 0.03). Females demonstrated larger pituitary glands than males in the age 14 to 17 year old groups (p = 0.04). Young (19 years and under) and old (20 years and older) females demonstrated a correlation between pituitary volume and age. Males did not show this relationship. These findings provide additional evidence for gender differences in the normative anatomy of the pituitary and may have relevance for the study of various childhood onset neuropsychiatric disorders in which pituitary dysfunction has been implicated. PMID:17174342

  13. Development and sexual dimorphism of the pituitary gland.

    PubMed

    MacMaster, Frank P; Keshavan, Matcheri; Mirza, Yousha; Carrey, Normand; Upadhyaya, Ameet R; El-Sheikh, Rhonda; Buhagiar, Christian J; Taormina, S Preeya; Boyd, Courtney; Lynch, Michelle; Rose, Michelle; Ivey, Jennifer; Moore, Gregory J; Rosenberg, David R

    2007-02-13

    The pituitary gland plays a central role in sexual development and brain function. Therefore, we examined the effect of age and gender on pituitary volume in a large sample of healthy children and adults. Volumetric magnetic resonance imaging (MRI) was conducted in one hundred and fifty four (77 males and 77 females) healthy participants. Males were between the ages of 7 to 35 years (16.91+/-5.89 years) and females were 7 to 35 years of age (16.75+/-5.75 years). Subjects were divided into subgroups of age (7 to 9, 10 to 13, 14 to 17, 18 to 21, 22 and older) and sex (male/female). Pituitary gland volume differed between sexes when comparing the age groups (F=3.55, df=2, 143, p=0.03). Females demonstrated larger pituitary glands than males in the age 14 to 17 year old groups (p=0.04). Young (19 years and under) and old (20 years and older) females demonstrated a correlation between pituitary volume and age. Males did not show this relationship. These findings provide additional evidence for gender differences in the normative anatomy of the pituitary and may have relevance for the study of various childhood onset neuropsychiatric disorders in which pituitary dysfunction has been implicated. PMID:17174342

  14. A senescence secretory switch mediated by PI3K/AKT/mTOR activation controls chemoprotective endothelial secretory responses.

    PubMed

    Bent, Eric H; Gilbert, Luke A; Hemann, Michael T

    2016-08-15

    Cancer therapy targets malignant cells that are surrounded by a diverse complement of nonmalignant stromal cells. Therapy-induced damage of normal cells can alter the tumor microenvironment, causing cellular senescence and activating cancer-promoting inflammation. However, how these damage responses are regulated (both induced and resolved) to preserve tissue homeostasis and prevent chronic inflammation is poorly understood. Here, we detail an acute chemotherapy-induced secretory response that is self-limiting in vitro and in vivo despite the induction of cellular senescence. We used tissue-specific knockout mice to demonstrate that endothelial production of the proinflammatory cytokine IL-6 promotes chemoresistance and show that the chemotherapeutic doxorubicin induces acute IL-6 release through reactive oxygen species-mediated p38 activation in vitro. Doxorubicin causes endothelial senescence but, surprisingly, without a typical senescence secretory response. We found that endothelial cells repress senescence-associated inflammation through the down-regulation of PI3K/AKT/mTOR signaling and that reactivation of this pathway restores senescence-associated inflammation. Thus, we describe a mechanism by which damage-associated paracrine secretory responses are restrained to preserve tissue homeostasis and prevent chronic inflammation. PMID:27566778

  15. MR imaging analysis of posterior pituitary in patients with pituitary adenoma

    PubMed Central

    Wang, Shousen; Lin, Kunzhe; Xiao, Deyong; Zhao, Lin; Qin, Yong; Wei, Liangfeng

    2015-01-01

    Objective: This study is to investigate posterior pituitary bright spot (PPBS) occurrence, distribution and its influencing factors by analyzing MRI-T1WI images in patients with pituitary adenoma (PA). Methods: A total of 123 cases of PA patients were enrolled in this study. PPBS occurrence, distribution and MR signal characteristics were studied. The relationship of PPBS with PA morphology, tumor size, tumor height and immunohistochemical types were explored. Results: Among the 123 case of PA patients enrolled in the study, 98 cases were PPBS (+) and 25 cases were PPBS (-). According to tumor morphology, PA was divided into hourglass type (43 cases), barrel type (63 cases) and wedge type (17 cases). Occurrence rate of PPBS (+) in barrel type was less than those in hourglass and wedge types (P < 0.05). Tumor volume and height in PPBS (+) group were less than these in PPBS (-) group (P < 0.05). PPBS signal size in wedge and barrel types were larger than that of hourglass type (P < 0.05). Conclusions: Sagittal MRI-T1WI images could well show posterior pituitary and PPBS (+) was related to tumor morphology, volume and height but had nothing to do with immunohistochemical types. PMID:26221310

  16. Purification and cultivation of human pituitary growth hormone secreting cells

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.

    1978-01-01

    The maintainance of actively secreting human pituitary growth hormone cells (somatotrophs) in vitro was studied. The primary approach was the testing of agents which may be expected to increase the release of the human growth hormone (hGH). A procedure for tissue procurement is described along with the methodologies used to dissociate human pituitary tissue (obtained either at autopsy or surgery) into single cell suspensions. The validity of the Biogel cell column perfusion system for studying the dynamics of GH release was developed and documented using a rat pituitary cell system.

  17. Separation of cells from the rat anterior pituitary gland

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.; Hatfield, J. Michael

    1984-01-01

    Data concerned with analyzing the cellular organization of the rat anterior pituitary gland are examined. The preparation of the cell suspensions and the methods used to separate pituitary cell types are described. Particular emphasis is given to velocity sedimentation at unit gravity, density gradient centrifugation, affinity methods, fluorescence activated cell sorting, and density gradient and continuous-flow electrophoresis. The difficulties encountered when attempting to compare data from different pituitary cell separation studies are discussed, and results from various experiments are presented. The functional capabilities of the separated cell populations can be tested in various culture systems.

  18. Cellular and molecular specificity of pituitary gland physiology.

    PubMed

    Perez-Castro, Carolina; Renner, Ulrich; Haedo, Mariana R; Stalla, Gunter K; Arzt, Eduardo

    2012-01-01

    The anterior pituitary gland has the ability to respond to complex signals derived from central and peripheral systems. Perception of these signals and their integration are mediated by cell interactions and cross-talk of multiple signaling transduction pathways and transcriptional regulatory networks that cooperate for hormone secretion, cell plasticity, and ultimately specific pituitary responses that are essential for an appropriate physiological response. We discuss the physiopathological and molecular mechanisms related to this integrative regulatory system of the anterior pituitary gland and how it contributes to modulate the gland functions and impacts on body homeostasis. PMID:22298650

  19. [Primary Pituitary Malignant Lymphoma that was Difficult to Differentiate from Nonfunctioning Pituitary Adenoma:A Case Report].

    PubMed

    Murakami, Yuta; Sato, Taku; Jinguji, Shinya; Kishida, Yugo; Watanabe, Tadashi; Suzuki, Osamu; Ikeda, Kazuhiko; Homma, Miyuki; Midorikawa, Sanae; Saito, Kiyoshi

    2016-09-01

    We report a rare case of primary pituitary lymphoma in a 75-year-old immunocompetent woman. The patient was blind in the right eye and presented with visual disturbance in the left eye that started 2 months previously. She also exhibited right third and fifth cranial nerve palsy. Magnetic resonance imaging(MRI)revealed an intrasellar mass lesion with right cavernous sinus invasion and suprasellar extension with compression of the optic chiasm. The mass lesion was isointense on both T1WI and T2WI, and showed less enhancement than a normal pituitary gland on gadolinium-enhanced T1WI. We therefore suspected the tumor to be a nonfunctioning pituitary adenoma. The patient underwent endoscopic endonasal transsphenoidal surgery. The tumor was firm and grayish, and had an ill-defined border along the normal pituitary gland. Histological examination revealed a malignant CD5-positive diffuse large B-cell lymphoma. After surgery, the patient received both chemotherapy and radiotherapy. Although the visual acuity of the right eye did not improved, other symptoms improved. At the 34-month follow-up, no recurrence was detected on serial MRI. Patients with primary pituitary lymphoma often exhibit ophthalmoplegia and/or panhypopituitarism more frequently than expected from radiological findings. In cases of pituitary tumors with atypical symptoms, a biopsy and general physical examination should be performed immediately to determine the diagnosis and perform adjuvant therapy even when the tumor is assumed as nonfunctioning pituitary adenoma from the image findings. PMID:27605481

  20. Effects of cytoplasmic and periplasmic chaperones on secretory production of single-chain Fv antibody in Escherichia coli.

    PubMed

    Sonoda, Hiroyuki; Kumada, Yoichi; Katsuda, Tomohisa; Yamaji, Hideki

    2011-04-01

    The effects of cytoplasmic and periplasmic chaperones on the secretory production of an anti-bovine ribonuclease A single-chain variable fragment (scFv) 3A21 in Escherichia coli were investigated. Co-expression of a cytoplasmic chaperone, GroEL/ES, DnaK/DnaJ/GrpE, trigger factor, or SecB with 3A21 scFv affected the proportions of antigen-binding activity in the cytoplasmic soluble fraction, the periplasmic fraction, and the extracellular medium, but there was no significant difference in the total activity compared to the control without chaperone co-expression. On the other hand, co-expression of a periplasmic chaperone, Skp or FkpA, with the exception of DsbC, greatly increased the binding activity in all the soluble fractions. Co-expression of both Skp and FkpA had no synergistic effect. Combinations of cytoplasmic and periplasmic chaperones decreased the productivity. In shake-flask cultures of cells co-expressing Skp or FkpA, considerable amounts of 3A21 scFv were detected in the extracellular medium by enzyme-linked immunosorbent assay (ELISA) and Western blot, and the extracellular production level of 3A21 scFv was calculated to be around 40mg/l. The binding activity of 3A21 scFv co-expressed with Skp was slightly higher than that with FkpA. These results indicate that the co-expression of periplasmic chaperones Skp and FkpA is extremely useful for the secretory production of scFvs in a culture medium using E. coli, but cytoplasmic chaperones and multiple-chaperone combinations may not be effective. PMID:21324738

  1. Purification and cultivation of human pituitary growth hormone secreting cells

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.

    1984-01-01

    A multiphase study was conducted to examine the properties of growth hormone cells. Topics investigated included: (1) to determine if growth hormone (GH) cells contained within the rat pituitary gland can be separated from the other hormone producing cell types by continuous flow electrophoresis (CFE); (2) to determine what role, if any, gravity plays in the electrophoretic separation of GH cells; (3) to compare in vitro GH release from rat pituitary cells previously exposed to microgravity conditions vs release from cells not exposed to microgravity; (4) to determine if the frequency of different hormone producing pituitary cell types contained in cell suspensions can be quantitated by flow cytometry; and (5) to determine if GH contained within the human post mortem pituitary gland can be purified by CFE. Specific experimental procedures and results are included.

  2. Delayed Puberty due to Pituitary Stalk Dysgenesis and Ectopic Neurohypophysis

    PubMed Central

    Yoo, Hye Jin; Ryu, Ohk Hyun; Suh, Sang Il; Kim, Nan Hee; Baik, Sei Hyun; Choi, Dong Seop

    2006-01-01

    Hypopituitarism is not a common cause of delayed puberty. A 22 year old man was referred to our clinic because of the absence of the development of secondary sexual characteristics. The patient had no complaints of physical discomfort. Random serum testosterone and luteinizing hormone level were obtained and found to be low. The combined pituitary function stimulation test revealed a partial hypopituitarism. A pituitary magnetic resonance imaging (MRI) was obtained and showed decreased pituitary stalk enhancement and ectopic neurohypophysis. Therefore, we conclude that the delayed puberty was a result of hypopituitarism due to pituitary stalk dysgenesis and ectopic neurohypophysis. The patient was started on hormone replacement therapy and gradually developed secondary sexual characteristics. PMID:16646569

  3. Response of silent corticotroph pituitary carcinoma to chemotherapy: case report.

    PubMed

    He, Lucy; Forbes, Jonathan A; Carr, Kevin; Highfield Nickols, Hilary; Utz, Andrea; Moots, Paul; Weaver, Kyle

    2016-06-01

    Silent pituitary corticotroph carcinomas are rare, with only six previously described cases in the literature. We report a patient with a silent pituitary corticotroph adenoma treated with multiple trans-sphenoidal resections. Twelve years after her initial presentation, she returned with leptomeningeal metastases to the posterior fossa, foramen magnum, and numerous other subarachnoid locations involving the spine. Histopathology obtained from the metastatic foci was identical to previous trans-sphenoidal specimens - consistent with the diagnosis of corticotroph pituitary carcinoma. A carboplatin and etoposide chemotherapy regimen successfully arrested disease progression and produced regression of multiple radiographically documented leptomeningeal deposits. To the authors' knowledge, this is the first report of a patient with silent pituitary carcinoma treated successfully with chemotherapy. PMID:27150544

  4. Amelogenins as Potential Buffers during Secretory-stage Amelogenesis

    PubMed Central

    Guo, J.; Lyaruu, D.M.; Takano, Y.; Gibson, C.W.; DenBesten, P.K.

    2015-01-01

    Amelogenins are the most abundant protein species in forming dental enamel, taken to regulate crystal shape and crystal growth. Unprotonated amelogenins can bind protons, suggesting that amelogenins could regulate the pH in enamel in situ. We hypothesized that without amelogenins the enamel would acidify unless ameloblasts were buffered by alternative ways. To investigate this, we measured the mineral and chloride content in incisor enamel of amelogenin-knockout (AmelX-/-) mice and determined the pH of enamel by staining with methyl-red. Ameloblasts were immunostained for anion exchanger-2 (Ae2), a transmembrane pH regulator sensitive for acid that secretes bicarbonate in exchange for chloride. The enamel of AmelX-/- mice was 10-fold thinner, mineralized in the secretory stage 1.8-fold more than wild-type enamel and containing less chloride (suggesting more bicarbonate secretion). Enamel of AmelX-/- mice stained with methyl-red contained no acidic bands in the maturation stage as seen in wild-type enamel. Secretory ameloblasts of AmelX-/- mice, but not wild-type mice, were immunopositive for Ae2, and stained more intensely in the maturation stage compared with wild-type mice. Exposure of AmelX-/- mice to fluoride enhanced the mineral content in the secretory stage, lowered chloride, and intensified Ae2 immunostaining in the enamel organ in comparison with non-fluorotic mutant teeth. The results suggest that unprotonated amelogenins may regulate the pH of forming enamel in situ. Without amelogenins, Ae2 could compensate for the pH drop associated with crystal formation. PMID:25535204

  5. Secretory IgA: Designed for Anti-Microbial Defense

    PubMed Central

    Brandtzaeg, Per

    2013-01-01

    Prevention of infections by vaccination remains a compelling goal to improve public health. Mucosal vaccines would make immunization procedures easier, be better suited for mass administration, and most efficiently induce immune exclusion – a term coined for non-inflammatory antibody shielding of internal body surfaces, mediated principally by secretory immunoglobulin A (SIgA). The exported antibodies are polymeric, mainly IgA dimers (pIgA), produced by local plasma cells (PCs) stimulated by antigens that target the mucose. SIgA was early shown to be complexed with an epithelial glycoprotein – the secretory component (SC). A common SC-dependent transport mechanism for pIgA and pentameric IgM was then proposed, implying that membrane SC acts as a receptor, now usually called the polymeric Ig receptor (pIgR). From the basolateral surface, pIg-pIgR complexes are taken up by endocytosis and then extruded into the lumen after apical cleavage of the receptor – bound SC having stabilizing and innate functions in the secretory antibodies. Mice deficient for pIgR show that this is the only receptor responsible for epithelial export of IgA and IgM. These knockout mice show a variety of defects in their mucosal defense and changes in their intestinal microbiota. In the gut, induction of B-cells occurs in gut-associated lymphoid tissue, particularly the Peyer’s patches and isolated lymphoid follicles, but also in mesenteric lymph nodes. PC differentiation is accomplished in the lamina propria to which the activated memory/effector B-cells home. The airways also receive such cells from nasopharynx-associated lymphoid tissue but by different homing receptors. This compartmentalization is a challenge for mucosal vaccination, as are the mechanisms used by the mucosal immune system to discriminate between commensal symbionts (mutualism), pathobionts, and overt pathogens (elimination). PMID:23964273

  6. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities

    PubMed Central

    Tchkonia, Tamara; Zhu, Yi; van Deursen, Jan; Campisi, Judith; Kirkland, James L.

    2013-01-01

    Aging is the largest risk factor for most chronic diseases, which account for the majority of morbidity and health care expenditures in developed nations. New findings suggest that aging is a modifiable risk factor, and it may be feasible to delay age-related diseases as a group by modulating fundamental aging mechanisms. One such mechanism is cellular senescence, which can cause chronic inflammation through the senescence-associated secretory phenotype (SASP). We review the mechanisms that induce senescence and the SASP, their associations with chronic disease and frailty, therapeutic opportunities based on targeting senescent cells and the SASP, and potential paths to developing clinical interventions. PMID:23454759

  7. Ultrastructural similarity between bat and human mast cell secretory granules.

    PubMed

    Oliani, S M; Vugman, I; Jamur, M C

    1993-01-01

    Mast cells in the tongue of the bat (Artibeus lituratus) show a well-developed Golgi area and abundant mitochondria in the granule-free perinuclear cytoplasm. Rough endoplasmic reticulum profiles, free ribosomes, mitochondria, bundles of filaments and a great number of secretory granules are found throughout the remaining cytoplasm. The granules, of various shapes and sizes, are simple containing an electron-dense, homogeneous matrix, coarse particles or cylindrical scrolls, or combinations (cylindrical scrolls with either electron-dense, homogeneous matrix or coarse particle contents). Up to now, scroll-containing granules have been considered to be a unique feature of human mast cells. PMID:8453310

  8. Pituitary duplication associated with oral dermoid and corpus callosum hypogenesis.

    PubMed

    Mutlu, Hakan; Paker, Bilhan; Gunes, Nilufer; Emektar, Ali; Keceli, Merter; Kantarci, Mecit

    2004-12-01

    We report a case of pituitary duplication in a neonate girl whose magnetic resonance (MR) images showed unusual findings of hypogenesis of the corpus callosum and oral dermoid. Pituitary duplication is an extremely rare malformation, with only a few previously reported cases. It occurs most commonly in association with complicated midline and skull base anomalies. We present a case of this malformation with special emphasis on the hypogenesis of splenium of the corpus callosum and oral dermoid. PMID:15565346

  9. Serotonin and pituitary-adrenal function. [in rat under stress

    NASA Technical Reports Server (NTRS)

    Berger, P. A.; Barchas, J. D.; Vernikos-Danellis, J.

    1974-01-01

    An investigation is conducted to evaluate the response of the pituitary-adrenal system to a stress stimulus in the rat. In the investigation brain serotonin synthesis was inhibited with p-chlorophenylalanine. In other tests the concentration of serotonin was enhanced with precursors such as tryptophan or 5-hydroxytryptophan. On the basis of the results obtained in the study it is speculated that in some disease states there is a defect in serotonergic neuronal processes which impairs pituitary-adrenal feedback mechanisms.

  10. Outcome After Pituitary Radiosurgery for Thalamic Pain Syndrome

    SciTech Connect

    Hayashi, Motohiro Chernov, Mikhail F.; Taira, Takaomi; Ochiai, Taku; Nakaya, Kotaro; Tamura, Noriko; Goto, Shinichi; Yomo, Shoji; Kouyama, Nobuo; Katayama, Yoko; Kawakami, Yoriko; Izawa, Masahiro; Muragaki, Yoshihiro

    2007-11-01

    Purpose: To evaluate outcomes after pituitary radiosurgery in patients with post-stroke thalamic pain syndrome. Methods and Materials: From 2002 to 2006, 24 patients with thalamic pain syndrome underwent pituitary radiosurgery at Tokyo Women's Medical University and were followed at least 12 months thereafter. The radiosurgical target was defined as the pituitary gland and its connection with the pituitary stalk. The maximum dose varied from 140 to 180 Gy. Mean follow-up after treatment was 35 months (range, 12-48 months). Results: Initial pain reduction, usually within 48 h after radiosurgery, was marked in 17 patients (71%). However, in the majority of cases the pain recurred within 6 months after treatment, and at the time of the last follow-up examination durable pain control was marked in only 5 patients (21%). Ten patients (42%) had treatment-associated side effects. Anterior pituitary abnormalities were marked in 8 cases and required hormonal replacement therapy in 3; transient diabetes insipidus was observed in 2 cases, transient hyponatremia in 1, and clinical deterioration due to increase of the numbness severity despite significant reduction of pain was seen once. Conclusions: Pituitary radiosurgery for thalamic pain results in a high rate of initial efficacy and is accompanied by acceptable morbidity. It can be used as a primary minimally invasive management option for patients with post-stroke thalamic pain resistant to medical therapy. However, in the majority of cases pain recurrence occurs within 1 year after treatment.

  11. Role of PROP1 in pituitary gland growth.

    PubMed

    Ward, Robert D; Raetzman, Lori T; Suh, Hoonkyo; Stone, Brandon M; Nasonkin, Igor O; Camper, Sally A

    2005-03-01

    Mutations in the PROP1 transcription factor gene lead to reduced production of thyrotropin, GH, prolactin, and gonadotropins as well as to pituitary hypoplasia in adult humans and mice. Some PROP1-deficient patients initially exhibit pituitary hyperplasia that resolves to hypoplasia. To understand this feature and to explore the mechanism whereby PROP1 regulates anterior pituitary gland growth, we carried out longitudinal studies in normal and Prop1-deficient dwarf mice from early embryogenesis through adulthood, examining the volume of Rathke's pouch and its derivatives, the position and number of dividing cells, the rate of apoptosis, and cell migration by pulse labeling. The results suggest that anterior pituitary progenitors normally leave the perilumenal region of Rathke's pouch and migrate to form the anterior lobe as they differentiate. Some of the cells that seed the anterior lobe during organogenesis have proliferative potential, supporting the expansion of the anterior lobe after birth. Prop1-deficient fetal pituitaries are dysmorphic because mutant cells are retained in the perilumenal area and fail to differentiate. After birth, mutant pituitaries exhibit enhanced apoptosis and reduced proliferation, apparently because the mutant anterior lobe is not seeded with progenitors. These studies suggest a mechanism for Prop1 action and an explanation for some of the clinical findings in human patients. PMID:15591534

  12. Bovine myocardial epithelial inclusions.

    PubMed

    Baker, D C; Schmidt, S P; Langheinrich, K A; Cannon, L; Smart, R A

    1993-01-01

    Light microscopic, histochemical, immunohistochemical, and ultrastructural methods were used to examine myocardial epithelial masses in the hearts of ten cattle. The tissues consisted of paraffin-embedded or formalin-fixed samples from eight hearts that were being inspected in slaughter houses and from two hearts from calves that died of septicemia. The ages of the cattle ranged from 4 days to 12 years; the breeds were unspecified for all but one Hereford female and the two Holstein calves; and there were three males, four females, and three steers. The masses in these cases were compared with similar appearing lesions found in other animal species. The lesions in the bovine hearts were single to multiple, well circumscribed, found in the left ventricle wall, and composed of squamous to cuboidal epithelial cells that formed tubular, ductular, and acinar structures with lumens that were void or filled with amorphous protein globules. Electron microscopic examination revealed epithelial cells that had sparse apical microvilli, tight apical intercellular junctions, perinuclear bundles of filaments, and rare cilia. Almost half of the bovine epithelial masses (4/9) had occasional diastase-resistant periodic acid-Schiff-positive granules in their cytoplasm, and few had hyaluronidase-resistant alcian blue-positive granules (2/9) or colloidal iron-positive granules (1/9). All myocardial masses had abundant collagen surrounding the tubular and acinar structures, and 2/9 had elastin fibers as well. None of the myocardial masses had Churukian-Schenk or Fontana Masson's silver staining granules in epithelial cells. Immunohistochemically, all bovine myocardial tumors stained positively for cytokeratin (8/8), and occasional masses stained positively for vimentin (3/8) or carcinoembryonic antigen (3/8). None of the masses stained positively for desmin. The myocardial epithelial tumors most likely represent endodermal rests of tissue misplaced during organogenesis. PMID:7680178

  13. Enzootic Bovine Leukosis

    PubMed Central

    Reed, V. Ivan

    1981-01-01

    The author emphasizes the significance of enzootic bovine leukosis in Canada. He describes in detail diagnostic methods, various types of the disease and methods of transmission. Various aspects of the disease in Canada are compared with those in other countries. Prevention and control are discussed in a Canadian context and include the current policies of the Government of Canada in relationship to this disease. The possibility of developing a certification program for herds free of the disease is also discussed. The paper includes incidence in various parts of Canada. PMID:6265053

  14. Incidence of Pituitary Apoplexy and Its Risk Factors in Chinese People: A Database Study of Patients with Pituitary Adenoma

    PubMed Central

    Zhao, Xuelan; Jiang, Cuiping; Zhang, Qiongyue; Jiang, Wenjuan; Wang, Yan; Chen, Haixia; Shou, Xuefei; Zhao, Yao; Li, Yiming; Li, Shiqi; Ye, Hongying

    2015-01-01

    Background There are few studies of the incidence and clinical characteristics of pituitary apoplexy (PA) in pituitary adenoma patients, and the findings have been inconsistent. Objective The aim of the study was to retrospectively assess the incidence, clinical presentation, surgical management and postoperative complications of PA in pituitary adenoma patients. Methods A database was specifically designed to collect clinical, therapeutic, prognostic and histological information about pituitary adenoma patients. Using multivariate logistic regression, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to identify associated factors. Results A total of 2021 pituitary adenoma patients were recruited. 97 (4.8%) patients had PA. The incidence of PA was 10.11% in patients with pituitary macroadenoma, and 0.36% in patients with microadenoma. Variables for the logistic regression model independently associated with PA were sex (male vs. female, OR = 2.54, 95% CI: 1.59~4.07), tumor type (negative staining vs. positive staining, OR = 2.04, 95% CI: 1.29~3.23), and tumor size (macroadenoma vs. microadenoma, OR = 26.46, 95% CI = 9.66~72.46). Headache, visual deterioration, and vomiting were the most common symptoms in patients with pituitary adenoma. Patients with and without PA had similar frequency of visual deterioration, head trauma, acromegalic appearance, galactorrhoea, cold intolerance and Cushingoid appearance, but headache, vomiting, ptosis, diplopia, fever and blindness were significantly more common in patients with PA. Pearson Chi-Square tests revealed a significant difference in surgical approach between patients with and without PA (95.88% vs. 85.57%, P = 0.01). Conclusion Our findings suggest that PA is not a rare event. Male sex, non-functioning tumor, and macroadenoma are associated with an increased risk of PA. Compared with pituitary adenoma patients without PA, patients with PA have more severe symptoms. PMID:26407083

  15. (Controls of the plant endomembrane-secretory pathway): Performance report

    SciTech Connect

    Not Available

    1987-01-01

    This project has been directed towards an understanding of the cellular and molecular mechanisms by which higher plants control the composition of the plasma membrane, through analysis of the biosynthesis, modification and targeting of plasma membrane proteins and glycoproteins. We have undertaken an identification of molecular markers both for the plasma membrane and for the biosynthetic processes, and the development of techniques for the isolation of conditional-lethal mutants defective at defined stages within the endomembrane-secretory pathway responsible for the biosynthesis, modification and targeting of plasma membrane proteins and glycoproteins. For the identification of molecular markers for the plasma membrane, monoclonal antibodies directed against epitopes present at the plant cell surface have been developed. Novel molecular markers for the plant plasma membrane and for the endomembrane-secretory pathway have been sought. Methods for the analysis of beta-glucuronidase in higher plants have been developed. These technologies have involved the use of flow cytometry and fluorescence-activated cell sorting. In addition, we have been investigating the feasibility of expression of animal plasma membrane marker proteins in plants, specifically the VSV G-protein. 5 refs., 6 figs.

  16. Acid-induced secretory cell metaplasia in hamster bronchi

    SciTech Connect

    Christensen, T.G.; Lucey, E.C.; Breuer, R.; Snider, G.L.

    1988-02-01

    Hamsters were exposed to an intratracheal instillation of 0.5 ml of 0.08 N nitric, hydrochloric, or sulfuric acid to determine their airway epithelial response. Three weeks after exposure, the left intrapulmonary bronchi in Alcian blue/PAS-strained paraffin sections were evaluated for the amount of secretory product in the airway epithelium as a measure of secretory cell metaplasia (SCM). Compared to saline-treated control animals, all three acids caused statistically significant SCM. In addition to the bronchial lesion, all three acids caused similar interstitial fibrosis, bronchiolectasis, and bronchiolization of alveoli that varied in individual animals from mild to severe. In a separate experiment to study the persistence of the SCM, hamsters treated with a single instillation of 0.1 N nitric acid showed significant SCM 3, 7, and 17 weeks after exposure. There was a high correlation (r = 0.96) between a subjective assessment of SCM and objective assessment using a digital image-analysis system. We conclude that protons induce SCM independently of the associated anion; the SCM persists at least 17 weeks. Sulfuric acid is an atmospheric pollutant and nitric acid may form locally on the mucosa of lungs exposed to nitrogen dioxide. These acids may contribute to the development of maintenance of the SCM seen in the conducting airways of humans with chronic obstructive pulmonary disease.

  17. Widespread occurrence of expressed fungal secretory peroxidases in forest soils.

    PubMed

    Kellner, Harald; Luis, Patricia; Pecyna, Marek J; Barbi, Florian; Kapturska, Danuta; Krüger, Dirk; Zak, Donald R; Marmeisse, Roland; Vandenbol, Micheline; Hofrichter, Martin

    2014-01-01

    Fungal secretory peroxidases mediate fundamental ecological functions in the conversion and degradation of plant biomass. Many of these enzymes have strong oxidizing activities towards aromatic compounds and are involved in the degradation of plant cell wall (lignin) and humus. They comprise three major groups: class II peroxidases (including lignin peroxidase, manganese peroxidase, versatile peroxidase and generic peroxidase), dye-decolorizing peroxidases, and heme-thiolate peroxidases (e.g. unspecific/aromatic peroxygenase, chloroperoxidase). Here, we have repeatedly observed a widespread expression of all major peroxidase groups in leaf and needle litter across a range of forest ecosystems (e.g. Fagus, Picea, Acer, Quercus, and Populus spp.), which are widespread in Europe and North America. Manganese peroxidases and unspecific peroxygenases were found expressed in all nine investigated forest sites, and dye-decolorizing peroxidases were observed in five of the nine sites, thereby indicating biological significance of these enzymes for fungal physiology and ecosystem processes. Transcripts of selected secretory peroxidase genes were also analyzed in pure cultures of several litter-decomposing species and other fungi. Using this information, we were able to match, in environmental litter samples, two manganese peroxidase sequences to Mycena galopus and Mycena epipterygia and one unspecific peroxygenase transcript to Mycena galopus, suggesting an important role of this litter- and coarse woody debris-dwelling genus in the disintegration and transformation of litter aromatics and organic matter formation. PMID:24763280

  18. Salivary Secretory Disorders, Inducing Drugs, and Clinical Management

    PubMed Central

    Miranda-Rius, Jaume; Brunet-Llobet, Lluís; Lahor-Soler, Eduard; Farré, Magí

    2015-01-01

    Background: Salivary secretory disorders can be the result of a wide range of factors. Their prevalence and negative effects on the patient's quality of life oblige the clinician to confront the issue. Aim: To review the salivary secretory disorders, inducing drugs and their clinical management. Methods: In this article, a literature search of these dysfunctions was conducted with the assistance of a research librarian in the MEDLINE/PubMed Database. Results: Xerostomia, or dry mouth syndrome, can be caused by medication, systemic diseases such as Sjögren's Syndrome, glandular pathologies, and radiotherapy of the head and neck. Treatment of dry mouth is aimed at both minimizing its symptoms and preventing oral complications with the employment of sialogogues and topical acting substances. Sialorrhea and drooling, are mainly due to medication or neurological systemic disease. There are various therapeutic, pharmacologic, and surgical alternatives for its management. The pharmacology of most of the substances employed for the treatment of salivary disorders is well-known. Nevertheless, in some cases a significant improvement in salivary function has not been observed after their administration. Conclusion: At present, there are numerous frequently prescribed drugs whose unwanted effects include some kind of salivary disorder. In addition, the differing pathologic mechanisms, and the great variety of existing treatments hinder the clinical management of these patients. The authors have designed an algorithm to facilitate the decision making process when physicians, oral surgeons, or dentists face these salivary dysfunctions. PMID:26516310

  19. Aging and secretory reserve capacity of major salivary glands.

    PubMed

    Ghezzi, E M; Ship, J A

    2003-10-01

    A loss of acinar cells occurs with aging, while salivary production remains age-stable in healthy adults. It is hypothesized that a secretory reserve exists to preserve function despite a loss of acinar cells in normal aging. The purpose of this double-blind, placebo-controlled, crossover study was to determine age-related differences in salivary response to an anti-sialogogue (glycopyrrolate). Thirty-six healthy subjects (18 young--20-38 yrs; 18 older--60-77 yrs) received 4.0 microg/kg i.v. glycopyrrolate. Parotid and submandibular/sublingual saliva samples and xerostomia questionnaire responses were collected. Variables calculated for each subject were: times to initial and maximum suppression and xerostomic complaint; time to recovery; and durations of suppression and complaint. Salivary function was more adversely affected in older persons. There were no consistent age-associated questionnaire response differences. These findings suggest that salivary gland output is more adversely affected by an anti-sialogogue in healthy older vs. younger adults, supporting the secretory reserve hypothesis of salivary function. PMID:14514768

  20. Characterization of a Secretory Annexin in Echinococcus granulosus.

    PubMed

    Song, Xingju; Hu, Dandan; Zhong, Xiuqin; Wang, Ning; Gu, Xiaobin; Wang, Tao; Peng, Xuerong; Yang, Guangyou

    2016-03-01

    Cystic echinococcosis, caused by Echinococcus granulosus, is a widespread parasitic zoonosis causing economic loss and public health problems. Annexins are important proteins usually present in the plasma membrane, but previous studies have shown that an annexin B33 protein of E. granulosus (Eg-ANX) could be detected in the excretory/secretory products and cyst fluid. In this study, we cloned and characterized Eg-ANX. In silico analysis showed that the amino acid sequence of Eg-ANX was conserved and lacked any signal peptides. The phospholipid-binding activity of recombinant Eg-ANX (rEg-ANX) was tested; liposomes could bind to rEg-ANX only in the presence of Ca(2+). In addition, we performed western blotting and immunohistochemical analyses to further validate the secretory properties of Eg-ANX. The protein could be detected in the cyst fluid of E. granulosus and was also present in the intermediate host tissues, which suggested that Eg-ANX might play an important role in parasite-host interaction. PMID:26787154

  1. Widespread Occurrence of Expressed Fungal Secretory Peroxidases in Forest Soils

    PubMed Central

    Kellner, Harald; Luis, Patricia; Pecyna, Marek J.; Barbi, Florian; Kapturska, Danuta; Krüger, Dirk; Zak, Donald R.; Marmeisse, Roland; Vandenbol, Micheline; Hofrichter, Martin

    2014-01-01

    Fungal secretory peroxidases mediate fundamental ecological functions in the conversion and degradation of plant biomass. Many of these enzymes have strong oxidizing activities towards aromatic compounds and are involved in the degradation of plant cell wall (lignin) and humus. They comprise three major groups: class II peroxidases (including lignin peroxidase, manganese peroxidase, versatile peroxidase and generic peroxidase), dye-decolorizing peroxidases, and heme-thiolate peroxidases (e.g. unspecific/aromatic peroxygenase, chloroperoxidase). Here, we have repeatedly observed a widespread expression of all major peroxidase groups in leaf and needle litter across a range of forest ecosystems (e.g. Fagus, Picea, Acer, Quercus, and Populus spp.), which are widespread in Europe and North America. Manganese peroxidases and unspecific peroxygenases were found expressed in all nine investigated forest sites, and dye-decolorizing peroxidases were observed in five of the nine sites, thereby indicating biological significance of these enzymes for fungal physiology and ecosystem processes. Transcripts of selected secretory peroxidase genes were also analyzed in pure cultures of several litter-decomposing species and other fungi. Using this information, we were able to match, in environmental litter samples, two manganese peroxidase sequences to Mycena galopus and Mycena epipterygia and one unspecific peroxygenase transcript to Mycena galopus, suggesting an important role of this litter- and coarse woody debris-dwelling genus in the disintegration and transformation of litter aromatics and organic matter formation. PMID:24763280

  2. Localization of amylin-like immunoreactivity in melanocyte-stimulating hormone-containing cells of the pars intermedia but not those of the pars distalis in the axolotl (Ambystoma mexicanum) pituitary.

