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Sample records for gonadotropins pituitary

  1. Pituitary apoplexy following gonadotropin-releasing hormone agonist administration with gonadotropin-secreting pituitary adenoma.

    PubMed

    Sasagawa, Yasuo; Tachibana, Osamu; Nakagawa, Atsushi; Koya, Daisuke; Iizuka, Hideaki

    2015-03-01

    Gonadotropin-releasing hormone (GnRH) agonists are widely used in hormone therapy for prostate cancer. We report a patient with pituitary apoplexy following this therapy as a rare complication and review the related literature. A 62-year-old man presented with elevated prostate specific antigen. Transrectal ultrasound guided biopsy of the prostate gland revealed adenocarcinoma. Whole-body (18)F-fluorodeoxyglucose (FDG) positron emission tomography/CT scan showed FDG-uptake in the pituitary region. MRI also demonstrated a pituitary tumor, diagnosed as an incidental non-functioning adenoma. The patient received his first dose of GnRH agonist (leuprolide 11.25mg) against prostate cancer. He complained of a severe headache 10 minutes after leuprolide administration and suffered from right third nerve palsy in the next 48 hours. MRI demonstrated a high intensity area on T1-weighted images, diagnosed as pituitary apoplexy. The patient underwent transsphenoidal surgery. Pathology revealed predominantly necrotic tissue and a gonadotropin secreting pituitary adenoma. Overall, 15 patients, including ours, have been reported with pituitary apoplexy after GnRH agonists with pathologic gonadotropin secreting adenoma. Fourteen of 15 patients were male. Pituitary apoplexy developed within 4 hours after administration of the agents in 8/15 patients. The combined data suggest that GnRH agonists have the potential to precipitate pituitary apoplexy in men with gonadotropin secreting adenoma. Therefore, prior to GnRH agonist therapy for prostate cancer, a known pituitary adenoma should be treated. Otherwise, the patients should be cautiously observed for any symptomatic change following drug administration. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Gonadotropin-releasing hormone agonist-induced pituitary apoplexy.

    PubMed

    Keane, Fergus; Egan, Aoife M; Navin, Patrick; Brett, Francesca; Dennedy, Michael C

    2016-01-01

    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. 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.

  3. 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

  4. 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

  5. Progesterone and the distribution of pituitary gonadotropin isoforms in cattle.

    PubMed

    Perera-Marín, G; Gutiérrez, C G; Murcia, C; León, H; González-Padilla, E

    2008-03-03

    The objective of the present study was to determine the relative proportion of gonadotropin isoforms in bovine pituitary glands affected by progesterone. Twelve postpubertal heifers (Swiss-Zebu) were assigned to three groups (n=4): intact animals in the luteal phase of the estrous cycle (diestrus group); ovariectomized heifers with (OVXP) or without progesterone treatment (OVX). Prior to pituitary gland collection, a blood sample was taken from each animal to determine the circulating progesterone concentration. Pituitary protein extractions processed by chromatofocusing were eluted with a pH gradient ranging from 10.5 to 3.5. The LH and FSH eluent was grouped on the basis of the following three criteria: (1) as either a basic (pH>or=7.5), neutral (pH 7.4-6.5) and acid (pHor=10.5-3.5); (3) on the basis of distinct isoforms 12 peaks of which (A-L) were identified for LH and 11 (I-XI) for FSH. The analysis by range of pH and by pH of elution in the OVX and OVXP groups showed no difference in the LH and FSH isoform ratio, but diestrus cattle differs having a greater ratio (p<0.05) of basic LH isoforms (87.5+/-0.4%) and lesser ratio (p<0.05) of acid isoforms (5.4+/-0.7%). In the diestrus group, the ratio of acid FSH isoform increased (62.1+/-1.7%), while neutral isoforms decreased (5.7+/-0.4%, P<0.05). The analysis by isoform type of LH revealed a greater proportion of isoforms C (pH 9.4) and E (pH 9.0) in the groups with circulating progesterone when compared to the OVX group. The heterogeneity of FSH was quantitatively similar in most isoforms in the three groups, with the exception of the predominant isoform (VIII, pH 4.9) that was more abundant in the diestrus group (p<0.05). These results indicate that progesterone with other gonad factors influence the pituitary glicosylation altering the relative proportions of gonadotropin isoforms.

  6. Development of gonadotropin-releasing hormone secretion and pituitary response.

    PubMed

    Glanowska, Katarzyna M; Burger, Laura L; Moenter, Suzanne M

    2014-11-05

    Acquisition of a mature pattern of gonadotropin-releasing hormone (GnRH) secretion from the CNS is a hallmark of the pubertal process. Little is known about GnRH release during sexual maturation, but it is assumed to be minimal before later stages of puberty. We studied spontaneous GnRH secretion in brain slices from male mice during perinatal and postnatal development using fast-scan cyclic voltammetry (FSCV) to detect directly the oxidation of secreted GnRH. There was good correspondence between the frequency of GnRH release detected by FSCV in the median eminence of slices from adults with previous reports of in vivo luteinizing hormone (LH) pulse frequency. The frequency of GnRH release in the late embryonic stage was surprisingly high, reaching a maximum in newborns and remaining elevated in 1-week-old animals despite low LH levels. Early high-frequency GnRH release was similar in wild-type and kisspeptin knock-out mice indicating that this release is independent of kisspeptin-mediated excitation. In vivo treatment with testosterone or in vitro treatment with gonadotropin-inhibitory hormone (GnIH) reduced GnRH release frequency in slices from 1-week-old mice. RF9, a putative GnIH antagonist, restored GnRH release in slices from testosterone-treated mice, suggesting that testosterone inhibition may be GnIH-dependent. At 2-3 weeks, GnRH release is suppressed before attaining adult patterns. Reduction in early life spontaneous GnRH release frequency coincides with the onset of the ability of exogenous GnRH to induce pituitary LH secretion. These findings suggest that lack of pituitary secretory response, not lack of GnRH release, initially blocks downstream activation of the reproductive system.

  7. Novel action of pituitary urocortin 2 in the regulation of expression and secretion of gonadotropins.

    PubMed

    Nemoto, Takahiro; Yamauchi, Naoko; Shibasaki, Tamotsu

    2009-04-01

    Urocortins 2 (Ucn 2), one of the corticotropin releasing factor (CRF) peptide family, is thought to be an endogenous ligand for CRF type 2 receptor (CRF-R2). We previously demonstrated that Ucn 2 is expressed in the corticotrophs of rat pituitary, and the mRNA expression and secretion of Ucn 2 in corticotrophs of rat anterior pituitary are regulated by CRF and glucocorticoids. Since CRF-R2 has been reported to be expressed on gonadotrophs of the rat pituitary, we hypothesized that pituitary Ucn 2 may control the expression and secretion of gonadotropins. Monolayer culture of rat anterior pituitary cells showed that the secretion of gonadotropins was suppressed by Ucn 2. A CRF-R2 selective antagonist, adenoviral-mediated expression of short interfering RNA against CRF-R2, and anti-Ucn 2 rabbit IgG increased the secretion and mRNA expression of gonadotropins. intraperitoneal injection of anti-Ucn 2 IgG into immature male rats significantly increased the secretion and mRNA expression of gonadotropins compared with those in normal rabbit IgG-injected rats. Daily i.p. injection of anti-Ucn 2 IgG into immature female rats induced a tendency toward earlier occurrence of menarche compared with normal rabbit IgG-injected rats. These findings suggest that pituitary Ucn 2 is involved in the regulatory mechanism of the expression and secretion of gonadotropins through its tonic and inhibitory action on gonadotrophs in a paracrine manner.

  8. Effects of soy consumption on gonadotropin secretion and acute pituitary responses to gonadotropin-releasing hormone in women.

    PubMed

    Nicholls, Jill; Lasley, Bill L; Nakajima, Steven T; Setchell, Kenneth D R; Schneeman, Barbara O

    2002-04-01

    Soy contains the isoflavone phytoestrogens, genistein and daidzein. These isoflavones are partial estrogen agonists in cell and animal models, but effects from dietary soy in humans are unclear. Experiments were conducted in pre- and postmenopausal women to examine whether dietary isoflavones from soy behave as estrogen agonists, antagonists or have no effect on the estrogen-sensitive pituitary. Pituitary sensitivity to gonadotropin-releasing hormone (GnRH), an estrogen-sensitive endpoint, was measured during GnRH challenge tests administered before, during and after dietary soy consumption. The response to an isoflavone-rich soy food diet was examined in five premenopausal and seven postmenopausal women using transdermal estrogen replacement therapy. Estrogen agonists suppress gonadotropin concentrations and enhance GnRH priming (enhanced gonadotropin secretion in response to repeated doses of GnRH), whereas antagonists elevate gonadotropin concentrations and have no effect on GnRH priming. Each subject consumed 50 g textured soy protein containing 60 mg total isoflavones daily for 10-14 d. Baseline estradiol concentrations were consistent among study periods. In both pre- and postmenopausal women, soy consumption did not affect mean baseline or peak luteinizing hormone (LH) concentrations, indicating a lack of estrogen-like effect at the level of the pituitary. However, in postmenopausal subjects, mean LH secretion decreased after discontinuing soy, suggesting a residual estrogenic effect. In one premenopausal woman, enhanced LH secretion was observed after soy treatment, suggesting there may be subpopulations of women who are highly sensitive to isoflavones.

  9. Evidence for cAMP as a mediator of gonadotropin secretion from male pituitaries

    SciTech Connect

    Bourne, G.A.; Baldwin, D.M.

    1987-09-01

    The purpose of this study was to use sodium flufenamate, a compound that inhibits gonadotropin-releasing hormone (GnRH)-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) production in the pituitary, to evaluate the potential role of cAMP as a mediator of GnRH-stimulated gonadotropin secretion from male pituitaries. Quartered male pituitaries were perifused at 37/sup 0/C and sequential effluent fractions collected every 10 min. Infusions of GnRH resulted in a twofold increase in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion. Cycloheximide, 5 ..mu..M, completely inhibited the GnRH-stimulated LH and FSH secretion. Infusions of 0.1 mM flufenamate had similar effects on gonadotropin secretion as cycloheximide, whereas the administration of 5 mM dibutyryl cAMP in combination with GnRH and flufenamate restored the secretory responses of both hormones. The flufenamate-inhibited GnRH stimulated LH and FSH release, which was restored by DBcAMP and appeared to be protein synthesis dependent and specific for cAMP.These results suggest an indirect role for cAMP as a mediator of gonadotropin secretion from male pituitaries. However, in contrast to female pituitaries, the secretion of these hormones form male pituitaries is completely dependent on cAMP and de novo protein synthesis.

  10. Pituitary gonadotropin content in gonadectomized rats. Immunoassay measurements influenced by extraction solvent and testosterone replacement.

    PubMed

    Spitzbarth, T L; Horton, T H; Lifka, J; Schwartz, N B

    1988-01-01

    Increasing interest in events regulating gonadotropin synthesis and secretion led to the reexamination, by radioimmunoassay (RIA), of the pituitary content of luteinizing hormone (LH) and follicle stimulating hormone (FSH). In a preliminary experiment, the importance of the composition of the solvent used to homogenize pituitaries on the detection of LH and FSH was demonstrated by RIA. Experiment 1 demonstrated that a drop in pituitary FSH occurred acutely following gonadectomy in males, but not in females. Experiment 2 tested whether this decline resulted from loss of testosterone or inhibin. Males were castrated and treated daily with oil or testosterone propionate, porcine follicular fluid, porcine serum, or testosterone plus follicular fluid for 2 to 14 days. Castration lowered pituitary FSH at 2, 4, and 6 days. Follicular fluid suppressed serum FSH, but not LH, and did not prevent the fall in pituitary FSH. Testosterone blocked the rise of serum LH and FSH and prevented the decline in pituitary FSH.

  11. Seasonal relationship between gonadotropin, growth hormone, and estrogen receptor mRNA expression in the pituitary gland of largemouth bass.

    PubMed

    Martyniuk, Christopher J; Kroll, Kevin J; Porak, Wesley F; Steward, Cheree; Grier, Harry J; Denslow, Nancy D

    2009-09-15

    The objectives of this study were to investigate the seasonal changes in pituitary gonadotropins, growth hormone (GH), and estrogen receptor (ER) isoform mRNA in wild female and male largemouth bass (LMB) (Micropterus salmoides) from an unpolluted habitat to better understand reproductive physiology in this ecologically important species. Female pituitary luteinizing hormone (LH) beta subunit and follicle stimulating hormone (FSH) beta subunit mRNA showed significant seasonal variation with levels peaking from January to April and were lowest from May to August. Male LMB showed more variation in gonadotropin subunit expression from month to month. Females had approximately 2-3 times higher gonadotropin mRNA levels in the pituitary when compared to males. All three gonadotropin mRNAs in females were positively correlated to gonadosomatic index (GSI), but only LHbeta mRNA was correlated to GSI in males. Gonadotropin mRNA expression also increased with increasing oocyte and sperm maturation. Gonadotropin beta subunit mRNA expression was positively correlated to GH mRNA in both sexes. The expression of all three ER isoforms was significantly correlated to each other in both sexes. The concurrent increase in all three ER mRNA isoforms with increasing gonadotropin mRNA in females and males suggests a prominent role for E2 feedback on pituitary gonadotropin synthesis in both sexes and that each of the three ER isoforms are likely to play a role in the pituitary during teleost reproduction.

  12. Seasonal Relationship between Gonadotropin, Growth Hormone, and Estrogen Receptor mRNA Expression in the Pituitary Gland of Largemouth Bass

    PubMed Central

    Martyniuk, Christopher J; Kroll, Kevin J.; Porak, Wesley F.; Steward, Cheree; Grier, Harry J.; Denslow, Nancy D.

    2011-01-01

    The objectives of this study were to investigate the seasonal changes in pituitary gonadotropins, growth hormone (GH), and estrogen receptor (ER) isoform mRNA in wild female and male largemouth bass (LMB) (Micropterus salmoides) from an unpolluted habitat to better understand reproductive physiology in this ecologically important species. Female pituitary luteinizing hormone (LH) β subunit and follicle-stimulating hormone (FSH) β subunit mRNA showed significant seasonal variation with levels peaking from January to April and were lowest from May through August. Male LMB showed more variation in gonadotropin subunit expression from month to month. Females had approximately 2–3 times higher gonadotropin mRNA levels in the pituitary when compared to males. All three gonadotropin mRNAs in females were positively correlated to gonadosomatic index (GSI), but only LHβ mRNA was correlated to GSI in males. Gonadotropin mRNA expression also increased with increasing oocyte and sperm maturation. Gonadotropin β subunit mRNA expression was positively correlated to GH mRNA in both sexes. The expression of all three ER isoforms was significantly correlated to each other in both sexes. The concurrent increase in all three ER mRNA isoforms with increasing gonadotropin mRNA in females and males suggests a prominent role for E2 feedback on pituitary gonadotropin synthesis in both sexes and that each of the three ER isoforms are likely to play a role in the pituitary during teleost reproduction. PMID:19416730

  13. Estradiol potentiation of gonadotropin-releasing hormone responsiveness in the anterior pituitary is mediated by an increase in gonadotropin-releasing hormone receptors

    SciTech Connect

    Menon, M.; Peegel, H.; Katta, V.

    1985-02-15

    In order to investigate the mechanism by which 17 beta-estradiol potentiates the action of gonadotropin-releasing hormone on the anterior pituitary in vitro, cultured pituitary cells from immature female rats were used as the model system. Cultures exposed to estradiol at concentrations ranging from 10(-10) to 10(-6) mol/L exhibited a significant augmentation of luteinizing hormone release in response to a 4-hour gonadotropin-releasing hormone (10 mumol/L) challenge at a dose of 10(-9) mol/L compared to that of control cultures. The estradiol augmentation of luteinizing hormone release was also dependent on the duration of estradiol exposure. When these cultures were incubated with tritium-labeled L-leucine, an increase in incorporation of radiolabeled amino acid into total proteins greater than that in controls was observed. A parallel stimulatory effect of estradiol on iodine 125-labeled D-Ala6 gonadotropin-releasing hormone binding was observed. Cultures incubated with estradiol at different concentrations and various lengths of time showed a significant increase in gonadotropin-releasing hormone binding capacity and this increase was abrogated by cycloheximide. Analysis of the binding data showed that the increase in gonadotropin-releasing hormone binding activity was due to a change in the number of gonadotropin-releasing hormone binding sites rather than a change in the affinity. These results suggest that (1) estradiol treatment increases the number of pituitary receptors for gonadotropin-releasing hormone, (2) the augmentary effect of estradiol on luteinizing hormone release at the pituitary level might be mediated, at least in part, by the increase in the number of binding sites of gonadotropin-releasing hormone, and (3) new protein synthesis may be involved in estradiol-mediated gonadotropin-releasing hormone receptor induction.

  14. Radioiodinated nondegradable gonadotropin-releasing hormone analogs: new probes for the investigation of pituitary gonadotropin-releasing hormone receptors.

    PubMed

    Clayton, R N; Shakespear, R A; Duncan, J A; Marshall, J C; Munson, P J; Rodbard, D

    1979-12-01

    Studies of pituitary plasma membrane gonadotropin-releasing hormone (GnRH) receptors using [125I]-iodo-GnRH suffer major disadvantages. Only a small (less than 25%) proportion of specific tracer binding is to high affinity sites, with more than 70% bound to low affinity sites (Ka = 1 x 10(6) M-1). [125I]Iodo-GnRH is also inactivated during incubation with pituitary plasma membrane preparations. Two superactive analongs of GnRH, substituted in positions 6 and 10, were used as the labeled ligand to overcome these problems. Both analogs bound to the same high affinity sites as GnRH on bovine pituitary plasma membranes, though the affinity of the analogs was higher than that of the natural decapeptide (Ka = 2.0 x 10(9), 6.0 x 10(9), and 3.0 x 10(8) M-1 for [D-Ser(TBu)6]des-Gly10-GnRH ethylamide, [D-Ala6]des-Gly10-GnRH ethylamide, and GnRH, respectively. The labeled analogs bound to a single class of high affinity sites with less than 15% of the specific binding being to low affinity sites (Ka approximately equal to 1 x 10(6) M-1). The labeled analogs were not inactivated during incubation with the pituitary membrane preparations. Using the analogs as tracer, a single class of high affinity sites (K1 = 4.0 x 10(9) M-1) was also demonstrated on crude 10,800 x g rat pituitary membrane preparations. Use of these analogs as both the labeled and unlabeled ligand offers substantial advantages over GnRH for investigation of GnRH receptors, allowing accurate determination of changes in their numbers and affinities under various physiological conditions.

  15. Stimulation of Spermiation by Human Chorionic Gonadotropin and Carp Pituitary Extract in Grass Puffer, Takifugu niphobles

    PubMed Central

    Goo, In Bon; Park, In-Seok; Gil, Hyun Woo; Im, Jae Hyun

    2015-01-01

    Spermiation was stimulated in the mature grass puffer, Takifugu niphobles, with an injection of human chorionic gonadotropin (HCG) or carp pituitary extract (CPE). Spermatocrit and sperm density were reduced, but milt production was increased in both the HCG and CPE treatment groups relative to those in the control group (P <0.05). These results should be useful for increasing the fertilization efficiency in grass puffer breeding programs. PMID:26973977

  16. Stimulation of Spermiation by Human Chorionic Gonadotropin and Carp Pituitary Extract in Grass Puffer, Takifugu niphobles.

    PubMed

    Goo, In Bon; Park, In-Seok; Gil, Hyun Woo; Im, Jae Hyun

    2015-12-01

    Spermiation was stimulated in the mature grass puffer, Takifugu niphobles, with an injection of human chorionic gonadotropin (HCG) or carp pituitary extract (CPE). Spermatocrit and sperm density were reduced, but milt production was increased in both the HCG and CPE treatment groups relative to those in the control group (P <0.05). These results should be useful for increasing the fertilization efficiency in grass puffer breeding programs.

  17. Gonadotropin-releasing hormone is prerequisite for the constitutive expression of pituitary annexin A5.

    PubMed

    Yonezawa, Tomohiro; Watanabe, Aiko; Kurusu, Shiro; Kawaminami, Mitsumori

    2015-01-01

    Annexin A5 (ANXA5), a member of the structurally related family of annexin proteins, is expressed in pituitary gonadotropes. We previously reported that ANXA5 expression is stimulated by gonadotropin-releasing hormone (GnRH). In the present study, we investigated ANXA5 expression in the anterior pituitary gland of GnRH-deficient mutant hypogonadal (hpg) mice. RT-PCR demonstrated that luteinizing hormone β subunit (LHβ) and ANXA5 mRNA levels were both lower in the pituitary gland of hpg mice than in wild-type mice. Immunohistochemistry showed that ANXA5 expression throughout the pituitary gland was very low in hpg mice, suggesting that ANXA5 is diminished in gonadotropes and also in other cell types. Subcutaneous administration of a GnRH analogue, des-gly10 (Pro9)-GnRH ethylamide (1 μg/day for 7 days), augmented the expression of LHβ and ANXA5 in the pituitary gland in hpg mice. However, LHβ- and ANXA5-positive cells did not show exactly matched spatial distributions. These findings suggest that GnRH is necessary for constitutive ANXA5 expression in the pituitary gland, not only in gonadotropes but also in other pituitary gland cell types. A close relationship between ANXA5 and LHβ expression was confirmed. It is suggested that a significant role of ANXA5 in the physiologic secretion of LH.

  18. The forkhead transcription factor, FOXP3, is required for normal pituitary gonadotropin expression in mice.

    PubMed

    Jung, Deborah O; Jasurda, Jake S; Egashira, Noboru; Ellsworth, Buffy S

    2012-05-01

    The hypothalamic-pituitary-gonadal axis is central to normal reproductive function. This pathway begins with the release of gonadotropin-releasing hormone in systematic pulses by the hypothalamus. Gonadotropin-releasing hormone is bound by receptors on gonadotroph cells in the anterior pituitary gland and stimulates the synthesis and secretion of luteinizing hormone and, to some extent, follicle-stimulating hormone. Once stimulated by these glycoprotein hormones, the gonads begin gametogenesis and the synthesis of sex hormones. In humans, mutations of the forkhead transcription factor, FOXP3, lead to an autoimmune disorder known as immunodysregulation, polyendocrinopathy, and enteropathy, X-linked syndrome. Mice with a mutation in the Foxp3 gene have a similar autoimmune syndrome and are infertile. To understand why FOXP3 is required for reproductive function, we are investigating the reproductive phenotype of Foxp3 mutant mice (Foxp3(sf/Y)). Although the gonadotroph cells appear to be intact in Foxp3(sf/Y) mice, luteinizing hormone beta (Lhb) and follicle-stimulating hormone beta (Fshb) expression are significantly decreased, demonstrating that these mice exhibit a hypogonadotropic hypogonadism. Hypothalamic expression of gonadotropin-releasing hormone is not significantly decreased in Foxp3(sf/Y) males. Treatment of Foxp3(sf/Y) males with a gonadotropin-releasing hormone receptor agonist does not rescue expression of Lhb or Fshb. Interestingly, we do not detect Foxp3 expression in the pituitary or hypothalamus, suggesting that the infertility seen in Foxp3(sf/Y) males is a secondary effect, possibly due to loss of FOXP3 in immune cells. Pituitary expression of glycoprotein hormone alpha (Cga) and prolactin (Prl) are significantly reduced in Foxp3(sf/Y) males, whereas the precursor for adrenocorticotropic hormone, pro-opiomelanocortin (Pomc), is increased. Human patients diagnosed with IPEX often exhibit thyroiditis due to destruction of the thyroid gland by

  19. The Forkhead Transcription Factor, FOXP3, Is Required for Normal Pituitary Gonadotropin Expression in Mice1

    PubMed Central

    Jung, Deborah O.; Jasurda, Jake S.; Egashira, Noboru; Ellsworth, Buffy S.

    2012-01-01

    ABSTRACT The hypothalamic-pituitary-gonadal axis is central to normal reproductive function. This pathway begins with the release of gonadotropin-releasing hormone in systematic pulses by the hypothalamus. Gonadotropin-releasing hormone is bound by receptors on gonadotroph cells in the anterior pituitary gland and stimulates the synthesis and secretion of luteinizing hormone and, to some extent, follicle-stimulating hormone. Once stimulated by these glycoprotein hormones, the gonads begin gametogenesis and the synthesis of sex hormones. In humans, mutations of the forkhead transcription factor, FOXP3, lead to an autoimmune disorder known as immunodysregulation, polyendocrinopathy, and enteropathy, X-linked syndrome. Mice with a mutation in the Foxp3 gene have a similar autoimmune syndrome and are infertile. To understand why FOXP3 is required for reproductive function, we are investigating the reproductive phenotype of Foxp3 mutant mice (Foxp3sf/Y). Although the gonadotroph cells appear to be intact in Foxp3sf/Y mice, luteinizing hormone beta (Lhb) and follicle-stimulating hormone beta (Fshb) expression are significantly decreased, demonstrating that these mice exhibit a hypogonadotropic hypogonadism. Hypothalamic expression of gonadotropin-releasing hormone is not significantly decreased in Foxp3sf/Y males. Treatment of Foxp3sf/Y males with a gonadotropin-releasing hormone receptor agonist does not rescue expression of Lhb or Fshb. Interestingly, we do not detect Foxp3 expression in the pituitary or hypothalamus, suggesting that the infertility seen in Foxp3sf/Y males is a secondary effect, possibly due to loss of FOXP3 in immune cells. Pituitary expression of glycoprotein hormone alpha (Cga) and prolactin (Prl) are significantly reduced in Foxp3sf/Y males, whereas the precursor for adrenocorticotropic hormone, pro-opiomelanocortin (Pomc), is increased. Human patients diagnosed with IPEX often exhibit thyroiditis due to destruction of the thyroid gland by

  20. Relationship between serum gonadotropins and pituitary immunoreactive gonadotropins and steroid receptors during the first FSH increase of the estrous cycle and following steroid treatment in heifers.

    PubMed

    Lane, Elizabeth A; Sweeney, Torres; Ryan, Marion; Roche, James F; Crowe, Mark A

    2009-05-01

    The objectives were to determine the effects of (i) time during the first FSH increase of the estrous cycle (time-course study) and (ii) exogenous steroid treatment (steroid feedback study) on the relationship between circulating serum gonadotropins, and the proportions of pituitary cells immunoreactive for gonadotropins and steroid receptors during the estrous cycle in heifers. Pituitaries were collected from heifers (n=40) slaughtered at 13h (n=8), 30h (n=24) and 66h (n=8) after estrous onset, corresponding to before, during and after the first FSH increase of the estrous cycle. Heifers slaughtered during the FSH increase (at 30h) either received no treatment (n=8), or were treated (n=16) with estradiol benzoate and/or progesterone before slaughter. During the time-course study, the proportion of pituitary cells immunoreactive for FSH increased (P<0.05) during the first transient FSH increase reflecting serum concentrations. The proportion of pituitary cells immunoreactive for LH was unaltered, a reflection of serum LH concentrations. The proportion of estrogen receptors (ER)-alpha, but not ER-beta, was decreased (P<0.05) at 30h compared with at either 13 or 66h. During the steroid feedback study, exogenous progesterone with or without estradiol suppressed (P<0.05) the proportions of pituitary cells immunoreactive for gonadotropins, serum FSH concentrations and LH pulse frequency. Steroid treatment did not alter the proportion of pituitary cells positive for estrogen receptors (alpha and beta). While progesterone receptors (PR) were not detected in the anterior pituitary by immunohistochemistry during the early estrous cycle or in response to steroid treatment, quantitative real-time PCR revealed that mRNA for progesterone receptors was expressed at very low levels. The expression of pituitary PR mRNA was decreased (P<0.05) at 30 and 66h compared with 13h, and was suppressed (P<0.05) following steroid treatments. Alterations in pituitary steroid receptors are

  1. Regulation of genes encoding steroidogenic factor-1 (SF-1) and gonadotropin subunits in the ovine pituitary gland.

    PubMed

    Baratta, M; Turzillo, A M; Arreguin-Arevalo, A; Clay, C M; Nett, T M

    2003-07-01

    Steroidogenic factor-1 (SF-1) is a transcription factor originally characterized as a mediator of gene expression in steroidogenic tissues. Studies in SF-1 knockout mice revealed that SF-1 has additional roles at multiple levels of the hypothalamic-pituitary-gonadal axis, including regulation of gene expression in pituitary gonadotropes. Specific binding sites for SF-1 have been demonstrated in several pituitary genes with essential roles in gonadotropin synthesis, including alpha subunit, LHbeta subunit, and GnRH receptor. In studies aimed at identifying physiological factors controlling pituitary expression of SF-1, GnRH has been implicated as a co-regulator of SF-1 and gonadotropin subunit genes. In both rats and ewes, elevated endogenous secretion of GnRH following ovariectomy was associated with increased amounts of SF-1 mRNA in the anterior pituitary gland. Conversely, removal of GnRH input to the pituitary gland by hypothalamic-pituitary disconnection (HPD) in ovariectomized (OVX) ewes reduced SF-1 expression. Despite these changes, however, treatment of OVX ewes with GnRH following HPD only partially restored levels of SF-1 mRNA in the pituitary gland. Therefore, it is possible that regulation of SF-1 gene expression by GnRH during the estrous cycle may involve ovarian hormones or other hypothalamic factors. Additional studies are required to further define the physiological roles of SF-1 in regulation of the hypothalamic-pituitary-gonadal axis in domestic ruminants.

  2. Evidence for cAMP as a mediator of gonadotropin secretion from female pituitaries

    SciTech Connect

    Bourne, G.A.; Baldwin, D.M.

    1987-09-01

    Sodium flufenamate, which inhibited gonadotropin-releasing hormone (GnRH)-stimulated increases in adenosine 3',5'-cyclic monophosphate (cAMP), was used to evaluate the potential role of cAMP as a mediator of GnRH-stimulated gonadotropin secretion. Quartered pituitaries from diestrous II female rats were perifused at 37/sup 0/C, and sequential effluent fractions were collected every 10 min. Administration of GnRH resulted in a characteristic biphasic response for both luteinizing hormone (LH) and follicle-stimulating hormone (FSH), whereas 5 ..mu..M cycloheximide inhibited the secondary augmented responses (phase II) of both hormones. Infusions of 0.1 mM flufenamate inhibited GnRH-stimulated gonadotropin secretion in a manner similar to that of cycloheximide, whereas the administration of 5 mM dibutyryl cAMP in combination with GnRH and flufenamate resulted in the restoration of LH and FSH secretion. The dibutyryl cAMP-restored response appeared to be protein synthesis dependent and specific for cAMP. These results suggest that although the cyclic nucleotide is not involved in the acute release of LH and FSH, it does appear to play a pivotal but indirect role in phase II release of the hormones, by effects involving the stimulation of de novo protein synthesis.

  3. Pituitary thyrotropin and gonadotropin of coho salmon (Oncorhynchus kisutch): separation by chromatofocusing.

    PubMed

    Swanson, P; Dickhoff, W W; Gorbman, A

    1987-02-01

    Thyrotropin (TSH) and gonadotropin (GTH) were isolated from adult female coho salmon pituitary glands. After final extraction in acidic alcohol and precipitation in 85% ethanol, proteins were fractionated using gel filtration chromatography and chromatofocusing. Homologous bioassay systems were used to monitor bioactivity during the purification procedures. TSH activity was measured in vivo in coho salmon parr. GTH (steroidogenic) activity was determined in vitro using cultures of adult coho salmon ovarian follicles. Using these procedures, TSH and GTH activities were separated. TSH activity eluted as one major peak at pH 6.3 whereas GTH activity eluted as five major peaks at pH's 5.4, 5.0, 4.7, 4.3, and after 1.0 M NaCl on chromatofocusing. Molecular weights of the TSH and GTHs were estimated by gel filtration chromatography as 35 and 40 kDa, respectively. Like other vertebrate TSHs and gonadotropins, the coho salmon TSH and GTHs appeared to consist of two subunits. Coho salmon TSH and bovine TSH (bTSH) were equipotent in the TSH bioassay. The five coho salmon GTHs exhibited similar potencies in stimulating ovarian estradiol synthesis in vitro. Further biochemical analysis and tests for other gonadotropic activities are warranted to determine if these five GTHs are isoforms of one GTH or if they can be distinguished functionally in other GTH bioassays. Sufficient quantities of coho salmon TSH were isolated in this study for future studies of the hypothalamic-pituitary-thyroid axis in fish.

  4. Factors affecting pituitary gonadotropin function in users of oral contraceptive steroids.

    PubMed

    Scott, J A; Brenner, P F; Kletzky, O A; Mishell, D R

    1978-04-01

    In order to determine whether certain factors influence the direct pituitary suppressive effect of contraceptive steroid, 50 subjects who had used various formulations of oral contraceptive steroids for periods of time ranging from one to nine years were stimulated with 50 microgram of gonadotropin-releasing hormone (GnRH) during the last week of oral contraceptive ingestion. The response of lutinizing hormone (LH) and follicle-stimulating hormone (FSH) was compared to the results obtained in nine control subjects with regard to: (1) age of subject. (2) type of contraceptive formulation used, and (3) length of use. Prestimulation levels of LH and FSH, respectively, were significantly decreased in 37 (74 per cent) and 42 (84 per cent) of the subjects. Following GnRH stimulation, peak responses of serum LH and FSH, respectively, were also significantly lower than those in the control subjects in 40 (80 per cent) and 45 (90 per cent of the subjects. The degree of suppression of pituitary gonadotropins, both before and after GnRH administration was significantly correlated with the type of steroid formulation used, being greatest with a combination of d-norgestrel and ethinyl estradiol. No correlation was found with length of use of oral contraceptives or age of the subjects.

  5. Regulation of pituitary gonadotropin-releasing hormone receptors by androgens in the male rabbit.

    PubMed

    Limonta, P; Ladizhenskaya, A; Gunsalus, G L; Bardin, C W; Thau, R B

    1986-01-01

    The regulation of pituitary GnRH receptors was studied in adult male rabbits after castration and androgen replacement with testosterone (T) or 7 alpha-methyl-19-nortestosterone acetate (U-15,614; T analog) supplied by Silastic capsules implanted sc. Castration increased pituitary GnRH receptors significantly, from 99.3 to 329.5 fmol/mg protein within 4 weeks, without a change in the equilibrium association constant. Serum LH concentrations increased from 0.45 to maximum levels of 2.6 ng/ml by day 8 after orchiectomy; these levels persisted throughout the 4 weeks of study. Serum FSH reached maximum levels of 33.6 ng/ml 5 days after castration. T replacement with 250, 500, and 1000 micrograms/kg X day, prevented a postcastration rise in both pituitary GnRH receptor concentrations and gonadotropin secretion, while 100 micrograms/kg X day prevented an increase in GnRH receptors, but did not completely inhibit hypersecretion of gonadotropins. Administration of T analog at doses of 6.25 and 12.5 micrograms/kg X day partially suppressed the castration-induced increase in pituitary GnRH receptor concentrations, while 25, 50, and 100 micrograms/kg X day suppressed GnRH-binding sites to the levels found in intact controls in 15 of 16 rabbits. By contrast, none of the T analog doses was able to prevent completely LH and FSH hypersecretion. The fact that both T and T analog induced dose-dependent stimulation of prostate and seminal vesicle weights indicates that there are tissue-specific differences in the sensitivity to androgens. We conclude that in the male rabbit 1) pituitary GnRH receptors significantly increase after castration; 2) this increase may partially mediate the postcastration hypersecretion of LH and FSH; 3) castration-induced effects can be prevented by androgen replacement. These results are similar to those obtained in rats, where castration increases LHRH receptors, but contrast with results in mice and hamsters, where castration either reduces or does not

  6. Serum levels of beta-subunit of chorionic gonadotropin in patients with pituitary tumors.

    PubMed

    Gil-del-Alamo, P; Saccomanno, K; Lania, A; Pettersson, K S; Beck-Peccoz, P; Spada, A

    1995-07-01

    Many studies have shown that normal and tumoral pituitary is able to synthesize chorionic gonadotropin (CG). The aim of the present work was to investigate the circulating levels of free beta-subunit of CG (CG-beta) in a large number of patients with pituitary tumors in basal conditions and after thyrotropin-releasing hormone (TRH) injection. The study includes 27 healthy subjects, 23 patients with prolactinoma, 20 with growth hormone-secreting adenoma and 77 with non-functioning pituitary adenoma (NFPA). The CG-beta was evaluated using a new one-step immunometric assay employing two monoclonal antibodies directed against epitopes present only on the free CG-beta and showing a detection limit of 0.04 U/l and a cross-reactivity with complete CG < 0.01%. In basal conditions, serum CG-beta was undetectable in healthy subjects and in the majority of patients, while in seven patients with NFPA and four with prolactinoma the CG-beta values ranged between 0.05 and 0.72 U/l. In these 11 patients serum levels of intact CG were found within the normal range (normal range < 5 U/l), while two patients with NFPA and one with prolactinoma had levels of free alpha-subunit inappropriately high with respect to gonadotropins and thyrotropin. Injection of TRH caused CG-beta to increase in two out of 16 patients with NFPA, whereas it was ineffective in 12 healthy subjects and 10 patients with prolactinoma. The present data indicate that detectable level of CG-beta not associated with hypersecretion of the intact CG molecule may be observed in about 10% of patients with NFPA or prolactinoma, while abnormal CG-beta responses to TRH are observed infrequently in individual patients with NFPA.

  7. Effects of castration on androgen receptors and gonadotropins in the pituitary of adult male viscachas.

    PubMed

    Filippa, Verónica; Godoy, Daiana; Perez, Edith; Mohamed, Fabian

    2014-08-01

    The aims of the present study were to determine whether castration results in quantitative immunohistochemical changes in androgen receptors (AR), LH-immunoreactive (IR) cells and FSH-IR cells, and to analyse the colocalisation of AR and gonadotropins in the pituitary pars distalis (PD) of viscachas. Pituitaries were processed for light and electron microscopy. AR-IR, LH-IR and FSH-IR cells were detected by immunohistochemistry. In morphometric studies, the percentage of AR-IR, LH-IR, FSH-IR, LH-IR/AR-IR and FSH-IR/AR-IR cells was determined. In intact viscachas, AR were distributed throughout the PD; they were numerous at the caudal end, with intense immunostaining. LH-IR cells and FSH-IR cells were found mainly in the ventral region and at the rostral end of the PD. Approximately 45%-66% of LH-IR cells and 49%-57% of FSH-IR cells expressed AR in the different zones of the PD. In castrated viscachas, there was a significant decrease in the percentage of AR-IR, LH-IR, FSH-IR, and FSH-IR/AR-IR cells. Some pituitary cells from castrated viscachas also exhibited ultrastructural changes. These results provide morphological evidence that gonadal androgens are directly related to the immunolabelling of AR, LH and FSH. Moreover, the colocalisation of AR and FSH is most affected by castration, suggesting the existence of a subpopulation of gonadotrophs with different regulatory mechanisms for hormonal synthesis, storage and secretion.

  8. 2,3,7,8-tetrachlorodibenzo-p-dioxin potentially attenuates the gene expression of pituitary gonadotropin β-subunits in a fetal age-specific fashion: a comparative study using cultured pituitaries.

    PubMed

    Takeda, Tomoki; Yamamoto, Midori; Himeno, Masaru; Takechi, Shinji; Yamaguchi, Tadatoshi; Ishida, Takumi; Ishii, Yuji; Yamada, Hideyuki

    2011-04-01

    Our previous studies have demonstrated that maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes a reduction in gonadotropin biosynthesis in the fetal pituitary, resulting in the attenuated expression of steroidogenic proteins in the fetal gonads and the impairment of sexual behaviors in adulthood. However, the mechanism of the attenuation remains unknown. To address this issue, we investigated whether TCDD affects the pituitary production of gonadotropins, using cultured pituitary. In the absence of gonadotropin-releasing hormone (GnRH), a regulator of gonadotropin biosynthesis, TCDD did not affect the expression of gonadotropin mRNAs both in fetal and postnatal pituitaries. On the other hand, in the presence of GnRH, TCDD interfered with the synthesis of gonadotropin β-subunit mRNAs only in the fetal pituitary. A protein kinase C (PKC) activator (phorbol 12-myristate 13-acetate) and a PKA activator (8-bromoadenosine-3' 5'-cyclic monophosphate) induced the expression of gonadotropin mRNAs in the fetal pituitary. Among the subunits, only the induction of β-subunit was reduced by TCDD treatment. These results suggest that TCDD reduces gonadotropin biosynthesis via damage to GnRH-stimulated PKC and PKA signaling in a β-subunit- and fetal age-specific manner.

  9. Secretoneurin is a potential paracrine factor from lactotrophs stimulating gonadotropin release in the goldfish pituitary.