    PubMed

    Suzuki, Hirohumi; Yamamoto, Toshiharu

    2016-04-01

    Immunohistochemical techniques were employed to investigate the distribution of amylin-like immunoreactivity in the axolotl (Ambystoma mexicanum) pituitary. Amylin-immunoreactive cells were observed in the pars intermedia, and these cells were found to be immunoreactive for α-melanocyte-stimulating hormone (αMSH) as well. In contrast, αMSH-immunoreactive cells in the pars distalis were immuno-negaitive for amylin. These light microscopic findings were confirmed by immunoelectron microscopy. Amylin-immunoreactive signals were located on the haloes of presumable secretory granules in association with αMSH-immunoreactive signals in the amylin-positive cells. However, in the pars distalis, the αMSH-positive cells did not contain amylin-immunoreactive secretory granules. Western blot analysis of axolotl pituitary extracts revealed the labeling of a protein band at approximately 10.5-kDa by the anti-rat amylin serum, which was not labeled by the anti-αMSH antibody. These findings indicate that amylin secreted from MSH-producing cells in the pars intermedia may modulate MSH secretion in an autocrine fashion and may participate in MSH functions such as fatty homeostasis together with MSH. PMID:26797189

  3. Direct effects of vitamin D3 analogues on G-protein mediated signalling systems in rat osteosarcoma cells and rat pituitary adenoma cells.

    PubMed

    Mortensen, B M; Lund, H W; Jablonski, G; Paulssen, R H; Gordeladze, J O

    1995-06-01

    In normal rats treated with 1,25(OH)2D3 or 24,25(OH)2D3, serum Ca2+, ALP, PRL and GH are significantly altered. In order to study the primary effect of vitamin D3 analogues on target organ function, rat UMR 106 osteosarcoma and GH3 pituitary adenoma cells in monolayer culture were exposed accordingly. Surprisingly, prolonged exposure of these cell lines to physiological levels of either 1,25(OH)2D3 or 24,25(OH)2D3 did not significantly affect the secretory parameters (ALP, PRL or GH) tested. However, 1,25(OH)2D3 exposure significantly reduced PTH- and Gpp(NH)p-elicited AC as well as Gpp(NH)p-stimulated PLC activities in the UMR 106 cells. These changes were accompanied by an increase and decrease in the membrane contents of the G-protein subunits G36 beta and Gq/11 alpha, respectively. In contrast, 24,25(OH)2D3 remained without significant biological effect on these signalling systems despite concomitantly augmented levels of G36 beta. TRH- and Gpp(NH)p-elicited PLC activities in the GH3 cells were significantly reduced by 1,25(OH)2D3 with a concurrent reduction in cellular amounts of Gq/11 alpha, however, 24,25(OH)2D3 did not significantly alter any signalling systems nor G-proteins analyzed. It is concluded that the osteoblastic and pituitary cell secretion of ALP, PRL and GH remain unaffected by the presence of 1,25(OH)2D3 and 24,25(OH)2D3, despite distinct alterations in components of G-protein mediated signalling pathways. Hence, other factors like ambient Ca2+ may be responsible for the perturbed secretory patterns of ALP and PRL seen in vitamin D3 treated rats. PMID:7579039

  4. Cathepsin L Plays a Major Role in Cholecystokinin Production in Mouse Brain Cortex and in Pituitary AtT-20 Cells: Protease Gene Knockout and Inhibitor Studies

    PubMed Central

    Beinfeld, Margery C.; Funkelstein, Lydiane; Foulon, Thierry; Cadel, Sandrine; Kitagawa, Kouki; Toneff, Thomas; Reinheckel, Thomas; Peters, Christoph; Hook, Vivian

    2009-01-01

    Cholecystokinin (CCK) is a peptide neurotransmitter whose production requires proteolytic processing of the proCCK precursor to generate active CCK8 neuropeptide in brain. This study demonstrates the significant role of the cysteine protease cathepsin L for CCK8 production. In cathepsin L knockout (KO) mice, CCK8 levels were substantially reduced in brain cortex by an average of 75%. To evaluate the role of cathepsin L in producing CCK in the regulated secretory pathway of neuroendocrine cells, pituitary AtT-20 cells that stably produce CCK were treated with the specific cathepsin L inhibitor, CLIK-148. CLIK-148 inhibitor treatment resulted in decreased amounts of CCK secreted from the regulated secretory pathway of AtT-20 cells. CLIK-148 also reduced cellular levels of CCK9 (Arg-CCK8), consistent with CCK9 as an intermediate product of cathepsin L, shown by the decreased ratio of CCK9/CCK8. The decreased CCK0/CCK8 ratio also suggests a shift in the production to CCK8 over CCK9 during inhibition of cathepsin L. During reduction of the PC1/3 processing enzyme by siRNA, the ratio of CCK9/CCK8 was increased, suggesting a shift to the cathepsin L pathway for production of CCK9. The changes in ratios of CCK9 compared to CCK8 are consistent with dual roles of the cathepsin L protease pathway that includes aminopeptidase B to remove NH2-terminal Arg or Lys, and the PC1/3 protease pathway. These results suggest that cathepsin L functions as a major protease responsible for CCK8 production in mouse brain cortex, and participates with PC1/3 for CCK8 production in pituitary cells. PMID:19589362

  5. Discovery and characterization of secretory IgD in rainbow trout: secretory IgD is produced through a novel splicing mechanism

    USGS Publications Warehouse

    Ramirez-Gomez, F.; Greene, W.; Rego, K.; Hansen, J.D.; Costa, G.; Kataria, P.; Bromage, E.S.

    2012-01-01

    The gene encoding IgH δ has been found in all species of teleosts studied to date. However, catfish (Ictalurus punctatus) is the only species of fish in which a secretory form of IgD has been characterized, and it occurs through the use of a dedicated δ-secretory exon, which is absent from all other species examined. Our studies have revealed that rainbow trout (Oncorhynchus mykiss) use a novel strategy for the generation of secreted IgD. The trout secretory δ transcript is produced via a run-on event in which the splice donor site at the end of the last constant domain exon (D7) is ignored and transcription continues until a stop codon is reached 33 nt downstream of the splice site, resulting in the production of an in-frame, 11-aa secretory tail at the end of the D7 domain. In silico analysis of several published IgD genes suggested that this unique splicing mechanism may also be used in other species of fish, reptiles, and amphibians. Alternative splicing of the secretory δ transcript resulted in two δ-H chains, which incorporated Cμ1 and variable domains. Secreted IgD was found in two heavily glycosylated isoforms, which are assembled as monomeric polypeptides associated with L chains. Secretory δ mRNA and IgD+ plasma cells were detected in all immune tissues at a lower frequency than secretory IgM. Our data demonstrate that secretory IgD is more prevalent and widespread across taxa than previously thought, and thus illustrate the potential that IgD may have a conserved role in immunity.

  6. [Bovine immunodeficiency virus: short review].

    PubMed

    Bouillant, A M; Archambault, D

    1990-01-01

    A bovine visna-like virus was isolated by Van Der Maaten et al (1972) but it did not draw attention since, at that time, most efforts were directed towards research on bovine leukemia virus. However, new interest was shown on the bovine visna-like virus after the isolation of the human immunodeficiency virus (HIV), because of the urgent need for developing animal models for the acquired immunodeficiency syndrome (AIDS). The purpose of this paper is to describe the different stages of the identification of the bovine virus and to up-date knowledge about it. The bovine visna-like virus has recently been named the bovine immuno-deficiency-like virus (BIV) and is the sole bovine lentivirus known to-date. BIV shares morphologic, antigenic and genomic characteristics with other lentiviruses. It grows and induces large syncytia in vitro and generates virus-productive and latent infections in cell culture. It causes persistent infection and slow progressive disease in cattle and probably in sheep. As target cells of the virus are leukocytes, the type of which is unknown, perturbations of the immune system are expected. Consequently, BIV may potentiate the occurrence of secondary infections and play a role in retroviral, multiple infections. It is not oncogenic. Transmission appears to occur in cattle by contact, but evidence of transmission in human beings has not been shown. Finally, BIV may be a potential model in vitro and in vivo for HIV and AIDS. PMID:1963056

  7. Mammary analogue secretory carcinoma (MASC) of the salivary gland: A new tumor entity

    PubMed Central

    Damjanov, Ivan; Skenderi, Faruk; Vranic, Semir

    2016-01-01

    Mammary analogue secretory carcinoma (MASC) is a recently described low-grade malignant tumor of the salivary glands, biologically and morphologically equivalent to secretory breast carcinoma. We give a brief overview of this new entity, including morphological, immunohistochemical, molecular-genetic, clinical, epidemiologic features, differential diagnosis, and outcome results.

  8. The secretory pathway of protists: spatial and functional organization and evolution.

    PubMed Central

    Becker, B; Melkonian, M

    1996-01-01

    All cells secrete a diversity of macromolecules to modify their environment or to protect themselves. Eukaryotic cells have evolved a complex secretory pathway consisting of several membrane-bound compartments which contain specific sets of proteins. Experimental work on the secretory pathway has focused mainly on mammalian cell lines or on yeasts. Now, some general principles of the secretory pathway have become clear, and most components of the secretory pathway are conserved between yeast cells and mammalian cells. However, the structure and function of the secretory system in protists have been less extensively studied. In this review, we summarize the current knowledge about the secretory pathway of five different groups of protists: Giardia lamblia, one of the earliest lines of eukaryotic evolution, kinetoplastids, the slime mold Dictyostelium discoideum, and two lineages within the "crown" of eukaryotic cell evolution, the alveolates (ciliates and Plasmodium species) and the green algae. Comparison of these systems with the mammalian and yeast system shows that most elements of the secretory pathway were presumably present in the earliest eukaryotic organisms. However, one element of the secretory pathway shows considerable variation: the presence of a Golgi stack and the number of cisternae within a stack. We suggest that the functional separation of the plasma membrane from the nucleus-endoplasmic reticulum system during evolution required a sorting compartment, which became the Golgi apparatus. Once a Golgi apparatus was established, it was adapted to the various needs of the different organisms. PMID:8987360

  9. Mammary Analogue Secretory Carcinoma (MASC) of the salivary gland: A new tumor entity.

    PubMed

    Damjanov, Ivan; Skenderi, Faruk; Vranic, Semir

    2016-08-01

    Mammary analogue secretory carcinoma (MASC) is a recently described low-grade malignant tumor of the salivary glands, biologically and morphologically equivalent to secretory breast carcinoma. We give a brief overview of this new entity, including morphological, immunohistochemical, molecular-genetic, clinical, epidemiologic features, differential diagnosis, and outcome results. PMID:27483184

  10. Mammary Analogue Secretory Carcinoma (MASC) of the salivary gland: A new tumor entity.

    PubMed

    Damjanov, Ivan; Skenderi, Faruk; Vranic, Semir

    2016-08-01

    Mammary analogue secretory carcinoma (MASC) is a recently described low-grade malignant tumor of the salivary glands, biologically and morphologically equivalent to secretory breast carcinoma. We give a brief overview of this new entity, including morphological, immunohistochemical, molecular-genetic, clinical, epidemiologic features, differential diagnosis, and outcome results. PMID:27131022

  11. Expression pattern of the Hedgehog signaling pathway in pituitary adenomas.

    PubMed

    Yavropoulou, Maria P; Maladaki, Anna; Topouridou, Konstantina; Kotoula, Vasiliki; Poulios, Chris; Daskalaki, Emily; Foroglou, Nikolaos; Karkavelas, George; Yovos, John G

    2016-01-12

    Several studies have demonstrated the role of Wnt and Notch signaling in the pathogenesis of pituitary adenomas, but data are scarce regarding the role of Hedgehog signaling. In this study we investigated the differential expression of gene targets of the Hedgehog signaling pathway. Formalin-fixed, paraffin-embedded specimens from adult patients who underwent transphenoidal resection and normal human pituitary tissues that were obtained from autopsies were used. Clinical information and data from pre-operative MRI scan (extracellular tumor extension, tumor size, displacement of the optic chiasm) were retrieved from the Hospital's database. We used a customized RT(2) Profiler PCR Array, to investigate the expression of genes related to Notch and Hedgehog signaling pathways (PTCH1, PTCH2, GLI1, GLI3, NOTCH3, JAG1, HES1, and HIP). A total of 52 pituitary adenomas (32 non-functioning adenomas, 15 somatotropinomas and 5 prolactinomas) were used in the final analysis. In non-functioning pituitary adenomas there was a significant decrease (approximately 75%) in expression of all Hedgehog related genes that were tested, while Notch3 and Jagged-1 expression was found significantly increased, compared with normal pituitary tissue controls. In contrast, somatotropinomas demonstrated a significant increase in expression of all Hedgehog related genes and a decrease in the expression of Notch3 and Jagged-1. There was no significant difference in the expression of Hedgehog and Notch related genes between prolactinomas and healthy pituitary tissues. Hedgehog signalling appears to be activated in somatotropinomas but not in non-functioning pituitary adenomas in contrast to the expression pattern of Notch signalling pathway. PMID:26620835

  12. Inherent capacity of the pituitary gland to produce gonadotropins is not influenced by the number of ovarian follicles > or = 3 mm in diameter in cattle.

    PubMed

    Mossa, F; Jimenez-Krassel, F; Walsh, S; Berry, D P; Butler, S T; Folger, J; Smith, G W; Ireland, J L H; Lonergan, P; Ireland, J J; Evans, A C O

    2010-01-01

    We hypothesised that higher serum FSH concentrations in cattle with low v. high follicle numbers during follicular waves are caused by a different capacity of the pituitary gland to produce gonadotropins. Dairy cows with high (> or = 30; n = 5) and low (< or = 15; n = 5) follicle numbers were selected and serum concentrations of oestradiol and FSH during an oestrous cycle were measured. Cows were ovariectomised at oestrus and bled frequently up to 8 days after ovariectomy. After 33 days, cows were injected with gonadotropin-releasing hormone (GnRH) and bled intensively up to 8 h after GnRH injection. One day later, animals were injected with follicular fluid (FF) from bovine follicles and were bled intensively up to 2 days after the first injection. Serum concentrations of FSH and LH were measured. After 2 days, cows were killed and their pituitary glands collected. Prior to ovariectomy, serum oestradiol concentrations were similar between groups, whereas FSH concentrations were higher in cattle with low v. high numbers of follicles. No differences were detected in serum gonadotropin concentrations after ovariectomy, GnRH injection or FF challenge between groups. The results indicate that the inherent capacity of the pituitary gland to secrete gonadotropins does not differ between cattle with high v. low numbers of follicles during follicular waves. PMID:20188028

  13. Factors Influencing Disconnection Hyperprolactinemia and Reversal of Serum Prolactin after Pituitary Surgery in a Non-Functioning Pituitary Macroadenoma

    PubMed Central

    Kumran, Thinesh; Haspani, Saffari; Malin Abdullah, Jafri; Alias, Azmi; Ven, Fan Rui

    2016-01-01

    Background To investigate factors influencing disconnection hyperprolactinemia, including tumour volume, degree of pituitary stalk displacement and extent of tumour growth based on a modified Wilson-Hardy classification in a non-functioning pituitary macroadenoma and to confirm reductions in serum prolactin levels after endoscopic transphenoidal surgery. Methods This prospective, descriptive study was conducted in the Department of Neurosurgery, General Hospital Kuala Lumpur from Jan 1, 2011 to Jan 1, 2013. Forty patients fulfilling the inclusion criteria were enrolled. All patients underwent endoscopic transphenoidal resection of non-functioning pituitary macroadenoma. Pituitary stalk angle, tumour volume and extent of tumour growth were measured from Magnetic Resonance Imaging (MRI) pre- and post-operatively. These variables were compared to serum prolactin levels measured pre and post operatively. SPSS 21 was used to perform statistical analyses. Results In 40 patients, the mean tumour volumes were 10.58 cm3 (SD 7.81) pre-operatively and 3.1 cm3 (SD 3.45) post-operatively. There was a 70% reduction in tumour volume post-operatively (P < 0.01). The mean serum prolactin was 457 mIU/L (SD 66.93) pre-operatively and 297 mIU/L (SD 6.73) post-operatively. There was a 65% reduction in prolactin serum levels after surgery (P < 0.01). The mean pituitary stalk angles were 93.45 ± 3.89 degrees pre-operatively and 51.45 ± 1.46 degrees post-operatively (P = 0.01). The mean pituitary stalk angle in the control group was 50.4 ± 8.80 degrees. Hence, there was a 98% reduction in pituitary stalk angle after surgery (P < 0.01). This study showed a linear correlation between the pre-operative and post-operative tumour volumes and serum prolactin levels (P = 0.01 pre-and post-operative) and between serum prolactin levels and pituitary stalk angle (P = 0.20 pre-operative; P = 0.01 post-operative). Conclusion Tumour volume and pituitary stalk angle displacement have positive

  14. The evolution of plant secretory structures and emergence of terpenoid chemical diversity.

    PubMed

    Lange, Bernd Markus

    2015-01-01

    Secretory structures in terrestrial plants appear to have first emerged as intracellular oil bodies in liverworts. In vascular plants, internal secretory structures, such as resin ducts and laticifers, are usually found in conjunction with vascular bundles, whereas subepidermal secretory cavities and epidermal glandular trichomes generally have more complex tissue distribution patterns. The primary function of plant secretory structures is related to defense responses, both constitutive and induced, against herbivores and pathogens. The ability to sequester secondary (or specialized) metabolites and defense proteins in secretory structures was a critical adaptation that shaped plant-herbivore and plant-pathogen interactions. Although this review places particular emphasis on describing the evolution of pathways leading to terpenoids, it also assesses the emergence of other metabolite classes to outline the metabolic capabilities of different plant lineages. PMID:25621517

  15. Development and essential oil content of secretory glands of sage (Salvia officinalis)

    SciTech Connect

    Venkatachalam, K.V.; Kjonaas, R.; Croteau, R.

    1984-09-01

    Scanning electron microscopy of sage (Salvia officinalis L.) leave confirmed the presence of two basic types of glandular trichomes consisting of a capitate stalked form containing a multicellular stalk and surmounted by a unicellular secretory head, and a capitate sessile form containing a unicellular stalk and unicellular, or multicellular, secretory head. In the latter type, secretory activity and filling of the subcuticular cavity may begin at virtually any stage of the division cycle affording fully developed glands containing from one to twelve cells in the secretory head. Gas liquid chromatographic analysis of the oil content of the most numerous gland species (capitate stalked, capitate sessile with one and with eight secretory cells) indicated only minor quantitative differences in essential oil composition. Thus, each gland type is capable of producing the four major monoterpene families (p-menthanes, pinanes, bornanes and thujanes) characteristic of sage. 21 references, 2 figures.

  16. Familial Isolated Pituitary Adenomas (FIPA) and the Pituitary Adenoma Predisposition due to Mutations in the Aryl Hydrocarbon Receptor Interacting Protein (AIP) Gene

    PubMed Central

    Aaltonen, Lauri A.; Daly, Adrian F.

    2013-01-01

    Pituitary adenomas are one of the most frequent intracranial tumors and occur with a prevalence of approximately 1:1000 in the developed world. Pituitary adenomas have a serious disease burden, and their management involves neurosurgery, biological therapies, and radiotherapy. Early diagnosis of pituitary tumors while they are smaller may help increase cure rates. Few genetic predictors of pituitary adenoma development exist. Recent years have seen two separate, complimentary advances in inherited pituitary tumor research. The clinical condition of familial isolated pituitary adenomas (FIPA) has been described, which encompasses the familial occurrence of isolated pituitary adenomas outside of the setting of syndromic conditions like multiple endocrine neoplasia type 1 and Carney complex. FIPA families comprise approximately 2% of pituitary adenomas and represent a clinical entity with homogeneous or heterogeneous pituitary adenoma types occurring within the same kindred. The aryl hydrocarbon receptor interacting protein (AIP) gene has been identified as causing a pituitary adenoma predisposition of variable penetrance that accounts for 20% of FIPA families. Germline AIP mutations have been shown to associate with the occurrence of large pituitary adenomas that occur at a young age, predominantly in children/adolescents and young adults. AIP mutations are usually associated with somatotropinomas, but prolactinomas, nonfunctioning pituitary adenomas, Cushing disease, and other infrequent clinical adenoma types can also occur. Gigantism is a particular feature of AIP mutations and occurs in more than one third of affected somatotropinoma patients. Study of pituitary adenoma patients with AIP mutations has demonstrated that these cases raise clinical challenges to successful treatment. Extensive research on the biology of AIP and new advances in mouse Aip knockout models demonstrate multiple pathways by which AIP may contribute to tumorigenesis. This review assesses

  17. Fallopian tube secretory cell expansion: a sensitive biomarker for ovarian serous carcinogenesis

    PubMed Central

    Wang, Yiying; Li, Li; Wang, Yue; Tang, Sarah Ngocvi; Zheng, Wenxin

    2016-01-01

    Recent advances suggest that precancerous lesions of pelvic serous carcinoma originate from tubal secretory cells. The purpose of our study was to determine if an increased number of secretory cells vary with age or location in the fallopian tube and to examine its association with serous neoplasia. Three groups (benign control, high-risk, and pelvic serous carcinoma) of age-matched patients were studied. The age data were stratified into 10-year intervals ranging from 20-29 to older than 80. The number of secretory and ciliated cells from both tubal fimbria and ampulla segments was counted by microscopy and immunohistochemical staining methods. The data were analyzed by standard contingency table and Poisson distribution methods after age justification. We found that the absolute number of tubal secretory cells increased significantly with age in all three groups. But a more dramatic increase of secretory cells was observed in high-risk and pelvic serous carcinoma patients. Secretory cell expansion is more prevalent than secretory cell outgrowth in both fimbria and ampulla tubal segments and is significantly associated with serous neoplasia (p < 0.001). Furthermore, age remained a significant risk factor for serous neoplasia after age adjustment. These findings suggest that secretory cell expansion could serve as a potential sensitive biomarker for early serous carcinogenesis within the fallopian tube. The study also supports a relationship between serous neoplasia and increased secretory to ciliated cell ratios, and the relationship between frequency of secretory cell expansion within the fallopian tube and increasing age and-more significantly-presence of high-risk factors or co-existing serous cancers. PMID:27069556

  18. Fallopian tube secretory cell expansion: a sensitive biomarker for ovarian serous carcinogenesis

    PubMed Central

    Wang, Yiying; Li, Li; Wang, Yue; Tang, Sarah Ngocvi; Zheng, Wenxin

    2015-01-01

    Recent advances suggest that precancerous lesions of pelvic serous carcinoma originate from tubal secretory cells. The purpose of our study was to determine if an increased number of secretory cells varies with age or location in the fallopian tube and to examine its association with serous neoplasia. Three groups (benign control, high-risk, and pelvic serous carcinoma) of age-matched patients were studied. The age data were stratified into 10-year intervals ranging from 20-29 to older than 80. The number of secretory and ciliated cells from both tubal fimbria and ampulla segments was counted by microscopy and immunohistochemical staining methods. The data were analyzed by standard contingency table and Poisson distribution methods after age justification. We found that the absolute number of tubal secretory cells increased significantly with age in all three groups. But a more dramatic increase of secretory cells was observed in high-risk and pelvic serous carcinoma patients. Secretory cell expansion is more prevalent than secretory cell outgrowth in both fimbria and ampulla tubal segments and is significantly associated with serous neoplasia (P < 0.001). Furthermore, age remained a significant risk factor for serous neoplasia after age adjustment. These findings suggest that secretory cell expansion could serve as a potential sensitive biomarker for early serous carcinogenesis within the fallopian tube. The study also supports a relationship between serous neoplasia and increased secretory to ciliated cell ratios, and the relationship between frequency of secretory cell expansion within the fallopian tube and increasing age and-more significantly-presence of high-risk factors or co-existing serous cancers. PMID:26692952

  19. Mapping of corticotropic cells in the normal human pituitary.

    PubMed

    Trouillas, J; Guigard, M P; Fonlupt, P; Souchier, C; Girod, C

    1996-05-01

    We accomplished the first mapping of corticotropic cells in the whole human adult pituitary. Corticotropic cells were identified by immunocytochemistry (ICC) and quantified by image analysis on 12 pituitaries obtained from people who had died suddenly. An overall view of each pituitary was given by 15-21 sections (mean 18 sections) at 300-micron intervals on six slides. Each section was systematically treated by indirect immunoperoxidase using an anti-ACTH[17-39] polyclonal antiserum. All the measures were done with a x 6.3 objective lens, each field (0. 5 mm2) being considered as the unit area. The mean pituitary density (surface of labeled cells/total surface) of corticotropic cells (9.5 +/- 3.0% per 0. 5 mm2) is significantly higher in men (11.5 +/- 5.1%) than in women (7.0 +/- 1.3%). This difference is due to an inverse relationship between the corticotropic cell density and the weight of the pituitary, which is higher in women than in men. The mean diameter of corticotropic cells is 14.9 micron and their total number per pituitary is approximately 10(7) cells. We confirmed that the spatial distribution of corticotropic cells is nonuniform: they are mainly distributed in the anteromedian part of the anterior lobe. In addition, our results demonstrated that the inferior part of the pituitary contained three times more corticotropic cells than the superior part (mean density 18.0% vs 6.0%) and the anterior part twice as many as the posterior part (mean density 12.3% vs 6.8%). On the horizontal plane, the pituitary was divided into eight zones, in which the mean of area was 2.5-21.0%. The maximal cell density may reach 40-60%. The use of this map should help the pathologist to recognize if there is corticotropic hyperplasia in a small pituitary fragment surgically removed from a patient with Cushing's disease. On the basis of this study, we put forward some criteria for diagnosing corticotropic hyperplasia. PMID:8627004

  20. Gene expression profiling analysis of MENX-associated rat pituitary adenomas contributes to understand molecular mechanisms of human pituitary adenomas

    PubMed Central

    ZHANG, HONGZHI; XU, CHUAN; SUN, NINGYANG; ZHOU, YINTING; YU, XIAOFEI; YAN, XUE; ZHANG, QIUJUAN

    2016-01-01

    The present study aimed to screen potential genes associated with pituitary adenomas to obtain further understanding with regard to the pathogenesis of pituitary adenomas. The microarray GSE23207 dataset, containing 16 pituitary adenoma samples from multiple endocrine neoplasia syndrome-associated rats and 5 normal pituitary tissue samples, was downloaded from Gene Expression Omnibus. The Linear Models for Microarray Data package was used to identify the differentially-expressed genes (DEGs) with the cut-off criteria of a |log2fold change (FC)|>1 and adjusted P-values of <0.05. The potential functions of the DEGs were predicted by functional and pathway enrichment analysis with the Database for Annotation, Visualization and Integrated Discovery. Furthermore, the interaction associations of the up- and downregulated DEGs obtained from the Search Tool for the Retrieval of Interacting Genes database were respectively revealed by the protein-protein interaction networks visualized with Cytoscape. A total of 391 upregulated and 238 downregulated DEGs in were screened in the pituitary adenoma samples. The upregulated DEGs with a higher degree in the protein-protein interaction network (e.g., CCNA2, CCNB1 and CDC20) were significantly involved in cell cycle and cell division. Notably, PTTG1 was enriched in every functional term. These DEGs interacted with each other. The downregulated DEGs (e.g., GABRA1, GABRA4 and GABRB1) also interacted with each other, and were relevant to neuroactive ligand-receptor interaction; the DEG POU1F1, interacting with POMC, was correlated with the development of the pituitary gland, adenohypophysis and endocrine system. Certain DEGs, including CCNB1, CCNA2, CDC20, GABRA1, GABRA4, GABRB1, POU1F1 and POMC, and particularly PTTG1, were shown to be closely involved in the pathogenesis of pituitary adenomas. PMID:26870179

  1. Casein phosphopeptides drastically increase the secretion of extracellular proteins in Aspergillus awamori. Proteomics studies reveal changes in the secretory pathway

    PubMed Central

    2012-01-01

    Background The secretion of heterologous animal proteins in filamentous fungi is usually limited by bottlenecks in the vesicle-mediated secretory pathway. Results Using the secretion of bovine chymosin in Aspergillus awamori as a model, we found a drastic increase (40 to 80-fold) in cells grown with casein or casein phosphopeptides (CPPs). CPPs are rich in phosphoserine, but phosphoserine itself did not increase the secretion of chymosin. The stimulatory effect is reduced about 50% using partially dephosphorylated casein and is not exerted by casamino acids. The phosphopeptides effect was not exerted at transcriptional level, but instead, it was clearly observed on the secretion of chymosin by immunodetection analysis. Proteomics studies revealed very interesting metabolic changes in response to phosphopeptides supplementation. The oxidative metabolism was reduced, since enzymes involved in fermentative processes were overrepresented. An oxygen-binding hemoglobin-like protein was overrepresented in the proteome following phosphopeptides addition. Most interestingly, the intracellular pre-protein enzymes, including pre-prochymosin, were depleted (most of them are underrepresented in the intracellular proteome after the addition of CPPs), whereas the extracellular mature form of several of these secretable proteins and cell-wall biosynthetic enzymes was greatly overrepresented in the secretome of phosphopeptides-supplemented cells. Another important 'moonlighting' protein (glyceraldehyde-3-phosphate dehydrogenase), which has been described to have vesicle fusogenic and cytoskeleton formation modulating activities, was clearly overrepresented in phosphopeptides-supplemented cells. Conclusions In summary, CPPs cause the reprogramming of cellular metabolism, which leads to massive secretion of extracellular proteins. PMID:22234238

  2. Three years prospective investigation of pituitary functions following subarachnoid haemorrhage.

    PubMed

    Karaca, Z; Tanriverdi, F; Dagli, A T; Selcuklu, A; Casanueva, F F; Unluhizarci, K; Kelestimur, F

    2013-03-01

    Subarachnoid haemorrhage (SAH) is known to be related to pituitary dysfuntion in retrospective and short-term prospective studies. We aimed to investigate pituitary functions in patients with SAH in longer follow-up periods to demonstrate if pituitary hormone deficiencies recover, persist or new hormone deficiencies occur. Twenty patients with SAH, who were followed up for 3 years, were included in the present study. Patients were evaluated with basal hormone levels and glucagon stimulation test (GST).Serum basal cortisol and adrenocorticotropic hormone (ACTH) levels were found to be significantly elevated at 3rd year of SAH compared to 1st year. Other basal hormone levels at 3rd year did not show a significant change from the levels found at 1st year. One of the patients had ACTH deficiency at 1st year of SAH and recovered at 3rd year. Growth hormone (GH) deficiency, according to GST,was diagnosed in 4 patients. One patient with GH deficiency at first year was still deficient, 3 of them recovered and 3 patients were found to have new-onset GH deficiency 3 years after SAH. SAH is associated with anterior pituitary dysfunction and GH is the most frequently found deficient hormone in the patients. Although one year after SAH seems to be an appropriate time for the evaluation of pituitary functions, further follow-up may be required at least in some cases due to recovered and new-onset hormone deficiencies at 3rd year of SAH. PMID:22315089

  3. Pituitary tumors. Current concepts in diagnosis and management.

    PubMed Central

    Aron, D C; Tyrrell, J B; Wilson, C B

    1995-01-01

    Diagnostic advances have resulted in earlier and more frequent recognition of pituitary tumors. Pituitary tumors cause problems owing to the hormones they secrete or the effects of an expanding sellar mass--hypopituitarism, visual field abnormalities, and neurologic deficits. Prolactin-secreting tumors (prolactinomas), which cause amenorrhea, galactorrhea, and hypogonadism, constitute the most common type of primary pituitary tumors, followed by growth hormone-secreting tumors, which cause acromegaly, and corticotropin-secreting tumors, which cause Cushing's syndrome. Hypersecretion of thyroid-stimulating hormone, the gonadotrophins, or alpha-subunits is unusual. Nonfunctional tumors currently represent only 10% of all clinically diagnosed pituitary adenomas, and some of these are alpha-subunit-secreting adenomas. Insights into the pathogenesis and biologic behavior of these usually benign tumors have been gained from genetic studies. We review some of the recent advances and salient features of the diagnosis and management of pituitary tumors, including biochemical and radiologic diagnosis, transsphenoidal surgery, radiation therapy, and medical therapy. Each type of lesion requires a comprehensive but individualized treatment approach, and regardless of the mode of therapy, careful follow-up is essential. Images PMID:7747500

  4. Overview of genetic testing in patients with pituitary adenomas.

    PubMed

    Beckers, Albert; Rostomyan, Liliya; Daly, Adrian F

    2012-04-01

    Clinically-relevant pituitary adenomas occur with a prevalence of one case per 1000-1300 of the general population. Although most are sporadic, there are several inherited conditions that incur an increased risk of developing a pituitary adenoma. Multiple endocrine neoplasia type 1 and Carney complex (due to mutations in MEN1 and PRKAR1A, respectively) are established pituitary adenoma predisposition conditions, while multiple endocrine neoplasia type 4 (due to CDKN1B mutations) is an emerging rare condition. Familial isolated pituitary adenomas (FIPA) is a novel condition not associated with these multiple endocrine neoplasias. Mutations in the aryl hydrocarbon receptor interacting protein gene account for about 15% of FIPA kindreds and are associated with about 10-20% of macroadenomas that occur in children, adolescents and young adults. When treating a pituitary adenoma patient, relevant familial and clinical factors such as associated tumors or syndromic features should be assessed at the outset in order to guide the correct choice of genetic testing in appropriate individuals. PMID:22503805

  5. Secretory expression of a heterologous nattokinase in Lactococcus lactis.

    PubMed

    Liang, Xiaobo; Zhang, Lixin; Zhong, Jin; Huan, Liandong

    2007-05-01

    Nattokinase has been reported as an oral health product for the prevention of atherosclerosis. We developed a novel strategy to express a nattokinase from Bacillus subtilis in a live delivery vehicle, Lactococcus lactis. Promoter P( nisZ) and signal peptide SP(Usp) were used for inducible and secretory expression of nattokinase in L. lactis. Western blotting analysis demonstrated that nattokinase was successfully expressed, and about 94% of the enzyme was secreted to the culture. The recombinant nattokinase showed potent fibrinolytic activity, equivalent to 41.7 urokinase units per milliliter culture. Expression and delivery of such a fibrinolytic enzyme in the food-grade vehicle L. lactis would facilitate the widespread application of nattokinase in the control and prevention of thrombosis diseases. PMID:17225095

  6. The secretory granule matrix: a fast-acting smart polymer.

    PubMed

    Nanavati, C; Fernandez, J M

    1993-02-12

    The secretory granule matrix is a miniature biopolymer that consists of a charged polymer network that traps peptides and transmitters when it condenses and releases them on exocytotic decondensation. Models of exocytotic fusion have treated this matrix as a short circuit and have neglected its electrical contributions. This matrix responded to negative voltages by swelling, which was accompanied by a large increase in conductance, and to positive voltages by condensing. Thus, the matrix resembled a diode. The swollen matrix exerted large pressures on the order of 12 bar. The responses took place within milliseconds of the application of the electric field. These findings suggest that matrix decondensation, and therefore product release, is controlled by potential gradients. PMID:8438154

  7. Characterization of Mast Cell Secretory Granules and Their Cell Biology

    PubMed Central

    Azouz, Nurit Pereg; Hammel, Ilan

    2014-01-01

    Exocytosis and secretion of secretory granule (SG) contained inflammatory mediators is the primary mechanism by which mast cells exert their protective immune responses in host defense, as well as their pathological functions in allergic reactions and anaphylaxis. Despite their central role in mast cell function, the molecular mechanisms underlying the biogenesis and secretion of mast cell SGs remain largely unresolved. Early studies have established the lysosomal nature of the mast cell SGs and implicated SG homotypic fusion as an important step occurring during both their biogenesis and compound secretion. However, the molecular mechanisms that account for key features of this process largely remain to be defined. A novel high-resolution imaging based methodology allowed us to screen Rab GTPases for their phenotypic and functional impact and identify Rab networks that regulate mast cell secretion. This screen has identified Rab5 as a novel regulator of homotypic fusion of the mast cell SGs that thereby regulates their size and cargo composition. PMID:24988214

  8. Age-Dependent Labeling and Imaging of Insulin Secretory Granules

    PubMed Central

    Ivanova, Anna; Kalaidzidis, Yannis; Dirkx, Ronald; Sarov, Mihail; Gerlach, Michael; Schroth-Diez, Britta; Müller, Andreas; Liu, Yanmei; Andree, Cordula; Mulligan, Bernard; Münster, Carla; Kurth, Thomas; Bickle, Marc; Speier, Stephan; Anastassiadis, Konstantinos; Solimena, Michele

    2013-01-01

    Insulin is stored within the secretory granules of pancreatic β-cells, and impairment of its release is the hallmark of type 2 diabetes. Preferential exocytosis of newly synthesized insulin suggests that granule aging is a key factor influencing insulin secretion. Here, we illustrate a technology that enables the study of granule aging in insulinoma cells and β-cells of knock-in mice through the conditional and unequivocal labeling of insulin fused to the SNAP tag. This approach, which overcomes the limits encountered with previous strategies based on radiolabeling or fluorescence timer proteins, allowed us to formally demonstrate the preferential release of newly synthesized insulin and reveal that the motility of cortical granules significantly changes over time. Exploitation of this approach may enable the identification of molecular signatures associated with granule aging and unravel possible alterations of granule turnover in diabetic β-cells. Furthermore, the method is of general interest for the study of membrane traffic and aging. PMID:23929935

  9. Age-dependent labeling and imaging of insulin secretory granules.

    PubMed

    Ivanova, Anna; Kalaidzidis, Yannis; Dirkx, Ronald; Sarov, Mihail; Gerlach, Michael; Schroth-Diez, Britta; Müller, Andreas; Liu, Yanmei; Andree, Cordula; Mulligan, Bernard; Münster, Carla; Kurth, Thomas; Bickle, Marc; Speier, Stephan; Anastassiadis, Konstantinos; Solimena, Michele

    2013-11-01

    Insulin is stored within the secretory granules of pancreatic β-cells, and impairment of its release is the hallmark of type 2 diabetes. Preferential exocytosis of newly synthesized insulin suggests that granule aging is a key factor influencing insulin secretion. Here, we illustrate a technology that enables the study of granule aging in insulinoma cells and β-cells of knock-in mice through the conditional and unequivocal labeling of insulin fused to the SNAP tag. This approach, which overcomes the limits encountered with previous strategies based on radiolabeling or fluorescence timer proteins, allowed us to formally demonstrate the preferential release of newly synthesized insulin and reveal that the motility of cortical granules significantly changes over time. Exploitation of this approach may enable the identification of molecular signatures associated with granule aging and unravel possible alterations of granule turnover in diabetic β-cells. Furthermore, the method is of general interest for the study of membrane traffic and aging. PMID:23929935

  10. Voltage-activated Ca2+ channels and their role in the endocrine function of the pituitary gland in newborn and adult mice

    PubMed Central

    Sedej, Simon; Tsujimoto, Tetsuhiro; Zorec, Robert; Rupnik, Marjan

    2004-01-01

    We have prepared fresh pituitary gland slices from adult and, for the first time, from newborn mice to assess modulation of secretory activity via voltage-activated Ca2+ channels (VACCs). Currents through VACCs and membrane capacitance have been measured with the whole-cell patch-clamp technique. Melanotrophs in newborns were significantly larger than in adults. In both newborn and adult melanotrophs activation of VACCs triggered exocytosis. All pharmacologically isolated VACC types contributed equally to the secretory activity. However, the relative proportion of VACCs differed between newborns and adults. In newborn cells L-type channels dominated and, in addition, an exclusive expression of a toxin-resistant R-type-like current was found. The expression of L-type VACCs was up-regulated by the increased oestrogen levels observed in females, and was even more emphasized in the cells of pregnant females and oestrogen-treated adult male mice. We suggest a general mechanism modulating endocrine secretion in the presence of oestrogen and particularly higher sensitivity to treatments with L-type channel blockers during high oestrogen physiological states. PMID:14724188

  11. Rac1 Regulates Endometrial Secretory Function to Control Placental Development.

    PubMed

    Davila, Juanmahel; Laws, Mary J; Kannan, Athilakshmi; Li, Quanxi; Taylor, Robert N; Bagchi, Milan K; Bagchi, Indrani C

    2015-08-01

    During placenta development, a succession of complex molecular and cellular interactions between the maternal endometrium and the developing embryo ensures reproductive success. The precise mechanisms regulating this maternal-fetal crosstalk remain unknown. Our study revealed that the expression of Rac1, a member of the Rho family of GTPases, is markedly elevated in mouse decidua on days 7 and 8 of gestation. To investigate its function in the uterus, we created mice bearing a conditional deletion of the Rac1 gene in uterine stromal cells. Ablation of Rac1 did not affect the formation of the decidua but led to fetal loss in mid gestation accompanied by extensive hemorrhage. To gain insights into the molecular pathways affected by the loss of Rac1, we performed gene expression profiling which revealed that Rac1 signaling regulates the expression of Rab27b, another GTPase that plays a key role in targeting vesicular trafficking. Consequently, the Rac1-null decidual cells failed to secrete vascular endothelial growth factor A, which is a critical regulator of decidual angiogenesis, and insulin-like growth factor binding protein 4, which regulates the bioavailability of insulin-like growth factors that promote proliferation and differentiation of trophoblast cell lineages in the ectoplacental cone. The lack of secretion of these key factors by Rac1-null decidua gave rise to impaired angiogenesis and dysregulated proliferation of trophoblast cells, which in turn results in overexpansion of the trophoblast giant cell lineage and disorganized placenta development. Further experiments revealed that RAC1, the human ortholog of Rac1, regulates the secretory activity of human endometrial stromal cells during decidualization, supporting the concept that this signaling G protein plays a central and conserved role in controlling endometrial secretory function. This study provides unique insights into the molecular mechanisms regulating endometrial secretions that mediate stromal

  12. Uncoupling of Secretion From Growth in Some Hormone Secretory Tissues

    PubMed Central

    2014-01-01

    Context: Most syndromes with benign primary excess of a hormone show positive coupling of hormone secretion to size or proliferation in the affected hormone secretory tissue. Syndromes that lack this coupling seem rare and have not been examined for unifying features among each other. Evidence Acquisition: Selected clinical and basic features were analyzed from original reports and reviews. We examined indices of excess secretion of a hormone and indices of size of secretory tissue within the following three syndromes, each suggestive of uncoupling between these two indices: familial hypocalciuric hypercalcemia, congenital diazoxide-resistant hyperinsulinism, and congenital primary hyperaldosteronism type III (with G151E mutation of the KCNJ5 gene). Evidence Synthesis: Some unifying features among the three syndromes were different from features present among common tumors secreting the same hormone. The unifying and distinguishing features included: 1) expression of hormone excess as early as the first days of life; 2) normal size of tissue that oversecretes a hormone; 3) diffuse histologic expression in the hormonal tissue; 4) resistance to treatment by subtotal ablation of the hormone-secreting tissue; 5) causation by a germline mutation; 6) low potential of the same mutation to cause a tumor by somatic mutation; and 7) expression of the mutated molecule in a pathway between sensing of a serum metabolite and secretion of hormone regulating that metabolite. Conclusion: Some shared clinical and basic features of uncoupling of secretion from size in a hormonal tissue characterize three uncommon states of hormone excess. These features differ importantly from features of common hormonal neoplasm of that tissue. PMID:25004249

  13. Rac1 Regulates Endometrial Secretory Function to Control Placental Development

    PubMed Central

    Davila, Juanmahel; Laws, Mary J.; Kannan, Athilakshmi; Li, Quanxi; Taylor, Robert N.; Bagchi, Milan K.; Bagchi, Indrani C.

    2015-01-01

    During placenta development, a succession of complex molecular and cellular interactions between the maternal endometrium and the developing embryo ensures reproductive success. The precise mechanisms regulating this maternal-fetal crosstalk remain unknown. Our study revealed that the expression of Rac1, a member of the Rho family of GTPases, is markedly elevated in mouse decidua on days 7 and 8 of gestation. To investigate its function in the uterus, we created mice bearing a conditional deletion of the Rac1 gene in uterine stromal cells. Ablation of Rac1 did not affect the formation of the decidua but led to fetal loss in mid gestation accompanied by extensive hemorrhage. To gain insights into the molecular pathways affected by the loss of Rac1, we performed gene expression profiling which revealed that Rac1 signaling regulates the expression of Rab27b, another GTPase that plays a key role in targeting vesicular trafficking. Consequently, the Rac1-null decidual cells failed to secrete vascular endothelial growth factor A, which is a critical regulator of decidual angiogenesis, and insulin-like growth factor binding protein 4, which regulates the bioavailability of insulin-like growth factors that promote proliferation and differentiation of trophoblast cell lineages in the ectoplacental cone. The lack of secretion of these key factors by Rac1-null decidua gave rise to impaired angiogenesis and dysregulated proliferation of trophoblast cells, which in turn results in overexpansion of the trophoblast giant cell lineage and disorganized placenta development. Further experiments revealed that RAC1, the human ortholog of Rac1, regulates the secretory activity of human endometrial stromal cells during decidualization, supporting the concept that this signaling G protein plays a central and conserved role in controlling endometrial secretory function. This study provides unique insights into the molecular mechanisms regulating endometrial secretions that mediate stromal

  14. Atrial natriuretic factor: radioimmunoassay and effects on adrenal and pituitary glands

    SciTech Connect

    Gutkowska, J.; Horky, K.; Schiffrin, E.L.; Thibault, G.; Garcia, R.; De Lean, A.; Hamet, P.; Tremblay, J.; Anand-Srivastava, M.B.; Januszewicz, P.

    1986-06-01

    A simple and sensitive radioimmunoassay was developed for measurement of immunoreactive atrial natriuretic factor (IR-ANF) in rat and human plasma and in rat atria. The two atria contain about 20 ..mu..g ANF per rat. The right atrium contained 2.5 times more ANF than did the left. Ether anesthesia and morphine markedly increased IR-ANF in rat plasma. The concentration of IR-ANF in plasma of clinically normal human subjects was 65.3 +/- 2.5 pg/ml. Paroxysmal tachycardia and rapid atrial pacing significantly increased IR-ANF in human plasma. Two- to seven-fold higher concentrations were found in coronary sinus blood than in the peripheral circulation. In the plasma of rats and humans, circulating ANF is probably a small-molecular-weight peptide. ANF acts on the adrenal and the pituitary. ANF inhibits aldosterone secretion from rat zona glomerulosa and steroid secretion by bovine adrenal zona glomerulosa and fasciculata. ANF stimulated the basal secretion of arginine vasopressin (AVP) in vitro and inhibited KCl-stimulated release of AVP.

  15. Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells

    PubMed Central

    Ozone, Chikafumi; Suga, Hidetaka; Eiraku, Mototsugu; Kadoshima, Taisuke; Yonemura, Shigenobu; Takata, Nozomu; Oiso, Yutaka; Tsuji, Takashi; Sasai, Yoshiki

    2016-01-01

    Anterior pituitary is critical for endocrine systems. Its hormonal responses to positive and negative regulators are indispensable for homeostasis. For this reason, generating human anterior pituitary tissue that retains regulatory hormonal control in vitro is an important step for the development of cell transplantation therapy for pituitary diseases. Here we achieve this by recapitulating mouse pituitary development using human embryonic stem cells. We find that anterior pituitary self-forms in vitro following the co-induction of hypothalamic and oral ectoderm. The juxtaposition of these tissues facilitated the formation of pituitary placode, which subsequently differentiated into pituitary hormone-producing cells. They responded normally to both releasing and feedback signals. In addition, after transplantation into hypopituitary mice, the in vitro-generated corticotrophs rescued physical activity levels and survival of the hosts. Thus, we report a useful methodology for the production of regulator-responsive human pituitary tissue that may benefit future studies in regenerative medicine. PMID:26762480

  16. Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells.

    PubMed

    Ozone, Chikafumi; Suga, Hidetaka; Eiraku, Mototsugu; Kadoshima, Taisuke; Yonemura, Shigenobu; Takata, Nozomu; Oiso, Yutaka; Tsuji, Takashi; Sasai, Yoshiki

    2016-01-01

    Anterior pituitary is critical for endocrine systems. Its hormonal responses to positive and negative regulators are indispensable for homeostasis. For this reason, generating human anterior pituitary tissue that retains regulatory hormonal control in vitro is an important step for the development of cell transplantation therapy for pituitary diseases. Here we achieve this by recapitulating mouse pituitary development using human embryonic stem cells. We find that anterior pituitary self-forms in vitro following the co-induction of hypothalamic and oral ectoderm. The juxtaposition of these tissues facilitated the formation of pituitary placode, which subsequently differentiated into pituitary hormone-producing cells. They responded normally to both releasing and feedback signals. In addition, after transplantation into hypopituitary mice, the in vitro-generated corticotrophs rescued physical activity levels and survival of the hosts. Thus, we report a useful methodology for the production of regulator-responsive human pituitary tissue that may benefit future studies in regenerative medicine. PMID:26762480

  17. Non-functioning pituitary adenomas: growth and aggressiveness.

    PubMed

    Øystese, Kristin Astrid; Evang, Johan Arild; Bollerslev, Jens

    2016-07-01

    Pituitary adenomas (PAs) are common, comprising approximately one third of all intracranial tumors. Non-functioning pituitary adenomas (NFPAs) are the most common PAs. Although usually benign, the NFPAs represent therapeutic challenges because of their location close to the optic chiasm and nerves, and the proximity to the pituitary gland. The therapeutic alternatives are surgery and radiation. To date there is no effective medical treatment. NFPAs are classified according to different modalities, but there are no reliable marker of aggressiveness to guide the clinician in monitoring the patient. More information on growth patterns with constituent biological markers are needed to tailor the care of this patient group. Studies characterizing the membrane receptors of NFPAs have shown promising results, which may give rise to the development of medical treatment. PMID:27066792

  18. Endothelin: A novel peptide in the posterior pituitary system

    SciTech Connect

    Yoshizawa, Toshihiro; Kanazawa, Ichiro; Shinmi, Osamu; Kimura, Sadao; Yanagisawa, Masashi; Masaki, Tomoh; Uchiyama, Yasuo ); Giaid, A.; Gibson, S.J.; Polak, J.M. )

    1990-01-26

    Endothelin (ET), originally characterized as a 21-residue vasoconstrictor peptide from endothelial cells, is present in the porcine spinal cord and may act as a neuropeptide. Endothelin-like immunoreactivity has now been demonstrated by immunohistochemistry in the paraventricular and supraoptic nuclear neurons and their terminals in the posterior pituitary of the pig and the rat. The presence of ET in the porcine hypothalamus was confirmed by reversed-phase high-pressure liquid chromatography and radioimmunoassay. Moreover, in situ hybridization demonstrated ET messenger RNA in porcine paraventricular nuclear neurons. Endothelin-like immunoreactive products in the posterior pituitary of the rat were depleted by water deprivation, suggesting a release of ET under physiological conditions. These findings indicate that ET is synthesized in the posterior pituitary system and may be involved in neurosecretory functions.

  19. Growth hormone secreting pituitary adenoma with admixed gangliocytoma and ganglioglioma.

    PubMed

    Jukes, Alistair; Allan, Rodney; Rawson, Robert; Buckland, Michael E

    2016-09-01

    Pituitary adenomas are the most common tumours found in the sellar region and, when both functioning and non-functioning adenomas are combined, account for 7-15% of primary brain tumours in adults. Rarely, admixed or discrete groups of cells comprising two or more tumour subtypes are seen; the so-called 'collision tumour'. We present a case of a 54-year-old-woman with a growth hormone-secreting pituitary adenoma admixed with both ganglioglioma and gangliocytoma. The possible mechanisms by which this may occur include a pre-existing gangliocytoma promoting the development of pituitary adenoma by hypersecretion of releasing hormones or aberrant migration of hypothalamic neurons in early embryogenesis. PMID:27068013

  20. Ovarian Hyperstimulation Caused by Gonadotroph Pituitary Adenoma--Review.

    PubMed

    Halupczok, Jowita; Kluba-Szyszka, Anna; Bidzińska-Speichert, Bożena; Knychalski, Bartłomiej

    2015-01-01

    Ovarian hyperstimulation syndrome (OHSS) occurs mostly as an iatrogenic complication of assisted reproductive technology. Gonadotroph pituitary adenomas are rarely associated with OHSS. To the authors' knowledge, to date only 30 cases of spontaneous ovarian stimulation associated with gonadotroph adenomas have been reported in women and only 2 in children. The most common symptoms in such cases included menstrual disturbances, abdominal or pelvic pain, abdominal distension and increased girth. Galactorrhea, nausea and vomiting were also reported. Neurological symptoms occurred when the size of the pituitary tumor reached at least 20 mm. Transvaginal ultrasound examination usually demonstrated enlarged multicystic ovaries. MRIs of the pituitary revealed macroadenomas up to 61 mm in maximum diameter. The hormonal profiles of the reported cases showed normal or elevated FSH levels, suppressed LH levels, elevated estradiol levels and supranormal concentrations of prolactin. Transsphenoidal surgery is the therapy of choice, however other treatment modalities can be utilized in selected cases. PMID:26469116

  1. [Intrasellar small TSH secreting pituitary adenomas, 2 case reports].

    PubMed

    Ogawa, Yoshikazu; Tominaga, Teiji; Ikeda, Hidetoshi

    2007-07-01

    Thyroid-stimulating hormone (TSH)-secreting pituitary adenoma accounts for 1% of pituitary adenoma and often manifests as invasive macroadenoma. If the TSH value is not high enough to cause clinical symptoms presenting as inappropriate secretion of TSH, the tumor may be missed or misdiagnosed as Graves disease. Some of these patients receive inadequate treatment with the antithyroid agent, radioiodine treatment, and thyroidectomy. This tumor is also known as a tough and firm tumor because of the significant interstitial fibrosis. We report two cases of TSH-secreting pituitary adenomas which were comparatively small. Although a tough and difficult operation was expected, actual tumor dissection was easy and gross total removal was achieved within less than 3 hours. We discuss the relationship between the intraoperative findings and histopathology, as well as the ultrastructure and endocrinology. PMID:17633511

  2. Beneficial effects of secretory leukocyte protease inhibitor after spinal cord injury

    PubMed Central

    Ghasemlou, Nader; Bouhy, Delphine; Yang, Jingxuan; López-Vales, Rubèn; Haber, Michael; Thuraisingam, Thusanth; He, Guoan; Radzioch, Danuta; Ding, Aihao

    2010-01-01

    Secretory leukocyte protease inhibitor is a serine protease inhibitor produced by various cell types, including neutrophils and activated macrophages, and has anti-inflammatory properties. It has been shown to promote wound healing in the skin and other non-neural tissues, however, its role in central nervous system injury was not known. We now report a beneficial role for secretory leukocyte protease inhibitor after spinal cord injury. After spinal cord contusion injury in mice, secretory leukocyte protease inhibitor is expressed primarily by astrocytes and neutrophils but not macrophages. We show, using transgenic mice over-expressing secretory leukocyte protease inhibitor, that this molecule has an early protective effect after spinal cord contusion injury. Furthermore, wild-type mice treated for the first week after spinal cord contusion injury with recombinant secretory leukocyte protease inhibitor exhibit sustained improvement in locomotor control and reduced secondary tissue damage. Recombinant secretory leukocyte protease inhibitor injected intraperitoneally localizes to the nucleus of circulating leukocytes, is detected in the injured spinal cord, reduces activation of nuclear factor-κB and expression of tumour necrosis factor-α. Administration of recombinant secretory leukocyte protease inhibitor might therefore be useful for the treatment of acute spinal cord injury. PMID:20047904

  3. Lipids implicated in the journey of a secretory granule: from biogenesis to fusion.

    PubMed

    Tanguy, Emeline; Carmon, Ophélie; Wang, Qili; Jeandel, Lydie; Chasserot-Golaz, Sylvette; Montero-Hadjadje, Maité; Vitale, Nicolas

    2016-06-01

    The regulated secretory pathway begins with the formation of secretory granules by budding from the Golgi apparatus and ends by their fusion with the plasma membrane leading to the release of their content into the extracellular space, generally following a rise in cytosolic calcium. Generation of these membrane-bound transport carriers can be classified into three steps: (i) cargo sorting that segregates the cargo from resident proteins of the Golgi apparatus, (ii) membrane budding that encloses the cargo and depends on the creation of appropriate membrane curvature, and (iii) membrane fission events allowing the nascent carrier to separate from the donor membrane. These secretory vesicles then mature as they are actively transported along microtubules toward the cortical actin network at the cell periphery. The final stage known as regulated exocytosis involves the docking and the priming of the mature granules, necessary for merging of vesicular and plasma membranes, and the subsequent partial or total release of the secretory vesicle content. Here, we review the latest evidence detailing the functional roles played by lipids during secretory granule biogenesis, recruitment, and exocytosis steps. In this review, we highlight evidence supporting the notion that lipids play important functions in secretory vesicle biogenesis, maturation, recruitment, and membrane fusion steps. These effects include regulating various protein distribution and activity, but also directly modulating membrane topology. The challenges ahead to understand the pleiotropic functions of lipids in a secretory granule's journey are also discussed. This article is part of a mini review series on Chromaffin cells (ISCCB Meeting, 2015). PMID:26877188

  4. Sorting and storage during secretory granule biogenesis: looking backward and looking forward.

    PubMed Central

    Arvan, P; Castle, D

    1998-01-01

    Secretory granules are specialized intracellular organelles that serve as a storage pool for selected secretory products. The exocytosis of secretory granules is markedly amplified under physiologically stimulated conditions. While granules have been recognized as post-Golgi carriers for almost 40 years, the molecular mechanisms involved in their formation from the trans-Golgi network are only beginning to be defined. This review summarizes and evaluates current information about how secretory proteins are thought to be sorted for the regulated secretory pathway and how these activities are positioned with respect to other post-Golgi sorting events that must occur in parallel. In the first half of the review, the emerging role of immature secretory granules in protein sorting is highlighted. The second half of the review summarizes what is known about the composition of granule membranes. The numerous similarities and relatively limited differences identified between granule membranes and other vesicular carriers that convey products to and from the plasmalemma, serve as a basis for examining how granule membrane composition might be established and how its unique functions interface with general post-Golgi membrane traffic. Studies of granule formation in vitro offer additional new insights, but also important challenges for future efforts to understand how regulated secretory pathways are constructed and maintained. PMID:9620860

  5. Borjeson-Forssman-Lehmann syndrome and multiple pituitary hormone deficiency.

    PubMed

    Birrell, G; Lampe, A; Richmond, S; Bruce, S N; Gécz, J; Lower, K; Wright, M; Cheetham, T D

    2003-12-01

    We describe two brothers with Borjeson-Forssman-Lehmann syndrome and the 22A-->T (Lys8X) PHF6 mutation, who presented with the symptoms and signs of multiple pituitary hormone deficiency. Biochemical investigations and radiology confirmed growth hormone (GH), thyroid stimulating hormone (TSH) and adrenocorticotrophic hormone (ACTH) as well as gonadotrophin deficiency. They were also found to have optic nerve hypoplasia. This family suggests that the BFL gene product may play an important role in midline neuro-development including the hypothalamo-pituitary axis. PMID:14714754

  6. An uncommon cause of recurrent pyogenic meningitis: pituitary abscess

    PubMed Central

    Walia, Rama; Bhansali, Anil; Dutta, Pinaki; Shanmugasundar, G; Mukherjee, Kanchan Kumar; Upreti, Vimal; Das, Ashim

    2010-01-01

    The authors report a 36-year-old male who presented with headache and hypopituitarism, and MRI revealed a ring enhancing lesion with pituitary stalk thickening. During follow-up, he presented with recurrent pyogenic meningitis with persistence of the lesion, therefore a diagnosis of pituitary abscess was considered. He underwent trans-sphenoidal surgery (TSS) with evacuation of pus and received antibiotic treatment for the same. After this he remarkably improved and had no recurrence of symptoms. He is on levothyroxine, glucocorticoids and testosterone replacement therapy for his respective hormone deficits. PMID:22767626

  7. Intrasellar schwannoma mimicking pituitary adenoma: a case report.

    PubMed

    Whee, Sung Mock; Lee, Jung Il; Kim, Jong Hyun

    2002-02-01

    Intrasellar location of schwannoma is extremely rare, although intracranial schwannomas account for up to 8% of all primary brain tumors. An unusual case of an intrasellar schwannoma radiographically and clinically simulating a pituitary adenoma is reported. A 39-yr-old man presented a 10-month history of visual disturbance and decreased libido. Neurological examination showed poor visual acuity of both eyes with bitemporal hemianopsia. Computed tomography and magnetic resonance imaging showed a sellar tumor with suprasellar extension. Pituitary adenoma was considered as a preoperative diagnosis. The tumor was removed through a trans-sphenoidal approach. Microscopic examination of the tumor revealed schwannoma. PMID:11850608

  8. Purification and cultivation of human pituitary growth hormone secreting cells

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.

    1979-01-01

    Efforts were directed towards maintenance of actively secreting human pituitary growth hormone cells (somatotrophs) in vitro. The production of human growth hormone (hGH) by this means would be of benefit for the treatment of certain human hypopituitary diseases such as dwarfism. One of the primary approaches was the testing of agents which may logically be expected to increase hGH release. The progress towards this goal is summarized. Results from preliminary experiments dealing with electrophoresis of pituitary cell for the purpose of somatotroph separation are described.

  9. Partial pneumoencephalography in following-up pituitary tumours 1

    PubMed Central

    Olmsted, William W.; Wilson, Gabriel H.; Rand, Robert W.; Gartland, John P.

    1974-01-01

    The `limited' pneumoencephalogram has been used with excellent success at UCLA for the continuing follow-up of pituitary tumours. It is most useful in following nonsecretory adenomas since tumour regrowth can occur in the absence of clinical signs and symptoms. Total serial pneumoencephalography has not been accepted previously for follow-up of pituitary tumours since there is a significant morbidity. The `limited' pneumoencephalogram of the diseased area drastically reduces the morbidity of the procedure so that the patients are willing to undergo serial studies on an outpatient basis. Images PMID:4844132

  10. Modulating the pituitary-adrenal response to stress

    NASA Technical Reports Server (NTRS)

    Vernikos-Danellis, J.

    1975-01-01

    Serotonin is believed to be a transmitter or regulator of neuronal function. A possible relationship between the pituitary-adrenal secretion of steroids and brain serotonin in the rat was investigated by evaluating the effects of altering brain 5-hydroxy tryptamine (HT) levels on the daily fluctuation of plasma corticosterone and on the response of the pituitary-adrenal system to a stressful or noxious stimulus in the rat. The approach was either to inhibit brain 5-HT synthesis with para-chlorophenyl alanine or to raise its level with precursors such as tryptophan or 5-hydroxy tryptophan.

  11. 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...

  12. Bovine respiratory disease model based on dual infections with infection with bovine viral diarrhea virus and bovine corona virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine respiratory disease complex (BRDC) is the leading cause of economic loss in the U.S. cattle industry. BRDC likely results from simultaneous or sequential infections with multiple pathogens including both viruses and bacteria. Bovine viral diarrhea virus (BVDV) and bovine corona virus (BoCV...

  13. Complete Genome Sequences of Two Novel European Clade Bovine Foamy Viruses from Germany and Poland

    PubMed Central

    Hechler, Torsten; Materniak, Magdalena; Kehl, Timo; Kuzmak, Jacek

    2012-01-01

    Bovine foamy virus (BFV), or bovine spumaretrovirus, is an infectious agent of cattle with no obvious disease association but high prevalence in its host. Here, we report two complete BFV sequences, BFV-Riems, isolated in 1978 in East Germany, and BFV100, isolated in 2005 in Poland. Both new BFV isolates share the overall genetic makeup of other foamy viruses (FV). Although isolated almost 25 years apart and propagated in either bovine (BFV-Riems) or nonbovine (BFV100) cells, both viruses are highly related, forming the European BFV clade. Despite clear differences, BFV-Riems and BFV100 are still very similar to BFV isolates from China and the United States, comprising the non-European BFV clade. The genomic sequences presented here confirm the concept of high sequence conservation across most of the FV genome. Analyses of cell culture-derived genomes reveal that proviral DNA may specifically lack introns in the env-bel coding region. The spacing of the splice sites in this region suggests that BFV has developed a novel mode to express a secretory but nonfunctional Env protein. PMID:22966195

  14. Complete genome sequences of two novel European clade bovine foamy viruses from Germany and Poland.

    PubMed

    Hechler, Torsten; Materniak, Magdalena; Kehl, Timo; Kuzmak, Jacek; Löchelt, Martin

    2012-10-01

    Bovine foamy virus (BFV), or bovine spumaretrovirus, is an infectious agent of cattle with no obvious disease association but high prevalence in its host. Here, we report two complete BFV sequences, BFV-Riems, isolated in 1978 in East Germany, and BFV100, isolated in 2005 in Poland. Both new BFV isolates share the overall genetic makeup of other foamy viruses (FV). Although isolated almost 25 years apart and propagated in either bovine (BFV-Riems) or nonbovine (BFV100) cells, both viruses are highly related, forming the European BFV clade. Despite clear differences, BFV-Riems and BFV100 are still very similar to BFV isolates from China and the United States, comprising the non-European BFV clade. The genomic sequences presented here confirm the concept of high sequence conservation across most of the FV genome. Analyses of cell culture-derived genomes reveal that proviral DNA may specifically lack introns in the env-bel coding region. The spacing of the splice sites in this region suggests that BFV has developed a novel mode to express a secretory but nonfunctional Env protein. PMID:22966195

  15. Functional Characteristics of Multipotent Mesenchymal Stromal Cells from Pituitary Adenomas

    PubMed Central

    Megnis, Kaspars; Mandrika, Ilona; Petrovska, Ramona; Stukens, Janis; Rovite, Vita; Balcere, Inga; Jansone, Laima Sabine; Peculis, Raitis; Pirags, Valdis

    2016-01-01

    Pituitary adenomas are one of the most common endocrine and intracranial neoplasms. Although they are theoretically monoclonal in origin, several studies have shown that they contain different multipotent cell types that are thought to play an important role in tumor initiation, maintenance, and recurrence after therapy. In the present study, we isolated and characterized cell populations from seven pituitary somatotroph, nonhormonal, and lactotroph adenomas. The obtained cells showed characteristics of multipotent mesenchymal stromal cells as observed by cell morphology, cell surface marker CD90, CD105, CD44, and vimentin expression, as well as differentiation to osteogenic and adipogenic lineages. They are capable of growth and passaging under standard laboratory cell culture conditions and do not manifest any hormonal cell characteristics. Multipotent mesenchymal stromal cells are present in pituitary adenomas regardless of their clinical manifestation and show no considerable expression of somatostatin 1–5 and dopamine 2 receptors. Most likely obtained cells are a part of tissue-supportive cells in pituitary adenoma microenvironment. PMID:27340409

  16. Atrial natriuretic factor-like activity in rat posterior pituitary

    SciTech Connect

    Gutkowska, J.; Debinski, W.; Racz, K.; Thibault, G.; Garcia, R.; Kuchel, O.; Genest, J.; Cantin, M.

    1986-03-05

    The presence of a biologically active peptide: Atrial Natriuretic Factor (ANF) has been demonstrated in rat and human circulation and ANF is considered now as a new hormone. ANF may be involved in body fluid regulation. A very sensitive radioimmunoassay for rat ANF allowed the authors to search for immunoreactive ANF (IR-ANF) in rat posterior pituitary. Serial dilutions of homogenates of rat posterior pituitary showed a good parallelism with a reference curve in a radioimmunoassay system. The IR-ANF was extracted from rat posterior pituitary homogenates by activated Vycor glass beads. The lyophilized extract was purified by HPLC on C/sub 18/ ..mu.. Bondapak column. The HPLC yielded two IR-ANF peaks. Both isolated ANF-like material showed biological activity. The IR-ANF eluted with 33% acetonitrile, inhibited ACTH-stimulated aldosterone secretion with a similar potency as synthetic (Arg 101 - Tyr 126) ANF (0.7 x 10/sup -10/M). A much less potent ANF-like material was found in the second peak eluted with 36% acetonitrile. They conclude that ANF-like material is present in rat posterior pituitary and this suggest a possible role in ANF on AVP secretion directly in situ.

  17. Functional Characteristics of Multipotent Mesenchymal Stromal Cells from Pituitary Adenomas.

    PubMed

    Megnis, Kaspars; Mandrika, Ilona; Petrovska, Ramona; Stukens, Janis; Rovite, Vita; Balcere, Inga; Jansone, Laima Sabine; Peculis, Raitis; Pirags, Valdis; Klovins, Janis

    2016-01-01

    Pituitary adenomas are one of the most common endocrine and intracranial neoplasms. Although they are theoretically monoclonal in origin, several studies have shown that they contain different multipotent cell types that are thought to play an important role in tumor initiation, maintenance, and recurrence after therapy. In the present study, we isolated and characterized cell populations from seven pituitary somatotroph, nonhormonal, and lactotroph adenomas. The obtained cells showed characteristics of multipotent mesenchymal stromal cells as observed by cell morphology, cell surface marker CD90, CD105, CD44, and vimentin expression, as well as differentiation to osteogenic and adipogenic lineages. They are capable of growth and passaging under standard laboratory cell culture conditions and do not manifest any hormonal cell characteristics. Multipotent mesenchymal stromal cells are present in pituitary adenomas regardless of their clinical manifestation and show no considerable expression of somatostatin 1-5 and dopamine 2 receptors. Most likely obtained cells are a part of tissue-supportive cells in pituitary adenoma microenvironment. PMID:27340409

  18. Hyperprolactinemia Secondary to Allergic Fungal Sinusitis Compressing the Pituitary Gland

    PubMed Central

    Chapurin, Nikita; Wang, Cynthia; Steinberg, David M.; Jang, David W.

    2016-01-01

    Objective. We aim to describe the first case in the literature of allergic fungal sinusitis (AFS) presenting with hyperprolactinemia due to compression of the pituitary gland. Case Presentation. A 37-year-old female presented with bilateral galactorrhea and occipital headaches of several weeks. Workup revealed elevated prolactin of 94.4, negative pregnancy test, and normal thyroid function. MRI and CT demonstrated a 5.0 × 2.7 × 2.5 cm heterogeneous expansile mass in the right sphenoid sinus with no pituitary adenoma as originally suspected. Patient was placed on cabergoline for symptomatic control until definitive treatment. Results. The patient underwent right endoscopic sphenoidotomy, which revealed nasal polyps and fungal debris in the sphenoid sinus, consistent with AFS. There was bony erosion of the sella and clivus. Pathology and microbiology were consistent with allergic fungal sinusitis caused by Curvularia species. Prolactin levels normalized four weeks after surgery with resolution of symptoms. Conclusion. Functional endoscopic sinus surgery alone was able to reverse the patient's pituitary dysfunction. To our knowledge, this is the first case of AFS presenting as hyperprolactinemia due to pituitary compression. PMID:26998375

  19. Early effects of cranial irradiation on hypothalamic-pituitary function

    SciTech Connect

    Lam, K.S.; Tse, V.K.; Wang, C.; Yeung, R.T.; Ma, J.T.; Ho, J.H.

    1987-03-01

    Hypothalamic-pituitary function was studied in 31 patients before and after cranial irradiation for nasopharyngeal carcinoma. The estimated radiotherapy (RT) doses to the hypothalamus and pituitary were 3979 +/- 78 (+/- SD) and 6167 +/- 122 centiGrays, respectively. All patients had normal pituitary function before RT. One year after RT, there was a significant decrease in the integrated serum GH response to insulin-induced hypoglycemia. In the male patients, basal serum FSH significantly increased, while basal serum LH and testosterone did not change. Moreover, in response to LHRH, the integrated FSH response was increased while that of LH was decreased. Such discordant changes in FSH and LH may be explained by a defect in LHRH pulsatile release involving predominantly a decrease in pulse frequency. The peak serum TSH response to TRH became delayed in 28 patients, suggesting a defect in TRH release. Twenty-one patients were reassessed 2 yr after RT. Their mean basal serum T4 and plasma cortisol levels had significantly decreased. Hyperprolactinemia associated with oligomenorrhoea was found in 3 women. Further impairment in the secretion of GH, FSH, LH, TSH, and ACTH had occurred, and 4 patients had hypopituitarism. Thus, progressive impairment in hypothalamic-pituitary function occurs after cranial irradiation and can be demonstrated as early as 1 yr after RT.

  20. Genetic Regulation of Pituitary Gland Development in Human and Mouse

    PubMed Central

    Kelberman, Daniel; Rizzoti, Karine; Lovell-Badge, Robin; Robinson, Iain C. A. F.; Dattani, Mehul T.