    PubMed

    Zhao, E; Grey, Caleb L; Zhang, Dapeng; Mennigen, Jan A; Basak, Ajoy; Chang, John P; Trudeau, Vance L

    2010-11-01

    Secretoneurin (SN) is a functional neuropeptide derived from the evolutionarily conserved part of precursor protein secretogranin II (SgII). In the time course study, SN (10 nM) stimulates luteinizing hormone (LH) production and secretion after 6 h of static incubation of goldfish pituitary cells. Due to the existence of SN-immunoreactivity (SN-IR) in goldfish lactotrophs, endogenous SN might exert a paracrine effect on LH in the pituitary. In an in vitro immunoneutralization experiment, coincubation with anti-SN antiserum reduces the stimulatory effect of salmon gonadotropin-releasing hormone (sGnRH) on LH release by 64%. Using Western blot analysis, we demonstrate that sGnRH significantly increases the expression of the major SgII-derived peptide (∼57 kDa, with SN-IR) and prolactin (PRL) after 12 h in the static culture of goldfish pituitary cells. Furthermore, there exists a significant correlation between the levels of these two proteins (R = 0.76, P = 0.004). Another ∼30 kDa SgII-derived peptide containing SN is only observed in sGnRH-treated pituitary cells. Consistent with the Western blot analysis results, real-time RT-PCR analysis shows that a 12-h treatment with sGnRH induced 1.6- and 1.7-fold increments in SgII and PRL mRNA levels, respectively. SgII gene expression was also associated with PRL gene expression (R = 0.66; P = 0.02). PRL cells loaded with the calcium-sensitive dye, fura 2/AM, respond to sGnRH treatment with increases in intracellular Ca(2+) concentration level, suggesting a potential mechanism of GnRH on PRL cells and thus SgII processing and SN secretion. Taken together, endogenous lactotroph-generated SN, under the control of hypothalamic GnRH, exerts a paracrine action on neighboring gonadotrophs to stimulate LH release.

  10. Intrinsic and Regulated Gonadotropin-Releasing Hormone Receptor Gene Transcription in Mammalian Pituitary Gonadotrophs

    PubMed Central

    Janjic, Marija M.; Stojilkovic, Stanko S.; Bjelobaba, Ivana

    2017-01-01

    The hypothalamic decapeptide gonadotropin-releasing hormone (GnRH), acting via its receptors (GnRHRs) expressed in pituitary gonadotrophs, represents a critical molecule in control of reproductive functions in all vertebrate species. GnRH-activated receptors regulate synthesis of gonadotropins in a frequency-dependent manner. The number of GnRHRs on the plasma membrane determines the responsiveness of gonadotrophs to GnRH and varies in relation to age, sex, and physiological status. This is achieved by a complex control that operates at transcriptional, translational, and posttranslational levels. This review aims to overview the mechanisms of GnRHR gene (Gnrhr) transcription in mammalian gonadotrophs. In general, Gnrhr exhibits basal and regulated transcription activities. Basal Gnrhr transcription appears to be an intrinsic property of native and immortalized gonadotrophs that secures the presence of a sufficient number GnRHRs to preserve their functionality independently of the status of regulated transcription. On the other hand, regulated transcription modulates GnRHR expression during development, reproductive cycle, and aging. GnRH is crucial for regulated Gnrhr transcription in native gonadotrophs but is ineffective in immortalized gonadotrophs. In rat and mouse, both basal and GnRH-induced Gnrhr transcription rely primarily on the protein kinase C signaling pathway, with subsequent activation of mitogen-activated protein kinases. Continuous GnRH application, after a transient stimulation, shuts off regulated but not basal transcription, suggesting that different branches of this signaling pathway control transcription. Pituitary adenylate cyclase-activating polypeptide, but not activins, contributes to the regulated transcription utilizing the protein kinase A signaling pathway, whereas a mechanisms by which steroid hormones modulate Gnrhr transcription has not been well characterized.

  11. Pituitary gonadotropins FSH and LH are oppositely regulated by the activin/follistatin system in a basal teleost, the eel.

    PubMed

    Aroua, Salima; Maugars, Gersende; Jeng, Shan-Ru; Chang, Ching-Fong; Weltzien, Finn-Arne; Rousseau, Karine; Dufour, Sylvie

    2012-01-01

    European eels are blocked at a prepubertal silver stage due to a deficient production of pituitary gonadotropins. We investigated the potential role of activin/follistatin system in the control of eel gonadotropins. Through the development of qPCR assays for European eel activin β(B) and follistatin, we first analyzed the tissue distribution of the expression of these two genes. Both activin β(B) and follistatin are expressed in the brain, pituitary and gonads. In addition, a striking expression of both transcripts was also found in the retina and in adipose tissue. The effects of recombinant human activins and follistatin on eel gonadotropin gene expression were studied using primary cultures of eel pituitary cells. Activins A and B strongly stimulated FSHβ subunit expression in a time- and dose-dependent manner. In contrast, activin reduced LHβ expression, an inhibitory effect which was highlighted in the presence of testosterone, a known activator of eel LHβ expression. No effect of activin was observed on other pituitary hormones. Follistatin antagonized both the stimulatory and inhibitory effects of activin on FSHβ and LHβ expression, respectively. Activin is the first major stimulator of FSH expression evidenced in the eel. These results in a basal teleost further support the ancient origin and strong conservation of the activin/follistatin system in the control of FSH in vertebrates. In contrast, the opposite regulation of FSH and LH may have emerged in the teleost lineage.

  12. Internalization and recycling of receptor-bound gonadotropin-releasing hormone agonist in pituitary gonadotropes

    SciTech Connect

    Schvartz, I.; Hazum, E.

    1987-12-15

    The fate of cell surface gonadotropin-releasing hormone (GnRH) receptors on pituitary cells was studied utilizing lysosomotropic agents and monensin. Labeling of pituitary cells with a photoreactive GnRH derivative, (azidobenzoyl-D-Lys6)GnRH, revealed a specific band of Mr = 60,000. When photoaffinity-labeled cells were exposed to trypsin immediately after completion of the binding, the radioactivity incorporated into the Mr = 60,000 band decreased, with a concomitant appearance of a proteolytic fragment (Mr = 45,000). This fragment reflects cell surface receptors. Following GnRH binding, the hormone-receptor complexes underwent internalization, partial degradation, and recycling. The process of hormone-receptor complex degradation was substantially prevented by lysosomotropic agents, such as chloroquine and methylamine, or the proton ionophore, monensin. Chloroquine and monensin, however, did not affect receptor recycling, since the tryptic fragment of Mr = 45,000 was evident after treatment with these agents. This suggests that recycling of GnRH receptors in gonadotropes occurs whether or not the internal environment is acidic. Based on these findings, we propose a model describing the intracellular pathway of GnRH receptors.

  13. Interaction of Gonadal Steroids and Gonadotropin-Releasing Hormone on Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and PACAP Receptor Expression in Cultured Rat Anterior Pituitary Cells

    PubMed Central

    Zheng, Weiming; Grafer, Constance M.

    2014-01-01

    Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors are expressed in the hypothalamus, the gonadotrope cells of the anterior pituitary gland, and the gonads, forming an autocrine–paracrine system in these tissues. Within the pituitary, PACAP functions either alone or synergistically with gonadotropin-releasing hormone (GnRH) to stimulate gonadotropin gene expression and secretion. Our goal was to define the hormonal regulation of pituitary PACAP and PACAP receptor (PAC1) gene expression by dihydrotestosterone (DHT), estradiol, and progesterone alone or in conjunction with GnRH. Treatment of adult male rat pituitary cell cultures with DHT or progesterone augmented GnRH-mediated increase in PACAP messenger RNA (mRNA) levels, but neither had an effect when present alone. Conversely, estradiol treatment blunted PACAP gene expression but did not alter GnRH effects on PACAP expression. Expression of PACAP receptor mRNA was decreased by GnRH treatment, minimally increased by DHT treatment, but not altered by the addition of estradiol or progesterone. DHT and GnRH together blunted PACAP receptor gene expression. Taken together, these results suggest that the activity of the intrapituitary PACAP-PAC1 system is regulated via the complex interaction of gonadal steroids and hypothalamic GnRH. PMID:23690336

  14. Fundulus heteroclitus gonadotropins.5: Small scale chromatographic fractionation of pituitary extracts into components with different steroidogenic activities using homologous bioassays

    PubMed Central

    Lin, Yu-Wai Peter; Petrino, Teresa R; Wallace, Robin A

    2004-01-01

    Fractionation and characterization of gonadotropins (GtH) from Fundulus heteroclitus pituitary extracts were carried out using a biocompatible liquid chromatographic procedure (Pharmacia FPLC system). Chromatographic fractions were monitored for gonadotropic activities (induction of oocyte maturation and steroid production) using homologous follicle bioassays in vitro. Size-exclusion chromatography eluted gonadotropic activity in one major protein peak (Mr ~ 30,000). Anion-exchange and hydrophobic-interaction chromatography (HIC) yielded two distinct peaks of 17beta-estradiol (E2)- and 17alpha-hydroxy,20beta-dihydroprogesterone (DHP)-promoting activity with associated oocyte maturation. Two-dimensional chromatography (chromatofocusing followed by HIC) resolved pituitary extracts into two active fractions; both induced E2 synthesis, but one was relatively poor in eliciting DHP and testosterone production. Thus, using homologous bioassays, at least two quantitatively different gonadotropic (steroidogenic) activities: an E2-promoting gonadotropin (GtH I-like) and a DHP-promoting gonadotropin (GtH II-like), which has a lower isoelectric point but greater hydrophobicity than the former, can be distinguished from F. heteroclitus pituitaries by a variety of chromatographic procedures. This study complements previous biochemical and molecular data in F. heteroclitus and substantiates the duality of GtH function in a multiple-spawning teleost. PMID:15040801

  15. Pituitary apoplexy induced by Gonadotropin-releasing hormone agonists for treating prostate cancer-report of first Asian case

    PubMed Central

    2013-01-01

    We present the first Asian case of a 77-year-old man who developed pituitary apoplexy (PA) soon after gonadotropin-releasing hormone agonist (GnRHa) (leuprorelin) injection to treat prostate cancer. Headache, ophthalmoplegia, visual field deficit, nausea, and vomiting are the typical characteristics of pituitary apoplexy. Though the occurrence rate is rare, the consequence of this condition can vary from mild symptoms such as headache to life-threatening scenarios like conscious change. Magnetic resonance imaging is the best imaging modality to detect PA and sublabial trans-sphenoid pituitary tumor removal can resolve most of PA symptoms and is so far the best solution in consensus. We also review 11 previous reported cases receiving GnRHa for androgen deprivation therapy of prostate cancer, and hope to alert clinicians to use GnRHa with caution. PMID:24088191

  16. Immunoreactive gonadotropin-releasing hormone-like material in the brain and the pituitary gland during the periovulatory period in the brown trout (Salmo trutta L.): relationships with the plasma and pituitary gonadotropin.

    PubMed

    Breton, B; Motin, A; Billard, R; Kah, O; Geoffre, S; Precigoux, G

    1986-01-01

    In fish there are few data on the gonadotropin-releasing hormone (Gn-RH) neurosecretory activity, which could explain long- and short-term variations of the gonadotropin secretion. There is no biological species specificity between mammal and fish Gn-RH; although there is a structural difference, they are, on the contrary, characterized by a high immunological specificity which does not allow measurement of fish Gn-RH using radioimmunoassay for LH-RH. We have synthesized salmon Gn-RH according to the formula recently proposed by Sherwood (N. Sherwood, L. Eiden, M. Brownstein, J. Spies, J. Rivier, and W. Vale, 1983. Proc. Natl. Acad. Sci. USA 80, 2794-2798). Its activity has been tested by its ability to stimulate the gonadotropin hormone (GtH) secretion in vivo in testosterone-implanted juvenile rainbow trout, and for the recognition of synthesized Gn-RH (s-Gn-RH) perykaria by a specific antibody raised against the s-Gn-RH in regions of the brain described as containing LH-RH immunoreactive-like material. A radioimmunoassay has been developed for the salmon Gn-RH, and its specificity to measure trout Gn-RH has been tested. Using this assay, the brain and pituitary Gn-RH contents have been measured throughout the final phases of maturation and ovulation. Brain Gn-RH increases from the end of vitellogenesis (8.9 +/- 0.76 ng/brain) to ovulation (more than 15 ng/brain). Pituitary Gn-RH is lower (1.58 +/- 0.69 ng/pituitary) at the end of vitellogenesis and follows a similar profile as in the brain, except for a significant decrease just prior the beginning of oocyte maturation. The correlations between Gn-RH levels and GtH pituitary and plasma levels show that total brain Gn-RH is never correlated to the GtH, suggesting that the increase in the brain Gn-RH content is related to a Gn-RH system closely related to maturation and ovulation, which remains to be investigated. On the contrary, pituitary Gn-RH levels are well correlated with pituitary and plasma GtH levels

  17. Gonadotropin-secreting pituitary adenoma with concomitant hypersecretion of testosterone and elevated sperm count. Treatment with LRH agonist.

    PubMed

    Zárate, A; Fonseca, M E; Mason, M; Tapia, R; Miranda, R; Kovacs, K; Schally, A V

    1986-09-01

    Hypersecretion of both FSH and LH was demonstrated in a man with pituitary macroadenoma, who also presented elevated levels of blood testosterone and an increased sperm count. The patient underwent transsphenoidal surgery followed immediately by cranial irradiation. Immunocytochemical analysis of the tumour revealed the presence of FSH, LH, TSH and the alpha-subunit. Gel chromatography of the serum on Sephadex G-100 revealed immunoactive FSH, LH and the alpha-subunit which coeluted with the labelled standards of corresponding hormones. Blood levels of both gonadotropins and testosterone remained persistently elevated up to one year following surgical decompression of the tumour and radiotherapy. It was decided to treat this patient with sc administration of 100 micrograms D-Trp6-LRH biweekly. After 20 weeks, LRH-analogue treatment resulted in the reduction of serum FSH and LH levels and a diminishing in tumour size as assessed by computed tomography scan of the pituitary. This report shows that in a patient with clinically and biochemically documented gonadotropin-secreting adenoma, inducing a state of persistent gonadal hyperfunction, pituitary surgery and cranial irradiation failed to normalize the biochemical abnormality; however, therapy with D-Trp6-LRH agonist induced clinical, biochemical and radiologic improvement.

  18. Glucocorticoid regulation of gonadotropin release from gonadotropes of ovine pituitary gland in vitro

    SciTech Connect

    Nangalama, A.W.

    1989-01-01

    In order to understand the role of glucocorticoids in the regulation of gonadotropin release by the pituitary gland, the short-term effects of cortisol perifusion (1.5 h to 8 hrs) on GnRH-induced LH secretion were investigated. To determine the biochemical mechanism(s) by which cortisol can act to modulate GnRH-induced LH release, the interactions of cortisol and arachidonic acid in GnRH-stimulated LH release were examined. Cortisol perifusion for 1.5 hr had no effect on GnRH-induced LH release, but longer treatment periods (4 hr-8 hrs) significantly reduced GnRH-stimulated LH release (4.0 hr, p < 0.01; 6.0 hr, p < 0.001; 8.0 hr, p < 0.01). Treatment and animal effects were highly significant (p < 0.001). There were significant interactions (p < 0.001) between treatment and animal as determined by a two-way ANOVA. Cortisol treatment also produced progressive increases in basal LH secretion with time (1.5 hr, p < 0.05; 4.0 hr, p < 0.01; 6.0 hr, p < 0.01; 8.0 hr, p < 0.001). Incubation of pituitary tissue with arachidonic acid (AA) resulted in a linear dose-response of LH (p < 0.001). Cortisol infusion failed to inhibit GnRH-induced LH release in which 10{sup {minus}4}M AA was administered for 20 min before a 10 min, 10{sup {minus}10}M GnRH pulse. Like cortisol, chloroquine also failed to inhibit AA-induced LH release. Perifusion with 10{sup {minus}6}M cortisol for 6.0 hours significantly (p < 0.001) blocked GnRH-stimulated (H{sup 3})AA release 24% below the basal (100%) ({sup 3}H)AA secretion. Reduction of ({sup 3}H)AA release was accompanied by decreased GnRH-stimulated LH secretion.

  19. The direct pituitary effect of testosterone to inhibit gonadotropin secretion in men is partially mediated by aromatization to estradiol.

    PubMed

    Bagatell, C J; Dahl, K D; Bremner, W J

    1994-01-01

    In men, administration of exogenous testosterone (T) exerts direct negative feedback effects at the pituitary as well as at the hypothalamic level. This study was undertaken to determine whether T itself causes the inhibitory effects on the pituitary, or whether conversion to estradiol (E2) or dihydrotestosterone (DHT) is required. We assessed the biological activity of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as immunoactivity. Blood samples were drawn before, during, and after a continuous, 72-hour i.v. infusion of T (15 mg/day), E2 (90 micrograms/day), or DHT (500 micrograms/day). Each of these doses is twice the daily production rate of the steroid. Each man received each of the three steroid infusions. We studied four men, ages 23-35, with idiopathic hypothalamic hypogonadism (IHH), who were treated with pulsatile gonadotropin releasing hormone (GnRH) until their gonadotropins reached the normal range. Serum levels of T, E2, DHT, and levels of immunologically active and biologically active LH and FSH were measured. We found that administration of each steroid increased serum levels of the infused steroid to the upper physiologic range. Administration of T or E2 resulted in decreased mean levels of biologically and immunologically active LH and FSH; administration of DHT did not alter gonadotropin secretion. These data suggest that some of the direct effect of T at the pituitary level in men is mediated by E2, whereas peripherally formed DHT may not play an important role in this process.

  20. Pituitary gonadotropin and testicular gonadotropin receptor expression in Atlantic cod (Gadusmorhua L.) during the first reproductive season: Effects of photoperiod modulation.

    PubMed

    de Almeida, Fernanda Ferreira Loureiro; Andersson, Eva; Mittelholzer, Christian; Karlsen, Orjan; Taranger, Geir Lasse; Schulz, Rüdiger W

    2011-08-01

    Pituitary mRNA levels of gonadotropin β-subunits and of their cognate receptors in the testis were studied during puberty in Atlantic cod under normal and experimental photoperiod conditions that suppressed, delayed or accelerated testis maturation. Results are discussed in context with changes in testicular histology and plasma androgen levels, considered as end points of gonadotropic regulation. Up-regulation of fshb was closely associated with the onset of puberty, decreased when spermatogenesis was completed and reached minimum levels after spawning. These results demonstrate, for the first time using an experimental approach, that activation of Fsh-dependent signaling is associated with spermatogonial proliferation and formation of spermatogenic cysts. Changes in fshr expression were less prominent and could be explained by changes in the cellular composition and RNA content of cod testis tissue. At more advanced stages of development (spermiogenesis, spermiation and spawning), lhb and, one month later, lhcgr transcript levels increased and reached peak values in spawning fish, in a positive feedback loop involving plasma androgens and Lh/Lhcgr-dependent signaling. This loop was broken by a loss of lhb expression at the end of the spawning season. Continuous light (LL) from summer solstice, ~8 months prior to spawning, suppressed the start of testis maturation and the changes in gonadotropin and receptor mRNA levels, while LL from winter solstice initially up-regulated lhb and lhcgr expression, before resulting in a precocious termination of the spawning season and low expression of all four genes. Our studies provide experimental evidence for a clear functional discrimination of cod gonadotropins. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Effects of lamprey PQRFamide peptides on brain gonadotropin-releasing hormone concentrations and pituitary gonadotropin-β mRNA expression.

    PubMed

    Daukss, Dana; Gazda, Kristen; Kosugi, Takayoshi; Osugi, Tomohiro; Tsutsui, Kazuyoshi; Sower, Stacia A

    2012-06-01

    Within the RFamide peptide family, PQRFamide peptides that include neuropeptide FF and AF possess a C-terminal Pro-Gln-Arg-Phe-NH(2) motif. We previously identified PQRFamide peptides, lamprey PQRFa, PQRFa-related peptide (RP)-1 and -RP-2 by immunoaffinity purification in the brain of lamprey, one of the most ancient vertebrate species [13]. Lamprey PQRFamide peptide precursor mRNA was expressed in regions predicted to be involved in neuroendocrine regulation in the hypothalamus. However, the putative function(s) of lamprey PQRFamide peptides (PQRFa, PQRFa-RP-1 and PQRFa-RP-2) were not examined nor was the distribution of PQRFamide peptides examined in other tissues besides the brain. The objective of this study was to determine tissue distribution of lamprey PQRFamide peptide precursor mRNA, and to examine the effects of PQRFamide peptides on brain gonadotropin-releasing hormone (GnRH)-I, -II, and -III protein concentrations, and pituitary gonadotropin (GTH)-β mRNA expression in adult lampreys. Lamprey PQRFamide peptide precursor mRNA was expressed in the eye and the brain. Lamprey PQRFa at 100 μg/kg increased brain concentrations of lamprey GnRH-II compared with controls. PQRFa, PQRFa-RP-1 and PQRFa-RP-2 did not significantly change brain protein concentrations of either lamprey GnRH-I, -III, or lamprey GTH-β mRNA expression in the pituitary. These data suggest that one of the PQRFamide peptides may act as a neuroregulator of at least the lamprey GnRH-II system in adult female lamprey.