    2009-01-01

    Normal hypothalamopituitary development is closely related to that of the forebrain and is dependent upon a complex genetic cascade of transcription factors and signaling molecules that may be either intrinsic or extrinsic to the developing Rathke’s pouch. These factors dictate organ commitment, cell differentiation, and cell proliferation within the anterior pituitary. Abnormalities in these processes are associated with congenital hypopituitarism, a spectrum of disorders that includes syndromic disorders such as septo-optic dysplasia, combined pituitary hormone deficiencies, and isolated hormone deficiencies, of which the commonest is GH deficiency. The highly variable clinical phenotypes can now in part be explained due to research performed over the last 20 yr, based mainly on naturally occurring and transgenic animal models. Mutations in genes encoding both signaling molecules and transcription factors have been implicated in the etiology of hypopituitarism, with or without other syndromic features, in mice and humans. To date, mutations in known genes account for a small proportion of cases of hypopituitarism in humans. However, these mutations have led to a greater understanding of the genetic interactions that lead to normal pituitary development. This review attempts to describe the complexity of pituitary development in the rodent, with particular emphasis on those factors that, when mutated, are associated with hypopituitarism in humans. PMID:19837867

  1. Hyperprolactinemia Secondary to Allergic Fungal Sinusitis Compressing the Pituitary Gland.

    PubMed

    Chapurin, Nikita; Wang, Cynthia; Steinberg, David M; Jang, David W

    2016-01-01

    Objective. We aim to describe the first case in the literature of allergic fungal sinusitis (AFS) presenting with hyperprolactinemia due to compression of the pituitary gland. Case Presentation. A 37-year-old female presented with bilateral galactorrhea and occipital headaches of several weeks. Workup revealed elevated prolactin of 94.4, negative pregnancy test, and normal thyroid function. MRI and CT demonstrated a 5.0 × 2.7 × 2.5 cm heterogeneous expansile mass in the right sphenoid sinus with no pituitary adenoma as originally suspected. Patient was placed on cabergoline for symptomatic control until definitive treatment. Results. The patient underwent right endoscopic sphenoidotomy, which revealed nasal polyps and fungal debris in the sphenoid sinus, consistent with AFS. There was bony erosion of the sella and clivus. Pathology and microbiology were consistent with allergic fungal sinusitis caused by Curvularia species. Prolactin levels normalized four weeks after surgery with resolution of symptoms. Conclusion. Functional endoscopic sinus surgery alone was able to reverse the patient's pituitary dysfunction. To our knowledge, this is the first case of AFS presenting as hyperprolactinemia due to pituitary compression. PMID:26998375

  2. Clinical Concerns about Recurrence of Non-Functioning Pituitary Adenoma

    PubMed Central

    Lee, Min Ho; Lee, Ju Hee; Seol, Ho Jun; Lee, Jung-Il; Kim, Jong Hyun; Kong, Doo-Sik

    2016-01-01

    Background Non-functioning pituitary adenomas (NFPA) are clinically challenging because they present at a late stage with local mass effects or hypopituitarism. Surgery for non-functioning pituitary adenoma requires a special strategic approach for both minimal morbidity and radical resection. However, the clinical predictive factors associated with recurrence are limited. Here, we investigated optimal treatment of non-functioning pituitary adenoma. Methods We enrolled 289 patients who presented with non-functioning pituitary adenoma between January 2000 and January 2012 and who had received follow-up for at least one year for this retrospective study. Of these patients, 152 were male and 137 were female, with a median age of 51 years (range 15.79 years) and a median follow-up of four years (range 1.12.6 years). Characteristics of patients and tumors were reviewed with electronic medical records and radiologic images, retrospectively. Results Of the tumors, 193 were gross-totally resected, 53 were near-totally resected, and 43 were sub-totally resected. The extent of resection and adjuvant radiotherapy were both statistically significant prognostic factors of recurrence. Immunohistochemistry of tumor specimens did not yield consistent results. Conclusion With a high rate of recurrence, NFPA should be closely followed-up over a long-term period. Improvement of surgical techniques with advanced surgical equipment and adjuvant radiosurgery would lead to reduce the recurrence rate and improve patients' outcome. PMID:27195254

  3. Pituitary tumors following fallout radiation exposure. [Marshall Islands

    SciTech Connect

    Adams, W.H.; Harper, J.A.; Rittmaster, R.S.; Grimson, R.C.

    1984-08-03

    Two pituitary tumors were diagnosed in a small population of Marshallese accidentally exposed to radioactive fallout in 1954. Endocrinologic findings in the exposed population, are reported and the possible relation of the tumors to radiation exposure and thyroid disease is discussed.

  4. The chronic syndromes after previous treatment of pituitary tumours.

    PubMed

    Romijn, Johannes A

    2016-09-01

    Ultimately, almost all patients who are appropriately treated for pituitary tumours enter a chronic phase with control or cure of hormonal excess, adequate treatment of pituitary insufficiency and relief of mass effects. This phase is associated with improvement of initial signs and symptoms, but also with the persistent consequences of the initial disease and associated treatments. Pituitary insufficiency is a common denominator in many of these patients, and is associated with a reduction in quality of life, despite adequate endocrine substitution. Hypothalamic dysfunction can be present in patients previously treated for visual impairments caused by large suprasellar adenomas, or craniopharyngiomas. In addition to hypopituitarism, these patients can have multisystem morbidities caused by altered hypothalamic function, including weight gain and disturbed regulation of sleep-wake cycles. Mortality can also be affected. Patients cured of Cushing disease or acromegaly have chronic multisystem morbidities (in the case of Cushing disease, also affecting mortality) caused by irreversible effects of the previous excesses of cortisol in Cushing disease and growth hormone and insulin-like growth factor 1 in acromegaly. In addition to early diagnosis and treatment of pituitary tumours, research should focus on the amenability of these chronic post-treatment syndromes to therapeutic intervention, to improve quality of life and clinical outcomes. PMID:27259177

  5. Hypothalamic-Pituitary Autoimmunity and Traumatic Brain Injury

    PubMed Central

    Guaraldi, Federica; Grottoli, Silvia; Arvat, Emanuela; Ghigo, Ezio

    2015-01-01

    Background: Traumatic brain injury (TBI) is a leading cause of secondary hypopituitarism in children and adults, and is responsible for impaired quality of life, disabilities and compromised development. Alterations of pituitary function can occur at any time after the traumatic event, presenting in various ways and evolving during time, so they require appropriate screening for early detection and treatment. Although the exact pathophysiology is unknown, several mechanisms have been hypothesized, including hypothalamic-pituitary autoimmunity (HP-A). The aim of this study was to systematically review literature on the association between HP-A and TBI-induced hypopituitarism. Major pitfalls related to the HP-A investigation were also discussed. Methods: The PubMed database was searched with a string developed for this purpose, without temporal or language limits, for original articles assessing the association of HP-A and TBI-induced hypopituitarism. Results: Three articles from the same group met the inclusion criteria. Anti-pituitary and anti-hypothalamic antibodies were detected using indirect immunofluorescence in a significant number of patients with acute and chronic TBI. Elevated antibody titer was associated with an increased risk of persistent hypopituitarism, especially somatotroph and gonadotroph deficiency, while no correlations were found with clinical parameters. Conclusion: HPA seems to contribute to TBI-induced pituitary damage, although major methodological issues need to be overcome and larger studies are warranted to confirm these preliminary data. PMID:26239463

  6. Early development of the secretory cavity of peltate glands in Humulus lupulus L. (Cannabaceae).

    PubMed

    Kim, E S; Mahlberg, P G

    2000-10-31

    Early development of the secretory cavity of chemically fixed peltate glands in Humulus lupulus L. showed secretions with different densities, light, gray and dark, in the cytoplasm of disc cells and in the periplasmic space adjacent to the developing secretory cavity. Secretions were detected in the disc cell wall and subsequently in the developing secretory cavity under the subcuticular wall of the sheath. Light and gray secretions in the cavity possessed a membrane-like surface feature. Secretions were in contact with the irregular inner surface of the cuticle. Secretions contributed to the thickening of the cuticle, whereas the membrane-like surface feature contributed to a network of Cannabis striae distributed throughout the cuticle. This study supports an early development and organization of the secretory cavity in H. lupulus, parallel to those in Cannabis, and may represent common features for lipophilic glands in angiosperms. PMID:11101137

  7. Astrocytes as secretory cells of the central nervous system: idiosyncrasies of vesicular secretion.

    PubMed

    Verkhratsky, Alexei; Matteoli, Michela; Parpura, Vladimir; Mothet, Jean-Pierre; Zorec, Robert

    2016-02-01

    Astrocytes are housekeepers of the central nervous system (CNS) and are important for CNS development, homeostasis and defence. They communicate with neurones and other glial cells through the release of signalling molecules. Astrocytes secrete a wide array of classic neurotransmitters, neuromodulators and hormones, as well as metabolic, trophic and plastic factors, all of which contribute to the gliocrine system. The release of neuroactive substances from astrocytes occurs through several distinct pathways that include diffusion through plasmalemmal channels, translocation by multiple transporters and regulated exocytosis. As in other eukaryotic cells, exocytotic secretion from astrocytes involves divergent secretory organelles (synaptic-like microvesicles, dense-core vesicles, lysosomes, exosomes and ectosomes), which differ in size, origin, cargo, membrane composition, dynamics and functions. In this review, we summarize the features and functions of secretory organelles in astrocytes. We focus on the biogenesis and trafficking of secretory organelles and on the regulation of the exocytotic secretory system in the context of healthy and diseased astrocytes. PMID:26758544

  8. Isolated double adrenocorticotropic hormone-secreting pituitary adenomas: A case report and review of the literature

    PubMed Central

    PU, JIUJUN; WANG, ZHIMING; ZHOU, HUI; ZHONG, AILING; JIN, KAI; RUAN, LUNLIANG; YANG, GANG

    2016-01-01

    Only a few cases of double or multiple pituitary adenomas have previously been reported in the literature; however, isolated double adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas are even more rare. The present study reports a rare case of a 50-year-old female patient who presented with typical clinical features of Cushing's disease and was diagnosed with isolated double ACTH-secreting pituitary adenomas. Endocrinological examination revealed an ACTH-producing pituitary adenoma, and preoperative magnetic resonance imaging (MRI) demonstrated a microadenoma with a lower intensity on the right side of the pituitary gland. The patient underwent endoscopic endonasal transsphenoidal surgery, which revealed another pituitary tumor in the left side of the pituitary gland. The two, clearly separated, pituitary adenomas identified in the same gland were completely resected. Immunohistochemistry and pathology revealed that the clearly separated double pituitary adenomas were positive for ACTH, thyroid-stimulating, growth and prolactin hormones. Postoperatively, the levels of ACTH and cortisol hormone decreased rapidly. The case reported in the present study is considerably rare, due to the presence of a second pituitary adenoma in the same gland, which was not detected by preoperative MRI scan, but was noticed during surgery. Intraoperative evaluation may be important in the identification of double or multiple pituitary adenomas. PMID:27347184

  9. Characterization of the ovine ortholog of secretory leukoprotease inhibitor.

    PubMed

    Brown, Thomas I; Mistry, Rohit; Gray, Robert; Imrie, Margaret; Collie, David D; Sallenave, Jean-Michel

    2005-08-01

    There is great interest in the use of the sheep as a model for the investigation of inflammation in the lung. The serine antiproteases secretory leukoprotease inhibitor (SLPI) and elafin are important "alarm antiproteases" in the lung and have potentially important roles in the innate immune response. SLPI was first characterized in man and subsequently in murine, porcine, and rat tissues. Here we present the first data concerning the gene and cDNA sequence encoding for the ovine ortholog of SLPI, a protein of 132 amino acids with 66% sequence identity at the amino acid level with human SLPI. A 24-amino-acid signal sequence signifies that, like the other mammalian orthologs, ovine SLPI is a secreted protein. Tissue distribution of expression is demonstrated by reverse transcription polymerase chain reaction (RT-PCR) and shows features similar to SLPI expression in other mammals, specifically at mucosal surfaces such as the upper respiratory and intestinal tracts, and also the skin, liver, and kidney. This distribution lends credence to SLPI having important roles in innate immunity. We have also cloned the ovine SLPI cDNA into an expression vector and expressed the ovine SLPI protein in vitro. This has enabled us to demonstrate that ovine SLPI is correctly processed (Western blot analysis and SELDI-TOF mass spectrometry analysis) and has biological antihuman neutrophil elastase activity. In summary, the ovine ortholog of SLPI shows similarities to other members of the SLPI family and has all the features of a modulator of innate immunity. PMID:16180144

  10. The complete general secretory pathway in gram-negative bacteria.

    PubMed Central

    Pugsley, A P

    1993-01-01

    The unifying feature of all proteins that are transported out of the cytoplasm of gram-negative bacteria by the general secretory pathway (GSP) is the presence of a long stretch of predominantly hydrophobic amino acids, the signal sequence. The interaction between signal sequence-bearing proteins and the cytoplasmic membrane may be a spontaneous event driven by the electrochemical energy potential across the cytoplasmic membrane, leading to membrane integration. The translocation of large, hydrophilic polypeptide segments to the periplasmic side of this membrane almost always requires at least six different proteins encoded by the sec genes and is dependent on both ATP hydrolysis and the electrochemical energy potential. Signal peptidases process precursors with a single, amino-terminal signal sequence, allowing them to be released into the periplasm, where they may remain or whence they may be inserted into the outer membrane. Selected proteins may also be transported across this membrane for assembly into cell surface appendages or for release into the extracellular medium. Many bacteria secrete a variety of structurally different proteins by a common pathway, referred to here as the main terminal branch of the GSP. This recently discovered branch pathway comprises at least 14 gene products. Other, simpler terminal branches of the GSP are also used by gram-negative bacteria to secrete a more limited range of extracellular proteins. PMID:8096622

  11. THE SECRETORY PATHWAYS OF RAT SERUM GLYCOPROTEINS AND ALBUMIN

    PubMed Central

    Redman, Colvin M.; Cherian, M. George

    1972-01-01

    These studies compare the secretory pathways of newly formed rat serum glycoproteins and albumin by studying their submicrosomal localization at early times after the beginning of their synthesis and also by determining the submicrosomal site of incorporation of N-acetylglucosamine, mannose, galactose, and leucine into protein. N-acetylglucosamine, mannose, and galactose were only incorporated in vitro into proteins from membrane-attached polysomes and not into proteins from free polysomes. Mannose incorporation occurred in the rough endoplasmic reticulum, was stimulated by puromycin but not by cycloheximide, and 90% of the mannose-labeled protein was bound to the membranes. Galactose incorporation, by contrast, occurred in the smooth microsome fraction and 89% of the radioactive protein was in the cisternae. Albumin was mostly recovered (98%) in the cisternae, with negligible amounts in the membranes. To determine whether the radio-active sugars were being incorporated into serum proteins or into membrane protein, the solubilized in vivo-labeled proteins were treated with specific antisera to rat serum proteins or to albumin. Immunoelectrophoresis of the 14C-labeled leucine membrane and cisternal proteins showed that the membranes contained radioactive serum glycoprotein but no albumin, while the cisternal fraction contained all of the radioactive albumin and some glycoproteins. The results indicate that newly formed serum glycoproteins remain attached to the membranes of the rough endoplasmic reticulum after they are released from the membrane-attached polysomes, while albumin passes directly into the cisternae. PMID:5057975

  12. Remodeling of secretory compartments creates CUPS during nutrient starvation.

    PubMed

    Cruz-Garcia, David; Curwin, Amy J; Popoff, Jean-François; Bruns, Caroline; Duran, Juan M; Malhotra, Vivek

    2014-12-22

    Upon starvation, Grh1, a peripheral membrane protein located at endoplasmic reticulum (ER) exit sites and early Golgi in Saccharomyces cerevisiae under growth conditions, relocates to a compartment called compartment for unconventional protein secretion (CUPS). Here we report that CUPS lack Golgi enzymes, but contain the coat protein complex II (COPII) vesicle tethering protein Uso1 and the Golgi t-SNARE Sed5. Interestingly, CUPS biogenesis is independent of COPII- and COPI-mediated membrane transport. Pik1- and Sec7-mediated membrane export from the late Golgi is required for complete assembly of CUPS, and Vps34 is needed for their maintenance. CUPS formation is triggered by glucose, but not nitrogen starvation. Moreover, upon return to growth conditions, CUPS are absorbed into the ER, and not the vacuole. Altogether our findings indicate that CUPS are not specialized autophagosomes as suggested previously. We suggest that starvation triggers relocation of secretory and endosomal membranes, but not their enzymes, to generate CUPS to sort and secrete proteins that do not enter, or are not processed by enzymes of the ER-Golgi pathway of secretion. PMID:25512390

  13. Decreased gastric secretory functions in diabetic patients with autonomic neuropathy.

    PubMed

    Nakamura, T; Takebe, K; Imamura, K; Miyazawa, T; Ishii, M; Kudoh, K; Terada, A; Machida, K; Kikuchi, H; Kasai, F

    1994-06-01

    A total of 37 subjects consisted of 10 healthy subjects (Group III), 15 diabetic patients without autonomic neuropathy (Group II), and 12 diabetic patients with autonomic neuropathy including gastroparesis in 6 cases (Group I). All three groups were comparable in age. In order to clarify the gastric function in diabetic patients with autonomic neuropathy, secretion of serum gastrin, gastric secretory function, endoscopic Congo red test of fundic glands, and coefficiency of variance of electrocardiographic beat-to-beat intervals (C.V. R-R) were examined. In Group I, 5 patients had hypergastrinemia, but its elevation was inhibited when an acid solution was injected into the stomach. Gastric secretion and C.V. R-R were markedly lower in Group I, compared with Groups II and III. In Group I, the area of fundic glands (parietal cells) was reduced considerably. The C.V. R-R was significantly correlated with fasting serum gastrin concentration and with maximal acid output. From these results, in diabetic patients with autonomic neuropathy (vagal neuropathy), gastric acid secretion in response to tetragastrin stimulation was lowered with a reduction in area of fundic gland distribution. Hypergastrinemia may reflect a negative feedback mechanism responding to decreased acidity of gastric content in the antrum. PMID:7817384

  14. Secretory immunity in defense against cariogenic mutans streptococci.

    PubMed

    Russell, M W; Hajishengallis, G; Childers, N K; Michalek, S M

    1999-01-01

    Specific immune defense against cariogenic mutans streptococci is provided largely by salivary secretory IgA antibodies, which are generated by the common mucosal immune system. This system is functional in newborn infants, who develop salivary IgA antibodies as they become colonized by oral microorganisms. The mechanisms of action of salivary IgA antibodies include interference with sucrose-independent and sucrose- dependent attachment of mutans streptococci to tooth surfaces, as well as possible inhibition of metabolic activities. The goal of protecting infants against colonization by mutans streptococci might be accomplished by applying new strategies of mucosal immunization that would induce salivary IgA antibodies without the complications of parenteral immunization. Strategies of mucosal immunization against mutans streptococci currently under development include the use of surface adhesins and glucosyltransferase as key antigens, which are being incorporated into novel mucosal vaccine delivery systems and adjuvants. The oral application of preformed, genetically engineered antibodies to mutans streptococcal antigens also offers new prospects for passive immunization against dental caries. PMID:9831775

  15. Elimination diets in the treatment of secretory otitis media.

    PubMed

    Ruokonen, J; Paganus, A; Lehti, H

    1982-03-01

    The significance of elimination diets in the treatment of secretory otitis media (SOM) and the usefulness of the cytotoxic leucocyte test (CLT) in the planning of elimination diets were investigated. Sixty-seven children with SOM were tested with CLT and treated with or without elimination diets in addition to the established SOM-treatment. After two years of observation in patients with multiple CLT-reactions (50) there was an almost significant difference (P less than 0.06) in the cure rates and a significant difference (P less than 0.02) in the percentages of therapeutic failures between those treated with (32) and those treated without (18) elimination diets. No marked difference was found between patients, who did not have multiple CLT-reactions (17) and were treated without diets and patients who were treated with diets for multiple CLT-reactions (32). It was concluded that elimination diets are needed in the treatment of SOM for those patients who have multiple reactions in the CLT and that the CLT is useful in the planning of these elimination diets. PMID:7201458

  16. Secretory compartments as instances of dynamic self-evolving structures.

    PubMed

    Képès, François

    2002-01-01

    Biological objects are often "constructive dynamic systems" whose structures evolve as a consequence of their internal dynamics, which in turn is affected by the overall structure. As very few tools are presently adapted to tackle constructive dynamic systems, they constitute fascinating challenges for modeling/simulation. In cell biology, the secretory process in eukaryotic cells corresponds to this type of system, as it appears to autonomously generate new structures as a result of its molecular dynamics. Here I briefly review the only documented case of a membrane-bounded intracellular compartment whose very existence strictly depends on its continued functioning. Indeed, the Golgi apparatus of the yeast Saccharomyces cerevisiae appears at steady-state as a continuously renewed set of transitory membrane-bounded structures that self-mature, rather than as a permanent entity. On the basis of this case and of recent advances in related molecular studies, a detailed model is proposed, that encompasses the birth of a yeast Golgi element and bridges its molecular and morphogenetic aspects. This model is extended to briefly outline three evolutionary "inventions", from S. cerevisiae to another yeast, Pichia pastoris, on to plant, and on to animal cells: stacking, stabilizing and aggregating the primary Golgi elements. PMID:12675528

  17. NF90 coordinately represses the senescence-associated secretory phenotype

    PubMed Central

    Tominaga-Yamanaka, Kumiko; Abdelmohsen, Kotb; Martindale, Jennifer L.; Yang, Xiaoling; Taub, Dennis D.; Gorospe, Myriam

    2012-01-01

    A hallmark trait of cellular senescence is the acquisition of a senescence-associated secretory phenotype (SASP). SASP factors include cytokines and their receptors (IL-6, IL-8, osteoprotegerin, GM-CSF), chemokines and their ligands (MCP-1, HCC4), and oncogenes (Gro1 and Gro2), many of them encoded by mRNAs whose stability and translation are tightly regulated. Using two models of human fibroblast senescence (WI-38 and IDH4 cells), we report the identification of RNA-binding protein NF90 as a post-transcriptional repressor of several SASP factors. In ‘young’, proliferating fibroblasts, NF90 was highly abundant, associated with numerous SASP mRNAs, and inhibited their expression. By contrast, senescent cells expressed low levels of NF90, thus allowing SASP factor expression to increase. NF90 elicited these effects mainly by repressing the translation of target SASP mRNAs, since silencing NF90 did not increase the steady-state levels of SASP mRNAs but elevated key SASP factors including MCP-1, GROa, IL-6, and IL-8. Our findings indicate that NF90 contributes to maintaining low levels of SASP factors in non-senescent cells, while NF90 reduction in senescent cells allows SASP factor expression to rise. PMID:23117626

  18. Gut Microbial Succession Follows Acute Secretory Diarrhea in Humans

    PubMed Central

    David, Lawrence A.; Weil, Ana; Ryan, Edward T.; Calderwood, Stephen B.; Harris, Jason B.; Chowdhury, Fahima; Begum, Yasmin; Qadri, Firdausi

    2015-01-01

    ABSTRACT Disability after childhood diarrhea is an important burden on global productivity. Recent studies suggest that gut bacterial communities influence how humans recover from infectious diarrhea, but we still lack extensive data and mechanistic hypotheses for how these bacterial communities respond to diarrheal disease and its treatment. Here, we report that after Vibrio cholerae infection, the human gut microbiota undergoes an orderly and reproducible succession that features transient reversals in relative levels of enteric Bacteroides and Prevotella. Elements of this succession may be a common feature in microbiota recovery from acute secretory diarrhea, as we observed similar successional dynamics after enterotoxigenic Escherichia coli (ETEC) infection. Our metagenomic analyses suggest that multiple mechanisms drive microbial succession after cholera, including bacterial dispersal properties, changing enteric oxygen and carbohydrate levels, and phage dynamics. Thus, gut microbiota recovery after cholera may be predictable at the level of community structure but is driven by a complex set of temporally varying ecological processes. Our findings suggest opportunities for diagnostics and therapies targeting the gut microbiota in humans recovering from infectious diarrhea. PMID:25991682

  19. Colonic secretory effect in response to enteral feeding in humans.

    PubMed Central

    Bowling, T E; Raimundo, A H; Grimble, G K; Silk, D B

    1994-01-01

    Diarrhoea complicating enteral feeding is a common clinical problem affecting up to 25% of patients. Its pathogenesis remains unknown. A new technique of human in vivo segmental colonic perfusion was used to investigate colonic water and electrolyte movement in response to enteral feeding. Four groups of studies were performed in which low and high load polymeric enteral diet infusions were undertaken, either intragastrically or intraduodenally (n = 6 each group). Net absorption of sodium, chloride, and water occurred during fasting throughout the colon in all groups. There was a significant net secretion of sodium, chloride, and water in the ascending colon during low load (sodium: -42 mmol/h; 95% confidence limits -52 to -19, Chloride: -18 mmol/h; -50 to +16, water: -174 ml/h; -348 to -30) and high load (sodium: -24 mmol/h; -60 to +8, chloride: -18 mmol/h; -31 to +16, water: -120 ml/h; -246 to +6) gastric feeding, and during high load duodenal feeding (sodium: -12 mmol/h; -22 to -6, chloride; -6 mmol/h; -16 to +3, water: -72 ml/h; -144 to -6). Net secretion persisted in the distal colon only during high load gastric feeding. In the other three groups there was a net absorption in the distal colon. This study identified a significant colonic secretory response to enteral feeding, which is related to the site and load of the diet infusion. This response may play an important part in the pathogenesis of enteral feeding related diarrhoea. PMID:7829011

  20. Pituitary carcinoma with intraspinal metastasis: report of two cases and review of the literature

    PubMed Central

    Wang, Yin Qian; Fan, Tao; Zhao, Xin Gang; Liang, Cong; Qi, Xue Ling; Li, Jian Yi

    2015-01-01

    Pituitary carcinomas are rare malignant neoplasms with diagnostic and management challenges. Patients with pituitary carcinomas have extremely poor outcomes. In this report, the authors describe two cases of pituitary carcinomas with intraspinal metastasis (Case 1: 42-year-old man with a history of pituitary adenoma 16 years ago developed an intraspinal lesion at C4-C5; Case 2: 26-year-old women with a history of growth hormone-producing pituitary adenoma 9 years ago developed intraspinal lesion in the sacral canal). Both patients underwent spine surgery. The intraspinal lesions were confirmed as metastatic pituitary carcinomas based on the histomorphology and immunohistochemical stains. The authors reviewed the literature for the diagnosis, treatment, and prognosis of intraspinal metastasis from pituitary carcinomas. PMID:26464743

  1. Bronchioloalveolar carcinoma with metastasis to the pituitary gland: a case report.

    PubMed Central

    Lau, G; Tan, S Y; Chiang, G; Poh, W T

    1998-01-01

    An unusual case of metastatic bronchioloalveolar carcinoma of the lung presented as a pituitary tumour in a young adult Chinese female, who subsequently died after having undergone trans-sphenoidal resection. Metastatic cancers of the pituitary are uncommon even in necropsy series and rarely give rise to clinical symptoms. This case draws attention to the fact that, although uncommon, pituitary metastases have been noted with increasing frequency and their distinction from primary pituitary tumours is often difficult. A metastatic pituitary tumour may be the initial presentation of an unknown primary malignancy, wherein the metastatic deposits may also be limited to the pituitary gland. Clinicians and pathologists alike should consider a metastatic lesion in the differential diagnosis of a non-functioning pituitary tumour. Images PMID:10070337

  2. GH and Pituitary Hormone Alterations After Traumatic Brain Injury.

    PubMed

    Karaca, Züleyha; Tanrıverdi, Fatih; Ünlühızarcı, Kürşad; Kelestimur, Fahrettin

    2016-01-01

    Traumatic brain injury (TBI) is a crucially important public health problem around the world, which gives rise to increased mortality and is the leading cause of physical and psychological disability in young adults, in particular. Pituitary dysfunction due to TBI was first described 95years ago. However, until recently, only a few papers have been published in the literature and for this reason, TBI-induced hypopituitarism has been neglected for a long time. Recent studies have revealed that TBI is one of the leading causes of hypopituitarism. TBI which causes hypopituitarism may be characterized by a single head injury such as from a traffic accident or by chronic repetitive head trauma as seen in combative sports including boxing, kickboxing, and football. Vascular damage, hypoxic insult, direct trauma, genetic predisposition, autoimmunity, and neuroinflammatory changes may have a role in the development of hypopituitarism after TBI. Because of the exceptional structure of the hypothalamo-pituitary vasculature and the special anatomic location of anterior pituitary cells, GH is the most commonly lost hormone after TBI, and the frequency of isolated GHD is considerably high. TBI-induced pituitary dysfunction remains undiagnosed and therefore untreated in most patients because of the nonspecific and subtle clinical manifestations of hypopituitarism. Treatment of TBI-induced hypopituitarism depends on the deficient anterior pituitary hormones. GH replacement therapy has some beneficial effects on metabolic parameters and neurocognitive dysfunction. Patients with TBI without neuroendocrine changes and those with TBI-induced hypopituitarism share the same clinical manifestations, such as attention deficits, impulsion impairment, depression, sleep abnormalities, and cognitive disorders. For this reason, TBI-induced hypopituitarism may be neglected in TBI victims and it would be expected that underlying hypopituitarism would aggravate the clinical picture of TBI itself

  3. Effects of Carbenoxolone on the Canine Pituitary-Adrenal Axis

    PubMed Central

    Teshima, Takahiro; Matsumoto, Hirotaka; Okusa, Tomoko; Nakamura, Yumi; Koyama, Hidekazu

    2015-01-01

    Cushing’s disease caused by pituitary corticotroph adenoma is a common endocrine disease in dogs. A characteristic biochemical feature of corticotroph adenomas is their relative resistance to suppressive negative feedback by glucocorticoids. The abnormal expression of 11beta-hydroxysteroid dehydrogenase (11HSD), which is a cortisol metabolic enzyme, is found in human and murine corticotroph adenomas. Our recent studies demonstrated that canine corticotroph adenomas also have abnormal expression of 11HSD. 11HSD has two isoforms in dogs, 11HSD type1 (HSD11B1), which converts cortisone into active cortisol, and 11HSD type2 (HSD11B2), which converts cortisol into inactive cortisone. It has been suggested that glucocorticoid resistance in corticotroph tumors is related to the overexpression of HSD11B2. Therefore it was our aim to investigate the effects of carbenoxolone (CBX), an 11HSD inhibitor, on the healthy dog’s pituitary-adrenal axis. Dogs were administered 50 mg/kg of CBX twice each day for 15 days. During CBX administration, no adverse effects were observed in any dogs. The plasma adrenocorticotropic hormone (ACTH), and serum cortisol and cortisone concentrations were significantly lower at day 7 and 15 following corticotropin releasing hormone stimulation. After completion of CBX administration, the HSD11B1 mRNA expression was higher, and HSD11B2 mRNA expression was significantly lower in the pituitaries. Moreover, proopiomelanocortin mRNA expression was lower, and the ratio of ACTH-positive cells in the anterior pituitary was also significantly lower after CBX treatment. In adrenal glands treated with CBX, HSD11B1 and HSD11B2 mRNA expression were both lower compared to normal canine adrenal glands. The results of this study suggested that CBX inhibits ACTH secretion from pituitary due to altered 11HSD expressions, and is potentially useful for the treatment of canine Cushing’s disease. PMID:26262685

  4. Oligomerization of green fluorescent protein in the secretory pathway of endocrine cells.

    PubMed Central

    Jain, R K; Joyce, P B; Molinete, M; Halban, P A; Gorr, S U

    2001-01-01

    Green fluorescent protein (GFP) is used extensively as a reporter protein to monitor cellular processes, including intracellular protein trafficking and secretion. In general, this approach depends on GFP acting as a passive reporter protein. However, it was recently noted that GFP oligomerizes in the secretory pathway of endocrine cells. To characterize this oligomerization and its potential role in GFP transport, cytosolic and secretory forms of enhanced GFP (EGFP) were expressed in GH4C1 and AtT-20 endocrine cells. Biochemical analysis showed that cytosolic EGFP existed as a 27 kDa monomer, whereas secretory forms of EGFP formed disulphide-linked oligomers. EGFP contains two cysteine residues (Cys(49) and Cys(71)), which could play a role in this oligomerization. Site-directed mutagenesis of Cys(49) and Cys(71) showed that both cysteine residues were involved in disulphide interactions. Substitution of either cysteine residue resulted in a reduction or loss of oligomers, although dimers of the secretory form of EGFP remained. Mutation of these residues did not adversely affect the fluorescence of EGFP. EGFP oligomers were stored in secretory granules and secreted by the regulated secretory pathway in endocrine AtT-20 cells. Similarly, the dimeric mutant forms of EGFP were still secreted via the regulated secretory pathway, indicating that the higher-order oligomers were not necessary for sorting in AtT-20 cells. These results suggest that the oligomerization of EGFP must be considered when the protein is used as a reporter molecule in the secretory pathway. PMID:11736655

  5. Rab27b regulates exocytosis of secretory vesicles in acinar epithelial cells from the lacrimal gland

    PubMed Central

    Chiang, Lilian; Ngo, Julie; Schechter, Joel E.; Karvar, Serhan; Tolmachova, Tanya; Seabra, Miguel C.; Hume, Alistair N.

    2011-01-01

    Tear proteins are supplied by the regulated fusion of secretory vesicles at the apical surface of lacrimal gland acinar cells, utilizing trafficking mechanisms largely yet uncharacterized. We investigated the role of Rab27b in the terminal release of these secretory vesicles. Confocal fluorescence microscopy analysis of primary cultured rabbit lacrimal gland acinar cells revealed that Rab27b was enriched on the membrane of large subapical vesicles that were significantly colocalized with Rab3D and Myosin 5C. Stimulation of cultured acinar cells with the secretagogue carbachol resulted in apical fusion of these secretory vesicles with the plasma membrane. Evaluation of morphological changes by transmission electron microscopy of lacrimal glands from Rab27b−/− and Rab27ash/ash/Rab27b−/− mice, but not ashen mice deficient in Rab27a, showed changes in abundance and organization of secretory vesicles, further confirming a role for this protein in secretory vesicle exocytosis. Glands lacking Rab27b also showed increased lysosomes, damaged mitochondria, and autophagosome-like organelles. In vitro, expression of constitutively active Rab27b increased the average size but retained the subapical distribution of Rab27b-enriched secretory vesicles, whereas dominant-negative Rab27b redistributed this protein from membrane to the cytoplasm. Functional studies measuring release of a cotransduced secretory protein, syncollin-GFP, showed that constitutively active Rab27b enhanced, whereas dominant-negative Rab27b suppressed, stimulated release. Disruption of actin filaments inhibited vesicle fusion to the apical membrane but did not disrupt homotypic fusion. These data show that Rab27b participates in aspects of lacrimal gland acinar cell secretory vesicle formation and release. PMID:21525430

  6. Salivary alpha-amylase, secretory IgA and free cortisol as neurobiological components of the stress response in the acute phase of anorexia nervosa.

    PubMed

    Paszynska, E; Dmitrzak-Weglarz, M; Tyszkiewicz-Nwafor, M; Slopien, A

    2016-06-01

    Objectives One novel hypothesis of the pathogenesis of anorexia nervosa (AN) is the possible role of mental stress in hyperactivity of the autonomic nervous system (ANS) and of the hypothalamic-pituitary-adrenal (HPA) axis. Two components of stress response - salivary alpha-amylase (sAA) and free cortisol - have been proposed. They can be determined in saliva, which closely reflects their concentrations in plasma. The purpose of this study was to measure salivary free cortisol, sAA and their correlation to secretory IgA (sIgA) of patients with AN in comparison to the average population. Methods A controlled clinical trial was designed for a matched group of 47 AN patients and 54 healthy individuals. After clinical examination, unstimulated salivary samples were taken during the acute stage of AN (BMI < 15 kg/m(2)) in the first week of hospitalisation. An enzyme-linked immunosorbent assay (ELISA) suitable for measuring sAA, sIgA and free cortisol were used. Results Anorexic patients exhibited disturbances in sAA secretion, and significantly increased cortisol and sIgA levels with a distinct correlation between these two parameters. Conclusions The behaviour of cortisol, sAA and sIgA levels can be assessed as an effect of stress reaction among AN patients with hyperactivity of the HPA axis and ANS dysregulation. The effect of stress response can be assessed reliably in saliva. PMID:26983011

  7. Oil Secretory System in Vegetative Organs of Three Arnica Taxa: Essential Oil Synthesis, Distribution and Accumulation.

    PubMed

    Kromer, Krystyna; Kreitschitz, Agnieszka; Kleinteich, Thomas; Gorb, Stanislav N; Szumny, Antoni

    2016-05-01

    Arnica, a genus including the medicinal species A. montana, in its Arbo variety, and A. chamissonis, is among the plants richest in essential oils used as pharmaceutical materials. Despite its extensive use, the role of anatomy and histochemistry in the internal secretory system producing the essential oil is poorly understood. Anatomical sections allowed differentiation between two forms of secretory structures which differ according to their distribution in plants. The first axial type is connected to the vascular system of all vegetative organs and forms canals lined with epithelial cells. The second cortical type is represented by elongated intercellular spaces filled with oil formed only between the cortex cells of roots and rhizomes at maturity, with canals lacking an epithelial layer.Only in A. montana rhizomes do secretory structures form huge characteristic reservoirs. Computed tomography illustrates their spatial distribution and fusiform shape. The axial type of root secretory canals is formed at the interface between the endodermis and cortex parenchyma, while, in the stem, they are located in direct contact with veinal parenchyma. The peripheral phloem parenchyma cells are arranged in strands around sieve tube elements which possess a unique ability to accumulate large amounts of oil bodies. The cells of phloem parenchyma give rise to the aforementioned secretory structures while the lipid components (triacylglycerols) stored there support the biosynthesis of essential oils by later becoming a medium in which these oils are dissolved. The results indicate the integrity of axial secretory structures forming a continuous system in vegetative plant organs. PMID:26936790

  8. The use of lectins as markers for differentiated secretory cells in planarians.

    PubMed

    Zayas, Ricardo M; Cebrià, Francesc; Guo, Tingxia; Feng, Junjie; Newmark, Phillip A

    2010-11-01

    Freshwater planarians have reemerged as excellent models to investigate mechanisms underlying regeneration. The introduction of molecular tools has facilitated the study of planarians, but cell- and tissue-specific markers are still needed to examine differentiation of most cell types. Here we report the utility of fluorescent lectin-conjugates to label tissues in the planarian Schmidtea mediterranea. We show that 16 lectin-conjugates stain planarian cells or tissues; 13 primarily label the secretory cells, their cytoplasmic projections, and terminal pores. Thus, we examined regeneration of the secretory system using lectin markers and functionally characterized two genes expressed in the secretory cells: marginal adhesive gland-1 (mag-1) and Smed-reticulocalbin1 (Smed-rcn1). RNAi knockdown of these genes caused a dramatic reduction of secretory cell lectin staining, suggesting a role for mag-1 and Smed-rcn1 in secretory cell differentiation. Our results provide new insights into planarian secretory system regeneration and add new markers for labeling several planarian tissues. PMID:20865784

  9. In-silico prediction of blood-secretory human proteins using a ranking algorithm

    PubMed Central

    2010-01-01

    Background Computational identification of blood-secretory proteins, especially proteins with differentially expressed genes in diseased tissues, can provide highly useful information in linking transcriptomic data to proteomic studies for targeted disease biomarker discovery in serum. Results A new algorithm for prediction of blood-secretory proteins is presented using an information-retrieval technique, called manifold ranking. On a dataset containing 305 known blood-secretory human proteins and a large number of other proteins that are either not blood-secretory or unknown, the new method performs better than the previous published method, measured in terms of the area under the recall-precision curve (AUC). A key advantage of the presented method is that it does not explicitly require a negative training set, which could often be noisy or difficult to derive for most biological problems, hence making our method more applicable than classification-based data mining methods in general biological studies. Conclusion We believe that our program will prove to be very useful to biomedical researchers who are interested in finding serum markers, especially when they have candidate proteins derived through transcriptomic or proteomic analyses of diseased tissues. A computer program is developed for prediction of blood-secretory proteins based on manifold ranking, which is accessible at our website http://csbl.bmb.uga.edu/publications/materials/qiliu/blood_secretory_protein.html. PMID:20465853

  10. Cytokine levels in groups of patients with different duration of chronic secretory otitis.

    PubMed

    Matković, Svjetlana; Vojvodić, Danilo; Baljosevic, Ivan

    2007-11-01

    Chronic secretory otitis relates to the permanent presence of secretion in the middle ear for more than 3 months. The reason why applied therapy is often ineffective is that, for now, etiopathogenic molecular mechanisms responsible for the cause and the course of the secretory process in the mucus of the middle ear have not been precisely defined. Cytokines are the key mediators in middle ear inflammation with secretory otitis and regulating different inflammation states can add to the cause of the molecular processes that lead to hystopathological changes in mucus and submucus characteristically for the chronic state of secretory otitis. The aim of our work was to define the pro-inflammatory, immunoregulatory and allergy-associated cytokine levels in middle ear secretion samples of diseased children and to compare the defined values with the secretory process continuance in groups of patients who were diseased for more or less than 3 months. According to the results that have showed higher concentration of all ten examined cytokines in the secretion samples of the children who had secretory otitis for a longer time, it can be concluded that the disturbance expression regulation of the pro-inflammatory TNFalpha, TNFbeta, IL1beta, IFNgamma, IL-6 and IL-8, as well as immunoregulatory IL-2 and IL-10, and allergy associated cytokines IL-4 and IL-5 relating to the hyper production can add to the conversion of the inflammatory process to the chronic state, which has been maintained for longer than 3 months. PMID:17643258

  11. Identification of Stem Cells in the Secretory Complex of Salivary Glands.

    PubMed

    Kwak, M; Alston, N; Ghazizadeh, S

    2016-07-01

    Salivary glands have an essential secretory function for maintaining oral and overall health. The epithelial compartment of the gland is composed of several highly specialized cell types that cooperate to secrete and deliver saliva to the oral cavity. The mouse submandibular gland has been used as a model for major salivary glands in human. The secretory complex in this model is composed of 2 secretory compartments, including acini and granular ducts connected by intercalated ducts. Contractile myoepithelial cells surround the secretory complex to facilitate salivary flow. Whether differentiated cells in the secretory complex are maintained by self-duplication or contribution from stem cells has remained an open question. Here, in analyzing the expression of basal cytokeratin (K) 14 in the secretory complex, we discovered a subset of K14(+) ductal cells in the intercalated ducts of the adult gland. These cells are distinct from the K14-expressing basal/myoepithelial cells, proliferate at a significantly higher rate than any other epithelial cell type in the gland, and reside in a spatially defined domain within the intercalated duct. Using inducible genetic lineage tracing, we show that K14(+) ductal cells represent a long-lived yet cycling population of stem cells that are established during development and contribute to the formation and maintenance of the granular ducts throughout life. Our data provide direct evidence for the existence of stem cells contributing to homeostasis of salivary glands, as well as new insights into glandular pathobiology. PMID:26936214

  12. AP-1 and clathrin are essential for secretory granule biogenesis in Drosophila

    PubMed Central

    Burgess, Jason; Jauregui, Miluska; Tan, Julie; Rollins, Janet; Lallet, Sylvie; Leventis, Peter A.; Boulianne, Gabrielle L.; Chang, Henry C.; Le Borgne, Roland; Krämer, Helmut; Brill, Julie A.

    2011-01-01

     Regulated secretion of hormones, digestive enzymes, and other biologically active molecules requires the formation of secretory granules. Clathrin and the clathrin adaptor protein complex 1 (AP-1) are necessary for maturation of exocrine, endocrine, and neuroendocrine secretory granules. However, the initial steps of secretory granule biogenesis are only minimally understood. Powerful genetic approaches available in the fruit fly Drosophila melanogaster were used to investigate the molecular pathway for biogenesis of the mucin-containing “glue granules” that form within epithelial cells of the third-instar larval salivary gland. Clathrin and AP-1 colocalize at the trans-Golgi network (TGN) and clathrin recruitment requires AP-1. Furthermore, clathrin and AP-1 colocalize with secretory cargo at the TGN and on immature granules. Finally, loss of clathrin or AP-1 leads to a profound block in secretory granule formation. These findings establish a novel role for AP-1– and clathrin-dependent trafficking in the biogenesis of mucin-containing secretory granules. PMID:21490149

  13. Epithelial Cell Culture from Human Adenoids: A Functional Study Model for Ciliated and Secretory Cells

    PubMed Central

    González, Claudia; Espinosa, Marisol; Sánchez, María Trinidad; Droguett, Karla; Ríos, Mariana; Fonseca, Ximena; Villalón, Manuel

    2013-01-01

    Background. Mucociliary transport (MCT) is a defense mechanism of the airway. To study the underlying mechanisms of MCT, we have both developed an experimental model of cultures, from human adenoid tissue of ciliated and secretory cells, and characterized the response to local chemical signals that control ciliary activity and the secretion of respiratory mucins in vitro. Materials and Methods. In ciliated cell cultures, ciliary beat frequency (CBF) and intracellular Ca2+ levels were measured in response to ATP, UTP, and adenosine. In secretory cultures, mucin synthesis and secretion were identified by using immunodetection. Mucin content was taken from conditioned medium and analyzed in the presence or absence of UTP. Results. Enriched ciliated cell monolayers and secretory cells were obtained. Ciliated cells showed a basal CBF of 10.7 Hz that increased significantly after exposure to ATP, UTP, or adenosine. Mature secretory cells showed active secretion of granules containing different glycoproteins, including MUC5AC. Conclusion. Culture of ciliated and secretory cells grown from adenoid epithelium is a reproducible and feasible experimental model, in which it is possible to observe ciliary and secretory activities, with a potential use as a model to understand mucociliary transport control mechanisms. PMID:23484122

  14. Material Properties of Inorganic Bovine Cancellous Bovine: Nukbone

    NASA Astrophysics Data System (ADS)

    Piña, Cristina; Palma, Benito; Munguía, Nadia

    2006-09-01

    In this work, inorganic cancellous bovine bone implants prepared in the Instituto de Investigaciones en Materiales — UNAM were characterized. Elementary chemical analysis was made, toxic elements concentration were measured and the content of organic matter also. These implants fulfill all the requirements of the ASTM standards, and therefore it is possible their use in medical applications.

  15. Correlation between catecholamine secretion from bovine isolated chromaffin cells and [3H]-ouabain binding to plasma membranes

    PubMed Central

    Aunis, Dominique; García, Antonio G.

    1981-01-01

    1 Secretion of catecholamines (CA) evoked by ouabain, chlormadinone acetate (CMA), phenoxybenzamine (Pbz) and vanadate, four agents known to inhibit Na+, K+-dependent Mg2+-activated adenosine triphosphatase (ATPase) activity has been studied in suspensions of bovine isolated adrenal medullary cells. 2 Acetylcholine (ACh) evoked a 5 fold increase of the basal CA secretion from isolated cells suspended in oxygenated Krebs-bicarbonate solution kept at 27°C. Secretion was antagonized by Ca2+-deprivation or hexamethonium, indicating good functional viability of the cells. 3 Ouabain (10-7 to 10-4 M) evoked a progressive, dose-dependent release of CA from cell suspensions. Study of the time course of the secretory response for 2 h allowed the separation of two components in the secretory response at all doses studied: a slow initial component (0.011 pg/min CA) and a second faster component (0.032 pg/min CA). 4 CMA evoked a clear-cut CA secretory response. The ED50 for CMA was 10-4 M, as compared to 3 × 10-6 M for ouabain. Pbz and vanadate did not induce CA release. 5 [3H]-ouabain was taken up and bound to intact isolated cells by a non-saturable binding process. However, in semi-purified plasma membranes from bovine adrenal medulla a saturable specific [3H]-ouabain binding process was observed with a KD of 8.1 nM. Binding to the membranes was ATP-dependent and antagonized by K+. 6 [3H]-ouabain specific binding to membranes was antagonized by ouabain and CMA, but not by Pbz or vanadate; the ID50 for ouabain and CMA were 10-6 and 10-5 M respectively. 7 Ouabain partially inhibited, in a dose-dependent manner, Na+, K+-Mg2+ ATPase activity of the semi-purified plasma membranes. 8 The results demonstrate a good correlation between the ability of different drugs, known to inhibit ATPase activity, to displace [3H]-ouabain binding to adreno—medullary plasma membranes and their capacity to evoke a CA secretory response from isolated chromaffin cells. The data also suggest that

  16. Ultrastructural features of the early secretory pathway in Trichoderma reesei.

    PubMed

    Nykänen, Marko; Birch, Debra; Peterson, Robyn; Yu, Hong; Kautto, Liisa; Gryshyna, Anna; Te'o, Junior; Nevalainen, Helena

    2016-05-01

    We have systematically analysed the ultrastructure of the early secretory pathway in the Trichoderma reesei hyphae in the wild-type QM6a, cellulase-overexpressing Rut-C30 strain and a Rut-C30 transformant BV47 overexpressing a recombinant BiP1-VenusYFP fusion protein with an endoplasmic reticulum (ER) retention signal. The hyphae were studied after 24 h of growth using transmission electron microscopy, confocal microscopy and quantitative stereological techniques. All three strains exhibited different spatial organisation of the ER at 24 h in both a cellulase-inducing medium and a minimal medium containing glycerol as a carbon source (non-cellulase-inducing medium). The wild-type displayed a number of ER subdomains including parallel tubular/cisternal ER, ER whorls, ER-isolation membrane complexes with abundant autophagy vacuoles and dense bodies. Rut-C30 and its transformant BV47 overexpressing the BiP1-VenusYFP fusion protein also contained parallel tubular/cisternal ER, but no ER whorls; also, there were very few autophagy vacuoles and an increasing amount of punctate bodies where particularly the recombinant BiP1-VenusYFP fusion protein was localised. The early presence of distinct strain-specific features such as the dominance of ER whorls in the wild type and tub/cis ER in Rut-C30 suggests that these are inherent traits and not solely a result of cellular response mechanisms by the high secreting mutant to protein overload. PMID:26699139

  17. Myosin Vc Is Specialized for Transport on a Secretory Superhighway.

    PubMed

    Sladewski, Thomas E; Krementsova, Elena B; Trybus, Kathleen M

    2016-08-22

    A hallmark of the well-studied vertebrate class Va myosin is its ability to take multiple steps on actin as a single molecule without dissociating, a feature called "processivity." Therefore, it was surprising when kinetic and single-molecule assays showed that human myosin Vc (MyoVc) was not processive on single-actin filaments [1-3]. We explored the possibility that MyoVc is processive only under conditions that resemble its biological context. Recently, it was shown that zymogen vesicles are transported on actin "superhighways" composed of parallel actin cables nucleated by formins from the plasma membrane [4]. Loss of these cables compromises orderly apical targeting of vesicles. MyoVc has been implicated in transporting secretory vesicles to the apical membrane [5]. We hypothesized that actin cables regulate the processive properties of MyoVc. We show that MyoVc is unique in taking variable size steps, which are frequently in the backward direction. Results obtained with chimeric constructs implicate the lever arm/rod of MyoVc as being responsible for these properties. Actin bundles allow single MyoVc motors to move processively. Remarkably, even teams of MyoVc motors require actin bundles to move continuously at physiological ionic strength. The irregular stepping pattern of MyoVc, which may result from flexibility in the lever arm/rod of MyoVc, appears to be a unique structural adaptation that allows the actin track to spatially restrict the activity of MyoVc to specialized actin cables in order to co-ordinate and target the final stages of vesicle secretion. PMID:27498562

  18. Nociceptive sensitization by the secretory protein Bv8

    PubMed Central

    Negri, Lucia; Lattanzi, Roberta; Giannini, Elisa; Metere, Alessio; Colucci, Mariantonella; Barra, Donatella; Kreil, Günther; Melchiorri, Pietro

    2002-01-01

    The small protein Bv8, isolated from amphibian skin, belongs to a novel family of secretory proteins (Bv8-Prokineticin family, SWISS-PROT: Q9PW66) whose orthologues have been conserved throughout evolution, from invertebrates to humans. When injected intravenously or subcutaneously (from 0.06 to 500 pmol kg−1) or intrathecally (from 6 fmol to 250 pmol) in rats, Bv8 produced an intense systemic nociceptive sensitization to mechanical and thermal stimuli applied to the tail and paws. Topically delivered into one rat paw, 50 fmol of Bv8 decreased by 50% the nociceptive threshold to pressure in the injected paw without affecting the threshold in the contralateral paw. The two G-protein coupled prokineticin receptors, PK-R1 and PK-R2, were expressed in rat dorsal root ganglia (DRG) and in dorsal quadrants of spinal cord (DSC) and bound Bv8 and the mammalian orthologue, EG-VEGF, with high affinity. In DSC, PK-R1 was more abundant than PK-R2, whereas both receptors were equally expressed in DRG. IC50 of Bv8 and EG-VEGF to inhibit [125I]-Bv8 binding to rat DRG and DSC were 4.1±0.4 nM Bv8 and 76.4±7.6 nM EG-VEGF, in DRG; 7.3±0.9 nM Bv8 and 330±41 nM EG-VEGF, in DSC. In the small diameter neurons (<30 μm) of rat DRG cultures, Bv8 concentrations, ranging from 0.2 to 10 nM, raised [Ca2+]i in a dose-dependent manner. These data suggest that Bv8, through binding to PK receptors of DSC and primary sensitive neurons, results in intense sensitization of peripheral nociceptors to thermal and mechanical stimuli. PMID:12466223

  19. Secretory pathway Ca2+/Mn2+-ATPase isoform 2 and lactation: specific localization of plasmalemmal and secretory pathway Ca2+ pump isoforms in the mammary gland

    SciTech Connect

    Faddy, Helen M.; Smart, Chanel E.; Xu, Ren; Lee, Genee Y.; Kenny, Paraic A.; Feng, Mingye; Rao, Rajini; Brown, Melissa A.; Bissell, Mina J.; Roberts-Thomson, Sarah J.; Monteith, Gregory R.

    2008-04-09

    The supply of calcium to the developing neonate via milk is an important physiological process. Until recently the mechanism for the enrichment of milk with calcium was thought to be almost entirely mediated via the secretory pathway. However, recent studies suggest that a specific isoform of the plasma membrane calcium ATPase, PMCA2, is the primary mechanism for calcium transport into milk, highlighting a major role for apical calcium transport. We compared the expression of the recently identified secretory calcium ATPase, SPCA2, and SPCA1, in the mouse mammary gland during different stages of development. SPCA2 levels increased over 35 fold during lactation, while SPCA1 increased only a modest two fold. The potential importance of SPCA2 in lactation was also highlighted by its localization to luminal secretory cells of the mammary gland during lactation, while SPCA1 was expressed throughout the cells of the mammary gland. We also observed major differences in the localization of PMCA2 and PMCA1 during lactation. Using the SCp2 mouse mammary epithelial cell 3D culture model, differences in the sub-cellular distribution of PMCA2 and PMCA1 were clear. These studies highlight the likely specific roles of PMCA2 and SPCA2 in lactation, and link the recently characterized SPCA2 calcium pump to the supply of calcium into milk and the regulation of Golgi resident enzymes important in lactation. They also indicate that calcium transport into milk is a complex interplay between apical and secretory pathways.

  20. Identification of members of the Wnt signaling pathway in the embryonic pituitary gland.

    PubMed

    Douglas, K R; Brinkmeier, M L; Kennell, J A; Eswara, P; Harrison, T A; Patrianakos, A I; Sprecher, B S; Potok, M A; Lyons, R H; MacDougald, O A; Camper, S A

    2001-11-01

    Prop1 is one of several transcription factors important for the development of the pituitary gland. Downstream targets of PROP1 and other critical pituitary transcription factors remain largely unknown. We have generated a partial expression profile of the developing pituitary gland containing over 350 transcripts, using cDNA subtractive hybridization between Prop1(df/df) and wild-type embryonic pituitary gland primordia. Numerous classes of genes including transcription factors, membrane associated molecules, and cell cycle regulators were identified in this study. Of the transcripts, 34% do not have sequence similarity to known genes, but are similar to ESTs, and 4% represent novel sequences. Pituitary gland expression of a number of clones was verified using in situ hybridization. Several members of the Wnt signaling pathway were identified in the developing pituitary gland. The frizzled2 receptor, Apc, beta-catenin, groucho, and a novel isoform of TCF4 (officially named Tcf7l2) were identified in developing pituitary libraries. Three N-terminal alternatively spliced Tcf7l2 isoforms are reported here, each of which lacks a DNA-binding domain. Functional studies indicate that these isoforms can act as endogenous inhibitors of Wnt signaling in some contexts. This is the first report of Tcf7l2 and Fzd2 expression in the developing pituitary. These molecules may be important in mediating Wnt signaling during pituitary ontogeny. We expect other transcripts from these libraries to be involved in pituitary gland development. PMID:11845287

  1. Pituitary apoplexy presenting as isolated third cranial nerve palsy with ptosis : two case reports.

    PubMed

    Cho, Won-Jin; Joo, Sung-Pil; Kim, Tae-Sun; Seo, Bo-Ra

    2009-02-01

    Pituitary apoplexy is a clinical syndrome caused by an acute ischemic or hemorrhagic vascular accident involving a pituitary adenoma or an adjacent pituitary gland. Pituitary apoplexy may be associated with a variety of neurological and endocrinological signs and symptoms. However, isolated third cranial nerve palsy with ptosis as the presenting sign of pituitary apoplexy is very rare. We describe two cases of pituitary apoplexy presenting as sudden-onset unilateral ptosis and diplopia. In one case, brain magnetic resonance imaging (MRI) revealed a mass in the pituitary fossa with signs of hemorrhage, upward displacement of the optic chiasm, erosion of the sellar floor and invasion of the right cavernous sinus. In the other case, MRI showed a large area of insufficient enhancement in the anterior pituitary consistent with pituitary infarction or Sheehan's syndrome. We performed neurosurgical decompression via a transsphenoidal approach. Both patients showed an uneventful recovery. Both cases of isolated third cranial nerve palsy with ptosis completely resolved during the early postoperative period. We suggest that pituitary apoplexy should be included in the differential diagnosis of patients presenting with isolated third cranial nerve palsy with ptosis and that prompt neurosurgical decompression should be considered for the preservation of third cranial nerve function. PMID:19274125

  2. Pituitary Tumors in Childhood: an update in their diagnosis, treatment and molecular genetics

    PubMed Central

    Keil, Margaret F.; Stratakis, Constantine A.

    2009-01-01

    Pituitary tumors are rare in childhood and adolescence, with a reported prevalence of up to 1 per million children. Only 2 - 6% of surgically treated pituitary tumors occur in children. Although pituitary tumors in children are almost never malignant and hormonal secretion is rare, these tumors may result in significant morbidity. Tumors within the pituitary fossa are of two types mainly, craniopharyngiomas and adenomas; craniopharyngiomas cause symptoms by compressing normal pituitary, causing hormonal deficiencies and producing mass effects on surrounding tissues and the brain; adenomas produce a variety of hormonal conditions such as hyperprolactinemia, Cushing disease and acromegaly or gigantism. Little is known about the genetic causes of sporadic lesions, which comprise the majority of pituitary tumors, but in children, more frequently than in adults, pituitary tumors may be a manifestation of genetic conditions such as multiple endocrine neoplasia type 1 (MEN 1), Carney complex, familial isolated pituitary adenoma (FIPA), and McCune-Albright syndrome. The study of pituitary tumorigenesis in the context of these genetic syndromes has advanced our knowledge of the molecular basis of pituitary tumors and may lead to new therapeutic developments. PMID:18416659

  3. Isolated nerve endings (neurosecretosomes) from the posterior pituitary. Partial separation of vasopressin and oxytocin and the isolation of microvesicles.

    PubMed

    Bindler, E; Labella, F S; Sanwal, M

    1967-07-01

    Subcellular fractions of the bovine posterior pituitary, including one composed almost exclusively of pinched-off nerve endings (neurosecretosomes), were characterized electron microscopically, hormonally, and enzymically. 15% of the nerve terminals in the gland were isolated as neurosecretosomes, as estimated from determinations of lactic dehydrogenase, a soluble, cytoplasmic enzyme. Neurosecretosomes were subdivided into three fractions by density-gradient centrifugation. The three subfractions, each shown to be nearly homogeneous populations of neurosecretosomes by means of electron microscopic and enzymic criteria, differed from each other in their vasopressin/oxytocin (VP/OT) ratios. The VP/OT ratio increased from the lightest to the densest fraction, indicating that VP is localized to denser and OT to lighter neurosecretosomes; similar results have been obtained previously for subfractions of neurosecretory granules (NSG). No morphological differences were apparent in neurosecretosomes among the three subfractions. Although complete separation of VP and OT was not achieved, the findings suggest that VP and OT are each stored in a different species of nerve ending and support the hypothesis that a given neurosecretory cell synthesizes, stores, and secretes only one of the peptide hormones. Microvesicles, 40-80 mmicro diameter and contained in typical neurosecretory cell terminals, are believed to be degradation products of membrane ghosts of depleted NSG; electron micrographs indicative of this transformation are presented. A fraction rich in microvesicles, but containing some NSG membranes, was prepared by density-gradient centrifugation of an osmolysate of neurosecretosomes. Smaller, apparently nonneurosecretory nerve endings, lacking NSG but filled with small vesicles, are occasionally seen in sections from whole gland. The vesicles in these atypical posterior pituitary nerve endings may be true neurohumor-containing, "synaptic" vesicles. PMID:6040535

  4. Primary pituitary abscess in an adolescent boy: a rare occurrence

    PubMed Central

    Hazra, Samik; Acharyya, Saugata; Acharyya, Kakoli

    2012-01-01

    Primary pituitary abscess is a rare clinical condition at a young age. It is characterised by atypical clinical features which makes the diagnosis difficult. Correct diagnosis and therapy are mandatory due to the potentially lethal outcome. We report the case of a 14–year-old healthy boy. The onset was acute with fever, gait imbalance, slurring of speech and amnesia. MRI brain revealed a hyperintense lesion in T2-weighted image (T2WI) in sellar and suprasellar region, which was hypointense in T1WI. After administration of contrast, there was peripheral rim enhancement suggesting pituitary abscess. The diagnosis was confirmed following evacuation of purulent material, during surgery, through a trans-sphenoidal approach. Postoperatively, the boy needed prolonged intensive care support. He was discharged on day 42 after surgery. Follow-up at 3 months revealed complete motor recovery. He required hormone replacement and was intermittently showing features suggestive of frontal lobe syndrome. PMID:23257693

  5. 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

  6. Pituitary adenomas: historical perspective, surgical management and future directions

    PubMed Central

    Theodros, Debebe; Patel, Mira; Ruzevick, Jacob; Lim, Michael; Bettegowda, Chetan

    2016-01-01

    Pituitary adenomas are among the most common central nervous system tumors. They represent a diverse group of neoplasms that may or may not secrete hormones based on their cell of origin. Epidemiologic studies have documented the incidence of pituitary adenomas within the general population to be as high as 16.7%. A growing body of work has helped to elucidate the pathogenesis of these tumors. Each subtype has been shown to demonstrate unique cellular changes potentially leading to tumorigenesis. Surgical advancements over several decades have included microsurgery and the employment of the endoscope for surgical resection. These advancements increase the likelihood of gross-total resection and have resulted in decreased patient morbidity. PMID:26497533

  7. Separation of cells from the rat anterior pituitary gland

    NASA Technical Reports Server (NTRS)

    Hymer, Wesley C.; Hatfield, J. Michael

    1983-01-01

    Various techniques for separating the hormone-producing cell types from the rat anterior pituitary gland are examined. The purity, viability, and responsiveness of the separated cells depend on the physiological state of the donor, the tissue dissociation procedures, the staining technique used for identification of cell type, and the cell separation technique. The chamber-gradient setup and operation, the characteristics of the gradient materials, and the separated cell analysis of velocity sedimentation techniques (in particular Staput and Celsep) are described. Consideration is given to the various types of materials used in density gradient centrifugation and the operation of a gradient generating device. The use of electrophoresis to separate rat pituitary cells is discussed.

  8. Sustained remission of Cushing's disease with mitotane and pituitary irradiation

    SciTech Connect

    Schteingart, D.E.; Tsao, H.S.; Taylor, C.I.; McKenzie, A.; Victoria, R.; Therrien, B.A.

    1980-05-01

    Low doses of mitotane were given orally to 36 patients with Cushing's disease, concurrently with or after pituitary cobalt irradiation. Clinical and biochemical remission occurred in 29. The response to treatment occurred early in 17 patients and late in 12. The different pattern of response to mitotane was not related to the dose given or to its serum level. Early biochemical indicators of adrenal suppression with mitotane were a sharp decrease in adrenal response to the infusion of ACTH and in plasma levels of dehydroepiandrosterone sulfate. Although mitotane was given together with pituitary irradiation, initial remission was due mainly to the adrenal effect of mitotane. Plasma ACTH levels were still elevated when cortisol had returned to normal. In seventeen of the 29 patients who responded to treatment drug therapy has been discontinued, and they remain in remission of Cushing's syndrome. Side-effects have been dose dependent, with anorexia, nausea, decreased memory, and gynecomastia in men being the commonest.

  9. Gonadal steroid hormones and the hypothalamo-pituitary-adrenal axis.

    PubMed

    Handa, Robert J; Weiser, Michael J

    2014-04-01

    The hypothalamo-pituitary-adrenal (HPA) axis represents a complex neuroendocrine feedback loop controlling the secretion of adrenal glucocorticoid hormones. Central to its function is the paraventricular nucleus of the hypothalamus (PVN) where neurons expressing corticotropin releasing factor reside. These HPA motor neurons are a primary site of integration leading to graded endocrine responses to physical and psychological stressors. An important regulatory factor that must be considered, prior to generating an appropriate response is the animal's reproductive status. Thus, PVN neurons express androgen and estrogen receptors and receive input from sites that also express these receptors. Consequently, changes in reproduction and gonadal steroid levels modulate the stress response and this underlies sex differences in HPA axis function. This review examines the make up of the HPA axis and hypothalamo-pituitary-gonadal (HPG) axis and the interactions between the two that should be considered when exploring normal and pathological responses to environmental stressors. PMID:24246855

  10. Transsphenoidal pituitary resection with intraoperative MR guidance: preliminary results

    NASA Astrophysics Data System (ADS)

    Pergolizzi, Richard S., Jr.; Schwartz, Richard B.; Hsu, Liangge; Wong, Terence Z.; Black, Peter M.; Martin, Claudia; Jolesz, Ferenc A.

    1999-05-01

    The use of intraoperative MR image guidance has the potential to improve the precision, extent and safety of transsphenoidal pituitary resections. At Brigham and Women's Hospital, an open-bore configuration 0.5T MR system (SIGNA SP, GE Medical Systems, Milwaukee, WI) has been used to provide image guidance for nine transsphenoidal pituitary adenoma resections. The intraoperative MR system allowed the radiologist to direct the surgeon toward the sella turcica successfully while avoiding the cavernous sinus, optic chiasm and other sensitive structures. Imaging performed during the surgery monitored the extent of resection and allowed for removal of tumor beyond the surgeon's view in five cases. Dynamic MR imaging was used to distinguish residual tumor from normal gland and postoperative changes permitting more precise tumor localization. A heme-sensitive long TE gradient echo sequence was used to evaluate for the presence of hemorrhagic debris. All patients tolerated the procedure well without significant complications.

  11. Recurrent sterile meningitis caused by a pituitary abscess.

    PubMed

    Ford, J; Torres, L F; Cox, T; Hayward, R

    1986-10-01

    The case of a 21 year old woman who presented with recurrent sterile meningitis and bitemporal hemianopia is described. Computed tomographic scan showed a large low density ring enhancing lesion above and within the pituitary fossa which at operation and on histological examination was found to be compatible with an abscess. The visual field defect recovered completely and the scan appearances returned to normal postoperatively. PMID:3774724

  12. Flow cytometric immunofluorescence of rat anterior pituitary cells

    NASA Technical Reports Server (NTRS)

    Hatfield, J. Michael; Hymer, W. C.

    1985-01-01

    A flow cytometric immunofluorescence technique was developed for the quantification of growth hormone, prolactin, and luteinizing hormone producing cells. The procedure is based on indirect-immunofluorescence of intracellular hormone using an EPICS V cell sorter and can objectively count 50,000 cells in about 3 minutes. It can be used to study the dynamics of pituitary cell populations under various physiological and pharmacological conditions.

  13. Pulsatility of Hypothalamo-Pituitary Hormones: A Challenge in Quantification.

    PubMed

    Keenan, Daniel M; Veldhuis, Johannes D

    2016-01-01

    Neuroendocrine systems control many of the most fundamental physiological processes, e.g., reproduction, growth, adaptations to stress, and metabolism. Each such system involves the hypothalamus, the pituitary, and a specific target gland or organ. In the quantification of the interactions among these components, biostatistical modeling has played an important role. In the present article, five key challenges to an understanding of the interactions of these systems are illustrated and discussed critically. PMID:26674550

  14. Co-existent eosinophilic gastroenteritis and hypothalamic-pituitary dysfunction.

    PubMed Central

    Haeney, M. R.; Wilson, R. J.

    1977-01-01

    A case of eosinophilic gastroenteritis in a 42-year-old man is described. The patient had diarrhoea, faecal blood loss, a protein-losing enteropathy, malabsorption of fat, xylose and vitamin B12. Co-existent hypopituitarism, diabetes insipidus and hypothalamic dysfunction was demonstrated. Complete clinical recovery occurred with pituitary replacement therapy alone. The association of this endocrine abnormality with the picture of eosinophilic gastroenteritis has not previously been described. Images Fig. 1 PMID:882484

  15. Physiology of the Hypothalamic Pituitary Gonadal Axis in the Male.

    PubMed

    Corradi, Patricia Freitas; Corradi, Renato B; Greene, Loren Wissner

    2016-05-01

    Testosterone synthesis and male fertility are the results of the perfect coordination of the hypothalamic-pituitary-gonadal axis. A negative feedback finely controls the secretion of hormones at the 3 levels. Congenital or acquired disturbance at any level leads to an impairment of reproductive function and the clinical syndrome of hypogonadism. In some cases, this condition is reversible. Once the diagnosis is made, testosterone replacement therapy is the standard therapy; however, novel therapies may improve spermatogenesis while elevating testosterone levels. PMID:27132572

  16. 78 FR 72979 - Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-04

    ..., 2012, we published in the Federal Register (77 FR 15848-15913, Docket No. APHIS-2008-0010) a proposal... January 4, 2005 (70 FR 460-553, Docket No. 03-080-3). The delay of applicability was removed in a final... Products Derived from Bovines,'' published in the Federal Register on September 18, 2007 (72 FR...

  17. Feeding Frequency Affects Cultured Rat Pituitary Cells in Low Gravity

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.; Grindeland, R. E.; Salada, T.; Cenci, R.; Krishnan, K.; Mukai, C.; Nagaoka, S.

    1996-01-01

    In this report, we describe the results of a rat pituitary cell culture experiment done on STS-65 in which the effect of cell feeding on the release of the six anterior pituitary hormones was studied. We found complex microgravity related interactions between the frequency of cell feeding and the quantity and quality (i.e. biological activity) of some of the six hormones released in flight. Analyses of growth hormone (GH) released from cells into culture media on different mission days using gel filtration and ion exchange chromatography yielded qualitatively similar results between ground and flight samples. Lack of cell feeding resulted in extensive cell clumping in flight (but not ground) cultures. Vigorous fibroblast growth occurred in both ground and flight cultures fed 4 times. These results are interpreted within the context of autocrine and or paracrine feedback interactions. Finally the payload specialist successfully prepared a fresh trypsin solution in microgravity, detached the cells from their surface and reinserted them back into the culture chamber. These cells reattached and continued to release hormone in microgravity. In summary, this experiment shows that pituitary cells are microgravity sensitive and that coupled operations routinely associated with laboratory cel1 culture can also be accomplished in low gravity.