  2. Mouse Models for the Study of Synthesis, Secretion, and Action of Pituitary Gonadotropins.

    PubMed

    Kumar, T Rajendra

    2016-01-01

    Gonadotropins play fundamental roles in reproduction. More than 30years ago, Cga transgenic mice were generated, and more than 20years ago, the phenotypes of Cga null mice were reported. Since then, numerous mouse strains have been generated and characterized to address several questions in reproductive biology involving gonadotropin synthesis, secretion, and action. More recently, extragonadal expression, and in some cases, functions of gonadotropins in nongonadal tissues have been identified. Several genomic and proteomic approaches including novel mouse genome editing tools are available now. It is anticipated that these and other emerging technologies will be useful to build an integrated network of gonadotropin signaling pathways in various tissues. Undoubtedly, research on gonadotropins will continue to provide new knowledge and allow us transcend from benchside to the bedside.

  3. Immunohistochemical localization of gonadotropin releasing hormones in the brain and pituitary gland of the Nile perch, Lates niloticus (Teleostei, Centropomidae).

    PubMed

    Mousa, Mostafa A; Mousa, Shaaban A

    2003-02-15

    In the present study we investigated the distribution of gonadotropin-releasing hormones (GnRH) in the brain of Lates niloticus and their association with different pituitary cell types using immunohistochemical techniques. We found immunoreactive (ir) chicken GnRH-II (cGnRH-II) and mammalian GnRH (mGnRH) as the main components of the GnRH-ir system within the brain of the Nile perch. The results indicate that mGnRH and cGnRH are localized in different neurons: mGnRH-ir perikaria were observed in the preoptic region particularly in the organum vasculosum laminae terminalis (OVLT) and in the nucleus lateralis tuberis pars posterior (NLTP) of the mediobasal hypothalamus. These cell bodies are located along a continuum of ir-fibers that could be traced from the olfactory nerve to the pituitary. mGnRH-ir fibers were detected in many parts of the brain (olfactory bulbs, ventral telencephalon, hypothalamus, and mesencephalon) and in the pituitary. cGnRH-ir cell bodies are restricted to the optic tract, but few scattered fibers could be detected in different parts of the brain. The pituitary exhibited very few cGnRH-II ir fibers, contrasting with an extensive mGnRH innervation. Moreover, mGnRH-ir fibers were targeting the three areas of the pituitary gland: rostral pars distalis (RPD), proximal pars distalis (PPD), and pars intermedia (PI). Double immunolabeling studies showed GnRH-ir fibers in close proximity with prolactin (PRL)- and adrenocorticotropic hormone (ACTH)-producing cells in the RPD, growth hormone (GH)-producing cells in the PPD, gonadotropins (GTHs)-producing cells in the PPD in the external border of the PI, and with somatolactin (SL)- and alpha-melanocyte stimulating hormone (alpha-MSH)-producing cells in the PI. Our results showed direct morphological evidence for a close association of GnRH-ir fibers with the different adenohypophysial cell types. These results suggest a multiple role of GnRH in the regulation of various pituitary hormones' release

  4. Expression of gonadotropin-inhibitory hormone receptors in mouse pituitary gonadotroph LβT2 cells and hypothalamic gonadotropin-releasing hormone-producing GT1-7 cells.

    PubMed

    Sukhbaatar, Unurjargal; Kanasaki, Haruhiko; Mijiddorj, Tselmeg; Oride, Aki; Miyazaki, Kohji

    2014-01-01

    Gonadotropin-inhibitory hormone (GnIH) was first identified in quail as a novel neurohormone that acts directly on the anterior pituitary to inhibit gonadotropin release. GnIH inhibits not only gonadotropin release from the pituitary gland but also inhibits the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. In this study, we examined how GnIH receptors were regulated in pituitary gonadotroph cells and GnRH-producing neurons in the hypothalamus. In the mouse pituitary gonadotroph cell line LβT2, GnRH increased expression of the GnIH receptor, G-protein coupled receptor 74 (GPR74). GnRH also stimulated the expression of GPR74 and GPR147 in primary cultures of rat anterior pituitary cells. In addition, when GnRH was administered to LβT2 cells in a pulsatile manner, low frequency GnRH pulse stimulation stimulated GPR74 and GPR147 expression more than did high frequency GnRH pulses. In the mouse hypothalamic GnRH-producing cell line GT1-7, hypothalamic kisspeptin did not significantly increase the expression of GnIH receptors. However, the intermittent administration of kisspeptin to GT1-7 cells significantly increased GPR74 and GPR147 mRNA expression. The overexpression of either constitutively active MEK kinase (MEKK) or protein kinase A (PKA) in LβT2 cells increased the expression of GPR74 mRNA. Conversely, in GT1-7 cells, although the overexpression of either MEKK or PKA failed to stimulate GnIH receptor expression, the combined overexpression of both kinases together increased GPR74 and GPR147 mRNA levels. Our current observations suggest that two central controllers of reproductive function, GnRH and kisspeptin, stimulate the expression of GnIH receptors in pituitary gonadotroph cells and hypothalamic GnRH neurons.

  5. G proteins and autocrine signaling differentially regulate gonadotropin subunit expression in pituitary gonadotrope.

    PubMed

    Choi, Soon-Gang; Jia, Jingjing; Pfeffer, Robert L; Sealfon, Stuart C

    2012-06-15

    Gonadotropin-releasing hormone (GnRH) acts at gonadotropes to direct the synthesis of the gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). The frequency of GnRH pulses determines the pattern of gonadotropin synthesis. Several hypotheses for how the gonadotrope decodes GnRH frequency to regulate gonadotropin subunit genes differentially have been proposed. However, key regulators and underlying mechanisms remain uncertain. We investigated the role of individual G proteins by perturbations using siRNA or bacterial toxins. In LβT2 gonadotrope cells, FSHβ gene induction depended predominantly on Gα(q/11), whereas LHβ expression depended on Gα(s). Specifically reducing Gα(s) signaling also disinhibited FSHβ expression, suggesting the presence of a Gα(s)-dependent signal that suppressed FSH biosynthesis. The presence of secreted factors influencing FSHβ expression levels was tested by studying the effects of conditioned media from Gα(s) knockdown and cholera toxin-treated cells on FSHβ expression. These studies and related Transwell culture experiments implicate Gα(s)-dependent secreted factors in regulating both FSHβ and LHβ gene expression. siRNA studies identify inhibinα as a Gα(s)-dependent GnRH-induced autocrine regulatory factor that contributes to feedback suppression of FSHβ expression. These results uncover differential regulation of the gonadotropin genes by Gα(q/11) and by Gα(s) and implicate autocrine and gonadotrope-gonadotrope paracrine regulatory loops in the differential induction of gonadotropin genes.

  6. Identification of a novel pituitary-specific chicken gonadotropin-releasing hormone receptor and its splice variants.

    PubMed

    Shimizu, Mamiko; Bédécarrats, Grégoy Y

    2006-11-01

    In all vertebrates, GnRH regulates gonadotropin secretion through binding to a specific receptor on the surface of pituitary gonadotropes. At least two forms of GnRH exist within a single species, and several corresponding GnRH receptors (GNRHRs) have been isolated with one form being pituitary specific. In chickens, only one type of widely expressed GNRHR has previously been identified. The objectives of this study were to isolate a chicken pituitary-specific GNRHR and to determine its expression pattern during a reproductive cycle. Using a combined strategy of PCR and rapid amplification of cDNA ends (RACE), a new GNRHR (chicken GNRHR2) and two splice variants were isolated in domestic fowl (Gallus gallus domesticus). Full-length GNRHR2 and one of its splice variant mRNAs were expressed exclusively in the pituitary, whereas mRNA of the other splice variant was expressed in most brain tissues examined. The deduced amino acid sequence of full-length chicken GNRHR2 reveals a seven transmembrane domain protein with 57%-65% homology to nonmammalian GNRHRs. Semiquantitative real-time PCR revealed that mRNA levels of full-length chicken GNRHR2 in the pituitary correlate with the reproductive status of birds, with maximum levels observed during the peak of lay and 4 wk postphotostimulation in females and males, respectively. Furthermore, GnRH stimulation of GH3 cells that were transiently transfected with cDNA that encodes chicken GNRHR2 resulted in a significant increase in inositol phosphate accumulation. In conclusion, we isolated a novel GNRHR and its splice variants in chickens, and spatial and temporal gene expression patterns suggest that this receptor plays an important role in the regulation of reproduction.

  7. Expression of the putative gonadotropin-inhibitory hormone receptor, NPFFR1, in the anterior pituitary gland of the gilt is affected by age and sexual maturation

    USDA-ARS?s Scientific Manuscript database

    Gonadotropin-inhibitory hormone (GnIH) purportedly suppresses secretion of luteinizing hormone (LH) by acting through a G-protein coupled receptor (NPFFR1) in the anterior pituitary gland and hypothalamus. The objective of these studies was to determine if expression of mRNA for NPFFR1 in the reprod...

  8. Gonadotropin Inhibitory Hormone Down-Regulates the Brain-Pituitary Reproductive Axis of Male European Sea Bass (Dicentrarchus labrax).

    PubMed

    Paullada-Salmerón, José A; Cowan, Mairi; Aliaga-Guerrero, María; Morano, Francesca; Zanuy, Silvia; Muñoz-Cueto, José A

    2016-06-01

    Gonadotropin-inhibitory hormone (GnIH) inhibits gonadotropin synthesis and release from the pituitary of birds and mammals. However, the physiological role of orthologous GnIH peptides on the reproductive axis of fish is still uncertain, and their actions on the main neuroendocrine systems controlling reproduction (i.e., GnRHs, kisspeptins) have received little attention. In a recent study performed in the European sea bass, we cloned a cDNA encoding a precursor polypeptide that contained C-terminal MPMRFamide (sbGnIH-1) and MPQRFamide (sbGnIH-2) peptide sequences, developed a specific antiserum against sbGnIH-2, and characterized its central and pituitary GnIH projections in this species. In this study, we analyzed the effects of intracerebroventricular injection of sbGnIH-1 and sbGnIH-2 on brain and pituitary expression of reproductive hormone genes (gnrh1, gnrh2, gnrh3, kiss1, kiss2, gnih, lhbeta, fshbeta), and their receptors (gnrhr II-1a, gnrhr II-2b, kiss1r, kiss2r, and gnihr) as well as on plasma Fsh and Lh levels. In addition, we determined the effects of GnIH on pituitary somatotropin (Gh) expression. The results obtained revealed the inhibitory role of sbGnIH-2 on brain gnrh2, kiss1, kiss2, kiss1r, gnih, and gnihr transcripts and on pituitary fshbeta, lhbeta, gh, and gnrhr-II-1a expression, whereas sbGnIH-1 only down-regulated brain gnrh1 expression. However, at different doses, central administration of both sbGnIH-1 and sbGnIH-2 decreased Lh plasma levels. Our work represents the first study reporting the effects of centrally administered GnIH in fish and provides evidence of the differential actions of sbGnIH-1 and sbGnIH-2 on the reproductive axis of sea bass, the main inhibitory role being exerted by the sbGnIH-2 peptide. © 2016 by the Society for the Study of Reproduction, Inc.

  9. Four gonadotropin releasing hormone receptor genes in Atlantic cod are differentially expressed in the brain and pituitary during puberty.

    PubMed

    Hildahl, Jon; Sandvik, Guro K; Edvardsen, Rolf B; Norberg, Birgitta; Haug, Trude M; Weltzien, Finn-Arne

    2011-09-01

    Gonadotropin releasing hormones (GnRH) are an important part of the brain-pituitary-gonad axis in vertebrates. GnRH binding to its receptors (GnRH-R) stimulates synthesis and release of gonadotropins in the pituitary. GnRH-Rs also mediate other processes in the central nervous system such as reproductive behavior and neuromodulation. As many as five GnRH-R genes have been identified in two teleost fish species, but the function and phylogenetic relationship of these receptors is not fully understood. To gain a better understanding of the functional relationship between multiple GnRH-Rs in an important aquaculture species, the Atlantic cod (Gadus morhua), we identified four GnRH-Rs (gmGnRH-R) by RT-PCR, followed by full-length cloning and sequencing. The deduced amino acid sequences were used for phylogenetic analysis to identify conserved functional motifs and to clarify the relationship of gmGnRH-Rs with other vertebrate GnRH-Rs. The function of GnRH-R variants was investigated by quantitative PCR gene expression analysis in the brain and pituitary of female cod during a full reproductive cycle and in various peripheral tissues in sexually mature fish. Phylogenetic analysis revealed two types of teleost GnRH-Rs: Type I including gmGnRH-R1b and Type II including gmGnRH-R2a, gmGnRH-R2b and gmGnRH-R2c. All four gmGnRH-Rs are expressed in the brain, and gmGnRH-R1b, gmGnRH-R2a and gmGnRH-R2c are expressed in the pituitary. The only GnRH-R differentially expressed in the pituitary during the reproductive cycle is gmGnRH-R2a such that its expression is significantly increased during spawning. These data suggest that gmGnRH-R2a is the most likely candidate to mediate the hypophysiotropic function of GnRH in Atlantic cod.

  10. Endocrine disrupting effects of dichlorodiphenyltrichloroethane analogues on gonadotropin hormones in pituitary gonadotrope cells.

    PubMed

    Zhou, Jinghua; Yang, Ye; Xiong, Kang; Liu, Jing

    2014-05-01

    It has been shown that exposure to dichlorodiphenyltrichloroethane (DDT) analogues leads to disharmony of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). However, the effects and mechanisms of DDT analogues on the expression of gonadotropin genes (FSHβ, LHβ and Cgα), which is the rate-limiting step of FSH and LH biosynthesis, remain unknown. In this study, we assessed the effects of p,p'-DDT, o,p'-DDT, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and methoxychlor (MXC) on gonadotropin genes expression and hormones synthesis in gonadotrope cells. p,p'-DDT and MXC at test concentrations ranging from 10(-9) to 10(-7)mol/L, stimulated gonadotropin genes expression and hormones synthesis in a dose-dependent manner. The activation of extracellular signal-regulated kinase (ERK) was required for the induction of gonadotropin genes expression and hormones synthesis by p,p'-DDT or MXC exposure. This study showed for the first time that p,p'-DDT and MXC regulated gonadotropin genes expression and hormones synthesis through ERK pathway in gonadotrope cells. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Metformin decreases GnRH- and activin-induced gonadotropin secretion in rat pituitary cells: potential involvement of adenosine 5' monophosphate-activated protein kinase (PRKA).

    PubMed

    Tosca, Lucie; Froment, Pascal; Rame, Christelle; McNeilly, J R; McNeilly, A S; Maillard, Virginie; Dupont, Joelle

    2011-02-01

    Metformin is an insulin sensitizer molecule used for the treatment of infertility in women with polycystic ovary syndrome and insulin resistance. It modulates the reproductive axis, affecting the release of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH). However, metformin's mechanism of action in pituitary gonadotropin-secreting cells remains unclear. Adenosine 5' monophosphate-activated protein kinase (PRKA) is involved in metformin action in various cell types. Here, we investigated the effects of metformin on gonadotropin secretion in response to activin and GnRH in primary rat pituitary cells (PRP), and studied PRKA in rat pituitary. In PRP, metformin (10 mM) reduced LH and follicle-stimulating hormone (FSH) secretion induced by GnRH (10(-8) M, 3 h), FSH secretion, and mRNA FSHbeta subunit expression induced by activin (10(-8) M, 12 or 24 h). The different subunits of PRKA are expressed in pituitary. In particular, PRKAA1 is detected mainly in gonadotrophs and thyrotrophs, is less abundant in lactotrophs and somatotrophs, and is undetectable in corticotrophs. In PRP, metformin increased phosphorylation of both PRKA and acetyl-CoA carboxylase. Metformin decreased activin-induced SMAD2 phosphorylation and GnRH-induced mitogen-activated protein kinase (MAPK) 3/1 (ERK1/2) phosphorylation. The PRKA inhibitor compound C abolished the effects of metformin on gonadotropin release induced by GnRH and on FSH secretion and Fshb mRNA induced by activin. The adenovirus-mediated production of dominant negative PRKA abolished the effects of metformin on the FSHbeta subunit mRNA and SMAD2 phosphorylation induced by activin and on the MAPK3/1 phosphorylation induced by GnRH. Thus, in rat pituitary cells, metformin decreases gonadotropin secretion and MAPK3/1 phosphorylation induced by GnRH and FSH release, FSHbeta subunit expression, and SMAD2 phosphorylation induced by activin through PRKA activation.

  12. Valproate inhibits GnRH-induced gonadotropin release from anterior pituitary cells of male rat in vitro.

    PubMed

    Wasilewska-Dziubinska, Elzbieta; Gajewska, Alina; Wolinska-Witort, Ewa; Chmielowska, Magdalena; Martynska, Lidia; Elbanowski, Jerzy; Kochman, Kazimierz

    2011-01-01

    Valproate (VPA) a potent antiepileptic drug has been claimed to induce reproductive disturbances in men. Long-term VPA treatment can affect sperm morphology and induce testicular atrophy in non-epileptic rats. It has been reported that VPA reduced testosterone secretion stimulated by hCG in isolated rat Leydig cells. These results suggest direct effect of VPA on testes in rats. However centrally mediated effects at hypothalamo-pituitary level can therefore not be excluded. This study focused on the dose and time-dependent effects of VPA on basal and GnRH-induced LH and FSH release from the primary anterior pituitary cells culture of male rats. The dose-dependent effect of 10 nM-100 mM of VPA on basal LH release from anterior pituitary cells after 3h of incubation was examined. To determine the time-dependent effects on LH, FSH, TSH and PRL release short (3 h) and long-term (24 h) incubations in the presence of 10 nM, 100 nM and 1 μM of VPA were maintained.To assess whether VPA can affect GnRH-induced LH and FSH release, cells were incubated for 3 h with 10 nM, 100 nM and 1 μM of VPA in the presence of GnRH. The concentration of rLH, rFSH, rPRL and rTSH in incubation medium was determined by RIA method. VPA did not affect the basal LH, FSH, PRL and TSH release from the primary anterior pituitary cells culture of male rats. VPA in concentration 1µM significantly suppressed GnRH-induced LH secretion. However VPA at all tested doses diminished GnRH-induced FSH release. VPA may diminish gonadotropin release in vitro but this effect can only be achieved after GnRH-dependent specific receptor activation. Both gonadotropins differ in their pattern of response for increasing doses of VPA.

  13. Wastewater treatment plant effluent alters pituitary gland gonadotropin mRNA levels in juvenile coho salmon (Oncorhynchus kisutch).

    PubMed

    Harding, Louisa B; Schultz, Irvin R; da Silva, Denis A M; Ylitalo, Gina M; Ragsdale, Dave; Harris, Stephanie I; Bailey, Stephanie; Pepich, Barry V; Swanson, Penny

    2016-09-01

    It is well known that endocrine disrupting compounds (EDCs) present in wastewater treatment plant (WWTP) effluents interfere with reproduction in fish, including altered gonad development and induction of vitellogenin (Vtg), a female-specific egg yolk protein precursor produced in the liver. As a result, studies have focused on the effects of EDC exposure on the gonad and liver. However, impacts of environmental EDC exposure at higher levels of the hypothalamic-pituitary-gonad axis are less well understood. The pituitary gonadotropins, follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh) are involved in all aspects of gonad development and are subject to feedback from gonadal steroids making them a likely target of endocrine disruption. In this study, the effects of WWTP effluent exposure on pituitary gonadotropin mRNA expression were investigated to assess the utility of Lh beta-subunit (lhb) as a biomarker of estrogen exposure in juvenile coho salmon (Oncorhynchus kisutch). First, a controlled 72-h exposure to 17α-ethynylestradiol (EE2) and 17β-trenbolone (TREN) was performed to evaluate the response of juvenile coho salmon to EDC exposure. Second, juvenile coho salmon were exposed to 0, 20 or 100% effluent from eight WWTPs from the Puget Sound, WA region for 72h. Juvenile coho salmon exposed to 2 and 10ng EE2L(-1) had 17-fold and 215-fold higher lhb mRNA levels relative to control fish. Hepatic vtg mRNA levels were dramatically increased 6670-fold, but only in response to 10ng EE2L(-1) and Fsh beta-subunit (fshb) mRNA levels were not altered by any of the treatments. In the WWTP effluent exposures, lhb mRNA levels were significantly elevated in fish exposed to five of the WWTP effluents. In contrast, transcript levels of vtg were not affected by any of the WWTP effluent exposures. Mean levels of natural and synthetic estrogens in fish bile were consistent with pituitary lhb expression, suggesting that the observed lhb induction may be due to

  14. [Effect of primary ovarian insufficiency on the molecular heterogeneity of pituitary gonadotropins].