  18. Dense calcification in a GH-secreting pituitary macroadenoma

    PubMed Central

    Ibrahim, Ramez; Kalhan, Atul; Lammie, Alistair; Kotonya, Christine; Nannapanenni, Ravindra; Rees, Aled

    2014-01-01

    Summary A 30-year-old female presented with a history of secondary amenorrhoea, acromegalic features and progressive visual deterioration. She had elevated serum IGF1 levels and unsuppressed GH levels after an oral glucose tolerance test. Magnetic resonance imaging revealed a heterogeneously enhancing space-occupying lesion with atypical extensive calcification within the sellar and suprasellar areas. Owing to the extent of calcification, the tumour was a surgical challenge. Postoperatively, there was clinical, radiological and biochemical evidence of residual disease, which required treatment with a somatostatin analogue and radiotherapy. Mutational analysis of the aryl hydrocarbon receptor-interacting protein (AIP) gene was negative. This case confirms the relatively rare occurrence of calcification within a pituitary macroadenoma and its associated management problems. The presentation, biochemical, radiological and pathological findings are discussed in the context of the relevant literature. Learning points Calcification of pituitary tumours is relatively rare.Recognising calcification in pituitary adenomas on preoperative imaging is important in surgical decision-making.Gross total resection can be difficult to achieve in the presence of extensive calcification and dictates further management and follow-up to achieve disease control. PMID:24683483

  19. Anatomical and functional gonadotrope networks in the teleost pituitary

    PubMed Central

    Golan, Matan; Martin, Agnés O.; Mollard, Patrice; Levavi-Sivan, Berta

    2016-01-01

    Mammalian pituitaries exhibit a high degree of intercellular coordination; this enables them to mount large-scale coordinated responses to various physiological stimuli. This type of communication has not been adequately demonstrated in teleost pituitaries, which exhibit direct hypothalamic innervation and expression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in distinct cell types. We found that in two fish species, namely tilapia and zebrafish, LH cells exhibit close cell–cell contacts and form a continuous network throughout the gland. FSH cells were more loosely distributed but maintained some degree of cell–cell contact by virtue of cytoplasmic processes. These anatomical differences also manifest themselves at the functional level as evidenced by the effect of gap-junction uncouplers on gonadotropin release. These substances abolished the LH response to gonadotropin-releasing hormone stimulation but did not affect the FSH response to the same stimuli. Dye transfer between neighboring LH cells provides further evidence for functional coupling. The two gonadotropins were also found to be differently packaged within their corresponding cell types. Our findings highlight the evolutionary origin of pituitary cell networks and demonstrate how the different levels of cell–cell coordination within the LH and FSH cell populations are reflected in their distinct secretion patterns. PMID:27029812

  20. Management of clinically non-functioning pituitary adenoma.

    PubMed

    Chanson, Philippe; Raverot, Gerald; Castinetti, Frédéric; Cortet-Rudelli, Christine; Galland, Françoise; Salenave, Sylvie

    2015-07-01

    Clinically NFPA is currently the preferred term for designing all the pituitary adenomas which are not hormonally active (in other words, not associated with clinical syndromes such as amenorrhea-galactorrhea in the context of prolactinomas, acromegaly, Cushing's disease or hyperthyroidism secondary to TSH-secreting adenomas). They account for 15-30% of pituitary adenomas. Diagnosis is usually made either in the context of mass effect due to a macroadenoma or, increasingly, fortuitously during imaging performed for some unrelated purpose; the latter case is known as pituitary incidentaloma. Surgery is indisputably indicated in case of tumoral syndrome, but other aspects of NFPA (hormonal work-up, follow-up, and especially postoperative follow-up, management of remnant or recurrence, the special case of incidentaloma, or apoplexy) remain controversial. The French Endocrinology Society (SFE) therefore set up an expert working group of endocrinologists, neurosurgeons, ophthalmologists, neuroradiologists, pathologists and biologists to draw up guidelines, at the 2012 SFE Congress in Toulouse, France. The present article presents the guidelines suggested by this group of French-speaking experts. PMID:26072284

  1. Human Pituitary Adenoma Proteomics: New Progresses and Perspectives.

    PubMed

    Zhan, Xianquan; Wang, Xiaowei; Cheng, Tingting

    2016-01-01

    Pituitary adenoma (PA) is a common intracranial neoplasm that impacts on human health through interfering hypothalamus-pituitary-target organ axis systems. The development of proteomics gives great promises in the clarification of molecular mechanisms of a PA and discovery of effective biomarkers for prediction, prevention, early-stage diagnosis, and treatment for a PA. A great progress in the field of PA proteomics has been made in the past 10 years, including (i) the use of laser-capture microdissection, (ii) proteomics analyses of functional PAs (such as prolactinoma), invasive and non-invasive non-functional pituitary adenomas (NFPAs), protein post-translational modifications such as phosphorylation and tyrosine nitration, NFPA heterogeneity, and hormone isoforms, (iii) the use of protein antibody array, (iv) serum proteomics and peptidomics, (v) the integration of proteomics and other omics data, and (vi) the proposal of multi-parameter systematic strategy for a PA. This review will summarize these progresses of proteomics in PAs, point out the existing drawbacks, propose the future research directions, and address the clinical relevance of PA proteomics data, in order to achieve our long-term goal that is use of proteomics to clarify molecular mechanisms, construct molecular networks, and discover effective biomarkers. PMID:27303365

  2. Cushing Disease After Treatment of Nonfunctional Pituitary Adenoma

    PubMed Central

    Fang, Hongjuan; Tian, Rui; Wu, Huanwen; Xu, Jian; Fan, Hong; Zhou, Jian; Zhong, Liyong

    2015-01-01

    Abstract We describe a very rare case of nonfunctional pituitary adenoma (NFPA) that exhibited corticotrophic activity after resection and radiotherapy. The possible mechanisms of the transformation from NFPA to Cushing disease (CD) are discussed. A 43-year-old man presented with impaired vision, bilateral frontal headaches, and hyposexuality. He had no symptoms suggestive of hypercortisolism, and 8 am plasma cortisol concentration was 67.88 ng/mL. Brain imaging revealed a 15 × 15 × 21-mm sellar mass suggestive of a macroadenoma. The tumor was resected by transsphenoidal surgery and identified by immunohistochemical analysis as a chromophobic adenoma that did not stain for pituitary hormones. The patient was treated with prednisone and levothyroxine replacement therapy. After a third recurrence, the patient presented with clinical features and physical signs of Cushing syndrome. Plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations were elevated, and there was a loss of circadian rhythms. Inferior petrosal sinus sampling after desmopressin showed the central–peripheral ACTH ratio was greater than 3:1. A repeat transsphenoidal resection was undertaken. Immunohistochemistry revealed ACTH positivity. Three months following surgery, imaging showed little residual tumor, but plasma ACTH remained elevated. He was referred for postoperative Gamma Knife radiotherapy. The immunological activity and biological features of the hormones secreted from a pituitary adenoma vary with time. Because long-term outcomes are unpredictable, postoperative follow-up is essential to detect postoperative transformation from NFPA to CD. PMID:26705201

  3. Effect of cancer treatment on hypothalamic-pituitary function.

    PubMed

    Crowne, Elizabeth; Gleeson, Helena; Benghiat, Helen; Sanghera, Paul; Toogood, Andrew

    2015-07-01

    The past 30 years have seen a great improvement in survival of children and young adults treated for cancer. Cancer treatment can put patients at risk of health problems that can develop many years later, most commonly affecting the endocrine system. Patients treated with cranial radiotherapy often develop dysfunction of the hypothalamic-pituitary axis. A characteristic pattern of hormone deficiencies develops over several years. Growth hormone is disrupted most often, followed by gonadal, adrenal, and thyroid hormones, leading to abnormal growth and puberty in children, and affecting general wellbeing and fertility in adults. The severity and rate of development of hypopituitarism is determined by the dose of radiotherapy delivered to the hypothalamic-pituitary axis. Individual growth hormone deficiencies can develop after a dose as low as 10 Gy, whereas multiple hormone deficiencies are common after 60 Gy. New techniques in radiotherapy aim to reduce the effect on the hypothalamic-pituitary axis by minimising the dose received. Patients taking cytotoxic drugs do not often develop overt hypopituitarism, although the effect of radiotherapy might be enhanced. The exception is adrenal insufficiency caused by glucocorticosteroids which, although transient, can be life-threatening. New biological drugs to treat cancer can cause autoimmune hypophysitis and hypopituitarism; therefore, oncologists and endocrinologists should be vigilant and work together to optimise patient outcomes. PMID:25873572

  4. Optic nerve hypoplasia: septo-optic-pituitary dysplasia syndrome.

    PubMed Central

    Acers, T E

    1981-01-01

    Forty-five patients with the common clinical factor of optic nerve hypoplasia are analyzed regarding their clinical appearance, echographic and computed tomographic measurements of the optic nerves, and the correlation of anatomic size with visual function. Computed axial tomographic studies of the midline brain were performed on all 45 patients to determine the incidence of correlated structural defects, especially the septum pellucidum, and neuroendocrine dysfunction. Review of the spectrum of septo-optic-pituitary syndrome is separately developed to include historical background, embryogenesis, histopathology, and pathogenesis of the three major components of the syndrome. In summary, 45 patients had optic nerve hypoplasia, 32 with evidence of segmental or partial hypoplasia and 13 with evidence of complete or diffuse hypoplasia--the optic nerve hypoplasia syndrome. Twelve of these patients demonstrated absence of the septum pellucidum by computed axial tomography--the septo-optic dysplasia syndrome. Of these 12 patients with partial or complete absence of the septum pellucidum, six demonstrated evidence of pituitary hypofunction--the septo-optic-pituitary dysplasia syndrome. Images FIGURE 2 FIGURE 3 a FIGURE 3 b FIGURE 4 a FIGURE 4 b FIGURE 4 c FIGURE 4 d PMID:7043865

  5. Concurrent somatotroph and plurihormonal pituitary adenomas in a cat.

    PubMed

    Sharman, Mellora; FitzGerald, Louise; Kiupel, Matti

    2013-10-01

    An 8-year-old, male neutered, domestic longhair cat was referred for investigation of insulin-resistant diabetes mellitus. Routine haematology, serum biochemistry, urinalysis (including culture), total T4 and urine creatinine:cortisol ratio were unremarkable, but markedly increased insulin-like growth factor-1 concentration was identified and a pituitary mass was subsequently documented. The cat was treated conservatively with the dopamine agonist L-deprenyl and was re-presented 16 months later for worsening polyuria, polydipsia, polyphagia, marked lumbar muscle atrophy, development of a pendulous abdomen and marked thinning of the abdominal skin. Hyperadrenocorticism was diagnosed based on abdominal ultrasonography, dexamethasone suppression testing and endogenous adrenocorticotropic hormone (ACTH). The cat was treated with trilostane (30 mg q24h PO) and showed some clinical improvement, but developed an opportunistic fungal infection and skin fragility syndrome 4.5 months after commencing treatment, and was euthanased. A double-pituitary adenoma comprising a discrete somatotroph adenoma and a separate plurihormonal adenoma (positive immunoreactivity for ACTH, melanocyte-stimulating hormone and follicle-stimulating hormone) was identified on post-mortem examination. These two pituitary adenomas were suspected to have arisen as independent neoplastic entities with the plurihormonal tumour either being clinically silent at the initial presentation or having developed over the subsequent 16 months. PMID:23553410

  6. Clinicopathologic analysis of pituitary adenoma: a single institute experience.

    PubMed

    Cho, Hwa Jin; Kim, Hanna; Kwak, Yoon Jin; Seo, Jeong Wook; Paek, Sun Ha; Sohn, Chul-Ho; Yun, Jung Min; Kim, Da Seu Ran; Kang, Peter; Park, Peom; Park, Sung-Hye

    2014-03-01

    Pituitary adenoma (PA) is a common benign neuroendocrine tumor; however, the incidence and proportion of hormone-producing PAs in Korean patients remain unknown. Authors analyzed 506 surgically resected and pathologically proven pituitary lesions of the Seoul National University Hospital from 2006 to 2011. The lesions were categorized as: PAs (n = 422, 83.4%), Rathke's cleft cysts (RCCs) (n = 54, 10.6%), inflammatory lesions (n = 8, 1.6%), meningiomas (n = 4), craniopharyngiomas (n = 4), granular cell tumors (n = 1), metastatic renal cell carcinomas (n = 2), germinomas (n = 1), ependymomas (n = 1), and unsatisfactory specimens (n = 9, 1.8%). PAs were slightly more prevalent in women (M: F = 1:1.17) with a mean age of 48.8 yr (9-80 yr). Immunohistochemical analysis revealed that prolactin-producing PAs (16.6%) and growth hormone-producing adenomas (9.2%) were the most common functional PAs. Plurihormonal PAs and nonfunctioning (null cell) adenomas were found in 14.9% and 42.4% of patients with PAs, respectively. The recurrence rate of PAs was 11.1%, but nearly 0% for the remaining benign lesions such as RCCs. 25.4% of patients with PAs were treated by gamma-knife after surgery due to residual tumors or regrowth of residual tumor. In conclusion, the pituitary lesions and the proportions of hormone-producing PAs in Korean patients are similar to those of previous reports except nonfunctioning (null cell) PAs, which are unusually frequent. PMID:24616591

  7. Thyrotropin-secreting pituitary adenomas: epidemiology, diagnosis, and management.

    PubMed

    Amlashi, Fatemeh G; Tritos, Nicholas A

    2016-06-01

    Inappropriate secretion of TSH was first described in 1960 in a patient with evidence of hyperthyroidism and expanded sella on imaging. It was later found that a type of pituitary adenoma that secretes TSH (thyrotropinoma) was the underlying cause. The objective of the present review article is to summarize data on the epidemiology, pathogenesis, diagnosis, and management of thyrotropinomas. The prevalence of thyrotropinomas is lower than that of other pituitary adenomas. Early diagnosis is now possible thanks to the availability of magnetic resonance imaging and sensitive laboratory assays. As a corollary, many patients now present earlier in the course of their disease and have smaller tumors at the time of diagnosis. Treatment also has evolved over time. Transsphenoidal surgery is still considered definitive therapy. Meanwhile, radiation therapy, including radiosurgery, is effective in achieving tumor control in the majority of patients. In the past, radiation therapy was used as second line treatment in patients with residual or recurrent tumor after surgery. However, the availability of somatostatin analogs, which can lead to normalization of thyroid function as well as shrink these tumors, has led to an increase in the role of medical therapy in patients who are not in remission after pituitary surgery. In addition, dopamine agonists have shown some efficacy in the management of these tumors. Better understanding of the molecular pathogenesis of thyrotropinomas may lead to rationally designed therapies for patients with thyrotropinomas. PMID:26792794

  8. Ion Channels and Signaling in the Pituitary Gland

    PubMed Central

    Stojilkovic, Stanko S.; Tabak, Joël; Bertram, Richard

    2010-01-01

    Endocrine pituitary cells are neuronlike; they express numerous voltage-gated sodium, calcium, potassium, and chloride channels and fire action potentials spontaneously, accompanied by a rise in intracellular calcium. In some cells, spontaneous electrical activity is sufficient to drive the intracellular calcium concentration above the threshold for stimulus-secretion and stimulus-transcription coupling. In others, the function of these action potentials is to maintain the cells in a responsive state with cytosolic calcium near, but below, the threshold level. Some pituitary cells also express gap junction channels, which could be used for intercellular Ca2+ signaling in these cells. Endocrine cells also express extracellular ligand-gated ion channels, and their activation by hypothalamic and intrapituitary hormones leads to amplification of the pacemaking activity and facilitation of calcium influx and hormone release. These cells also express numerous G protein-coupled receptors, which can stimulate or silence electrical activity and action potential-dependent calcium influx and hormone release. Other members of this receptor family can activate calcium channels in the endoplasmic reticulum, leading to a cell type-specific modulation of electrical activity. This review summarizes recent findings in this field and our current understanding of the complex relationship between voltage-gated ion channels, ligand-gated ion channels, gap junction channels, and G protein-coupled receptors in pituitary cells. PMID:20650859

  9. An acute adrenal insufficiency revealing pituitary metastases of lung cancer in an elderly patient

    PubMed Central

    Marmouch, Hela; Arfa, Sondes; Mohamed, Saoussen Cheikh; Slim, Tensim; Khochtali, Ines

    2016-01-01

    Metastases of solid tumors to the pituitary gland are often asymptomatic or appereas as with diabetes insipid us. Pituitary metastases more commonly affect the posterior lobe and the infundibulum than the anterior lobe. The presentation with an acute adrenal insufficiency is a rare event. A 69-year-old men presented with vomiting, low blood pressure and hypoglycemia. Hormonal exploration confirmed a hypopituitarism. Appropriate therapy was initiated urgently. The hypothalamic-pituitary MRI showed a pituitary hypertrophy, a nodular thickening of the pituitary stalk. The chest X Rays revealed pulmonary opacity. Computed tomography scan of the chest showed a multiples tumors with mediastinal lymphadenopathy. Bronchoscopy and biopsy demonstrated a pulmonary adenocarcinoma. Hence we concluded to a lung cancer with multiple pituitary and adrenal gland metastases. This case emphasizes the need for an etiological investigation of acute adrenal insufficiency after treatment of acute phase. PMID:27200139

  10. [Pituitary abscess. Study of a case and review of the literature].

    PubMed

    Grosskopf, D; Chamouard, J M; Bosquet, F; Billet, R; Poisson, M; Buge, A

    1987-01-01

    The authors report one case of pituitary abscess; the diagnosis of which was particularly difficult due to its association to a multiple sclerosis that began twelve years before. A review of thirty-one pituitary abscess reported in the literature from 1970 to 1985 is made. Opto-chiasmatic compression is observed in fifty-five per cent of the cases, pituitary insufficiency in fifty-five per cent, and meningitis in sixty per cent of the cases. Although the characteristic association of meningitis and pituitary tumor symptoms occur in thirty per cent of the cases, the diagnosis is made at surgery. Pituitary adenoma and craniopharyngioma were the most frequent preoperative misdiagnosis for pituitary abscess. The extended use of cerebral C.T. Scan will allow an easier recognition of this rare entity. The discussion includes life and visual prognosis. The etiology remains unexplained in nearly half of the cases. PMID:3614500

  11. Sporadic Hemangioblastoma in the Pituitary Stalk: A Case Report and Review of the Literature

    PubMed Central

    Lee, Gun-Ill; Kim, Jae-Min; Choi, Kyu-Sun

    2015-01-01

    Hemangioblastomas in the pituitary stalk are especially rare. Most pituitary stalk hemangioblastomas reported in the literature were associated with von Hippel-Lindau (VHL) disease. Here, we report only the 3rd case of sporadic pituitary stalk hemangioblastoma diagnosed in a 60-year-old woman. Despite the danger of potential complications due to excessive vascularity or proximity to important neural structures, the tumor in our case was successfully removed while preserving pituitary function. In this case, complete surgical excision was shown to be an effective treatment option for symptomatic pituitary stalk hemangioblastoma, and we suggest careful evaluation of any highly enhancing mass with a signal void in the pituitary stalk preoperatively, even if no VHL disease is evident. PMID:26180617

  12. An acute adrenal insufficiency revealing pituitary metastases of lung cancer in an elderly patient.

    PubMed

    Marmouch, Hela; Arfa, Sondes; Mohamed, Saoussen Cheikh; Slim, Tensim; Khochtali, Ines

    2016-01-01

    Metastases of solid tumors to the pituitary gland are often asymptomatic or appereas as with diabetes insipid us. Pituitary metastases more commonly affect the posterior lobe and the infundibulum than the anterior lobe. The presentation with an acute adrenal insufficiency is a rare event. A 69-year-old men presented with vomiting, low blood pressure and hypoglycemia. Hormonal exploration confirmed a hypopituitarism. Appropriate therapy was initiated urgently. The hypothalamic-pituitary MRI showed a pituitary hypertrophy, a nodular thickening of the pituitary stalk. The chest X Rays revealed pulmonary opacity. Computed tomography scan of the chest showed a multiples tumors with mediastinal lymphadenopathy. Bronchoscopy and biopsy demonstrated a pulmonary adenocarcinoma. Hence we concluded to a lung cancer with multiple pituitary and adrenal gland metastases. This case emphasizes the need for an etiological investigation of acute adrenal insufficiency after treatment of acute phase. PMID:27200139

  13. Secretory Phospholipase A2-IIA and Cardiovascular Disease

    PubMed Central

    Holmes, Michael V.; Simon, Tabassome; Exeter, Holly J.; Folkersen, Lasse; Asselbergs, Folkert W.; Guardiola, Montse; Cooper, Jackie A.; Palmen, Jutta; Hubacek, Jaroslav A.; Carruthers, Kathryn F.; Horne, Benjamin D.; Brunisholz, Kimberly D.; Mega, Jessica L.; van Iperen, Erik P.A.; Li, Mingyao; Leusink, Maarten; Trompet, Stella; Verschuren, Jeffrey J.W.; Hovingh, G. Kees; Dehghan, Abbas; Nelson, Christopher P.; Kotti, Salma; Danchin, Nicolas; Scholz, Markus; Haase, Christiane L.; Rothenbacher, Dietrich; Swerdlow, Daniel I.; Kuchenbaecker, Karoline B.; Staines-Urias, Eleonora; Goel, Anuj; van 't Hooft, Ferdinand; Gertow, Karl; de Faire, Ulf; Panayiotou, Andrie G.; Tremoli, Elena; Baldassarre, Damiano; Veglia, Fabrizio; Holdt, Lesca M.; Beutner, Frank; Gansevoort, Ron T.; Navis, Gerjan J.; Mateo Leach, Irene; Breitling, Lutz P.; Brenner, Hermann; Thiery, Joachim; Dallmeier, Dhayana; Franco-Cereceda, Anders; Boer, Jolanda M.A.; Stephens, Jeffrey W.; Hofker, Marten H.; Tedgui, Alain; Hofman, Albert; Uitterlinden, André G.; Adamkova, Vera; Pitha, Jan; Onland-Moret, N. Charlotte; Cramer, Maarten J.; Nathoe, Hendrik M.; Spiering, Wilko; Klungel, Olaf H.; Kumari, Meena; Whincup, Peter H.; Morrow, David A.; Braund, Peter S.; Hall, Alistair S.; Olsson, Anders G.; Doevendans, Pieter A.; Trip, Mieke D.; Tobin, Martin D.; Hamsten, Anders; Watkins, Hugh; Koenig, Wolfgang; Nicolaides, Andrew N.; Teupser, Daniel; Day, Ian N.M.; Carlquist, John F.; Gaunt, Tom R.; Ford, Ian; Sattar, Naveed; Tsimikas, Sotirios; Schwartz, Gregory G.; Lawlor, Debbie A.; Morris, Richard W.; Sandhu, Manjinder S.; Poledne, Rudolf; Maitland-van der Zee, Anke H.; Khaw, Kay-Tee; Keating, Brendan J.; van der Harst, Pim; Price, Jackie F.; Mehta, Shamir R.; Yusuf, Salim; Witteman, Jaqueline C.M.; Franco, Oscar H.; Jukema, J. Wouter; de Knijff, Peter; Tybjaerg-Hansen, Anne; Rader, Daniel J.; Farrall, Martin; Samani, Nilesh J.; Kivimaki, Mika; Fox, Keith A.A.; Humphries, Steve E.; Anderson, Jeffrey L.; Boekholdt, S. Matthijs; Palmer, Tom M.; Eriksson, Per; Paré, Guillaume; Hingorani, Aroon D.; Sabatine, Marc S.; Mallat, Ziad; Casas, Juan P.; Talmud, Philippa J.

    2013-01-01

    Objectives This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease. Background Higher circulating levels of sPLA2-IIA mass or sPLA2 enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA2 inhibitor (varespladib) was stopped prematurely for lack of efficacy. Methods We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA2-IIA isoenzyme, as an instrumental variable. Results PLA2G2A rs11573156 C allele associated with lower circulating sPLA2-IIA mass (38% to 44%) and sPLA2 enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA2-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE. Conclusions Reducing sPLA2-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events. PMID:23916927

  14. Effects of 5-fluorouracil on the secretory process of the rat parotid gland

    SciTech Connect

    Sandborg, R.R.

    1986-01-01

    Experimental animals were injected intraperitoneally with 100 mg/kg 5-fluorouracil for three days. The total volume, amylase and protein content of cannulated parotid saliva were determined following stimulation with either 5 mg/kg pilocarpine or 5 mg/kg isoproterenol in experimental, pair-fed , and control animals. Saliva from experimental animals was significantly lower in volume, amylase and protein content than both control groups. 5-fluorouracil treatment reduced the total glandular amylase per unit DNA in both unstimulated and isoproterenol-stimulated parotid glands. Decreased protein synthesis may be the mechanism underlying depleted secretory protein stores since the contents of isolated secretory granules from experimental parotid glands contained less radiolabelled protein than either control group and whole gland homogenates showed marked reductions in the activities of three lysosomal enzymes and total RNA content. Experimental animals contained less labelled protein in their secretory granules than controls, but secreted a greater proportion of their total glandular radiolabelled secretory protein into saliva relative to amylase suggesting that newly synthesized secretory proteins are preferentially secreted.

  15. Not All Secretory Granules Are Created Equal: Partitioning of Soluble Content Proteins

    PubMed Central

    Sobota, Jacqueline A.; Ferraro, Francesco; Bäck, Nils; Eipper, Betty A.

    2006-01-01

    Secretory granules carrying fluorescent cargo proteins are widely used to study granule biogenesis, maturation, and regulated exocytosis. We fused the soluble secretory protein peptidylglycine α-hydroxylating monooxygenase (PHM) to green fluorescent protein (GFP) to study granule formation. When expressed in AtT-20 or GH3 cells, the PHM-GFP fusion protein partitioned from endogenous hormone (adrenocorticotropic hormone, growth hormone) into separate secretory granule pools. Both exogenous and endogenous granule proteins were stored and released in response to secretagogue. Importantly, we found that segregation of content proteins is not an artifact of overexpression nor peculiar to GFP-tagged proteins. Neither luminal acidification nor cholesterol-rich membrane microdomains play essential roles in soluble content protein segregation. Our data suggest that intrinsic biophysical properties of cargo proteins govern their differential sorting, with segregation occurring during the process of granule maturation. Proteins that can self-aggregate are likely to partition into separate granules, which can accommodate only a few thousand copies of any content protein; proteins that lack tertiary structure are more likely to distribute homogeneously into secretory granules. Therefore, a simple “self-aggregation default” theory may explain the little acknowledged, but commonly observed, tendency for both naturally occurring and exogenous content proteins to segregate from each other into distinct secretory granules. PMID:17005911

  16. Coordinated activation of the secretory pathway during notochord formation in the Xenopus embryo.

    PubMed

    Tanegashima, Kosuke; Zhao, Hui; Rebbert, Martha L; Dawid, Igor B

    2009-11-01

    We compared the transcriptome in the developing notochord of Xenopus laevis embryos with that of other embryonic regions. A coordinated and intense activation of a large set of secretory pathway genes was observed in the notochord, but not in notochord precursors in the axial mesoderm at early gastrula stage. The genes encoding Xbp1 and Creb3l2 were also activated in the notochord. These two transcription factors are implicated in the activation of secretory pathway genes during the unfolded protein response, where cells react to the stress of a build-up of unfolded proteins in their endoplasmic reticulum. Xbp1 and Creb3l2 are differentially expressed but not differentially activated in the notochord. Reduction of expression of Xbp1 or Creb3l2 by injection of antisense morpholinos led to strong deficits in notochord but not somitic muscle development. In addition, the expression of some, but not all, genes encoding secretory proteins was inhibited by injection of xbp1 morpholinos. Furthermore, expression of activated forms of Xbp1 or Creb3l2 in animal explants could activate a similar subset of secretory pathway genes. We conclude that coordinated activation of a battery of secretory pathway genes mediated by Xbp1 and Creb/ATF factors is a characteristic and necessary feature of notochord formation. PMID:19793890

  17. Coordinated activation of the secretory pathway during notochord formation in the Xenopus embryo

    PubMed Central

    Tanegashima, Kosuke; Zhao, Hui; Rebbert, Martha L.; Dawid, Igor B.

    2009-01-01

    Summary We compared the transcriptome in the developing notochord of Xenopus laevis embryos with that of other embryonic regions. A coordinated and intense activation of a large set of secretory pathway genes was observed in the notochord, but not in notochord precursors in the axial mesoderm at early gastrula stage. The genes encoding Xbp1 and Creb3l2 were also activated in the notochord. These two transcription factors are implicated in the activation of secretory pathway genes during the unfolded protein response, where cells react to the stress of a build-up of unfolded proteins in their endoplasmic reticulum. Xbp1 and Creb3l2 are differentially expressed but not differentially activated in the notochord. Reduction of expression of Xbp1 or Creb3l2 by injection of antisense morpholinos led to strong deficits in notochord but not somitic muscle development. In addition, the expression of some, but not all, genes encoding secretory proteins was inhibited by injection of xbp1 morpholinos. Furthermore, expression of activated forms of Xbp1 or Creb3l2 in animal explants could activate a similar subset of secretory pathway genes. We conclude that coordinated activation of a battery of secretory pathway genes mediated by Xbp1 and Creb/ATF factors is a characteristic and necessary feature of notochord formation. PMID:19793890

  18. Anaesthetic management for caesarean section in a case of previously operated with residual pituitary tumour

    PubMed Central

    Shah, Prerana N; Sonawane, Darshana; Appukutty, Jithesh

    2011-01-01

    Successful anaesthetic management for caesarean section in a case with previous pituitary tumour resection, with residual tumour, is reported. The pituitary gland undergoes global hyperplasia during pregnancy. Functional pituitary tumours may exhibit symptomatic enlargement during pregnancy. Growth hormone secreting tumour is associated with acromegaly which has associated anaesthetic implications of difficult airway, systemic hypertension, and diabetes and electrolyte imbalance. Intracranial space occupying lesions can increase intra cranial pressure and compromise cerebral perfusion or cause herniation. We report management of this case. PMID:22223910

  19. Regulation of Baboon Fetal Pituitary Prolactin Expression by Estrogen1

    PubMed Central

    Pepe, Gerald J.; Lynch, Terrie J.; Davies, William A.; Albrecht, Eugene D.

    2009-01-01

    We previously showed that fetal adrenal fetal zone growth was increased and the number of follicles in the fetal ovary reduced in baboons in which estradiol was suppressed by treatment with the aromatase inhibitor letrozole between mid and late gestation periods. Because adrenal/ovarian development was restored in animals treated with letrozole and estradiol, and both tissues express estrogen receptor, we proposed that estrogen regulates fetal adrenal/ovary development via a direct action. However, because prolactin can modulate fetal adrenal and adult pituitary/ovarian function, the current study determined whether estrogen action involved estradiol-regulated changes in fetal prolactin/luteinizing hormone (LH) expression. Fetal prolactin levels and the number of prolactin-positive fetal pituitary cells (per 0.37 mm2) were increased (P < 0.01) between mid (6 ± 1 ng/ml; 15.8 ± 2.4) and late (257 ± 28 ng/ml; 57.3 ± 5.1) gestation, reduced (P < 0.01) in late-gestation fetuses in which estradiol was suppressed (>95%) by letrozole (61 ± 11 ng/ml; 19.3 ± 2.0), and minimally but not significantly increased by letrozole and estradiol (99 ± 11 ng/ml; 32.7 ± 5.2). In contrast, the number of LH-positive fetal pituitary cells decreased (P < 0.01) between mid (48.8 ± 9.5) and late (17.4 ± 3.2) gestation, remained elevated (P < 0.01) in estrogen-suppressed animals (56.6 ± 5.1), and was partially but not significantly decreased by letrozole-estradiol (28.8 ± 5.2). We conclude that estrogen regulates fetal pituitary prolactin and LH expression and fetal prolactin levels. However, because prolactin and LH expressions in estrogen-suppressed fetuses were inversely related to previously demonstrated changes in adrenal/ovarian development, we propose that estrogen regulates the fetal ovary and adrenal gland directly and not via action on the fetal pituitary gland. PMID:19176882

  20. MALDI mass spectrometry imaging analysis of pituitary adenomas for near-real-time tumor delineation

    PubMed Central

    Calligaris, David; Feldman, Daniel R.; Norton, Isaiah; Olubiyi, Olutayo; Changelian, Armen N.; Machaidze, Revaz; Vestal, Matthew L.; Laws, Edward R.; Dunn, Ian F.; Santagata, Sandro; Agar, Nathalie Y. R.

    2015-01-01

    We present a proof of concept study designed to support the clinical development of mass spectrometry imaging (MSI) for the detection of pituitary tumors during surgery. We analyzed by matrix-assisted laser desorption/ionization (MALDI) MSI six nonpathological (NP) human pituitary glands and 45 hormone secreting and nonsecreting (NS) human pituitary adenomas. We show that the distribution of pituitary hormones such as prolactin (PRL), growth hormone (GH), adrenocorticotropic hormone (ACTH), and thyroid stimulating hormone (TSH) in both normal and tumor tissues can be assessed by using this approach. The presence of most of the pituitary hormones was confirmed by using MS/MS and pseudo-MS/MS methods, and subtyping of pituitary adenomas was performed by using principal component analysis (PCA) and support vector machine (SVM). Our proof of concept study demonstrates that MALDI MSI could be used to directly detect excessive hormonal production from functional pituitary adenomas and generally classify pituitary adenomas by using statistical and machine learning analyses. The tissue characterization can be completed in fewer than 30 min and could therefore be applied for the near-real-time detection and delineation of pituitary tumors for intraoperative surgical decision-making. PMID:26216958

  1. Pituitary gland levels of mercury, selenium, iron, and zinc in an Alzheimer`s disease study

    SciTech Connect

    Cornett, C.R.; Markesbery, W.R.; Wekstein, D.R.; Ehmann, W.D.

    1996-12-31

    Mercury, iron, selenium, and zinc imbalances have been observed in comparisons between Alzheimer`s disease (AD) and control subject brains. Analyses of the pituitary gland have demonstrated that this organ retains relatively high concentrations of trace elements, including mercury, iron, and zinc. Our previous work has shown that the pituitary glands of AD and control subjects are typically higher in these trace elements than brain samples from the same subject. Instrumental neutron activation analysis (INAA) was used to compare the pituitary trace element levels of AD and control subjects. This study also describes the intrasubject relationships of brain trace element levels to those in the pituitary gland of AD and control subjects.

  2. Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland

    PubMed Central

    Pyczek, Joanna; Buslei, Rolf; Schult, David; Hölsken, Annett; Buchfelder, Michael; Heß, Ina; Hahn, Heidi; Uhmann, Anja

    2016-01-01

    Hedgehog (HH) signaling is known to be essential during the embryonal development of the pituitary gland but the knowledge about its role in the adult pituitary and in associated tumors is sparse. In this report we investigated the effect of excess Hh signaling activation in murine pituitary explants and analyzed the HH signaling status of human adenopituitary lobes and a large cohort of pituitary adenomas. Our data show that excess Hh signaling led to increased proliferation of Sox2+ and Sox9+ adult pituitary stem cells and to elevated expression levels of adrenocorticotropic hormone (Acth), growth hormone (Gh) and prolactin (Prl) in the adult gland. Inhibition of the pathway by cyclopamine reversed these effects indicating that active Hh signaling positively regulates proliferative processes of adult pituitary stem cells and hormone production in the anterior pituitary. Since hormone producing cells of the adenohypophysis as well as ACTH-, GH- and PRL-immunopositive adenomas express SHH and its target GLI1, we furthermore propose that excess HH signaling is involved in the development/maintenance of hormone-producing pituitary adenomas. These findings advance the understanding of physiological hormone regulation and may open new treatment options for pituitary tumors. PMID:27109116

  3. MALDI mass spectrometry imaging analysis of pituitary adenomas for near-real-time tumor delineation.

    PubMed

    Calligaris, David; Feldman, Daniel R; Norton, Isaiah; Olubiyi, Olutayo; Changelian, Armen N; Machaidze, Revaz; Vestal, Matthew L; Laws, Edward R; Dunn, Ian F; Santagata, Sandro; Agar, Nathalie Y R

    2015-08-11

    We present a proof of concept study designed to support the clinical development of mass spectrometry imaging (MSI) for the detection of pituitary tumors during surgery. We analyzed by matrix-assisted laser desorption/ionization (MALDI) MSI six nonpathological (NP) human pituitary glands and 45 hormone secreting and nonsecreting (NS) human pituitary adenomas. We show that the distribution of pituitary hormones such as prolactin (PRL), growth hormone (GH), adrenocorticotropic hormone (ACTH), and thyroid stimulating hormone (TSH) in both normal and tumor tissues can be assessed by using this approach. The presence of most of the pituitary hormones was confirmed by using MS/MS and pseudo-MS/MS methods, and subtyping of pituitary adenomas was performed by using principal component analysis (PCA) and support vector machine (SVM). Our proof of concept study demonstrates that MALDI MSI could be used to directly detect excessive hormonal production from functional pituitary adenomas and generally classify pituitary adenomas by using statistical and machine learning analyses. The tissue characterization can be completed in fewer than 30 min and could therefore be applied for the near-real-time detection and delineation of pituitary tumors for intraoperative surgical decision-making. PMID:26216958

  4. Pituitary Morphology and Function in 43 Children with Central Diabetes Insipidus

    PubMed Central

    Liu, Wendong; Wang, Limin; Liu, Minghua; Li, Guimei

    2016-01-01

    Objective. In pediatric central diabetes insipidus (CDI), etiology diagnosis and pituitary function monitoring are usually delayed. This study aimed to illustrate the importance of regular follow-up and pituitary function monitoring in pediatric CDI. Methods. The clinical, hormonal, and neuroradiological characteristics of children with CDI at diagnosis and during 1.5–2-year follow-up were collected and analyzed. Results. The study included 43 CDI patients. The mean interval between initial manifestation and diagnosis was 22.29 ± 3.67 months (range: 2–108 months). The most common complaint was polyuria/polydipsia. Causes included Langerhans cell histiocytosis, germinoma, and craniopharyngioma in 2, 5, and 4 patients; the remaining were idiopathic. No significant changes were found during the 1.5–2 years after CDI diagnosis. Twenty-three of the 43 cases (53.5%) had ≥1 anterior pituitary hormone deficiency. Isolated growth hormone deficiency was the most frequent abnormality (37.5%) and was not associated with pituitary stalk diameter. Multiple pituitary hormone deficiencies were found in 8 cases with pituitary stalk diameter > 4.5 mm. Conclusion. Diagnosis of CDI is usually delayed. CDI with a pituitary stalk diameter > 4.5 mm carries a higher risk of multiple pituitary hormone deficiencies. Long-term MRI and pituitary function follow-ups are necessary for children with idiopathic CDI. PMID:27118970

  5. Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland.