    PubMed

    Mason, M; Fonseca, M E; Ruiz, J E; Morán, C; Zárate, A

    1992-08-01

    It is known that hypophysial gonadotropins circulate in different molecular forms which are provided with different biological activity and that the proportion of such varieties keep a relation with the concentrations of estrogens in circulation. In physiological menopause predominate the great molecular forms which have a lesser biological activity and when estrogens are administrated a change is produced to smaller molecular forms. The present study tries to determine if in cases of ovarian insufficiency of long duration as in precocious menopause and the syndrome of refractory ovary the chromatographic conduct of gonadotropin is similar. Six patients with precocious menopause, and three with the syndrome of refractory ovary, were studied, in order to make a comparison of chromatographic pattern of FSF and LH in serum, with the one found in women with normal ovarian function and with physiologic menopause. The chromatographic analysis was done by filtration in gel of the serum and the subsequent determination of LH and FSH by RIA of double antibody. It was found that the chromatographic pattern of patients with ovarian insufficiency of long duration, characteristically presents larger molecular forms, specially in the refractory ovary syndrome with a greater alteration in the profile of LH. With base on these results it is concluded that the duration of ovarian insufficiency determine the type of molecular form, predominant, of gonadotropins. Also it is suggested that for the syndrome of refractory ovary, the greater heterogenicity of gonadotropins may explain part of physiopathogeny.

  15. 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.

  16. Regulation and distribution of squirrel monkey chorionic gonadotropin and secretogranin II in the pituitary.

    PubMed

    Vasauskas, Audrey A; Hubler, Tina R; Mahanic, Christina; Gibson, Susan; Kahn, Andrea G; Scammell, Jonathan G

    2011-02-01

    Secretogranin II (SgII) is a member of the granin family of proteins found in neuroendocrine and endocrine cells. The expression and storage of SgII in the pituitary gland of Old World primates and rodents have been linked with those of luteinizing hormone (LH). However, New World primates including squirrel monkeys do not express LH in the pituitary gland, but rather CG is expressed. If CG takes on the luteotropic role of LH in New World primates, SgII may be associated with the expression and storage of CG in the pituitary gland. The goal of this study was to evaluate the regulation and distribution of CG and SgII in the squirrel monkey. A DNA fragment containing approximately 750 bp of squirrel monkey SgII promoter was isolated from genomic DNA and found to contain a cyclic-AMP response element that is also present in the human SgII promoter and important for GnRH responsiveness. The squirrel monkey and human SgII promoters were similarly activated by GnRH in luciferase reporter gene assays in LβT2 cells. Double immunofluorescence microscopy demonstrated close association of SgII and CG in gonadotrophs of squirrel monkey pituitary gland. These results suggest that CG and SgII have a similar intercellular distribution and are coregulated in squirrel monkey pituitary gland. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. Regulation of pituitary GnRH receptor and gonadotropin subunits by IGF1 and GnRH in prepubertal male coho salmon.

    PubMed

    Luckenbach, J Adam; Dickey, Jon T; Swanson, Penny

    2010-07-01

    Insulin-like growth factor 1 (IGF1) is a key somatotropic hormone that may convey growth status to the reproductive endocrine system. This study examined effects of IGF1 alone or in combination with gonadotropin-releasing hormone (GnRH) on pituitary transcripts for GnRH receptor (GnRHR) variants, follicle-stimulating hormone (FSH), luteinizing hormone (LH), growth hormone (GH), and IGF, as well as secretion of FSH in vitro. Three experiments were conducted with dispersed pituitary cells of prepubertal male coho salmon (Oncorhynchus kisutch) to determine the time course of the response to IGF1, IGF1 concentration response, and GnRH concentration response. IGF1 consistently elevated pituitary transcripts for gnrhr1 and the four gonadotropin subunits (fshb, lhb, cga1, and cga2) by day 10 of culture, while suppressing gh and igf2. Short-term treatment with GnRH (24h) induced minor increases in transcripts for fshb, cga1, and cga2, but suppressed lhb and strongly inhibited gnrhr1 expression. IGF1 significantly increased GnRH-stimulated FSH protein release by the pituitary cells, although not as robustly as previously observed in more reproductively advanced salmon. Our results demonstrate that IGF1 increases steady-state mRNA levels of gnrhr1 and four gonadotropin subunits, and may act alone or with GnRH to increase pituitary FSH release in male coho salmon, over 1year before puberty. These findings suggest that IGF1 may prime pituitary gonadotrope cells of prepubertal salmon to respond to GnRH by stimulating synthesis of GnRHR and FSH during puberty onset. (c) 2009 Elsevier Inc. All rights reserved.

  18. Molecular cloning of pituitary glycoprotein alpha-subunit and follicle stimulating hormone and chorionic gonadotropin beta-subunits from New World squirrel monkey and owl monkey.

    PubMed

    Scammell, Jonathan G; Funkhouser, Jane D; Moyer, Felricia S; Gibson, Susan V; Willis, Donna L

    2008-02-01

    The goal of this study was to characterize the gonadotropins expressed in pituitary glands of the New World squirrel monkey (Saimiri sp.) and owl monkey (Aotus sp.). The various subunits were amplified from total RNA from squirrel monkey and owl monkey pituitary glands by reverse transcription-polymerase chain reaction and the deduced amino acid sequences compared to those of other species. Mature squirrel monkey and owl monkey glycoprotein hormone alpha-polypeptides (96 amino acids in length) were determined to be 80% homologous to the human sequence. The sequences of mature beta subunits of follicle stimulating hormone (FSHbeta) from squirrel monkey and owl monkey (111 amino acids in length) are 92% homologous to human FSHbeta. New World primate glycoprotein hormone alpha-polypeptides and FSHbeta subunits showed conservation of all cysteine residues and consensus N-linked glycosylation sites. Attempts to amplify the beta-subunit of luteinizing hormone from squirrel monkey and owl monkey pituitary glands were unsuccessful. Rather, the beta-subunit of chorionic gonadotropin (CG) was amplified from pituitaries of both New World primates. Squirrel monkey and owl monkey CGbeta are 143 and 144 amino acids in length and 77% homologous with human CGbeta. The greatest divergence is in the C terminus, where all four sites for O-linked glycosylation in human CGbeta, responsible for delayed metabolic clearance, are predicted to be absent in New World primate CGbetas. It is likely that CG secreted from pituitary of New World primates exhibits a relatively short half-life compared to human CG.

  19. Prenatal development of gonadotropin-releasing hormone receptors in the rat anterior pituitary

    SciTech Connect

    Jennes, L. )

    1990-02-01

    The development of pituitary GnRH receptors was studied in the rat with in vitro and in vivo autoradiography. GnRH receptors were first seen in pituitary primordia of 13-day-old fetuses. The binding was specific and saturable and was abolished in the presence of 10 microM synthetic GnRH. To examine whether GnRH was available to the fetus, amnionic fluid was collected on days E 12-18. RIA analyses showed that GnRH levels in the amnionic fluid were low on days 12 and 13 (0-20 pM/ml) and rose to 225 pM/ml on day E 16 before they declined to 110 pM/ml on fetal day E 18. The highest levels of GnRH in the amnionic fluid on day E 16 coincided with the first appearance of immunoreactive LH cells, as determined by immunohistochemistry. Intravenous injection of 500 microliters amnionic fluid into pentobarbital-anesthetized adult rats caused a transient 40-60% increase in circulating serum LH in the recipient animal. To show that GnRH from the amnionic fluid has access to the developing pituitary, the 125I-labeled GnRH agonist Buserelin was injected into the amnionic fluid of 13-, 14-, and 15-day-old fetuses in the presence or absence of 10 microM unlabeled GnRH. Autoradiographic analysis of the fetal tissue indicated that the labeled GnRH agonist bound to specific receptors in the primordial pituitaries. The results suggest that the pituitary gonadotropes are differentiated before day E 13 because the expression of GnRH receptors is already an indication of cell determination. Since GnRH is present in the amnionic fluid in a biologically active form and can reach the fetal pituitary, it is concluded that GnRH may be an important factor determining the onset LH synthesis, but not the differentiation, of primordial pituitary cells.

  20. Estrogen negative feedback on gonadotropin secretion: evidence for a direct pituitary effect in women.

    PubMed

    Shaw, N D; Histed, S N; Srouji, S S; Yang, J; Lee, H; Hall, J E

    2010-04-01

    Studies in humans and animals indicate that estrogen negative feedback occurs at the level of the hypothalamus, but it is unclear whether estrogen also exerts an inhibitory effect directly at the pituitary. The aim of the study was to determine whether estrogen has a direct negative feedback effect at the pituitary and whether this varies with aging. A GnRH antagonist and graded doses of GnRH were used to isolate pituitary responsiveness before and after estrogen administration in Clinical Research Center studies at an academic medical center. Subjects were healthy postmenopausal women aged 48-56 yr (n = 8) or 70-75 yr (n= 8). A suppressive dose of the NAL-GLU GnRH antagonist was administered, followed by graded doses of GnRH before and after 1 month of estrogen administration. LH and FSH responses to GnRH decreased after estrogen administration (P = 0.01 and P = 0.0001, respectively). The ratio of FSH to LH amplitudes decreased in response to estrogen (P = 0.04) indicating a greater sensitivity of FSH than LH to inhibition by estrogen. The inhibitory effect of estrogen on FSH was attenuated with aging (P = 0.02), but was maintained for LH (P = 0.4). Studies that control for endogenous GnRH and estradiol demonstrate a direct pituitary site of estrogen negative feedback on LH and FSH responsiveness to GnRH in women. The effect of estrogen on FSH responsiveness is greater than on LH and is attenuated with aging. These studies indicate that estrogen negative feedback occurs directly at the pituitary and contributes to the differential regulation of FSH and LH secretion.

  1. Gonadotropin-releasing hormone and gonadal steroids regulate transcription factor mRNA expression in primary pituitary and immortalized gonadotrope cells.

    PubMed

    Zheng, Weiming; Grafer, Constance M; Kim, Jonathan; Halvorson, Lisa M

    2015-03-01

    Hormonal regulation of pituitary gonadotropin gene expression has been attributed to gonadotropin-releasing hormone (GnRH)-mediated stimulation of immediate early gene expression and gonadal steroid interactions with their respective nuclear receptors. A number of orphan nuclear receptors including steroidogenic factor 1, liver receptor homologue 1, dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1, and chicken ovalbumin upstream promoter-transcription factors I/II as well as the GATA family members, GATA2 and GATA4, have also been implicated in transcriptional regulation of the gonadotropin genes. We hypothesized that hormonally mediated changes in these latter transcription factors may provide an additional mechanism for mediating hormonal effects beyond the more classically appreciated pathways. In these studies, we demonstrate significant regulation of orphan nuclear receptor and GATA messenger RNA levels by GnRH, dihydrotestosterone, estradiol, and progesterone in both cultured primary pituitary cells and gonadotrope-derived cell line, LβT2. These results advance our understanding of the complex mechanisms by which GnRH and steroid hormones achieve precise regulation of anterior pituitary function. © The Author(s) 2015.

  2. Gonadotropin-Releasing hormones in the brain and pituitary of the white sucker

    USGS Publications Warehouse

    Robinson, T. Craig; Tobet, Stuart A.; Chase, Cindy; Waldron, Travis; Sower, Stacia A.

    2000-01-01

    The present study investigated GnRH forms within the brain of a representative of the order Cypriniformes, the white sucker, Catostomus commersoni, using HPLC, RIA, andimmunocytochemistry. Several immunoreactive (ir) GnRH forms were identified in the brain of the white sucker by chromatography and radioimmunoassay, including ir-salmon GnRH, ir-lamprey GnRH-I and -III, and ir-chicken GnRH-II. Results from immunocytochemical studies were consistent with multiple GnRH forms distributed in different patterns, particularly for fibers. Neuronal perikarya containing ir-salmon GnRH and ir-lamprey-like GnRH were found laterally within the preoptic area and rostralhypothalamus. Cells containing exclusively ir-salmon GnRH appeared slightly more rostrally, but in the same region. Fibers containing ir-salmon GnRH and ir-lamprey-like GnRH were seen throughout the caudal telencephalon and extended into thediencephalon, toward the pituitary. Fibers containing ir-chicken-II-like GnRH were also seen in the caudal telencephalon, but were concentrated more dorsally in the diencephalon. Within the pituitary, fibers containing ir-salmon GnRH and ir-lamprey-like GnRH entered the neurohypophysis, but differed in their destinations. Fibers containing ir-salmon GnRH remained within the neurohypophysis, while fibers containing ir-lamprey-like GnRH targeted adenohypophyseal tissue. These findings are consistent with the hypothesis that multiple GnRH forms with multiple functions exist within the brain and pituitary of teleosts and provide further evidence of a lamprey-like GnRH within an early evolved teleost species.

  3. Feedback inhibition of gonadotropins by testosterone in men with hypogonadotropic hypogonadism: comparison to the intact pituitary-testicular axis in primary hypogonadism.

    PubMed

    Shimon, Ilan; Lubina, Alexandra; Gorfine, Malka; Ilany, Jacob

    2006-01-01

    Men with hypogonadotropic hypogonadism (HH) due to hypothalamic-pituitary disease present with low serum testosterone levels combined with undetectable, low, or normal gonadotropin levels. Treatment consists of testosterone replacement to reverse the symptoms of androgen deficiency. The aim of this study was to examine the dynamics and feedback inhibition of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in relation to testosterone in 38 men with HH treated with testosterone. Findings were compared with 11 men with primary hypergonadism (PH). Testosterone replacement led to a suppression of FSH levels from 2.8 IU/L at baseline to 1.1 IU/L and to a suppression of LH levels from 2.3 to 0.8 IU/L. There was a linear correlation between levels of FSH and LH (after natural log transformation for both) and testosterone levels in both the HH and PH groups. However, the differences in intercepts and slopes between the groups were significant. To determine whether nonsuppressed FSH or LH during testosterone replacement reduces the probability of eugonadism, as reflected by normal testosterone levels, gonadotropin levels were measured and categorized as low (<0.5 IU/L), medium (0.5-2 IU/L), and high levels (>2 IU/L). The higher FSH or LH levels were found to significantly decrease the chance for achieving eugonadism. In conclusion, in men with HH due to hypothalamic-pituitary disease or injury, the pituitary-testicular hormonal axis maintains its physiological negative feedback between testosterone and gonadotropins. Thus, gonadotropin levels in men with HH might be useful, together with testosterone concentrations, for assessing the adequacy of androgen replacement.

  4. Comparison of therapeutic response to gonadotropin therapy between chinese male adolescents and young adults with hypogonadotropic hypogonadism caused by pituitary stalk interruption.

    PubMed

    Wang, Q; Jiang, W; Li, G; Tang, L; Hu, Y

    2014-08-01

    Hypogonadotropic hypogonadism (HH) is common in pituitary stalk interruption (PSI) patients. However, the optimal timing and effective regimen in the management of the pituitary-gonadal axis deficiency is still controversial. This study involved a retrospective review of 38 male patients with HH resulting from PSI. The HH patients were subdivided according to their ages into 2 experiment groups: Group I (adolescents, 14-18 years old, 25 cases) and Group II (young adults, 18-24 years old, 13 cases). To compare the therapeutic response to exogenous gonadotropin, a control analysis was carried out in the experimental groups with age-matched control groups. Before gonadotropin therapy, no significant increases in gonadal hormones were noted in either of the 2 experimental groups. After treatment with human chorionic gonadotropin (hCG) for less than 6 months, the hormone levels of pituitary-gonadal axis significantly increased in group I than in group II. After adding the human menopause gonadotropin (hMG) for 6 months, the gonadal hormone levels of group II were significantly increased. In addition, the Tanner stage and penis lengths in group I were significantly improved. There was no significant adverse impact on BMI and height velocity (HV) after less than one year therapy. A prolonged hypogonadotropic period without treatment may be responsible for testicular dysfunction in HH males caused by PSI. Early supplementary therapy with hCG and hMG is beneficial for the recovery of gonadal hormone and development of secondary sexual characteristics. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Evolutionary origin of a functional gonadotropin in the pituitary of the most primitive vertebrate, hagfish.

    PubMed

    Uchida, Katsuhisa; Moriyama, Shunsuke; Chiba, Hiroaki; Shimotani, Toyokazu; Honda, Kaori; Miki, Makoto; Takahashi, Akiyoshi; Sower, Stacia A; Nozaki, Masumi

    2010-09-07

    Hagfish, which lack both jaws and vertebrae, are considered the most primitive vertebrate known, living or extinct. Hagfish have long been the enigma of vertebrate evolution not only because of their evolutionary position, but also because of our lack of knowledge on fundamental processes. Key elements of the reproductive endocrine system in hagfish have yet to be elucidated. Here, the presence and identity of a functional glycoprotein hormone (GPH) have been elucidated from the brown hagfish Paramyxine atami. The hagfish GPH consists of two subunits, alpha and beta, which are synthesized and colocalized in the same cells of the adenohypophysis. The cellular and transcriptional activities of hagfish GPHalpha and -beta were significantly correlated with the developmental stages of the gonad. The purified native GPH induced the release of gonadal sex steroids in vitro. From our phylogenetic analysis, we propose that ancestral glycoprotein alpha-subunit 2 (GPA2) and beta-subunit 5 (GPB5) gave rise to GPHalpha and GPHbeta of the vertebrate glycoprotein hormone family, respectively. The identified hagfish GPHalpha and -beta subunits appear to be the typical gnathostome GPHalpha and -beta subunits based on the sequence and phylogenetic analyses. We hypothesize that the identity of a single functional GPH of the hagfish, hagfish GTH, provides critical evidence for the existence of a pituitary-gonadal system in the earliest divergent vertebrate that likely evolved from an ancestral, prevertebrate exclusively neuroendocrine mechanism by gradual emergence of a previously undescribed control level, the pituitary, which is not found in the Protochordates.

  6. Evolutionary origin of a functional gonadotropin in the pituitary of the most primitive vertebrate, hagfish

    PubMed Central

    Uchida, Katsuhisa; Moriyama, Shunsuke; Chiba, Hiroaki; Shimotani, Toyokazu; Honda, Kaori; Miki, Makoto; Takahashi, Akiyoshi; Sower, Stacia A.; Nozaki, Masumi

    2010-01-01

    Hagfish, which lack both jaws and vertebrae, are considered the most primitive vertebrate known, living or extinct. Hagfish have long been the enigma of vertebrate evolution not only because of their evolutionary position, but also because of our lack of knowledge on fundamental processes. Key elements of the reproductive endocrine system in hagfish have yet to be elucidated. Here, the presence and identity of a functional glycoprotein hormone (GPH) have been elucidated from the brown hagfish Paramyxine atami. The hagfish GPH consists of two subunits, α and β, which are synthesized and colocalized in the same cells of the adenohypophysis. The cellular and transcriptional activities of hagfish GPHα and -β were significantly correlated with the developmental stages of the gonad. The purified native GPH induced the release of gonadal sex steroids in vitro. From our phylogenetic analysis, we propose that ancestral glycoprotein α-subunit 2 (GPA2) and β-subunit 5 (GPB5) gave rise to GPHα and GPHβ of the vertebrate glycoprotein hormone family, respectively. The identified hagfish GPHα and -β subunits appear to be the typical gnathostome GPHα and -β subunits based on the sequence and phylogenetic analyses. We hypothesize that the identity of a single functional GPH of the hagfish, hagfish GTH, provides critical evidence for the existence of a pituitary-gonadal system in the earliest divergent vertebrate that likely evolved from an ancestral, prevertebrate exclusively neuroendocrine mechanism by gradual emergence of a previously undescribed control level, the pituitary, which is not found in the Protochordates. PMID:20733079

  7. Role of calcium in gonadotropin releasing hormone-induced luteinizing hormone secretion from the bovine pituitary

    SciTech Connect

    Kile, J.P.

    1986-01-01

    The hypothesis was tested that GnRH acts to release LH by increasing calcium uptake by gonadotroph which in turn stimulates calcium-calmodulin activity and results in LH release from bovine pituitary cells as it does in the rat. Pituitary glands of calves (4-10 months of age) were enzymatically dispersed (0.2% collagenase) and grown for 5 days to confluency in multiwell plates (3 x 10/sup 5//well). Cells treated with GnRH Ca/sup + +/ ionophore A23187, and ouabain all produced significant releases of LH release in a pronounced all or none fashion, while thorough washing of the cells with 0.5 mM EGTA in Ca/sup + +/-free media prevented the action of GnRH. GnRH caused a rapid efflux of /sup 45/Ca/sup + +/. Both GnRH-stimulated /sup 45/Ca efflux and LH release could be partially blocked by verapamil GnRH-induced LH release could also be blocked by nifedipine and tetrodotoxin, although these agents did not affect /sup 45/Ca efflux. The calmodulin antagonists calmidazolium and W7 were found to block GnRH induced LH release, as well as LH release induced by theophylline, KC PGE/sub 2/ and estradiol. These data indicated that: (1) calcium is required for GnRH action, but extracellular Ca/sup + +/ does not regulate LH release; (2) GnRH elevates intracellular Ca/sup + +/ by opening both voltage sensitive and receptor mediated Ca/sup + +/ channels; (3) activation of calmodulin is one mechanism involved in GnRH-induced LH release.