    PubMed

    Pyczek, Joanna; Buslei, Rolf; Schult, David; Hölsken, Annett; Buchfelder, Michael; Heß, Ina; Hahn, Heidi; Uhmann, Anja

    2016-01-01

    Hedgehog (HH) signaling is known to be essential during the embryonal development of the pituitary gland but the knowledge about its role in the adult pituitary and in associated tumors is sparse. In this report we investigated the effect of excess Hh signaling activation in murine pituitary explants and analyzed the HH signaling status of human adenopituitary lobes and a large cohort of pituitary adenomas. Our data show that excess Hh signaling led to increased proliferation of Sox2(+) and Sox9(+) adult pituitary stem cells and to elevated expression levels of adrenocorticotropic hormone (Acth), growth hormone (Gh) and prolactin (Prl) in the adult gland. Inhibition of the pathway by cyclopamine reversed these effects indicating that active Hh signaling positively regulates proliferative processes of adult pituitary stem cells and hormone production in the anterior pituitary. Since hormone producing cells of the adenohypophysis as well as ACTH-, GH- and PRL-immunopositive adenomas express SHH and its target GLI1, we furthermore propose that excess HH signaling is involved in the development/maintenance of hormone-producing pituitary adenomas. These findings advance the understanding of physiological hormone regulation and may open new treatment options for pituitary tumors. PMID:27109116

  6. Angiogenesis in Pituitary Adenomas: Human Studies and New Mutant Mouse Models

    PubMed Central

    Cristina, Carolina; Demarchi, Gianina; Lopez Vicchi, Felicitas; Perez Millan, Maria Ines; Perrone, Sofia; Ornstein, Ana Maria; Berner, Silvia Inés; Becu-Villalobos, Damasia

    2014-01-01

    The role of angiogenesis in pituitary tumor development has been questioned, as pituitary tumors have been usually found to be less vascularized than the normal pituitary tissue. Nevertheless, a significantly higher degree of vasculature has been shown in invasive or macropituitary prolactinomas when compared to noninvasive and microprolactinomas. Many growth factors and their receptors are involved in pituitary tumor development. For example, VEGF, FGF-2, FGFR1, and PTTG, which give a particular vascular phenotype, are modified in human and experimental pituitary adenomas of different histotypes. In particular, vascular endothelial growth factor, VEGF, the central mediator of angiogenesis in endocrine glands, was encountered in experimental and human pituitary tumors at different levels of expression and, in particular, was higher in dopamine agonist resistant prolactinomas. Furthermore, several anti-VEGF techniques lowered tumor burden in human and experimental pituitary adenomas. Therefore, even though the role of angiogenesis in pituitary adenomas is contentious, VEGF, making permeable pituitary endothelia, might contribute to adequate temporal vascular supply and mechanisms other than endothelial cell proliferation. The study of angiogenic factor expression in aggressive prolactinomas with resistance to dopamine agonists will yield important data in the search of therapeutical alternatives. PMID:25505910

  7. Structure and regulation of the murine Clara cell secretory protein gene.

    PubMed

    Stripp, B R; Huffman, J A; Bohinski, R J

    1994-03-01

    Clara cell secretory protein (CC10 or CCSP) is an abundant component of airway secretions and has the ability to bind small hydrophobic molecules. Genomic clones were isolated for the murine gene coding for Clara cell secretory protein. Nucleotide sequence analysis revealed that the gene was composed of three exons that span 4316 bp. Organization of the murine CCSP gene was very similar to that of the rabbit gene that codes for the biochemically related uteroglobin protein. Messenger RNAs for both genes were coded for by three exons, counterparts of which encode similar structural and functional protein domains. Transcriptional regulatory elements in the 5' flanking DNA were conserved between species, as were the functional properties of these elements when characterized in assays of promoter function. These data support the notion that Clara cell secretory protein genes from the rat and mouse, and the uteroglobin gene in rabbit, represent interspecies homologues. PMID:8020953

  8. Growing dendrites and axons differ in their reliance on the secretory pathway

    PubMed Central

    Ye, Bing; Zhang, Ye; Song, Wei; Younger, Susan H.; Jan, Lily Yeh; Jan, Yuh Nung

    2007-01-01

    SUMMARY Little is known about how the distinct architectures of dendrites and axons are established. From a genetic screen, we isolated dendritic arbor reduction (dar) mutants with reduced dendritic arbors but normal axons of Drosophila neurons. We identified dar2, dar3, and dar6 genes as the homologs of Sec23, Sar1, and Rab1 of the secretory pathway. In both Drosophila and rodent neurons, defects in Sar1 expression preferentially affected dendritic growth, revealing evolutionarily conserved difference between dendritic and axonal development in the sensitivity to limiting membrane supply from the secretory pathway. Whereas limiting ER to Golgi transport resulted in decreased membrane supply from soma to dendrites, membrane supply to axons remained sustained. We also show that dendritic growth is contributed by Golgi outposts, which are found predominantly in dendrites. The distinct dependence between dendritic and axonal growth on the secretory pathway helps to establish different morphology of dendrites and axons. PMID:17719548

  9. Identify Secretory Protein of Malaria Parasite with Modified Quadratic Discriminant Algorithm and Amino Acid Composition.

    PubMed

    Feng, Yong-E

    2016-06-01

    Malaria parasite secretes various proteins in infected red blood cell for its growth and survival. Thus identification of these secretory proteins is important for developing vaccine or drug against malaria. In this study, the modified method of quadratic discriminant analysis is presented for predicting the secretory proteins. Firstly, 20 amino acids are divided into five types according to the physical and chemical characteristics of amino acids. Then, we used five types of amino acids compositions as inputs of the modified quadratic discriminant algorithm. Finally, the best prediction performance is obtained by using 20 amino acid compositions, the sensitivity of 96 %, the specificity of 92 % with 0.88 of Mathew's correlation coefficient in fivefold cross-validation test. The results are also compared with those of existing prediction methods. The compared results shown our method are prominent in the prediction of secretory proteins. PMID:26286010

  10. Bovine ephemeral fever: a review.

    PubMed

    Nandi, S; Negi, B S

    1999-04-01

    Bovine ephemeral fever is a viral disease of cattle and buffaloes besides subclinical involvement of a variety of ruminant species. The subtropical and temperate regions of Africa, Asia and Australia have experienced the major epidemic of the bovine ephemeral fever but the occurrence in the tropics can not be overlooked. Although the substantial role played by the vectors viz., mosquitoes and culicoides in bovine ephemeral fever perpetuation and dissemination, other vector involvement if any should be extensively studied. The clinical severity of the disease is not apparent and the mortality is low. However, high morbidity, enormous economic losses in terms of significant reduction in production, disruption of national and international trade and finally a variety of complications resulting from the disease have drawn appreciable attention from the researchers around the world to resolve the unsolved questions in this area. In this review, detailed informations of all the aspects of the disease has been provided in a simple, lucid and easily understandable manner. PMID:10051179

  11. [Identification of serological antigens in excretory-secretory antigens of Trichinella spiralis muscle larvae].

    PubMed

    Huang, Xuegui; He, Lifang; Yuan, Shishan; Liu, Hui; Wang, Xin

    2016-05-01

    Objective To isolate and identify serological antigens in the excretory-secretory antigens of Trichinella spiralis muscle larvae by the combination of co-immunoprecipitation and mass spectrometric technology. Methods The serum IgG of New Zealand rabbits infected with Trichinella spiralis was isolated by ammonium sulfate precipitation. Muscle larvaes were isolated from the infected muscle, and then purified and cultured to collect excretory-secretory antigens. Serological antigens in excretory-secretory antigens were isolated by co-immunoprecipitation and SDS-PAGE, and analyzed by Western blotting. Moreover, the protein bands in New Zealand rabbit sera infected with Trichinella spiralis were identified by mass spectrometric technology. Results Indirect ELISA showed that the titer of serum antibody of New Zealand rabbits infected with Trichinella spiralis was 1:6400. The rabbit serum IgG was effectively isolated by ammonium sulfate precipitation. A total of four clear protein bands of the excretory-secretory antigens of Trichinella spiralis were obtained by electrophoresis. Among them, three clear protein bands with relative molecular mass (Mr) being 40 kDa, 50 kDa and 83 kDa were recognized by the rabbit sera infected with Trichinella spiralis but not recognized by the normal rabbit sera. The obtained four protein molecules were confirmed as serine protease, specific serine protease of muscle larvae, 43 kDa secreted glycoprotein and 53 kDa excretory-secretory antigen. Conclusion Four proteins were obtained from the excretory-secretory antigens of Trichinella spiralis muscle larvae by combination of co-immunoprecipitation and mass spectrometric technique analysis, which provided new sources and insights for the diagnosis and vaccine candidates of Trichinellosis. PMID:27126943

  12. Secretory end-feet, extracerebral cells, and cerebral sense organs in certain limicole oligochaete annelids.

    PubMed

    Golding, D W; Whittle, A C

    1975-01-01

    Secretory end-feet (or SEF) systems are present in Limnodrilus and Stylodrilus but are less highly organized than those of polychaetes. SEF contain secretory vesicles and abundant mitochondria. Typical neurosecretory terminals are not found within the brain although "neurosecretory" perikarya are present in all four species studied. In Limnodrilus, Stylodrilus and Enchytraeus extracerebral cells, of probable neurosecretory function, are invested by the pericapsular epithelium. Characteristically such cells bear several cilia. In these species and in Stylaria a pair of sensory cell groups is located anteriorly within the brain. These cells are ciliated but lack associated supporting cells. PMID:170709

  13. Secretory organelles in ECL cells of the rat stomach: an immunohistochemical and electron-microscopic study.

    PubMed

    Zhao, C M; Chen, D; Lintunen, M; Panula, P; Håkanson, R

    1999-12-01

    ECL cells are numerous in the rat stomach. They produce and store histamine and chromogranin-A (CGA)-derived peptides such as pancreastatin and respond to gastrin with secretion of these products. Numerous electron-lucent vesicles of varying size and a few small, dense-cored granules are found in the cytoplasm. Using confocal and electron microscopy, we examined these organelles and their metamorphosis as they underwent intracellular transport from the Golgi area to the cell periphery. ECL-cell histamine was found to occur in both cytosol and secretory vesicles. Histidine decarboxylase, the histamine-forming enzyme, was in the cytosol, while pancreastatin (and possibly other peptide products) was confined to the dense cores of granules and secretory vesicles. Dense-cored granules and small, clear microvesicles were more numerous in the Golgi area than in the docking zone, i.e. close to the plasma membrane. Secretory vesicles were numerous in both Golgi area and docking zone, where they were sometimes seen to be attached to the plasma membrane. Upon acute gastrin stimulation, histamine was mobilized and the compartment size (volume density) of secretory vesicles in the docking zone was decreased, while the compartment size of microvesicles was increased. Based on these findings, we propose the following life cycle of secretory organelles in ECL cells: small, electron-lucent microvesicles (pro-granules) bud off the trans Golgi network, carrying proteins and secretory peptide precursors (such as CGA and an anticipated prohormone). They are transformed into dense-cored granules (approximate profile diameter 100 nm) while still in the trans Golgi area. Pro-granules and granules accumulate histamine, which leads to their metamorphosis into dense-cored secretory vesicles. In the Golgi area the secretory vesicles have an approximate profile diameter of 150 nm. By the time they reach their destination in the docking zone, their profile diameter is between 200 and 500 nm

  14. The secretory membrane system studied in real-time. Robert Feulgen Prize Lecture, 2001.

    PubMed

    Lippincott-Schwartz, J

    2001-08-01

    The discovery and development of green fluorescent protein (GFP) from the jellyfish, Aequorea victoria, has revolutionized studies on protein localization and dynamics by allowing direct observation of a protein's life history and pathway in living cells, previously only deduced from genetic, biochemical, or immunolabeling studies. Applied to the secretory membrane system, which regulates delivery of newly synthesized proteins and lipids to the cell surface, GFP-based studies are providing important new insights into the maintenance and biogenesis of organelles, as well as the origin, pathway, and fate of secretory transport intermediates. PMID:11685538

  15. Continuous stress-induced dopamine dysregulation augments PAP-I and PAP-II expression in melanotrophs of the pituitary gland

    SciTech Connect

    Konishi, Hiroyuki; Ogawa, Tokiko; Kawahara, Shinichi; Matsumoto, Sakiko; Kiyama, Hiroshi

    2011-04-01

    Research highlights: {yields} We focused on the rat pituitary intermediate lobe (IL) under continuous stress (CS). {yields} CS induced PAP-I and PAP-II expression in melanotrophs of the IL. {yields} This gene induction was triggered by CS-related dopamine dysregulation. {yields} PAP-I and PAP-II may sustain homeostasis of the IL under CS. -- Abstract: Under continuous stress (CS) in rats, melanotrophs, the predominant cell-type in the intermediate lobe (IL) of the pituitary, are hyperactivated to secrete {alpha}-melanocyte-stimulating hormone and thereafter degenerate. Although these phenomena are drastic, the molecular mechanisms underlying the cellular changes are mostly unknown. In this study, we focused on the pancreatitis-associated protein (PAP) family members of the secretory lectins and characterized their expression in the IL of CS model rats because we had identified two members of this family as up-regulated genes in our previous microarray analysis. RT-PCR and histological studies demonstrated that prominent PAP-I and PAP-II expression was induced in melanotrophs in the early stages of CS, while another family member, PAP-III, was not expressed. We further examined the regulatory mechanisms of PAP-I and PAP-II expression and revealed that both were induced by the decreased dopamine levels in the IL under CS. Because the PAP family members are implicated in cell survival and proliferation, PAP-I and PAP-II secreted from melanotrophs may function to sustain homeostasis of the IL under CS conditions in an autocrine or a paracrine manner.

  16. 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

  17. Inhibitory effects of mitotane on viability and secretory activity in mouse gonadotroph cell lines.

    PubMed

    Gentilin, Erica; Molè, Daniela; Gagliano, Teresa; Minoia, Mariella; Ambrosio, Maria Rosaria; Degli Uberti, Ettore C; Zatelli, Maria Chiara

    2014-06-01

    Mitotane represents the mainstay medical treatment for metastatic, inoperable or recurrent adrenocortical carcinoma. Besides the well-known adverse events, mitotane therapy is associated also with endocrinological effects, including sexual and reproductive dysfunction. The majority of male patients undergoing adjuvant mitotane therapy show a picture of hypogonadism, characterized by low free testosterone and high sex hormone binding globulin levels and unmodified LH concentrations. Since mitotane has been shown to have direct pituitary effects, we investigated whether mitotane may influence both cell viability and function of gonadotroph cells in the settings of two pituitary cell lines. We found that mitotane reduces cell viability, induces apoptosis, modifies cell cycle phase distribution and secretion of gonadotroph cells. The present data strengthen previous evidence showing a direct mitotane effect at pituitary level and represent a possible explanation of the lack of LH increase following decrease in free testosterone in patients undergoing adjuvant mitotane therapy. PMID:24486453

  18. Impact of nasoseptal flap elevation on sinonasal quality of life in endoscopic endonasal approach to pituitary adenomas.

    PubMed

    Jalessi, Maryam; Jahanbakhshi, Amin; Amini, Elahe; Kamrava, Seyyed Kamran; Farhadi, Mohammad

    2016-05-01

    To evaluate the impact of nasoseptal flap (NSF) elevation on sinonasal quality of life (QOL) in patients with pituitary adenomas who underwent endoscopic endonasal trans-sphenoidal approach (EETSA), the data of 106 eligible patients were included from February 2011 to December 2014. The scores of Sinonasal Outcome Test (SNOT-22) Questionnaire were assessed in case (that received reconstruction with NSF) and control groups preoperatively as well as 1, 3, 6, and more than 12 months postoperatively. Nine most related sinonasal questions were evaluated separately (9Q). There were no significant inter-group differences in the mean SNOT-22, 9Q, and sense of taste/smell scores in preoperative and all postoperative assessments. Within each group, a significant improvement of SNOT-22 and 9Q scores were noted after 12 months of surgery compared to preoperative data. In the NSF group, comparison of the pre- and first postoperative evaluation revealed a significant deterioration in 9Q score (p = 0.007) and "sense of taste/smell" (p < 0.001) which both returned to baseline in the 3rd month. Patients who used nasal paper mask for more than 100 "hour-days" showed a better SNOT-22 scores at 1st (p = 0.04) and 3rd (p < 0.001) months after surgery. Patients with adrenocorticotropic hormone (ACTH) secretory adenomas showed significantly higher scores of SNOT-22 in all postoperative assessments compared to the others. Although nasal symptoms deteriorated at first postoperative month (compare to preoperative data) in the NSF group, no negative impacts on the sinonasal QOL was showed comparing to the control group. ACTH-secreting adenomas could be assumed as a risk factor for poorer sinonasal QOL in EETSA. PMID:26220192

  19. The Central Effect of β-Endorphin and Naloxone on The Biosynthesis of GnRH and GnRH Receptor (GnRHR) in The Hypothalamic-Pituitary Unit of Follicular-Phase Ewes.

    PubMed

    Ciechanowska, M; Łapot, M; Mateusiak, K; Paruszewska, E; Malewski, T; Krawczyńska, A; Przekop, F

    2016-08-01

    The effects of prolonged, intermittent infusion of β-endorphin or naloxone into the third cerebral ventricle of follicular-phase ewes on the expression of genes encoding GnRH and GnRHR in the hypothalamus and GnRHR in the anterior pituitary gland (AP) were examined by an enzyme-linked immunoabsorbent assay. Activation or blockade of μ-opioid receptors significantly decreased or increased the GnRH concentration and GnRHR abundance in the hypothalamus, respectively, and affected in the same way GnRHR quantity in the AP gland. The changes in the levels of GnRH and GnRHR after treatment with β-endorphin as well as following action of naloxone were reflected in fluctuations of plasma LH concentrations. On the basis of these results, it is suggested that β-endorphinergic system in the hypothalamus of follicular-phase ewes affects directly or via β-endorphin-sensitive interneurons GnRH and GnRHR biosynthesis leading to suppression in secretory activity of the hypothalamic-pituitary axis. PMID:27335238

  20. Long-Term Outcomes of Radiotherapy for Pituitary Adenomas

    SciTech Connect

    Snead, Felicia E. Amdur, Robert J. M.D.; Morris, Christopher G. M.S.; Mendenhall, William M.

    2008-07-15

    Purpose: To evaluate long-term local control and toxicity for pituitary adenomas treated with fractionated radiotherapy (RT). Methods and Materials: The records of 100 patients with pituitary adenomas treated between 1983 and 2003 were retrospectively reviewed. Thirty-one patients had hormone-secreting tumors; 69 patients were treated with surgery and postoperative RT. Median follow-up was 6.7 years (range, 0.6-20.2 years) for all patients and 6.2 years (range, 2-20.2 years) for living patients. The mean dose delivered was 45 Gy (range, 43-50.4 Gy). Results: The 10-year actuarial local control rates for nonsecreting and secreting adenomas were 98% and 73%, respectively (p 0.0015). Actuarial 10-year cause-specific survival (CSS) rates were 95% and 88%, and overall survival rates were 66% and 79% for nonsecreting and secreting adenomas, respectively. Involvement of the sphenoid sinus was found to be significantly associated with decreased 10-year CSS (p = 0.0453). When compared with the two- or three-field techniques, stereotactic RT was associated with improved CSS (p = 0.0775). CSS was not significantly associated with hormone excretion, extent of surgery, or whether RT was administrated postoperatively or for salvage after a postsurgical recurrence. New cases of hypopituitarism occurred in 35 patients. One patient experienced vision loss, and one patient developed a post-treatment glioma. Conclusions: This is one of the most mature series in the literature that documents excellent results with fractionated RT for pituitary adenoma. We recommend 45 Gy at 1.8 Gy per fraction using stereotactic noncoplanar fields.

  1. Dysregulation of circadian rhythms following prolactin-secreting pituitary microadenoma.

    PubMed

    Borodkin, Katy; Ayalon, Liat; Kanety, Hanna; Dagan, Yaron

    2005-01-01

    A patient who developed an irregular sleep-wake pattern following prolactin-secreting pituitary microadenoma is described. The patient reported difficulties in sleep onset and awakening at the desired time, which caused major dysfunction in his daily life activities. Despite these difficulties, the sleep-related complaints of the patient remained unrecognized for as long as three yrs. Statistical analyses of the patient's rest-activity patterns revealed that the disruption of the sleep-wake circadian rhythm originated from a disharmony between ultradian (semicircadian) and circadian components. The circadian component displayed shorter than 24 h periodicity most of the time, but the semicircadian component fluctuated between longer and shorter than 12 h periods. Additionally, desynchrony in terms of period length was found in the tentative analyses of the rest-activity pattern, salivary melatonin, and oral temperature. While the salivary melatonin time series data could be characterized by a best-fit cosine curve of 24 h, the time series data of oral temperature was more compatible with 28 h best-fit curve. The rest-activity cycle during the simultaneous measurements, however, was best approximated by a best-fit curve of 21 h. The dysregulation of circadian rhythms occurred concomitantly, but not beforehand, with the onset of pituitary disease, thus suggesting an association between the two phenomena. This association may have interesting implications to the modeling of the circadian time-keeping system. This case also highlights the need to raise the awareness to circadian rhythm sleep disorders and to consider disruptions of sleep-wake cycle in patients with pituitary adenoma. PMID:15865328

  2. Cerebral neuroblastoma and pituitary adenocarcinoma in two budgerigars (Melopsittacus undulatus).

    PubMed

    Dezfoulian, O; Abbasi, M; Azarabad, H; Nouri, M; Kiani, K

    2011-12-01

    Case 1: A tumor mass involving the rostral part of left cerebrum was found in a two-year-old female budgerigar (Melopsittacus undulatus) at necropsy. Histologically, the neoplastic cells were arranged in sheets or cords and occasionally showed nest growth patterns. These uniform tumor cells had a little cytoplasm and ovoid or round basophilic nuclei with clearly distinct cytoplasmic membranes. The tumor cells were strong diffusely immunostained with both neuron-specific enolase (NSE) and neurofilament protein and partially for synaptophysin. They lacked chromogranin A, glial fibrillary acidic protein (GFAP), vimentin, S-100, and cytokeratin antigen expression. Moreover, they had no reaction to antibodies against pituitary hormones, such as adrenocorticotrophic hormone (ACTH), growth hormone, and prolactin. The histological and immunohistochemical examination determined the tumor as neuroblastoma. Case 2: An extremely enlarged pituitary mass was found above the sella turcica of a male budgerigar. It was soft and well delineated from the adjacent structures. On histological examination, this tumor consisted of a sheet of large closely packed polyhedral cells that had scant to a large amount of pale to strongly eosinophilic cytoplasm. The pleomorphic nuclei were apparently variable in shape, from small round hyperchromatic to very large vesicular forms. The cell boundaries were not clearly distinct. The multifocal immunolabelling of neoplastic cells for NSE, synaptophysin, GFAP, and ACTH appeared, whereas a few cells reacted with vimentin and S-100 and stained negative for other markers, which were also utilized for case 1. Histological and immunohistochemical findings led to identification of corticotroph adenocarcinoma in the pituitary gland. PMID:22312997

  3. Mechanisms of melatonin action in the pituitary and SCN.

    PubMed

    Vanecek, J; Watanabe, K

    1999-01-01

    We have compared melatonin effects in two different cell types in order to determine general intracellular mechanisms of its action. In neonatal rat pituitary, melatonin acts via the specific membrane receptors to inhibit GnRH-induced LH release. The melatonin effect disappears in adulthood due to the disappearance of the receptors. The mechanism of the melatonin action involves inhibition of the GnRH induced increase of intracellular calcium ([Ca2+])i. Our observations indicate that melatonin has dual inhibitory effect on GnRH-induced [Ca2+]i: it inhibits mobilisation of Ca2+ from endoplasmic reticulum as well as Ca2+ influx through voltage sensitive channels. Besides, melatonin also decreases basal and GnRH- or forskolin-induced increase of cAMP concentration in the pituitary. Although cAMP is not of primary importance for regulation of LH release, the cAMP decrease may participate in the mechanism of inhibitory melatonin action on LH release. Rat suprachiasmatic nuclei (SCN) have a high density of the melatonin receptors throughout the postnatal life. Cultures of dispersed SCN cells show circadian rhythm of vasopressin (AVP) release, with several fold increase in the middle of the day and decrease during night. Melatonin inhibits the spontaneous AVP release. Melatonin also inhibits the AVP release induced by vasoactive intestinal peptide (VIP). Intracellular mechanisms of the melatonin effect may involve cAMP, because melatonin inhibits the VIP-induced increase of cAMP and increase of cAMP formation by forskolin stimulates AVP release from the cultures. On the other hand, involvement of intracellular calcium in the regulation of AVP release may not be excluded. VIP induces [Ca2+]i increase in 14% of the SCN cells and AVP release is stimulated by Ca2+ ionophore ionomycin. Our observations indicate that some of the mechanisms of melatonin action are similar in the pituitary and SCN. PMID:10810514

  4. Dopamine receptor expression and function in corticotroph pituitary tumors.

    PubMed

    Pivonello, Rosario; Ferone, Diego; de Herder, Wouter W; Kros, Johan M; De Caro, Maria Laura Del Basso; Arvigo, Marica; Annunziato, Lucio; Lombardi, Gaetano; Colao, Annamaria; Hofland, Leo J; Lamberts, Steven W J

    2004-05-01

    The role of dopamine agonist treatment in corticotroph pituitary tumors is controversial. The aim of this study was to evaluate D(2) receptor expression in 20 corticotroph pituitary tumors and to correlate it to the in vitro effect of dopamine agonists on ACTH secretion and the in vivo effect of short-term cabergoline treatment on cortisol secretion. D(2) expression was evaluated by receptor-ligand binding, immunohistochemistry, and RT-PCR. A 50% or more decrease in daily urinary cortisol levels was considered a significant clinical response. At receptor-ligand binding, specific binding of [(125)I]epidepride was found in 80% of cases. At immunohistochemistry, specific D(2) immunostaining was found in 75% of cases. D(2) expression was found in 83.3% of cases (D(2long) in 40%, D(2short) in 20%, and both in 40%) by RT-PCR. Significant in vitro inhibition of ACTH secretion was found in 100% of D(2)-positive cases, but not in 100% of D(2)-negative cases by either bromocriptine or cabergoline. A significant in vivo inhibition of cortisol secretion after 3-month cabergoline treatment was found in 60%, although a normalization of cortisol secretion was found in 40% of cases. All cabergoline-responsive cases were associated with D(2) expression, whereas all noncabergoline-responsive cases but one were not associated with D(2) expression. In conclusion, functional D(2) receptors were expressed in approximately 80% of corticotroph pituitary tumors. The effectiveness of cabergoline in normalizing cortisol secretion in 40% of cases supports its therapeutic use in the management of Cushing's disease. PMID:15126577

  5. [Hyperthyroidism caused by a TSH producing pituitary adenoma].

    PubMed

    Prasch, F; Knosp, S E; Steinbach, R; Wogritsch, S; Hurtl, I; Greifeneder, M; Holm, C; Najemnik, C; Dudczak, R

    1999-01-01

    Elevated levels of free triiodothyronine (fT3) of 8.8 ng/dl (normal range 2.0 to 4.2) and free thyroxin (fT4) of 3.5 pg/ml (0.8 to 1.7) were found in the course of an examination of a 53-year old patient due to a planned hysterectomy. As thyrotropin (TSH) also was elevated with 5.8 mU/l (0.4 to 4.5), these findings corresponded to an inappropriate secretion of TSH (IST). Additional examinations revealed a blunted rise of TSH secretion after i.v. injection of 200 micrograms thyrotropin releasing hormone (TRH) as well as lacking suppression of TSH secretion after oral doses of 75 micrograms T3 during one week. alpha-TSH levels with 3.7 micrograms/l were elevated in comparison to a matched normal sample just as the molar ratio alpha-TSH/TSH with 6.95 and sex hormone-binding globulin (SHBG) with 175 nmol/l and showed an absence of inhibition in the T3 suppression test. These results were suggestive of neoplastic inappropriate secretion of TSH (nIST) due to a TSH-secreting pituitary adenoma. In concordance, the magnetic resonance imaging (MRI) showed a 1 cm tumor in the sella. The adenoma could also be visualized by 111In-octreotide and 123I-epidepride scintigraphies of the pituitary gland. After transsphenoidal resection, histological examination of the tumor resulted in the finding of a TSH-secreting adenoma. Postoperative TSH levels were not detectable, indicating the complete removal of the adenoma. Levels of fT3 and fT4 were slightly below normal with 1.9 pg/ml and 0.7 ng/dl, respectively. A control scintigraphy with 111In-octreotide following an equivocal MRI showed no uptake in the pituitary. PMID:10230475

  6. Serum thyrotropin (TSH) levels in patients with suppressed pituitary function

    SciTech Connect

    Vasavada, P.; Chen, I.; Maxon, H.; Barnes, E.; Sperling, M.

    1984-01-01

    The diagnosis of borderline hyperthyroidism is difficult. A sensitive radioimmunoassay capable of detecting subnormal levels of serum TSH may be of value in confirming this diagnosis because of the suppressed pituitary function in this disease state. This sensitive assay may also be useful in monitoring the suppression of pituitary function in thyroid cancer patients receiving thyroid hormone therapy. A sensitive radioimmunoassay capable of detecting serum TSH levels as low as 0.25 ..mu..U/m1 with coefficients of variation less than 17.2% was used to measure serum TSH levels in 80 healthy subjects, 44 hyperthyroid patients, and 25 athyrotic thyroid cancer patients on daily suppressive doses of thyroxine. All healthy subjects had detectable TSH levels with a mean value of 1.17 and two standard deviation ranges of 0.41 - 2.70 ..mu..U/m1 (lognormal distribution). Although the mean +-1 SEM value of 0.63 +- 0.003 ..mu..Um1 for hyperthyroid patients and 0.76 +- 0.08 ..mu..U/ml for thyroid cancer patients were significantly lower than that of healthy subjects (t-test, p<0.05), subnormal levels of serum TSH were found in only 28.6% (12/42) and 24% (6/25) of hyperthyroid and thyroid cancer patients, respectively. TSH stimulation tests performed in 6 of the cancer patients all gave suppressed responses. Because of considerable overlap, serum TSH levels alone cannot distinguish hyperthyroidsm from euthyroidism. However, a sensitive TSH radioimmunoassay such as the one described here may be of value in evaluating the extent of pituitary suppression in thyroid cancer therapy.

  7. Brain-Pituitary Axis Development In The CEBAS Minimodule

    NASA Technical Reports Server (NTRS)

    Schreibman, Martin P.; Magliulo-Cepriano, Lucia

    2001-01-01

    The CEBAS minimodule system is a man-made aquatic ecological system that incorporates animals, plants, snails, and microorganisms. It has been proposed that CEBAS will lead to a multigenerational experimental facility for utilization in a space station as well as for the development of an aquatic CELSS to produce animal and plant biomass for human nutrition. In this context, research on the reproductive biology of the organisms within the system should receive the highest priority. 1bus, the goals of our proposal were to provide information on space-flight-induced changes in the brain-pituitary axis and in the organs that receive information from the environment in the vertebrate selected for the CEBAS Minimodule program, the freshwater teleost Xiphophorus helleri (the swordtail). We studied the development of the brain- pituitary axis in neonates, immature and mature swordtails using histology, cytology, immunohistochemistry, morphometry, and in situ histochemistry to evaluate the synthesis, storage, and release of neurotransmitters, neuroregulatory peptides, neurohormones, and pituitary hormones as well as the structure of the organs and cells that produce, store, or are the target organs for these substances. We flew experiments in the CEBAS-minimodule on two shuttle missions, STS-89 and STS-90. In both flights four gravid females and about 200 juvenile (7 days old) swordtails (Xiphophorus helleri) constituted the aquatic vertebrates to be studied, in addition to the plants and snails that were studied by other team members. In a sample sharing agreement developed with Dr. Volker Bluem, organizer of the CEBAS research program, we received a small number of the juveniles and shared the brains of two adult females.

  8. Mixed nicotinic and muscarinic features of cholinergic receptor coupled to secretion in bovine chromaffin cells.

    PubMed Central

    Shirvan, M H; Pollard, H B; Heldman, E

    1991-01-01

    Acetylcholine evokes release from cultured bovine chromaffin cells by a mechanism that is believed to be classically nicotinic. However, we found that the full muscarinic agonist oxotremorine-M (Oxo-M) induced a robust catecholamine (CA) secretion. By contrast, muscarine, pilocarpine, bethanechol, and McN-A-343 did not elicit any secretory response. Desensitization of the response to nicotine by Oxo-M and desensitization of the response to Oxo-M by nicotine suggest that both nicotine and Oxo-M were acting at the same receptor. Additional experiments supporting this conclusion show that nicotine-induced secretion and Oxo-M-induced secretion were similarly blocked by various muscarinic and nicotinic antagonists. Moreover, secretion induced by nicotine and Oxo-M were Ca2+ dependent, and both agonists induced 45Ca2+ uptake. Equilibrium binding studies showed that [3H]Oxo-M bound to chromaffin cell membranes with a Kd value of 3.08 x 10(-8) M and a Hill coefficient of 1.00, suggesting one binding site for this ligand. Nicotine inhibited Oxo-M binding in a noncompetitive manner, suggesting that both ligands bind at two different sites on the same receptor. We propose that the receptor on bovine chromaffin cells that is coupled to secretion represents an unusual cholinergic receptor that has both nicotinic and muscarinic features. Images PMID:2052567

  9. Interaction of Tritrichomonas foetus and the bovine oviduct in an organ culture model.

    PubMed

    Benchimol, Marlene; Dias, Angelo Burla; Fontes, Reginaldo

    2006-09-10

    Tritrichomonas foetus is an extracellular parasite of the reproductive tract in cattle. The mechanism by which T. foetus causes abortion in cattle is largely unknown. There are no studies of infection in the cow oviducts, almost all published papers are related to vagina infection and few articles focusing on the uterus. The aim of the present study was to establish a working model of bovine oviduct epithelial cells and submit these cells to Tritrichomonas foetus interaction. Twenty bovine oviducts were obtained from cows at a commercial abattoir and T. foetus was injected through the isthmus into the oviduct lumen. The whole oviduct was analyzed by scanning and transmission electron microscopy. The results reported here demonstrate that: (1) fresh whole oviducts can be used as a good model to study parasite-host cell interaction; (2) cow oviduct epithelium has been shown to consist of two cell types: ciliated and nonciliated secretory cells, and T. foetus displayed great specificity for the nonciliated cells localized in the deeper oviduct folds; (3) T. foetus adheres as single separate cells, and maintains the flagella externalized; (4) differently from T. vaginalis, T. foetus does not change its shape during the adhesion process; and (5) oviduct cells exhibited morphological characteristics of apoptosis after trichomonadal interaction. PMID:16713097

  10. Mixed nicotinic and muscarinic features of cholinergic receptor coupled to secretion in bovine chromaffin cells

    SciTech Connect

    Shirvan, M.H.; Pollard, H.B.; Heldman, E. )

    1991-06-01

    Acetylcholine evokes release from cultured bovine chromaffin cells by a mechanism that is believed to be classically nicotinic. However, the authors found that the full muscarinic agonist oxotremorine-M (Oxo-M) induced a robust catecholamine (CA) secretion. By contrast, muscarine, pilocarpine, bethanechol, and McN-A-343 did not elicit any secretory response. Desensitization of the response to nicotine by Oxo-M and desensitization of the response to Oxo-M by nicotine suggest that both nicotine and Oxo-M were acting at the same receptor. Additional experiments supporting this conclusion show that nicotine-induced secretion and Oxo-M-induced secretion were similarly blocked by various muscarinic and nicotinic antagonists. Moreover, secretion induced by nicotine and Oxo-M were Ca{sup 2+} dependent, and both agonists induced {sup 45}Ca{sup 2+} uptake. Equilibrium binding studies showed that ({sup 3}H)Oxo-M bound to chromaffin cell membranes with a K{sub d} value of 3.08 {times} 10{sup {minus}8}M and a Hill coefficient of 1.00, suggesting one binding site for this ligand. Nicotine inhibited Oxo-M binding in a noncompetitive manner, suggesting that both ligands bind at two different sites on the same receptor. They propose that the receptor on bovine chromaffin cells that is coupled to secretion represents an unusual cholinergic receptor that has both nicotinic and muscarinic features.