  8. Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization.

    PubMed

    Acharjee, Arup; Chaube, Radha; Joy, Keerikkattil Paily

    2015-10-01

    Gonadotropins are heterodimeric glycoproteins secreted by the pituitary, and consist of a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) or luteinizing hormone beta subunit (LHβ). In the present study, the subunit protein genes were cloned and characterized from the pituitary of the catfish Heteropneustes fossilis. Full-length cDNAs of GPα, FSHβ, and LHβ are 511 base pairs (bp), 659 bp and 660 bp long, and encode 92, 108, and 112 aminoacids long mature proteins, respectively. GPα has 10 cysteines with 2 N-linked glycosylation sites while LHβ contains 12 cysteines with a single N-linked glycosylation site. In contrast, FSHβ has 13 cysteines, 1 additional over the conserved 12 cysteines of other vertebrates, and a single glycosylation site between Cys 3 and Cys 4. Phylogenetic analyses of the deduced proteins confirm their homology and relationships with the respective gonadotropin subunit proteins of gnathostome vertebrates. Tissue expression analysis by semi-quantitative RT-PCR shows that GPα mRNA is expressed only in the pituitary while both FSHβ and LHβ mRNA are expressed in extra-pituitary sites. The subunit mRNAs show both seasonal and sex dimorphic variations especially in the expression of FSHβ and LHβ transcripts. In the sexually quiescent phase, the transcript expression is low while in the recrudescent phase, the expressions are differential, high, and varied with regard to sex and reproductive phase. In situ hybridization of the mRNAs gave positive signals in gonadotropes in the pars distalis of the pituitary, which exhibited seasonal variation in staining intensity and numbers. © 2015 Wiley Periodicals, Inc.

  9. Ovarian hormones and fasting differentially regulate pituitary receptors for estrogen and gonadotropin-releasing hormone in rabbit female.

    PubMed

    Parillo, F; Zerani, M; Maranesi, M; Dall'Aglio, C; Galeati, G; Brecchia, G; Boiti, C; González-Mariscal, G

    2014-03-01

    To investigate the mechanisms by which caloric restriction affects reproductive function in female rabbits, we measured, in animals intact or ovariectomized (OVX) estrogen-primed and fed ad libitum or fasted for 48 h, the adenohypophysial expression of estrogen receptor-alpha (ESR1) and gonadotropin releasing hormone receptor (GnRHR) and the dynamic secretion of LH following GnRH stimulation. Fasting increased the number of GnRHR-immunoreactive (-IR) cells in intact animals, whereas reduced the density of ESR1-IR cells in OVX rabbits. Estrogen priming decreased the number of ESR1-IR cells in fasted and OVX animals. Ovariectomy increased the number of ESR1-IR cells in fed rabbits, but caused an opposite effect in both fed and fasted animals treated with estrogen. Fasting down regulated the mRNA levels for ESR1 and GnRHR. Estrogen-priming reduced the abundance for ESR1 mRNA in both fed and fasted rabbits, and that for GnRHR in fasted rabbits. Ovariectomy halved ESR1 mRNA levels independently of treatment and feeding condition, whereas increased (P < 001) that for GnRHR in estrogen-primed rabbits. In all rabbits, an LH surge occurred 30 min after GnRH injection but the lowest levels were found in intact fasted rabbits and the highest in fasted, estrogen-primed animals. The LH profile was similar in intact and OVX rabbits and neither fasting nor estrogen priming modified it. In conclusion, fasting differentially modifies the ESR1 and GnRHR expression in the pituitary, depending on the presence of gonadal hormones, indicating complex interactions between metabolic signals and ovarian steroids. Copyright © 2013 Wiley Periodicals, Inc.

  10. Does prolonged pituitary down-regulation with gonadotropin-releasing hormone agonist improve the live-birth rate in in vitro fertilization treatment?

    PubMed

    Ren, Jianzhi; Sha, Aiguo; Han, Dongmei; Li, Ping; Geng, Jie; Ma, Chaihui

    2014-07-01

    To evaluate the effects of a prolonged duration of gonadotropin-releasing hormone agonist (GnRH-a) in pituitary down-regulation for controlled ovarian hyperstimulation (COH) on the live-birth rate in nonendometriotic women undergoing in vitro fertilization and embryo transfer (IVF-ET). Retrospective cohort study. University-affiliated hospital. Normogonadotropic women undergoing IVF. Three hundred seventy-eight patients receiving a prolonged pituitary down-regulation with GnRH-a before ovarian stimulation and 422 patients receiving a GnRH-a long protocol. Live-birth rate per fresh ET. In comparison with the long protocol, the prolonged down-regulation protocol required a higher total dose of gonadotropins. A lower serum luteinizing hormone (LH) level on the starting day of gonadotropin and the day of human chorionic gonadotropin (hCG) and a fewer number of oocytes and embryos were observed in the prolonged down-regulation protocol. However, the duration of stimulation and number of high-quality embryos were comparable between the two groups. A statistically significantly higher implantation rate (50.27% vs. 39.69%), clinical pregnancy rate (64.02% vs. 56.87%) and live-birth rate per fresh transfer cycle (55.56% vs. 45.73%) were observed in the prolonged protocol. Prolonged down-regulation in a GnRH-a protocol might increase the live-birth rates in normogonadotropic women. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  11. GnRH-Induced Ca(2+) Signaling Patterns and Gonadotropin Secretion in Pituitary Gonadotrophs. Functional Adaptations to Both Ordinary and Extraordinary Physiological Demands.

    PubMed

    Durán-Pastén, Maria Luisa; Fiordelisio, Tatiana

    2013-09-30

    PITUITARY GONADOTROPHS ARE A SMALL FRACTION OF THE ANTERIOR PITUITARY POPULATION, YET THEY SYNTHESIZE GONADOTROPINS: luteinizing (LH) and follicle-stimulating (FSH), essential for gametogenesis and steroidogenesis. LH is secreted via a regulated pathway while FSH release is mostly constitutive and controlled by synthesis. Although gonadotrophs fire action potentials spontaneously, the intracellular Ca(2+) rises produced do not influence secretion, which is mainly driven by Gonadotropin-Releasing Hormone (GnRH), a decapeptide synthesized in the hypothalamus and released in a pulsatile manner into the hypophyseal portal circulation. GnRH binding to G-protein-coupled receptors triggers Ca(2+) mobilization from InsP3-sensitive intracellular pools, generating the global Ca(2+) elevations necessary for secretion. Ca(2+) signaling responses to increasing (GnRH) vary in stereotyped fashion from subthreshold to baseline spiking (oscillatory), to biphasic (spike-oscillatory or spike-plateau). This progression varies somewhat in gonadotrophs from different species and biological preparations. Both baseline spiking and biphasic GnRH-induced Ca(2+) signals control LH/FSH synthesis and exocytosis. Estradiol and testosterone regulate gonadotropin secretion through feedback mechanisms, while FSH synthesis and release are influenced by activin, inhibin, and follistatin. Adaptation to physiological events like the estrous cycle, involves changes in GnRH sensitivity and LH/FSH synthesis: in proestrus, estradiol feedback regulation abruptly changes from negative to positive, causing the pre-ovulatory LH surge. Similarly, when testosterone levels drop after orquiectomy the lack of negative feedback on pituitary and hypothalamus boosts both GnRH and LH secretion, gonadotrophs GnRH sensitivity increases, and Ca(2+) signaling patterns change. In addition, gonadotrophs proliferate and grow. These plastic changes denote a more vigorous functional adaptation in response to an extraordinary

  12. GnRH-Induced Ca2+ Signaling Patterns and Gonadotropin Secretion in Pituitary Gonadotrophs. Functional Adaptations to Both Ordinary and Extraordinary Physiological Demands

    PubMed Central

    Durán-Pastén, Maria Luisa; Fiordelisio, Tatiana

    2013-01-01

    Pituitary gonadotrophs are a small fraction of the anterior pituitary population, yet they synthesize gonadotropins: luteinizing (LH) and follicle-stimulating (FSH), essential for gametogenesis and steroidogenesis. LH is secreted via a regulated pathway while FSH release is mostly constitutive and controlled by synthesis. Although gonadotrophs fire action potentials spontaneously, the intracellular Ca2+ rises produced do not influence secretion, which is mainly driven by Gonadotropin-Releasing Hormone (GnRH), a decapeptide synthesized in the hypothalamus and released in a pulsatile manner into the hypophyseal portal circulation. GnRH binding to G-protein-coupled receptors triggers Ca2+ mobilization from InsP3-sensitive intracellular pools, generating the global Ca2+ elevations necessary for secretion. Ca2+ signaling responses to increasing (GnRH) vary in stereotyped fashion from subthreshold to baseline spiking (oscillatory), to biphasic (spike-oscillatory or spike-plateau). This progression varies somewhat in gonadotrophs from different species and biological preparations. Both baseline spiking and biphasic GnRH-induced Ca2+ signals control LH/FSH synthesis and exocytosis. Estradiol and testosterone regulate gonadotropin secretion through feedback mechanisms, while FSH synthesis and release are influenced by activin, inhibin, and follistatin. Adaptation to physiological events like the estrous cycle, involves changes in GnRH sensitivity and LH/FSH synthesis: in proestrus, estradiol feedback regulation abruptly changes from negative to positive, causing the pre-ovulatory LH surge. Similarly, when testosterone levels drop after orquiectomy the lack of negative feedback on pituitary and hypothalamus boosts both GnRH and LH secretion, gonadotrophs GnRH sensitivity increases, and Ca2+ signaling patterns change. In addition, gonadotrophs proliferate and grow. These plastic changes denote a more vigorous functional adaptation in response to an extraordinary functional

  13. Human gonadotropin-releasing hormone receptor-activated cellular functions and signaling pathways in extra-pituitary tissues and cancer cells (Review).

    PubMed

    Aguilar-Rojas, Arturo; Huerta-Reyes, Maira

    2009-11-01

    Human gonadotropin-releasing hormone receptor (GnRHR) and its natural ligand human gonadotropin-releasing hormone (GnRH) were initially described as signaling complexes that play a key role in reproductive functions. By binding to specific receptors present on pituitary gonadotropes, GnRH regulates the sperm and ovum maturation, as well as steroidogenesis within the context of the hypothalamus-hypophysis axis. The expression of GnRH and its receptor has clearly been established in many extra-pituitary organs. Some of them are tumors from non-reproductive tissues such as liver, larynx, pancreas, colon, lymphoma, kidney, skin, blood and brain as well as tissues from reproductive track, for example ovary, endometrium, prostate and breast or tumors derived from these organs. Expression of GnRH and its receptor in these organs has gained much attention and several research groups have established their role during cell proliferation and cell motility. Although the signaling pathways and their effector proteins in these samples remain unclear, the molecular mechanism employed for GnRH and its receptor in extra-pituitary tissues could be related with non-classical GnRHR-signaling pathways. In the present review, we explore the vast literature reported on GnRH and GnRHR principally in tumors, describing how cross-talk between GnRHR and growth factor receptor, the coupling between GnRHR and many G proteins depending on cell context, and the regulation of several proteins associated with cell proliferation and cell motility are employed by GnRHR/GnRH to regulate their extra-pituitary activities.

  14. Distribution of LPXRFa, a gonadotropin-inhibitory hormone ortholog peptide, and LPXRFa receptor in the brain and pituitary of the tilapia.

    PubMed

    Ogawa, Satoshi; Sivalingam, Mageswary; Biran, Jakob; Golan, Matan; Anthonysamy, Rachel Shalini; Levavi-Sivan, Berta; Parhar, Ishwar S

    2016-10-01

    In vertebrates, gonadotropin-releasing hormone (GnRH) and gonadotropin-inhibitory hormone (GnIH), respectively, regulate reproduction in positive and negative manners. GnIH belongs to the LPXRFa family of peptides previously identified in mammalian and nonmammalian vertebrates. Studying the detailed distribution of LPXRFa as well as its receptor (LPXRFa-R) in the brain and pituitary is important for understanding their multiple action sites and potential functions. However, the distribution of LPXRFa and LPXRFa-R has not been studied in teleost species, partially because of the lack of fish-specific antibodies. Therefore, in the present study, we generated specific antibodies against LPXRFa and its receptor from Nile tilapia (Oreochromis niloticus), and examined their distributions in the brain and pituitary by immunohistochemistry. Tilapia LPXRFa-immunoreactive neurons lie in the posterior ventricular nucleus of the caudal preoptic area, whereas LPXRFa-R-immunoreactive cells are distributed widely. Double immunofluorescence showed that neither LPXRFa-immunoreactive fibers nor LPXRFa-R is closely associated or coexpressed with GnRH1, GnRH3, or kisspeptin (Kiss2) neurons. In the pituitary, LPXRFa fibers are closely associated with gonadotropic endocrine cells [expressing luteinizing hormone (LH) and follicle-stimulating hormone (FSH)], with adrenocorticomelanotropic cells [corticotropin (ACTH) and α-melanotropin (α-MSH)], and with somatolactin endocrine cells. In contrast, LPXRFa-R are expressed only in LH, ACTH, and α-MSH cells. These results suggest that LPXRFa and LPXRFa-R signaling acts directly on the pituitary cells independent from GnRH or kisspeptin and could play multiple roles in reproductive and nonreproductive functions in teleosts. J. Comp. Neurol. 524:2753-2775, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Seasonal changes in expression of genes encoding five types of gonadotropin-releasing hormone receptors and responses to GnRH analog in the pituitary of masu salmon.

    PubMed

    Jodo, Aya; Kitahashi, Takashi; Taniyama, Shinya; Ueda, Hiroshi; Urano, Akihisa; Ando, Hironori

    2005-10-01

    Five types of gonadotropin-releasing hormone receptor (GnRH-R) genes, designated as msGnRH-R1, R2, R3, R4, and R5, are expressed in the brain and pituitary of masu salmon (Oncorhynchus masou). In the present study, seasonal changes in the expression of these five genes were examined in the pituitary to elucidate their roles in GnRH action during growth and sexual maturation. In addition, the seasonal variation of these genes in response to GnRH was examined in a GnRH analog (GnRHa) implantation experiment. Pituitary samples were collected 1 week after the implantation every month from immaturity through spawning. The absolute amount of GnRH-R mRNA in single pituitaries was determined by real-time PCR assays. Among the five genes, R4 was predominantly expressed in the pituitaries. In the immature fish, the amount of GnRH-R mRNA varied with seasons and subtypes. In the pre-spawning period, R1 and R4 mRNAs in both sexes and R2 and R3 mRNAs in the females increased 4- to 20-fold and then decreased in the spawning season. The effects of GnRHa treatment were significantly different in both sexes. In the females, GnRHa tended to elevate the expression of all the subtypes of GnRH-R genes in various stages during the experimental period, whereas it had almost no apparent effects in the males. These results indicate that the expression of the five GnRH-R genes is seasonally variable and may be related to the responses of the pituitary hormone genes to GnRH, and the regulation of GnRH-R genes by GnRH is different in both sexes.

  16. Comparing stimulation requirements and final outcome between early follicular and mid luteal pituitary suppression in the long gonadotropin releasing hormone agonist protocol.

    PubMed

    Sarhan, Abdulmagid; Harira, Mervat; Elshazly, Sherine; Nouh, Ahmad

    2016-05-01

    To compare stimulation requirements and ICSI outcome when agonist treatment is started in the early follicular phase or in mid luteal phase of the cycle. 181 infertile patients were randomly assigned to: group A (N=66) and group B (N=115). GnRH-a (Triptorelin) subcutaneous daily injections started on day 20-22 of the previous cycle till pituitary suppression is achieved where gonadotropins stimulation commenced. In group A, agonist treatment was started on the first or second days of the cycle, in group B it was started on day 20-22 of the cycle. The agonist treatment was continued till the day of (hCG) administration. The stimulation requirements were similar in the two groups. The days of t agonist treatment required to reach pituitary suppression were higher in group A: 12.5±6.4 than in group B, 11±4.5. Days of stimulation (10.4±1.7 and 10.3±1.6) and number of gonadotropin vials (40.1±8.7and 39.3±9.5) did not differ between both groups. The mean number of oocytes retrieved, mean number of embryos produced (11.7±7.4 and 13.3±9.3) (5.9±4.2and 6±5.2) were similar in both groups. The rates of fertilization and cleavage were similar in the two groups. Pregnancy rates were similar in both groups. The clinical pregnancy rates per cycle was 31.8% and 33%, while pregnancy rates per embryo transfer was 36.2 % and 36.5% in groups A and B respectively. Starting pituitary suppression with GnRH agonist in the early follicular phase or mid luteal phase were comparable regarding stimulation requirements and final outcomes.

  17. Environmental impacts on the gonadotropic system in female Atlantic salmon (Salmo salar) during vitellogenesis: Photothermal effects on pituitary gonadotropins, ovarian gonadotropin receptor expression, plasma sex steroids and oocyte growth.

    PubMed

    Taranger, Geir Lasse; Muncaster, Simon; Norberg, Birgitta; Thorsen, Anders; Andersson, Eva

    2015-09-15

    The gonadotropic system and ovarian growth and development were studied during vitellogenesis in female Atlantic salmon subjected to either simulated natural photoperiod and ambient water temperature (NL-amb), or an accelerating photoperiod (short day of LD8:16 from May 10) combined with either warmed (ca 2°C above ambient; 8L-warm) or cooled water (ca 2°C below ambient; 8L-cold) from May to September. Monthly samples were collected from 10 females/group for determination of transcript levels of pituitary gonadotropin subunits (fshb and lhb) and ovarian gonadotropin receptors (fshr and lhr), plasma sex steroids (testosterone: T and estradiol-17β: E2), gonadosomatic index (GSI) and oocyte size. Short day in combination with either warmed or cooled water induced an earlier increase in pituitary fshb and lhb levels compared with NL-amb controls, and advanced ovarian growth and the seasonal profiles of T, E2. By contrast only minor effects were seen of the photothermal treatments on ovarian fshr and lhr. The 8L-cold had earlier increase in fshb, lhb and E2, but similar oocyte and gonadal growth as 8L-warm, suggesting that the 8L-cold group tried to compensate for the lower water temperature during the period of rapid gonadal growth by increasing fshb and E2 production. Both the 8L-warm and 8L-cold groups showed incomplete ovulation in a proportion of the females, possibly due to the photoperiod advancement resulting in earlier readiness of spawning occurring at a higher ambient temperature, or due to some reproductive dysfunction caused by photothermal interference with normal neuroendocrine regulation of oocyte development and maturation.

  18. Recombinant gonadotropins.

    PubMed

    Lathi, R B; Milki, A A

    2001-10-01

    Recombinant DNA technology makes it possible to produce large amounts of human gene products for pharmacologic applications, supplanting the need for human tissues. The genes for the alpha and beta subunits of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and human chorionic gonadotropin (hCG) have been characterized and cloned. Recombinant FSH (rFSH) has been shown to be safe and effective in the treatment of fertility disorders. In comparison with the urinary gonadotropin products, human menopausal gonadotropins (HMG), and urinary follitropins (uFSH), rFSH is more potent and better tolerated by patients. Recombinant HCG appears to be as efficacious as urinary HCG with the benefit of improved local tolerance. Recombinant LH (rLH) is likely to be recommended as a supplement to rFSH for ovulation induction in hypogonadotropic women. It may also benefit in vitro fertilization patients undergoing controlled ovarian hyperstimulation with rFSH combined with pituitary suppression, with a gonadotropin-releasing hormone agonist or antagonist.

  19. Comparative gene expression of gonadotropins (FSH and LH) and peptide levels of gonadotropin-releasing hormones (GnRHs) in the pituitary of wild and cultured Senegalese sole (Solea senegalensis) broodstocks.

    PubMed

    Guzmán, J M; Rubio, M; Ortiz-Delgado, J B; Klenke, U; Kight, K; Cross, I; Sánchez-Ramos, I; Riaza, A; Rebordinos, L; Sarasquete, C; Zohar, Y; Mañanós, E L

    2009-07-01

    The Senegalese sole (Solea senegalensis) is a valuable flatfish for aquaculture, but it presents important reproductive problems in captivity. Spawning is achieved by wild-caught breeders but cultured broodstocks fail to spawn spontaneously and, when they do, eggs are unfertilized. To gain knowledge on the physiological basis underlying this reproductive dysfunction, this study aimed at analyzing comparative hormone levels between wild and cultured broodstocks at the spawning season. The Senegalese sole gonadotropin (GTH) subunits, FSHbeta, LHbeta and GPalpha, were cloned and qualitative (in situ hybridization) and quantitative (real-time PCR) assays developed to analyze pituitary GTH gene expression. In females, FSHbeta and GPalpha mRNA levels were higher in wild than in cultured broodstocks, whereas in males all three subunits were highest in cultured. By ELISA, three GnRH forms were detected in the pituitary, displaying a relative abundance of GnRH2>GnRH1>GnRH3. All GnRHs were slightly more abundant in wild than cultured females, whereas no differences were observed in males. Plasma levels of vitellogenin and sex steroids were also analyzed. Results showed endocrine differences between wild and cultured broodstocks at the spawning period, which could be related to the endocrine failure of the reproductive axis in cultured breeders.