  11. Advances in Imaging of the Pediatric Pituitary Gland.

    PubMed

    Bou-Ayache, Jad M; Delman, Bradley N

    2016-06-01

    High-resolution MRI of the pediatric sella can help identity or confirm clinical abnormalities, assess pituitary gland size and structure, and reveal acquired lesions. This article reviews contemporary techniques for imaging of the sella and associated structures in this population. Strengths and weaknesses of conventional imaging are discussed, as are techniques that can enhance yield. Some new and emerging technologies are discussed, including MR elastography, perfusion imaging, spectroscopy, and diffusion-weighted and diffusion-tensor imaging. It is expected that this overview will provide insight as to where pediatric sella imaging is currently and where it may head in the future. PMID:27241974

  12. Methamphetamine and the hypothalamic-pituitary-adrenal axis

    PubMed Central

    Zuloaga, Damian G.; Jacobskind, Jason S.; Raber, Jacob

    2015-01-01

    Psychostimulants such as methamphetamine (MA) induce significant alterations in the function of the hypothalamic-pituitary-adrenal (HPA) axis. These changes in HPA axis function are associated with altered stress-related behaviors and might contribute to addictive processes such as relapse. In this mini-review we discuss acute and chronic effects of MA (adult and developmental exposure) on the HPA axis, including effects on HPA axis associated genes/proteins, brain regions, and behaviors such as anxiety and depression. A better understanding of the mechanisms through which MA affects the HPA axis may lead to more effective treatment strategies for MA addiction. PMID:26074755

  13. Xanthogranulomatous hypophysitis: a rare and often mistaken pituitary lesion

    PubMed Central

    Gopal-Kothandapani, Jaya Sujatha; Bagga, Veejay; Wharton, Stephen B; Connolly, Daniel J; Sinha, Saurabh

    2015-01-01

    Summary Xanthogranulomatous hypophysitis (XGH) is a very rare form of pituitary hypophysitis that may present both clinically and radiologically as a neoplastic lesion. It may either be primary with an autoimmune aetiology and can occur in isolation or as a part of autoimmune systemic disease or secondary as a reactive degenerative response to an epithelial lesion (e.g. craniopharyngioma (CP), Rathke's cleft cyst, germinoma and pituitary adenomas) or as a part of a multiorgan systemic involvement such as tuberculosis, sarcoidosis or granulomatosis. It may also present with a variation of symptoms in children and adults. Our case series compares the paediatric and adult presentations of XGH and the differential diagnoses considered in one child and two adult patients, highlighting the wide spectrum of this condition. Endocrine investigations suggested panhypopituitarism in all three patients and imaging revealed a suprasellar mass compressing the optic chiasm suggestive of CP or Rathke's cleft cyst in one patient and non-functioning pituitary macroadenoma in two patients. Magnetic resonance imaging (MRI) demonstrated mixed signal intensities on T1- and T2-weighted sequences. Following endoscopic transsphenoidal surgery, histological analysis revealed necrotic material with a xanthogranulomatous reaction confirming XGH in two patients and a necrobiotic granulomatous chronic inflammatory infiltrate with neutrophils in one patient, which is not typical of current descriptions of this disorder. This case series describes the wide spectrum of XGH disease that is yet to be defined. Mixed signal intensities on T1- and T2-weighted MRI sequences may indicate XGH and diagnosis is confirmed by histology. Histological variation may indicate an underlying systemic process. Learning points XGH is a rare form of pituitary hypophysitis with a wide clinical and histological spectrum and can mimic a neoplastic lesion.XGH primarily presents with growth arrest in children and pubertal

  14. Multiple cytosolic calcium buffers in posterior pituitary nerve terminals.

    PubMed

    McMahon, Shane M; Chang, Che-Wei; Jackson, Meyer B

    2016-03-01

    Cytosolic Ca(2+) buffers bind to a large fraction of Ca(2+) as it enters a cell, shaping Ca(2+) signals both spatially and temporally. In this way, cytosolic Ca(2+) buffers regulate excitation-secretion coupling and short-term plasticity of release. The posterior pituitary is composed of peptidergic nerve terminals, which release oxytocin and vasopressin in response to Ca(2+) entry. Secretion of these hormones exhibits a complex dependence on the frequency and pattern of electrical activity, and the role of cytosolic Ca(2+) buffers in controlling pituitary Ca(2+) signaling is poorly understood. Here, cytosolic Ca(2+) buffers were studied with two-photon imaging in patch-clamped nerve terminals of the rat posterior pituitary. Fluorescence of the Ca(2+) indicator fluo-8 revealed stepwise increases in free Ca(2+) after a series of brief depolarizing pulses in rapid succession. These Ca(2+) increments grew larger as free Ca(2+) rose to saturate the cytosolic buffers and reduce the availability of Ca(2+) binding sites. These titration data revealed two endogenous buffers. All nerve terminals contained a buffer with a Kd of 1.5-4.7 µM, and approximately half contained an additional higher-affinity buffer with a Kd of 340 nM. Western blots identified calretinin and calbindin D28K in the posterior pituitary, and their in vitro binding properties correspond well with our fluorometric analysis. The high-affinity buffer washed out, but at a rate much slower than expected from diffusion; washout of the low-affinity buffer could not be detected. This work has revealed the functional impact of cytosolic Ca(2+) buffers in situ in nerve terminals at a new level of detail. The saturation of these cytosolic buffers will amplify Ca(2+) signals and may contribute to use-dependent facilitation of release. A difference in the buffer compositions of oxytocin and vasopressin nerve terminals could contribute to the differences in release plasticity of these two hormones. PMID:26880753

  15. Building a Successful Endoscopic Skull Base and Pituitary Surgery Practice.

    PubMed

    Sindwani, Raj; Woodard, Troy D; Recinos, Pablo F

    2016-02-01

    Building an endoscopic cranial base practice can be challenging and is predicated on the right team. Successful outcomes stem from an efficient and talented team that improves its skills experientially in a supportive environment. As with most new endeavors that are beyond the traditional approach, there is a great deal of up-front effort and investment required. This article explores some of the key building blocks necessary for a successful endoscopic cranial base and pituitary program and highlights some of the lessons learned during the authors' journey at the Cleveland Clinic. PMID:26614825

  16. REGIONAL PATTERNING OF HORMONES IN THE FEMALE RAT ANTERIOR PITUITARY: DISPROPORTIONATE CHANGES OVER THE ESTROUS CYCLE

    EPA Science Inventory

    The present study addressed the possibility that regional differences exist in the typical patterning of anterlor pituitary hormones seen over the estrous cycle. he results show that LH in the rostral area of the pituitary, significantly higher than in other regions on diestrus, ...

  17. Disulfiram sensitizes pituitary adenoma cells to temozolomide by regulating O6-methylguanine-DNA methyltransferase expression.

    PubMed

    Zhao, Yachao; Xiao, Zheng; Chen, Wenna; Yang, Jinsheng; Li, Tao; Fan, Bo

    2015-08-01

    O6-methylguanine-DNA methyltransferase (MGMT) activity is responsible for temozolomide (TMZ) resistance in patients harboring aggressive pituitary adenomas. Recently, disulfiram (DSF) has been shown to induce the loss of MGMT protein and increase TMZ efficacy in glioblastoma cells, while CD133+ nestin+ cells isolated from the cell population have been implicated as pituitary adenoma stem-like cells. However, whether DSF is able to potentiate the cytotoxic effects of TMZ on human pituitary adenoma cells has not been investigated to date. In the present study, CD133+ nestin+ phenotype cells were isolated from primary cultured human pituitary adenoma cells using microbeads. It was found that DSF reduced MGMT protein expression and sensitized human pituitary adenoma cells and stem-like cells to TMZ in vitro, while the proteasome inhibitor PS-341 abrogated the inhibitory effect of DSF on MGMT in vitro. The sensitizing effect of DSF was also verified in primary cultured human pituitary adenoma cells in vivo. The results of the present study suggested that DSF can increase the efficacy of the anti-tumor effect of TMZ on human pituitary adenoma cells and CD133+ nestin+ stem like cells via the ubiquitin-proteasomal MGMT protein elimination route. DSF combined with TMZ may be an effective therapeutic strategy against aggressive pituitary adenomas. PMID:25937029

  18. In1-ghrelin splicing variant is overexpressed in pituitary adenomas and increases their aggressive features.

    PubMed

    Ibáñez-Costa, Alejandro; Gahete, Manuel D; Rivero-Cortés, Esther; Rincón-Fernández, David; Nelson, Richard; Beltrán, Manuel; de la Riva, Andrés; Japón, Miguel A; Venegas-Moreno, Eva; Gálvez, Ma Ángeles; García-Arnés, Juan A; Soto-Moreno, Alfonso; Morgan, Jennifer; Tsomaia, Natia; Culler, Michael D; Dieguez, Carlos; Castaño, Justo P; Luque, Raúl M

    2015-01-01

    Pituitary adenomas comprise a heterogeneous subset of pathologies causing serious comorbidities, which would benefit from identification of novel, common molecular/cellular biomarkers and therapeutic targets. The ghrelin system has been linked to development of certain endocrine-related cancers. Systematic analysis of the presence and functional implications of some components of the ghrelin system, including native ghrelin, receptors and the recently discovered splicing variant In1-ghrelin, in human normal pituitaries (n = 11) and pituitary adenomas (n = 169) revealed that expression pattern of ghrelin system suffers a clear alteration in pituitary adenomasas compared with normal pituitary, where In1-ghrelin is markedly overexpressed. Interestingly, in cultured pituitary adenoma cells In1-ghrelin treatment (acylated peptides at 100 nM; 24-72 h) increased GH and ACTH secretion, Ca(2+) and ERK1/2 signaling and cell viability, whereas In1-ghrelin silencing (using a specific siRNA; 100 nM) reduced cell viability. These results indicate that an alteration of the ghrelin system, specially its In1-ghrelin variant, could contribute to pathogenesis of different pituitary adenomas types, and suggest that this variant and its related ghrelin system could provide new tools to identify novel, more general diagnostic, prognostic and potential therapeutic targets in pituitary tumors. PMID:25737012

  19. Childhood maltreatment and adult psychopathology: pathways to hypothalamic-pituitary-adrenal axis dysfunction

    PubMed Central

    Mello, Marcelo F.; Faria, Alvaro A.; Mello, Andrea F.; Carpenter, Linda L.; Tyrka, Audrey R.; Price, Lawrence H.

    2015-01-01

    Objective The aim of this paper was to examine the relationship between childhood maltreatment and adult psychopathology, as reflected in hypothalamic-pituitary-adrenal axis dysfunction. Method A selective review of the relevant literature was undertaken in order to identify key and illustrative research findings. Results There is now a substantial body of preclinical and clinical evidence derived from a variety of experimental paradigms showing how early-life stress is related to hypothalamic-pituitary-adrenal axis function and psychological state in adulthood, and how that relationship can be modulated by other factors. Discussion The risk for adult psychopathology and hypothalamic-pituitary-adrenal axis dysfunction is related to a complex interaction among multiple experiential factors, as well as to susceptibility genes that interact with those factors. Although acute hypothalamic-pituitary-adrenal axis responses to stress are generally adaptive, excessive responses can lead to deleterious effects. Early-life stress alters hypothalamic-pituitary-adrenal axis function and behavior, but the pattern of hypothalamic-pituitary-adrenal dysfunction and psychological outcome in adulthood reflect both the characteristics of the stressor and other modifying factors. Conclusion Research to date has identified multiple determinants of the hypothalamic-pituitary-adrenal axis dysfunction seen in adults with a history of childhood maltreatment or other early-life stress. Further work is needed to establish whether hypothalamic-pituitary-adrenal axis abnormalities in this context can be used to develop risk endophenotypes for psychiatric and physical illnesses. PMID:19967199

  20. Pituitary Androgen Receptor Signalling Regulates Prolactin but Not Gonadotrophins in the Male Mouse

    PubMed Central

    O’Hara, Laura; Curley, Michael; Tedim Ferreira, Maria; Cruickshanks, Lyndsey; Milne, Laura; Smith, Lee B.

    2015-01-01

    Production of the androgen testosterone is controlled by a negative feedback loop within the hypothalamic-pituitary-gonadal (HPG) axis. Stimulation of testicular Leydig cells by pituitary luteinising hormone (LH) is under the control of hypothalamic gonadotrophin releasing hormone (GnRH), while suppression of LH secretion by the pituitary is controlled by circulating testosterone. Exactly how androgens exert their feedback control of gonadotrophin secretion (and whether this is at the level of the pituitary), as well as the role of AR in other pituitary cell types remains unclear. To investigate these questions, we exploited a transgenic mouse line (Foxg1Cre/+; ARfl/y) which lacks androgen receptor in the pituitary gland. Both circulating testosterone and gonadotrophins are unchanged in adulthood, demonstrating that AR signalling is dispensable in the male mouse pituitary for testosterone-dependent regulation of LH secretion. In contrast, Foxg1Cre/+; ARfl/y males have a significant increase in circulating prolactin, suggesting that, rather than controlling gonadotrophins, AR-signalling in the pituitary acts to suppress aberrant prolactin production in males. PMID:25799562

  1. In1-ghrelin splicing variant is overexpressed in pituitary adenomas and increases their aggressive features

    PubMed Central

    Ibáñez-Costa, Alejandro; Gahete, Manuel D.; Rivero-Cortés, Esther; Rincón-Fernández, David; Nelson, Richard; Beltrán, Manuel; de la Riva, Andrés; Japón, Miguel A.; Venegas-Moreno, Eva; Gálvez, Ma Ángeles; García-Arnés, Juan A.; Soto-Moreno, Alfonso; Morgan, Jennifer; Tsomaia, Natia; Culler, Michael D.; Dieguez, Carlos; Castaño, Justo P.; Luque, Raúl M.

    2015-01-01

    Pituitary adenomas comprise a heterogeneous subset of pathologies causing serious comorbidities, which would benefit from identification of novel, common molecular/cellular biomarkers and therapeutic targets. The ghrelin system has been linked to development of certain endocrine-related cancers. Systematic analysis of the presence and functional implications of some components of the ghrelin system, including native ghrelin, receptors and the recently discovered splicing variant In1-ghrelin, in human normal pituitaries (n = 11) and pituitary adenomas (n = 169) revealed that expression pattern of ghrelin system suffers a clear alteration in pituitary adenomasas comparedwith normal pituitary, where In1-ghrelin is markedly overexpressed. Interestingly, in cultured pituitary adenoma cells In1-ghrelin treatment (acylated peptides at 100 nM; 24–72 h) increased GH and ACTH secretion, Ca2+ and ERK1/2 signaling and cell viability, whereas In1-ghrelin silencing (using a specific siRNA; 100 nM) reduced cell viability. These results indicate that an alteration of the ghrelin system, specially its In1-ghrelin variant, could contribute to pathogenesis of different pituitary adenomas types, and suggest that this variant and its related ghrelin system could provide new tools to identify novel, more general diagnostic, prognostic and potential therapeutic targets in pituitary tumors. PMID:25737012

  2. Hyperplasia-adenoma sequence in pituitary tumorigenesis related to aryl hydrocarbon receptor interacting protein gene mutation.

    PubMed

    Villa, Chiara; Lagonigro, Maria Stefania; Magri, Flavia; Koziak, Maria; Jaffrain-Rea, Marie-Lise; Brauner, Raja; Bouligand, Jerome; Junier, Marie Pierre; Di Rocco, Federico; Sainte-Rose, Christian; Beckers, Albert; Roux, François Xavier; Daly, Adrian F; Chiovato, Luca

    2011-06-01

    Mutations of the aryl hydrocarbon receptor interacting protein (AIP) gene are associated with pituitary adenomas that usually occur as familial isolated pituitary adenomas (FIPA). Detailed pathological and tumor genetic data on AIP mutation-related pituitary adenomas are not sufficient. Non-identical twin females presented as adolescents to the emergency department with severe progressive headache caused by large pituitary macroadenomas require emergency neurosurgery; one patient had incipient pituitary apoplexy. Post-surgically, the patients were found to have silent somatotrope adenomas on pathological examination. Furthermore, the light microscopic, immunohistochemical, and electron microscopic studies demonstrated tumors of virtually identical characteristics. The adenomas were accompanied by multiple areas of pituitary hyperplasia, which stained positively for GH, indicating somatotrope hyperplasia. Genetic analyses of the FIPA kindred revealed a novel E216X mutation of the AIP gene, which was present in both the affected patients and the unaffected father. Molecular analysis of surgical specimens revealed loss of heterozygosity (LOH) in the adenoma but showed that LOH was not present in the hyperplastic pituitary tissue from either patient. AIP immunostaining confirmed normal staining in the hyperplastic tissue and decreased staining in the adenoma in the tumors from both patients. These results demonstrate that patients with AIP germline mutation can present with silent somatotrope pituitary adenomas. The finding of somatotrope hyperplasia unaccompanied by AIP LOH suggests that LOH at the AIP locus might be a late event in a potential progression from hyperplastic to adenomatous tissue. PMID:21450940

  3. EMT Involved in Migration of Stem/Progenitor Cells for Pituitary Development and Regeneration

    PubMed Central

    Yoshida, Saishu; Kato, Takako; Kato, Yukio

    2016-01-01

    Epithelial–mesenchymal transition (EMT) and cell migration are important processes in embryonic development of many tissues as well as oncogenesis. The pituitary gland is a master endocrine tissue and recent studies indicate that Sox2-expressing stem/progenitor cells actively migrate and develop this tissue during embryogenesis. Notably, although migration activity of stem/progenitor cells in the postnatal period seems to be reduced compared to that in the embryonic period, it is hypothesized that stem/progenitor cells in the adult pituitary re-migrate from their microenvironment niche to contribute to the regeneration system. Therefore, elucidation of EMT in the pituitary stem/progenitor cells will promote understanding of pituitary development and regeneration, as well as diseases such as pituitary adenoma. In this review, so as to gain more insights into the mechanisms of pituitary development and regeneration, we summarize the EMT in the pituitary by focusing on the migration of pituitary stem/progenitor cells during both embryonic and postnatal organogenesis. PMID:27058562

  4. A FSH-Secreting Pituitary Macroadenoma Causing A Testosterone Deficiency Syndrome.

    PubMed

    Wang, Xiong; Ge, Li; Cui, Yuanqing; Lang, Cuihong; Hao, Cuifang

    2014-04-01

    FSH-secreting pituitary adenomas can affect sexual and reproductive function. In this article, we have reported the case of a 32-year-old male with secondary infertility. The patient had sexual and reproductive disturbances. The test results of the blood samples indicated obviously decreased testosterone (T) and estradiol (E2) levels. Based on previous hormonal results, the patient received pituitary stimulation and human chorionic gonadotropin (hCG) tests. Both follicle stimulating hormone (FSH) and luteinizing hormone (LH) showed low response during the pituitary stimulation test. The results of the hCG test indicated that T/E2 could recover to a normal level. In addition, this patient was diagnosed with pituitary macroadenoma, which was supported by the pituitary MRI. The man's sexual and reproductive functions recovered following surgery. The pathological results confirmed that the tumor tissue was an FSH-secreting pituitary adenoma by immunohistochemical staining. The purpose of this report was to review the relative literature and discuss the influence of FSH-secreting pituitary adenomas on hormones through the hypothalamus-pituitary-testis axis. PMID:24696774

  5. EMT Involved in Migration of Stem/Progenitor Cells for Pituitary Development and Regeneration.

    PubMed

    Yoshida, Saishu; Kato, Takako; Kato, Yukio

    2016-01-01

    Epithelial-mesenchymal transition (EMT) and cell migration are important processes in embryonic development of many tissues as well as oncogenesis. The pituitary gland is a master endocrine tissue and recent studies indicate that Sox2-expressing stem/progenitor cells actively migrate and develop this tissue during embryogenesis. Notably, although migration activity of stem/progenitor cells in the postnatal period seems to be reduced compared to that in the embryonic period, it is hypothesized that stem/progenitor cells in the adult pituitary re-migrate from their microenvironment niche to contribute to the regeneration system. Therefore, elucidation of EMT in the pituitary stem/progenitor cells will promote understanding of pituitary development and regeneration, as well as diseases such as pituitary adenoma. In this review, so as to gain more insights into the mechanisms of pituitary development and regeneration, we summarize the EMT in the pituitary by focusing on the migration of pituitary stem/progenitor cells during both embryonic and postnatal organogenesis. PMID:27058562

  6. Purification and in vitro-phospholabeling of secretory envelope proteins E1 and E2 of hepatitis C virus expressed in insect cells.

    PubMed

    Hüssy, P; Schmid, G; Mous, J; Jacobsen, H

    1996-11-01

    The putative envelope glycoproteins of hepatitis C virus (HCV), E1 and E2, were expressed as recombinant, secretory proteins in Sf9 insect cells through infection with recombinant baculoviruses. The influenza virus hemagglutinin signal sequence (HASS) was inserted upstream of the HCV-cDNAs in order to effect secretion. Furthermore, a hexa-histidine tag for purification on a Ni(2+)-nitrilotriacetic acid (Ni(2+)-NTA) column and a protein kinase A (PKA) recognition sequence for in vitro-phospholabeling were fused upstream of the HCV-cDNA. E1- and E2 proteins lacking their carboxy-terminal, hydrophobic sequence were produced by baculovirus-infected insect cells in bioreactors of 23 1. The medium was concentrated and proteins were purified under native conditions on Ni(2+)-NTA columns. Purified proteins could be phospholabeled in vitro using the catalytic subunit of protein kinase. A isolated from bovine heart and gamma-[32P]ATP. Labeled E1 and E2 proteins expressed in insect cells could be immunoprecipitated with sera from HCV-infected patients. Co-expression of these E1 and E2 proteins led to the formation of E1-E2 complexes within the insect cell and to secretion of these complexes into the medium. PMID:8896240

  7. Antigenic analyses of tissues and excretory and secretory products from Strongylus vulgaris.

    PubMed

    Wynne, E; Slocombe, J O; Wilkie, B N

    1981-07-01

    Rabbit antisera were prepared against veronal buffered saline extracts of L4 and L5 Strongylus vulgaris, adult S. vulgaris and adult Strongylus equinus retrieved from naturally infected horses. In agar gel diffusion with these antisera, adult S vulgaris and S. equinus each appeared to have at least one unique antigen; larval S. vulgaris appeared to have two species-specific and two stage-specific antigens. There were several common antigens. Excretory and secretory products were collected also from L4 and L5 an maintained over several days in tissue culture fluid. In agar gel diffusion against the above rabbit antisera, a stage-specific antigen was found also in excretory and secretory products. In addition, excretory and secretory products had three antigens in common with adult and larval S. vulgaris, but only one of these was common to adult S. equinus. The excretory and secretory products appear, therefore, to have two species-specific and one stage-specific antigens. PMID:6804070

  8. Antigenic analyses of tissues and excretory and secretory products from Strongylus vulgaris.

    PubMed Central

    Wynne, E; Slocombe, J O; Wilkie, B N

    1981-01-01

    Rabbit antisera were prepared against veronal buffered saline extracts of L4 and L5 Strongylus vulgaris, adult S. vulgaris and adult Strongylus equinus retrieved from naturally infected horses. In agar gel diffusion with these antisera, adult S vulgaris and S. equinus each appeared to have at least one unique antigen; larval S. vulgaris appeared to have two species-specific and two stage-specific antigens. There were several common antigens. Excretory and secretory products were collected also from L4 and L5 an maintained over several days in tissue culture fluid. In agar gel diffusion against the above rabbit antisera, a stage-specific antigen was found also in excretory and secretory products. In addition, excretory and secretory products had three antigens in common with adult and larval S. vulgaris, but only one of these was common to adult S. equinus. The excretory and secretory products appear, therefore, to have two species-specific and one stage-specific antigens. Images Fig. 1 a and b. Fig. 2 a and b. Fig. 3 a and b. Fig. 4 a and b. Fig. 5 a and b. Fig. 6 a and b. Fig. 7 a and b. Fig. 8 a and b. PMID:6804070

  9. Regulation of renin processing and secretion: chemiosmotic control and novel secretory pathway.

    PubMed

    King, J A; Lush, D J; Fray, J C

    1993-08-01

    The renin-angiotensin-aldosterone system (RAAS) plays an important role in cardiovascular and electrolyte regulation in health and disease. Juxtaglomerular cells in the kidney regulate endocrine RAAS by physiologically controlling conversion of prorenin and secretion of renin. The classical baroceptor, neurogenic, and macula densa mechanisms regulate renin expression at the cellular level by Ca2+, adenosine 3',5'-cyclic monophosphate (cAMP), and chemiosmotic forces (K+, Cl-, and water flux coupled to H+ movement). The baroceptor mechanism (through Ca2+) activates K+ and Cl- channels in the surface membrane and deactivates a KCl-H+ exchange chemiosmotic transporter in the secretory granular membrane. The neurogenic mechanism (through cAMP) promotes prorenin processing to renin. The macula densa mechanism (through K+ and Cl-) involves the processing of prorenin to renin. Ca2+, by inhibiting the KCl-H+ exchange transporter, prevents secretory granules from engaging in chemiosmotically mediated exocytosis. cAMP, on the other hand, by stimulating H+ influx, provides the acidic granular environment for prorenin processing to renin. It is concluded that, in the presence of a favorable chemiosmotic environment, prorenin is processed to renin, which may then be secreted by regulative degranulation or divergence translocation, a novel secretory pathway used by several secretory proteins, including renin. PMID:7690183

  10. Secretory protein traffic. Chromogranin A contains a dominant targeting signal for the regulated pathway.

    PubMed Central

    Parmer, R J; Xi, X P; Wu, H J; Helman, L J; Petz, L N

    1993-01-01

    Secretory proteins are targeted into either constitutive (secreted upon synthesis) or regulated (stored in vesicles and released in response to a secretagogue) pathways. To investigate mechanisms of protein targeting into catecholamine storage vesicles (CSV), we stably expressed human chromogranin A (CgA), the major soluble protein in human CSV, in the rat pheochromocytoma PC-12 cell line. Chromaffin cell secretagogues (0.1 mM nicotinic cholinergic agonist, 55 mM K+, or 2 mM Ba++) caused cosecretion of human CgA and catecholamines from human CgA-expressing cells. Sucrose gradients colocalized human CgA and catecholamines to subcellular particles of the same buoyant density. Chimeric proteins, in which human CgA (either full-length [457 amino acids] or truncated [amino-terminal 226 amino acids]) was fused in-frame to the ordinarily nonsecreted protein chloramphenicol acetyltransferase (CAT), were expressed transiently in PC-12 cells. Both constructs directed CAT activity into regulated secretory vesicles, as judged by secretagogue-stimulated release. These data demonstrate that human CgA expressed in PC-12 cells is targeted to regulated secretory vesicles. In addition, human CgA can divert an ordinarily non-secreted protein into the regulated secretory pathway, consistent with the operation of a dominant targeting signal for the regulated pathway within the peptide sequence of CgA. Images PMID:8394383

  11. Analysis of Protein Localization and Secretory Pathway Function Using the Yeast "Saccharomyces Cerevisiae"

    ERIC Educational Resources Information Center

    Vallen, Elizabeth

    2002-01-01

    The isolation and characterization of mutants has been crucial in understanding a number of processes in the field of cell biology. In this exercise, students examine the effects of mutations in the secretory pathway on protein localization. Yeast strains deficient for synthesis of histidinol dehydrogenase are transformed with a plasmid encoding a…

  12. Calcium is involved in both positive and negative modulation of the secretory system for ANP.

    PubMed

    Doubell, A F; Thibault, G

    1994-05-01

    The calcium dependence of the atrial natriuretic peptide (ANP) secretory system is controversial. Some studies clearly support a stimulatory role, whereas others favor an inhibitory role for calcium in this endocrine system. We demonstrate that calcium is involved in both a positive modulatory role and a negative modulatory role, thereby providing some explanation for the seemingly irreconcilable findings previously published. The negative modulatory role performed by calcium is evident during basal secretion, whereas the positive modulatory role is especially evident in the sustained phase of the secretory response to stimulation. Furthermore, we demonstrate the calcium dependence of processing of the prohormone to the mature circulating form in a cell culture system. This supports the concept that processing is a function of the atrial myocyte rather than of the mesenchymal cells of the atrium. We have demonstrated previously that calcium is important for packaging of the prohormone into secretory granules. Together these findings support a multifaceted role for calcium in the regulation of the secretory apparatus for ANP. PMID:8203584

  13. Resin secretory structures of Boswellia papyrifera and implications for frankincense yield

    PubMed Central

    Tolera, Motuma; Menger, David; Sass-Klaassen, Ute; Sterck, Frank J.; Copini, Paul; Bongers, Frans

    2013-01-01

    Background and Aims Frankincense, a gum-resin, has been tapped from Boswellia papyrifera trees for centuries. Despite the intensive tapping and economic interest of B. papyrifera, information on the resin secretory structures, which are responsible for synthesis, storage and transport of frankincense, is virtually absent. This study describes the type, architecture and distribution of resin secretory structures of B. papyrifera and its relevance for the ecophysiology and economic use of the tree. Methods The type and architecture of resin secretory structures present in bark and wood was investigated from transversal, tangential and radial sections of bark and wood samples. The diameter and density (number of resin canals mm−2) of axial resin canals were determined from digital images of thin sections across the different zones of inner bark. Key Results Resin canals form a three-dimensional network within the inner bark. Yet, the intact resin-conducting and producing network is on average limited to the inner 6·6 mm of the inner bark. Within the inner bark, the density of non-lignified axial resin canals decreases and the density of lignified resin canals increases from the vascular cambium towards the outer bark. In the wood, only radial resin canals were encountered. Conclusions Frankincense tapping techniques can be improved based on knowledge of bark anatomy and distribution and architecture of resin secretory structures. The suggested new techniques will contribute to a more sustainable frankincense production that enhances the contribution of frankincense to rural livelihoods and the national economy. PMID:23223203

  14. Secretory vesicle rebound hyperacidification and increased quantal size due to prolonged methamphetamine exposure

    PubMed Central

    Markov, Dmitriy; Mosharov, Eugene V.; Setlik, Wanda; Gershon, Michael D.; Sulzer, David

    2009-01-01

    Acute exposure to amphetamines collapses secretory vesicle pH gradients, which increases cytosolic catecholamine levels while decreases the quantal size of catecholamine release during fusion events. Amphetamine and methamphetamine, however, are retained in tissues over long durations. We used optical and electron microscopic probes to measure the effects of long-term methamphetamine exposure on secretory vesicle pH, and amperometry and intracellular patch electrochemistry to observe the effects on neurosecretion and cytosolic catecholamines in cultured rat chromaffin cells. In contrast to acute methamphetamine effects, exposure to the drug for 6–48 h at 10 μM and higher concentrations produced a concentration-dependent rebound hyperacidification of secretory vesicles. At 5–10 μM levels, methamphetamine increased the quantal size and reinstated exocytotic catecholamine release, although very high (>100 μM) levels of the drug, while continuing to produce rebound hyperacidification, did not increase quantal size. Secretory vesicle rebound hyperacidification was temperature dependent with optimal response at ~ 37°C, was not blocked by the transcription inhibitor, puromycin, and appears to be a general compensatory response to prolonged exposure with membranophilic weak bases, including amphetamines, methylphenidate, cocaine, and ammonia. Thus, under some conditions of prolonged exposure, amphetamines and other weak bases can enhance, rather than deplete, the vesicular release of catecholamines via a compensatory response resulting in vesicle acidification. PMID:19014382

  15. Regulated phosphorylation of secretory granule membrane proteins of the rat parotid gland

    SciTech Connect

    Marino, C.R.; Castle, J.D.; Gorelick, F.S. )

    1990-07-01

    An antiserum raised against purified rat parotid secretory granule membrane proteins has been used to identify organelle-specific protein phosphorylation events following stimulation of intact cells from the rat parotid gland. After lobules were prelabeled with ({sup 32}P)orthophosphate and exposed to secretagogues, phosphoproteins were immunoprecipitated with the granule membrane protein antiserum, separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and visualized by autoradiography. Parallel studies of stimulated amylase release were performed. Isoproterenol treatment of parotid lobules resulted in an increase in the phosphate content of immunoprecipitable 60- and 72-kDa proteins that correlated with amylase release in a time-dependent manner. Forskolin addition mimicked these effects, but only the isoproterenol effects were reversed by propranolol treatment. To confirm the specificity of the antiserum to the secretory granule membrane fraction, subcellular isolation techniques were employed following in situ phosphorylation. The 60- and 72-kDa phosphoproteins were immunoprecipitated from both a particulate fraction and a purified secretory granule fraction. Furthermore, the extraction properties of both species suggest that they are integral membrane proteins. These findings support the possibility that stimulus-regulated secretion may involve phosphorylation of integral membrane proteins of the exocrine secretory granule.

  16. Effect of Semen on Vaginal Fluid Cytokines and Secretory Leukocyte Protease Inhibitor

    PubMed Central

    Agnew, Kathy J.; Aura, Jan; Nunez, Norma; Lee, Zandra; Lawler, Rick; Richardson, Carol E.; Culhane, Jennifer; Hitti, Jane

    2008-01-01

    The presence of semen in vaginal fluid, as identified by an acid phosphatase spot test, does not influence vaginal proinflammatory cytokine concentrations. Objective: determine whether semen, as detected by acid phosphatase, influences vaginal cytokines or secretory leukocyte protease inhibitor concentrations. Methods: 138 pregnant women had vaginal fluid collected for Gram stain, acid phosphatase detection by colorimetric assay, and interleukin 1-Beta, interleukin-6, interleukin-8, and secretory leukocyte protease inhibitor measurement by enzyme immunoassay. Results for women with and without acid phosphatase were compared by Mann-Whitney test. Results: of 138 subjects, 28 (20%) had acid phosphatase detected; of these, only 19 (68%) reported recent intercourse and 3 (11%) had sperm seen on Gram stain. There were no significant differences in proinflammatory cytokine concentrations; however, secretory leukocyte protease inhibitor concentrations were significantly higher among women with acid phosphatase. Conclusions: proinflammatory cytokine measurement does not appear to be affected by the presence of semen, but secretory leukocyte protease inhibitor is significantly higher when semen is present. Detection of semen by acid phosphatase was associated with higher vaginal SLPI concentrations, however, the presence of semen did not appear to influence vaginal proinflammatory cytokine concentrations. PMID:18615190

  17. 21 CFR 866.5380 - Free secretory component immuno-logical test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... system. 866.5380 Section 866.5380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test... body fluids. Measurement of free secretory component (protein molecules) aids in the diagnosis...

  18. 21 CFR 866.5380 - Free secretory component immuno-logical test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... system. 866.5380 Section 866.5380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test... body fluids. Measurement of free secretory component (protein molecules) aids in the diagnosis...

  19. 21 CFR 866.5380 - Free secretory component immuno-logical test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... system. 866.5380 Section 866.5380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test... body fluids. Measurement of free secretory component (protein molecules) aids in the diagnosis...

  20. 21 CFR 866.5380 - Free secretory component immuno-logical test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... system. 866.5380 Section 866.5380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test... body fluids. Measurement of free secretory component (protein molecules) aids in the diagnosis...