  20. Effects of estradiol or testosterone treatment on expression of gonadotropin subunit mRNAs and proteins in the pituitary of juvenile brown hagfish, Paramyxine atami.

    PubMed

    Nozaki, Masumi; Uchida, Katsuhisa; Honda, Kaori; Shimotani, Toyokazu; Nishiyama, Maki

    2013-08-01

    A single functional gonadotropin (GTH) comprising two subunits, α and β, was recently identified in the pituitary of brown hagfish (Paramyxine atami). Little is known about the feedback mechanisms that regulate these GTH subunits by sex steroids in the hagfish. The present study was designed to examine feedback effects of estradiol and testosterone on mRNA expression and protein expression of both GTHα and GTHβ subunits in the pituitary of the juvenile P. atami. Intraperitoneal administration of estradiol over the course of 27days resulted in substantial accumulation of immunoreactive (ir)-GTHα and ir-GTHβ in the adenohypophysis, but testosterone treatments over 27days had no effects on ir-GTHα or ir-GTHβ. Estradiol treatment for 1, 2, 4 or 14days had no effect on GTHα mRNA levels. In contrast, after 2days of estradiol treatment, GTHβ mRNA levels had increased significantly from baseline, while these levels were not affected after treatment over 1, 4, or 14days. After 14days of testosterone treatment, both GTHα and GTHβ mRNA levels had decreased significantly from baseline levels. These results indicate that estradiol acted primarily to suppress the secretion of GTH, and hence resulted in the accumulations of ir-GTHα and ir-GTHβ in the pituitary. On the other hand, testosterone appeared to suppress both the synthesis and the secretion of GTH. Thus, estradiol and testosterone probably differ in their effects on the regulation of pituitary GTH synthesis and secretion in juvenile hagfish. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Analysis of pituitary gonadotropin concentration in blood serum and immunolocalization and immunoexpression of follicle stimulating hormone and luteinising hormone receptors in ovaries of postmenopausal women.

    PubMed

    Brodowska, A; Laszczyńska, M; Brodowski, J; Masiuk, M; Starczewski, A

    2012-02-01

    The participation of gonadotropins in ovarian carcinogenesis is well known and is supported by studies with inhibition of pituitary gonadotropin secretion, which results in a diminished risk of cancer. However, there are few data on localization and expression of Follicle Stimulating Hormone and Luteinising Hormone Receptors (FSHR and LHR) in ovaries of healthy postmenopausal women, and their correlation with FSH and LH concentration in blood serum is unknown. The aim of our study was to analyze gonadotropin concentration in blood serum and the expression of FSHR and LHR in ovaries of 207 postmenopausal women. Patients included in the study were divided into three groups depending on the number of years since menopause. We analyzed the concentration of FSH and LH in blood serum and the expression of FSHR and LHR in ovaries. Ovaries of postmenopausal women showed numerous morphological changes in the cortex and medulla when compared to the structure of ovaries of women at reproductive age. In all groups of patients clefts in the surface epithelium and epithelial inclusion cysts were found. The concentration of FSH and LH in the blood serum of women studied increased significantly with time from menopause. Significant differences between analyzed menopausal groups were found. The highest FSH and LH concentration in blood serum were found in women with the longest period of time from menopause. Quantitatively similar expression of FSHR and LHR was found in ovarian surface epithelial cells, in epithelial inclusion cysts and in the connective tissue cells of ovarian stroma. The intensity of the immunohistochemical reaction decreased with time from menopause and with age.

  2. Immunoreactivity of gonadotrophs (FSH and LH Cells) and gonadotropin subunit gene expression in the male chub mackerel Scomber japonicus pituitary during the reproductive cycle.

    PubMed

    Nyuji, Mitsuo; Selvaraj, Sethu; Kitano, Hajime; Shiraishi, Tetsuro; Yamaguchi, Akihiko; Shimizu, Akio; Matsuyama, Michiya

    2012-09-01

    The gonadotropins (GtHs), follicle-stimulating hormone (FSH) and luteinizing hormone (LH), are heterodimers composed of a common α subunit (GPα) and a unique β subunit (FSHβ or LHβ); they are synthesized in and secreted from gonadotrophs (FSH and LH cells) in the pituitary. Little is known about the roles of FSH and LH during spermatogenesis in perciform fishes. In this study, we examined immunoreactive changes in FSH and LH cells, and changes in the gene expression of the three gonadotropin subunits in the pituitary of male chub mackerel Scomber japonicus during testicular development. FSHβ-immunoreactive (ir) and LHβ-ir cell area were measured immuno-histochemically based on the FSH and LH cell-occupying area in the proximal pars distalis. The FSHβ-ir cell area increased significantly during spermiation, while FSHβ mRNA levels, already high at the beginning of spermatogenesis, increased further, peaking during spermiation. In contrast, LHβ-ir cell area and LHβ mRNA levels, which were low at the beginning of spermatogenesis, increased significantly during late spermatogenesis, peaking during spermiation. For both FSH and LH, GtHβ-ir cell area and GtHβ mRNA levels decreased until gonadal resting. GPα mRNA levels showed similar changes to LHβ mRNA levels. These results suggest that in the chub mackerel, FSH may play an important role in the early and late phases of spermatogenesis, and that LH may play a role during late spermatogenesis and spermiation. Moreover, our results demonstrate that changes in GtHβ-ir cell area were accompanied by similar changes in the expression of the FSHβ and LHβ genes, both of which increased during testicular development.

  3. The effect of water quality on the immunoreactivity of stress-response cells and gonadotropin-secreting cells in the pituitary gland of Nile tilapia, Oreochromis niloticus.

    PubMed

    Mousa, Mostafa A; Ibrahim, Amal A E; Hashem, Amal M; Khalil, Noha A

    2015-03-01

    The present experiments investigated the effect of water quality characteristics on the condition factor, the ovarian activity, cortisol level, and the immunoreactivity of stress-response cells (adrenocorticotropic hormone; ACTH- and melanin stimulating hormone; MSH- and somatolactin; SL- secreting cells) and gonadotropin (GTH)-secreting cells in the pituitary gland of Nile tilapia, Oreochromis niloticus. After 3 months of exposure to mixtures of water from different sources (Tap and Lake Manzalah waters), with high levels of minerals and heavy metals, water quality affected the number, size, and immunostaining of stress-response-immunoreactive (ir) cells and GTH-ir cells, which showed a dramatic decrease in their size. The integrated optical density (IOD) of immunoreactivity of MSH- and GTH- cells was significantly increased; however, it was significantly decreased for ACTH- and SL- cells. Also, high levels of cortisol were observed in females exposed to waters with high concentrations of minerals and heavy metals. In parallel, low values of gonadosomatic index (GSI%) and the ovarian histology revealed a decrease of maturing follicles concomitant with an increase of atretic follicles in females exposed to Lake Manzalah polluted water. Taken together, the increased activity of stress-response-ir pituitary cells, serum cortisol level and ovarian atretic follicles in response to elevated concentrations of minerals and heavy metals, supports the possible role of ACTH, MSH, and SL in the adaptive stress response of fish. Therefore, minerals and heavy metals must be considered when discussing tilapia aquaculture status. © 2015 Wiley Periodicals, Inc.

  4. Alterations in the ability of the bovine pituitary gland to secrete gonadotropins in vitro during the first follicle-stimulating hormone increase of the estrous cycle and in response to exogenous steroids.

    PubMed

    Lane, E A; Padmanabhan, V; Roche, J F; Crowe, M A

    2005-02-01

    The objective was to determine if the endocrine status of the animal dictates the responsiveness of gonadotrophs to estradiol, activin, inhibin and follistatin; hormones implicated in the differential release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Bovine pituitaries were obtained at 13 (n=8), 30 (n=24) and 66 (n=8) h after the onset of estrus, corresponding to before, during and the end of the first FSH increase of the estrous cycle which follows the pre-ovulatory gonadotropin surge in heifers. Heifers slaughtered at 30 h received no treatment, or were treated with progesterone with or without estradiol before slaughter to suppress the first transient FSH increase. Secretion of FSH from cultured pituitary cells, reflecting the prior in vivo status, was greater (P<0.01) at 30 h than 13 or 66 h, whereas, LH secretion was less (P<0.01) at 13 h compared with 30 h. Treatment with exogenous steroids decreased (P<0.05) the pituitary gland's ability to subsequently secrete FSH and LH. Inhibin and, to a greater extent, estradiol decreased (P<0.01) mean FSH secretion but increased (P<0.05) mean LH secretion. These findings suggest that estradiol and inhibin both have the ability to differentially modulate basal gonadotropin secretion during the first FSH increase of the bovine estrous cycle. Differential regulation of LH and FSH is mediated via an alteration in gonadotropin biosynthesis and basal secretion. Furthermore, the secretory capability of cultured pituitary cells and basal gonadotropin secretion reflect the prior endocrine status of the animal from which pituitaries were obtained.

  5. Immunohistochemical detection of gonadotropin-like material in the pituitary of brown hagfish (Paramyxine atami) correlated with their gonadal functions and effect of estrogen treatment.

    PubMed

    Miki, Makoto; Shimotani, Toyokazu; Uchida, Katsuhisa; Hirano, Shigeki; Nozaki, Masumi

    2006-08-01

    Since hagfish are members of the most primitive group of living vertebrates, studies on their reproduction are indispensable for understanding phylogenetic aspects of vertebrate reproductive system. Nevertheless, our knowledge of the reproductive physiology of the hagfish, especially of the pituitary-gonadal axis, is almost completely lacking. In the present study, the relationship between the amount of immunoreactive gonadotropin (GTH)-like material in the pituitary gland and gonadal conditions was examined in the brown hagfish, Paramyxine atami. First, pituitary sections were stained immunohistochemically with anti-ovine LHbeta, and the degrees of the accumulation of GTH-like material were compared among three different groups of gonadal conditions; juveniles and adults with and without developing gonads. Immunoreactive GTH-like material was heavily accumulated in adults with developing gonads, whereas it was not or only weakly accumulated in juveniles or adults without developing gonads. Thus, there was a strong positive correlation between the amount of GTH-like material and gonadal conditions. Second, effect of estradiol benzoate on GTH-like material was examined using three groups of juvenile hagfish: initial control, sham control, and experimental animals. Experimental animals received estradiol benzoate resolved in sesame oil intraperitoneally every third day for 1 month, whereas sham control animals received the same doses of sesame oil. GTH-like material was heavily or moderately accumulated in most estrogen-treated animals, whereas it was not or weakly accumulated in initial or sham control animals. Thus, estrogen treatment in juvenile hagfish resulted in the large increase in the amount of GTH-like material. From these results, it is suggested the presence of not only GTH but also the hypophysial-gonadal feedback system in the hagfish.

  6. Phosphorylation substrates for protein kinase C in intact pituitary cells: characterization of a receptor-mediated event using novel gonadotropin-releasing hormone analogues

    SciTech Connect

    Strulovici, B.; Tahilramani, R.; Nestor, J.J. Jr.

    1987-09-22

    The involvement of protein kinase C in the signal transduction of gonadotropin-releasing hormone (GnRH) action was investigated with a GnRH superagonist, partial agonists, and antagonists in intact rat pituitary cells. Exposure of /sup 32/P-labeled cells to GnRH or to the superagonist (D-Nal(2)/sup 6/)GnRH induced the enhanced phosphorylation of 42-, 34-, 11-, and 10-kDa proteins and the dephosphorylation of a 15-kDa protein as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis/autoradiography. This effect was blocked in a dose-dependent manner by potent GnRG antagonists. Downregulation of protein kinase C by prolonged incubation of the pituitary cells with high concentrations of active phorbol esters abolished protein kinase C activity and also prevented the phosphorylation induced by GnRN, or (D-Nal(2)/sup 6/)GnRH. The same effect was obtained by preincubating the cells with the protein kinase C inhibitor H-7. In this study the authors identify for the first time physiological substrates for protein kinase C in intact pituitary cells. They demonstrate a close quantitative correlation between the extent of translocation of protein kinase C, levels of phosphorylation of specific substrates in the intact cells, and the biological activity of the GnRH analogues with varying affinity for the GnRH receptor. These data strengthen the contention that the physiological effects of GnRH are primarily mediated via the phosphatidylinositol/Ca/sup 2 +/ signal transfer system and represent a first step toward defining the physiological substrates of protein kinase C and their role in the cascade of events that starts upon binding of GnRH to its receptor.

  7. Biosynthesis of gonadotropin-releasing hormone (GnRH) and GnRH receptor (GnRHR) in hypothalamic-pituitary unit of anoestrous and cyclic ewes.

    PubMed

    Ciechanowska, M O; Łapot, M; Mateusiak, K; Paruszewska, E; Malewski, T; Przekop, F

    2017-02-01

    This study was performed to explain how the molecular processes governing the biosynthesis of gonadotropin-releasing hormone (GnRH) and GnRH receptor (GnRHR) in the hypothalamic-pituitary unit are reflected by luteinizing hormone (LH) secretion in sheep during anoestrous period and during luteal and follicular phases of the oestrous cycle. Using an enzyme-linked immunosorbent assay (ELISA), we analyzed the levels of GnRH and GnRHR in preoptic area (POA), anterior (AH) and ventromedial hypothalamus (VM), stalk-median eminence (SME), and GnRHR in the anterior pituitary gland (AP). Radioimmunoassay has also been used to define changes in plasma LH concentrations. The study provides evidence that the levels of GnRH in the whole hypothalamus of anoestrous ewes were lower than that in sheep during the follicular phase of the oestrous cycle (POA: p < 0.001, AH: p < 0.001, VM: p < 0.01, SME: p < 0.001) and not always than in luteal phase animals (POA: p < 0.05, SME: p < 0.05). It has also been demonstrated that the GnRHR amount in the hypothalamus-anterior pituitary unit, as well as LH level, in the blood in anoestrous ewes were significantly lower than those detected in animals of both cyclic groups. Our data suggest that decrease in LH secretion during the long photoperiod in sheep may be due to low translational activity of genes encoding both GnRH and GnRHR.

  8. Seasonal changes of responses to gonadotropin-releasing hormone analog in expression of growth hormone/prolactin/somatolactin genes in the pituitary of masu salmon.

    PubMed

    Bhandari, Ramji Kumar; Taniyama, Shinya; Kitahashi, Takashi; Ando, Hironori; Yamauchi, Kohei; Zohar, Yonathan; Ueda, Hiroshi; Urano, Akihisa

    2003-01-01

    Gonadotropin-releasing hormone (GnRH) is considered to stimulate secretion of growth hormone (GH), prolactin (PRL), and somatolactin (SL) at particular stages of growth and sexual maturation in teleost fishes. We therefore examined seasonal variation in the pituitary levels of GH/PRL/SL mRNAs, and tried to clarify seasonal changes of responses to GnRH in expression of GH/PRL/SL genes, in the pituitaries of growing and maturing masu salmon (Oncorhynchus masou). Pituitary samples were monthly collected one week after implantation with GnRH analog (GnRHa). The levels of mRNAs encoding GH, PRL, and SL precursors in single pituitaries were determined by a real-time polymerase chain reaction method. The fork lengths and body weights of control and GnRHa-implanted fish of both sexes gradually increased and peaked out in September of 2-year-old (2+) when fish spawned. GnRHa implantation did not stimulate somatic growth, nor elevate gonadosomatic index (GSI) of 1+ and 2+ males, whereas it significantly increased GSI of 2+ females in late August to early September. The GnRHa-implanted 1+ males had higher levels of GH and PRL mRNAs in July, and SL mRNA from June to August than the control males. The levels of GH, PRL, and SL mRNAs in the control and GnRHa-implanted 1+ females, however, did not show any significant changes. Afterward, the PRL mRNA levels elevated in the control 2+ fish of both sexes in spring. GnRHa elevated the GH mRNA levels in both males and females in 2+ winter, and the PRL mRNA levels in females in early spring. Regardless of sex and GnRHa-implantation, the SL mRNA levels increased during sexual maturation. In growing and maturing masu salmon, expression of genes encoding GH, PRL, and SL in the pituitary is thus sensitive to GnRH in particular seasons probably in relation to physiological roles of the hormones.

  9. Insight into the neuroendocrine site and cellular mechanism by which cortisol suppresses pituitary responsiveness to gonadotropin-releasing hormone.

    PubMed

    Breen, Kellie M; Davis, Tracy L; Doro, Lisa C; Nett, Terry M; Oakley, Amy E; Padmanabhan, Vasantha; Rispoli, Louisa A; Wagenmaker, Elizabeth R; Karsch, Fred J

    2008-02-01

    Stress-like elevations in plasma glucocorticoids rapidly inhibit pulsatile LH secretion in ovariectomized sheep by reducing pituitary responsiveness to GnRH. This effect can be blocked by a nonspecific antagonist of the type II glucocorticoid receptor (GR) RU486. A series of experiments was conducted to strengthen the evidence for a mediatory role of the type II GR and to investigate the neuroendocrine site and cellular mechanism underlying this inhibitory effect of cortisol. First, we demonstrated that a specific agonist of the type II GR, dexamethasone, mimics the suppressive action of cortisol on pituitary responsiveness to GnRH pulses in ovariectomized ewes. This effect, which became evident within 30 min, documents mediation via the type II GR. We next determined that exposure of cultured ovine pituitary cells to cortisol reduced the LH response to pulse-like delivery of GnRH by 50% within 30 min, indicating a pituitary site of action. Finally, we tested the hypothesis that suppression of pituitary responsiveness to GnRH in ovariectomized ewes is due to reduced tissue concentrations of GnRH receptor. Although cortisol blunted the amplitude of GnRH-induced LH pulses within 1-2 h, the amount of GnRH receptor mRNA or protein was not affected over this time frame. Collectively, these observations provide evidence that cortisol acts via the type II GR within the pituitary gland to elicit a rapid decrease in responsiveness to GnRH, independent of changes in expression of the GnRH receptor.

  10. Dose-response relationship of 15alpha-hydroxylated sex steroids to gonadotropin-releasing hormones and pituitary extract in male sea lampreys (Petromyzon marinus).

    PubMed

    Young, Bradley A; Bryan, Mara B; Glenn, Jessica R; Yun, Sang Seon; Scott, Alexander P; Li, Weiming

    2007-03-01

    The sea lamprey (Petromyzon marinus) is one of the earliest extant vertebrates for which the hypothalamic-pituitary-gonadal (HPG) axis has been shown to control and regulate reproduction in a similar fashion to gnathostome vertebrates. While the two forms of gonadotropin-releasing hormones in the sea lamprey (GnRH I and GnRH III) have been studied extensively, their in vivo effect on synthesis of 15alpha-hydroxytestosterone (15alpha-T) and 15alpha-hydroxyprogesterone (15alpha-P) have only been partially characterized. In the present study, plasma concentrations of 15alpha-T and 15alpha-P were measured in prespermiating sea lampreys that were given a single injection of either GnRH I or GnRH III in doses ranging from 5 to 100 microg/kg, or of pituitary extract (as a source of gonadotropin). Plasma was sampled at 1-6h and 6-48 h post-injection, in separate experiments, in order to characterize the peak and duration of responses. 15alpha-T plasma concentrations increased slightly in response to all three treatments, but not in a dose-dependent manner, and the timing of peak concentrations varied between doses. However, 15alpha-P plasma concentrations showed a greater range of response (between 1 and 100 ng/ml) and were clearly correlated with the injection dose. Plasma concentrations of 15alpha-P also responded to far lower doses of GnRH I and GnRH III than any other steroid previously investigated in lampreys. The plasma concentrations of 15alpha-P peaked at 6h after injection for all three treatments, and levels reached a mean of 53.1 ng/ml. In female lampreys that were injected twice with 50 microg/ml GnRH I or III, 15alpha-T concentrations did not exceed 0.5 ng/ml and 15alpha-P concentrations did not exceed 1 ng/ml. These results lend further support to the hypothesis that 15alpha-P plays an important role in the reproductive endocrinology of male lampreys.

  11. Pituitary binding and internalization of radioiodinated gonadotropin-releasing hormone agonist and antagonist ligands in vitro and in vivo

    SciTech Connect

    Wynn, P.C.; Suarez-Quian, C.A.; Childs, G.V.; Catt, K.J.

    1986-10-01

    In rat pituitary gonadotrophs, the rates of binding and endocytosis of two GnRH superagonist analogs, (D-Ala6,Pro9-NEt)GnRH and (D-Lys6,Pro9-NEt)GnRH, were compared with those of the potent antagonist analog (N-acetyl-D-pCl-Phe1,2,D-Trp3,D-Lys6,D-Ala10)GnRH by quantitative electron microscopic autoradiography. In dispersed pituitary cells, the two agonist analogs showed similar binding kinetics and comparable degrees of sequestration, as measured by their resistance to dissociation by low pH buffer. However, quantification of silver grain localization suggested that cellular internalization of the (D-Ala6)GnRH agonist increased more rapidly than that of the (D-Lys6)GnRH analog. These discrepancies, and the finding that a larger amount of the specifically bound /sup 125/I-(D-Ala6)GnRH agonist was removed during glutaraldehyde fixation, indicated that the proportional internalization of this analog was over estimated by quantitative autoradiography owing to loss of cell surface-bound radioligand. We, therefore, employed radioiodinated D-Lys6-substituted analogs to analyze the receptor binding and cellular uptake of GnRH agonist and antagonist derivatives in vivo. After iv injection, a high proportion of the /sup 125/I-(D-Lys6)GnRH agonist was translocated into pituitary gonadotrophs within 60 min, whereas the D-Lys6 antagonist was predominantly associated with the plasma membrane during that time. Four hours after injection of the antagonist, an appreciable proportion of silver grains was associated with intracellular organelles, and this trend increased progressively at later time points. The relatively prolonged cellular processing of the GnRH antagonist is consistent with in vivo binding kinetics, and its slower internalization may reflect the basal rate of GnRH receptor turnover in the cell membrane.

  12. New trends in combined use of gonadotropin-releasing hormone antagonists with gonadotropins or pulsatile gonadotropin-releasing hormone in ovulation induction and assisted reproductive technologies.

    PubMed

    Gordon, K; Danforth, D R; Williams, R F; Hodgen, G D

    1992-10-01

    The use of gonadotropin-releasing hormone agonists as adjunctive therapy with gonadotropins for ovulation induction in in vitro fertilization and other assisted reproductive technologies has become common clinical practice. With the recent advent of potent gonadotropin-releasing hormone antagonists free from the marked histamine-release effects that stymied earlier compounds, an attractive alternative method may be available. We have established the feasibility of combining gonadotropin-releasing hormone antagonist-induced inhibition of endogenous gonadotropins with exogenous gonadotropin therapy for ovulation induction in a nonhuman primate model. Here, the principal benefits to be gained from using the gonadotropin-releasing hormone antagonist rather than the gonadotropin-releasing hormone agonist are the immediate inhibition of pituitary gonadotropin secretion without the "flare effect," which brings greater safety and convenience for patients and the medical team and saves time and money. We have also recently demonstrated the feasibility of combining gonadotropin-releasing hormone antagonist with pulsatile gonadotropin-releasing hormone therapy for the controlled restoration of gonadotropin secretion and gonadal steroidogenesis culminating in apparently normal (singleton) ovulatory cycles. This is feasible only with gonadotropin-releasing hormone antagonists because, unlike gonadotropin-releasing hormone agonists, they achieve control of the pituitary-ovarian axis without down regulation of the gonadotropin-releasing hormone receptor system. This capacity to override gonadotropin-releasing hormone antagonist-induced suppression of pituitary-ovarian function may allow new treatment modalities to be employed for women who suffer from chronic hyperandrogenemia with polycystic ovarian disease.

  13. Long-term GnRH-induced gonadotropin secretion in a novel hypothalamo-pituitary slice culture from tilapia brain.

    PubMed

    Bloch, Corinne L; Kedar, Noa; Golan, Matan; Gutnick, Michael J; Fleidervish, Ilya A; Levavi-Sivan, Berta

    2014-10-01

    Organotypic cultures, prepared from hypothalamo-pituitary slices of tilapia, were developed to enable long-term study of secretory cells in the pituitary of a teleost. Values of membrane potential at rest were similar to those recorded from acute slices, and cells presented similar spontaneous spikes and spikelets. Some cells also exhibited slow spontaneous oscillations in membrane potential, which may be network-driven. Long-term (6days) continuous exposure to GnRH induced increases in LH and FSH secretion. FSH levels reached the highest levels after 24h of exposure to GnRH, and the highest secretion of LH was observed in days 4 and 5 of the experiment. Since slices were viable for several weeks in culture, maintaining the original cytoarchitecture, electrical membrane properties and the ability to secrete hormones in response to exogenous GnRH, this technique is ideal for studying the mechanisms regulating cell-to-cell communication under conditions resembling the in vivo tissue organization. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Changes in the expression of pituitary gonadotropin subunits during reproductive cycle of multiple spawning female chub mackerel Scomber japonicus.

    PubMed

    Nyuji, Mitsuo; Selvaraj, Sethu; Kitano, Hajime; Ohga, Hirofumi; Yoneda, Michio; Shimizu, Akio; Kaneko, Kensuke; Yamaguchi, Akihiko; Matsuyama, Michiya

    2012-06-01

    The endocrine regulation of reproduction in a multiple spawning fish with an asynchronous-type ovary remains largely unknown. The objectives of this study were to monitor changes in the mRNA expression of three gonadotropin (GtH) subunits (GPα, FSHβ, and LHβ) during the reproductive cycle of the female chub mackerel Scomber japonicus. Cloning and subsequent sequence analysis revealed that the cDNAs of chub mackerel GPα, FSHβ, and LHβ were 658, 535, and 599 nucleotides in length and encoded 117, 115, and 147 amino acids, respectively. We applied a quantitative real-time PCR assay to quantify the mRNA expression levels of these GtH subunits. During the seasonal reproductive cycle, FSHβ mRNA levels remained high during the vitellogenic stages, while GPα and LHβ mRNA levels peaked at the end of vitellogenesis. The expression of all three GtH subunits decreased during the post-spawning period. These results suggest that follicle-stimulating hormone (FSH) is involved in vitellogenesis, while luteinizing hormone (LH) functions during final oocyte maturation (FOM). Both GPα and FSHβ mRNA levels remained high during the FOM stages of the spawning cycle and increased further just after spawning. Thus, FSH synthesis may be strongly activated just after spawning to accelerate vitellogenesis in preparation for the next spawning. Alternatively, LHβ mRNA levels declined during hydration and then increased after ovulation. This study demonstrates that chub mackerel are a good model for investigating GtH functions in multiple spawning fish.

  15. The synthetic gestagen Levonorgestrel disrupts sexual development in Xenopus laevis by affecting gene expression of pituitary gonadotropins and gonadal steroidogenic enzymes.

    PubMed

    Lorenz, Claudia; Contardo-Jara, Valeska; Trubiroha, Achim; Krüger, Angela; Viehmann, Viola; Wiegand, Claudia; Pflugmacher, Stephan; Nützmann, Gunnar; Lutz, Ilka; Kloas, Werner

    2011-12-01

    In the present study, Xenopus laevis tadpoles were chronically exposed to four concentrations of the synthetic gestagen Levonorgestrel (LNG; 10(-11), 10(-10), 10(-9), and 10(-8)M) starting at Nieuwkoop and Faber (NF) stage 48 until completion of metamorphosis. At NF 58 and 66, brain-pituitary and gonad samples were taken for gene expression analyses of gonadotropins and gonadal steroidogenic enzymes. Exposure to 10(-9) and 10(-8)M LNG until NF 58 repressed messenger RNA (mRNA) expression of luteinizing hormone (LH) β in both genders. This decrease was persistent after further treatment until NF 66 in the 10(-8)M LNG treatment. Expression of follicle-stimulating hormone (FSH) β was affected sex-specifically. No effect was present in NF 58 females, whereas LNG at 10(-9) and 10(-8)M significantly increased FSHβ mRNA levels in males. In NF 66 females, 10(-9)M LNG treatment increased FSHβ gene expression, whereas a decrease was observed in NF 66 males exposed to 10(-8)M LNG. In gonads, expression of steroid-5-alpha-reductase was affected sex-specifically with increased mRNA levels in females but repressed levels in males. Gene expression of further gonadal steroidogenic factors was decreased by 10(-8)M LNG in both genders at NF 66. Assessment of gonad gross morphology and histology revealed poorly developed testes in the 10(-8)M LNG treatment. Our results reveal considerable effects of chronic LNG exposure on sexual development of amphibians. The persistent inhibition of LHβ expression concomitant with decreased mRNA levels of gonadal steroidogenic enzymes is suggested to result in the disruption of reproduction in adult amphibians.

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

    PubMed

    Rudolf, Faidiban O; Kadokawa, Hiroya

    2016-01-01

    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.

  17. Effect of very high dose D-leucine6-gonadotropin-releasing hormone proethylamide on the hypothalamic-pituitary testicular axis in patients with prostatic cancer.

    PubMed Central

    Warner, B; Worgul, T J; Drago, J; Demers, L; Dufau, M; Max, D; Santen, R J

    1983-01-01

    Potent synthetic analogs of gonadotropin-releasing hormone produce parodoxical antireproductive effects when administered chronically. These compounds are minimally toxic and may exhibit no plateau of the dose-response curve even at very high doses. These considerations served as the basis for our systematic evaluation of [D-leucine6-desarginine-glycine-NH2(10)]gonadotropin-releasing hormone (GnRH-A) proethylamide in the very high dose range (i.e., 10-fold larger amounts than previously used). In rats given the analog for 12 wk, prostate, testis, and seminal vesicle weights were suppressed to a greater extent with 200 micrograms q.d. than with 40 micrograms q.d. (P less than 0.01 prostate, less than 0.01 testis, less than 0.01 seminal vesicles), indicating dose-response effects in the very high dose range. 200 micrograms of [D-Leu6-des-Gly-NH2(10]-GnRH-A consistently suppressed leutinizing hormone (LH) values at 6 and 12 wk (basal 71 +/- 9.5; 6 wk 34 +/- 3.8; 12 wk 28 +/- 5 ng/ml) whereas 40 micrograms suppressed LH variably (basal 33 +/- 3.8; 6 wk 17 +/- 3.9; 12 wk 32 +/- 5.2). Testosterone fell to 15 +/- 2.4 and 19 +/- 2.0 ng/100 ml in response to 200 micrograms q.d. and to 27 +/- 6.4 and 22 +/- 7.4 ng/100 ml with the 40-micrograms dose. These findings in the rodent prompted treatment of stage D prostate cancer patients with similarly high doses of [D-Leu6-des-Gly-NH2(10)]-GnRH-A. After treatment for 11 wk with 1,000 or 10,000 micrograms/d of the analog, testosterone and dihydrotestosterone levels transiently rose and then fell into the surgically castrate range (testosterone 19 +/- 4.4 ng/100 ml [D-Leu6-des-Gly-NH2(10)]-GnRH-A vs. surgically castrate 11 +/- 0.9 ng/100 ml, P = NS; dihydrotestosterone 15 +/- 1.7 ng/100 ml GnRH-A vs. surgically castrate 15 +/- 4.1 ng/100 ml. P = NS). However, unlike the chronic stimulatory effect on the pituitary at lower doses, very high dose therapy resulted in profound suppression of plasma and urine LH. Plasma levels fell to

  18. Ghrelin stimulation of gonadotropin (LH) release from goldfish pituitary cells: presence of the growth hormone secretagogue receptor (GHS-R1a) and involvement of voltage-sensitive Ca2+ channels.

    PubMed

    Grey, Caleb L; Grayfer, Leon; Belosevic, Miodrag; Chang, John P

    2010-04-12

    Ghrelin (GRLN) stimulates maturational gonadotropin (LH) secretion in goldfish. This study identified GRLN receptors (GHS-Rs) in goldfish tissues and examined the involvement of voltage-sensitive Ca(2+) channels (VSCCs) in ghrelin action. A partial goldfish GHS-R1a sequence was obtained and expression observed in brain, pituitary, spleen, kidney, heart, gill, ovary, testis, and intestine. Synthetic goldfish GRLN (gGRLN(19)) stimulated LH secretion from dispersed goldfish pituitary cells in column perifusion and increased intracellular Ca(2+) ([Ca(2+)](i)) in identified goldfish gonadotropes. gGRLN(19) did not stimulate LH secretion either in the presence of Ca(2+)-free media, or the L-type VSCC inhibitors nifedipine and verapamil. Similarly, gGRLN(19)-elicited increases in [Ca(2+)](i) were attenuated by Ca(2+)-free media and nifedipine. Furthermore, when LH release and [Ca(2+)](i) were elevated by Bay K8644, gGRLN(19) had no further effect. These results indicate that GHS-R1a is present in goldfish pituitary and Ca(2+) entry through VSCC mediates direct gGRLN(19) action on LH release in goldfish pituitary cells.

  19. Up-regulation of gonadotropin mRNA-expression at the onset of gametogenesis in the roach (Rutilus rutilus): evidence for an important role of brain-type aromatase (cyp19a1b) in the pituitary.

    PubMed

    Trubiroha, Achim; Kroupova, Hana; Wuertz, Sven; Kloas, Werner

    2012-09-15

    The present study characterized changes in key parameters of reproduction in adult roach (Rutilus rutilus) from Lake Grosser Mueggelsee (Berlin, Germany) during natural gametogenesis. Fish of both sexes were sampled in monthly intervals between April and August in order to cover the onset of gametogenesis. Investigated parameters included gonad histology, plasma levels of 17β-oestradiol (E2), testosterone (T), 11-ketotestosterone (11-KT), and 17,20β-dihydroxy-4-pregnen-3-one (17,20β-P) as well as the expression of gonadotropin subunits in the pituitary. Furthermore, the mRNA-expression of brain-type aromatase (cyp19a1b), androgen receptor (ar), and estrogen receptor isoforms was studied at the pituitary level. The onset of gametogenesis - as indicated by follicles with cortical alveoli in females and first spermatogonia B in males - was observed in July, accompanied by a significant up-regulation of follicle-stimulating hormone β (fshβ) mRNA in the pituitary in both sexes. On the other hand, luteinizing hormone β (lhβ) mRNA increased later on in August. In males, the increase of fshβ mRNA in July coincided with a rise in plasma 11-KT concentrations. In females, E2 in plasma increased later, not until August, shortly before true vitellogenesis (late cortical alveoli stage). Expression of sex steroid receptors in the pituitary revealed only minor seasonal fluctuations. Most pronounced, ar mRNA displayed the highest level pre-spawning in both sexes. Interestingly, cyp19a1b mRNA-expression in the pituitary increased in parallel with fshβ already before any changes in plasma E2 or T occurred. These data suggest an important role of pituitary FSH and aromatase at the onset of gametogenesis in the roach. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Intracellular mechanisms involved in copper-gonadotropin-releasing hormone (Cu-GnRH) complex-induced cAMP/PKA signaling in female rat anterior pituitary cells in vitro.

    PubMed

    Gajewska, Alina; Zielinska-Gorska, Marlena; Wolinska-Witort, Ewa; Siawrys, Gabriela; Baran, Marta; Kotarba, Grzegorz; Biernacka, Katarzyna

    2016-01-01

    The copper-gonadotropin-releasing hormone molecule (Cu-GnRH) is a GnRH analog, which preserves its amino acid sequence, but which contains a Cu(2+) ion stably bound to the nitrogen atoms including that of the imidazole ring of Histidine(2). A previous report indicated that Cu-GnRH was able to activate cAMP/PKA signaling in anterior pituitary cells in vitro, but raised the question of which intracellular mechanism(s) mediated the Cu-GnRH-induced cAMP synthesis in gonadotropes. To investigate this mechanism, in the present study, female rat anterior pituitary cells in vitro were pretreated with 0.1 μM antide, a GnRH antagonist; 0.1 μM cetrorelix, a GnRH receptor antagonist; 0.1 μM PACAP6-38, a PAC-1 receptor antagonist; 2 μM GF109203X, a protein kinase C inhibitor; 50 mM PMA, a protein kinase C activator; the protein kinase A inhibitors H89 (30 μM) and KT5720 (60 nM); factors affecting intracellular calcium activity: 2.5 mM EGTA; 2 μM thapsigargin; 5 μM A23187, a Ca(2+) ionophore; or 10 μg/ml cycloheximide, a protein synthesis inhibitor. After one of the above pretreatments, cells were incubated in the presence of 0.1 μM Cu-GnRH for 0.5, 1, and 3 h. Radioimmunoassay analysis of cAMP confirmed the functional link between Cu-GnRH stimulation and cAMP/PKA signal transduction in rat anterior pituitary cells, demonstrating increased intracellular cAMP, which was reduced in the presence of specific PKA inhibitors. The stimulatory effect of Cu-GnRH on cAMP production was partly dependent on GnRH receptor activation. In addition, an indirect and Ca(2+)-dependent mechanism might be involved in intracellular adenylate cyclase stimulation. Neither activation of protein kinase C nor new protein synthesis was involved in the Cu-GnRH-induced increase of cAMP in the rat anterior pituitary primary cultures. Presented data indicate that conformational changes of GnRH molecule resulting from cooper ion coordination affect specific pharmacological properties of Cu

  1. Randomized, comparative pilot study of pituitary suppression with depot leuprorelin versus cetrorelix acetate 3 mg in gonadotropin stimulation protocols for oocyte donors.

    PubMed

    Martínez, Fracisca; Clua, Elisabeth; Santmartí, Paula; Boada, Montserrat; Rodriguez, Ignacio; Coroleu, Buenaventura

    2010-11-01

    In a pilot study, implantation and pregnancy rates per transfer were favorable in recipients of donated eggs treated with a single dose of cetrorelix acetate 3 mg compared with recipients of donated eggs treated with the long protocol (42.3% vs. 30.5%, and 71.0% vs. 46.7%, respectively; NS). The stimulation protocol based on gonadotropins and a single dose of cetrorelix acetate 3 mg is adequate in terms of safety and comfort of donors and the likelihood of pregnancy among recipients, although these favorable results require confirmation in future studies. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  2. Gonadotropin-like and adrenocorticotropin-like cells in the pituitary gland of hagfish, Paramyxine atami; immunohistochemistry in combination with lectin histochemistry.

    PubMed

    Nozaki, Masumi; Shimotani, Toyokazu; Uchida, Katsuhisa

    2007-06-01

    The pituitary system of the hagfish remains an enigma. The present study has aimed to detect possible adenohypophysial hormones in the pituitary gland of the brown hagfish, Paramyxine atami, by means of immunohistochemistry in combination with lectin histochemistry. Rabbit antisera raised against ovine luteinizing hormone (LH)beta, proopiomelanocortin (POMC)-related peptides, and the growth hormone/prolactin family of tetrapod and fish species were used, and 25 kinds of lectins were tested. Three different types of adenohypophysial cells were revealed in the pituitary of brown hagfish. The first was stained with both anti-ovine LH beta and several D-mannose-binding lectins, such as Lens culinaris agglutinin and Pisum sativum agglutinin. This cell type predominated in the adenohypophysis in adults with developing gonads and thus appeared to be involved in the regulation of gonadal functions. The second was negative for anti-ovine LH beta but was stained with several N-acetylglucosamine-binding lectins, such as wheat germ agglutinin and Lycopersicon esculentum lectin. This cell type exhibited a weak positive reaction with anti-lamprey adrenocorticotropin (ACTH) and thus appeared to be related to POMC-like cells. The second cell type was found in the adenohypophysis regardless of the developmental state of the gonads. The third cell type was negative for both antisera and lectins. Since this cell type was numerous in juveniles and adults without developing gonads, most cells of this type were probably undifferentiated. These findings suggest that GTH and ACTH are major adenohypophysial hormones in the hagfish.

  3. Klinefelter syndrome with low gonadotropin levels.

    PubMed

    Cherian, Kripa Elizabeth; Jebasingh, Felix K; Kapoor, Nitin; Paul, Thomas Vizhalil

    2015-12-29

    Klinefelter syndrome is usually characterised by the presence of a eunuchoid body habitus and testes that are usually small and firm, with low testosterone, and elevated luteinising hormone and follicle-stimulating hormone levels, consistent with hypergonadotropic hypogonadism. Low levels of gonadotropins in karyotypically proven cases are not expected, they are extremely rare occurrences. We report a case of a patient who was diagnosed to have Klinefelter syndrome (47 XXY) with low gonadotropin levels. The rest of his anterior pituitary hormonal profile was normal with no lesions in the pituitary gland on imaging. He was continued on androgen replacement therapy.

  4. Simvastatin effects on androgens, inflammatory mediators, and endogenous pituitary gonadotropins among patients with PCOS undergoing IVF: results from a prospective, randomized, placebo-controlled clinical trial.

    PubMed

    Rashidi, Batool; Abediasl, Jhila; Tehraninejad, Ensiyeh; Rahmanpour, Haleh; Sills, Eric Scott

    2011-08-01

    To evaluate effects of simvastatin on selected biochemical parameters and reproductive outcome among patients with polycystic ovary syndrome (PCOS) who undergo in vitro fertilization (IVF). Patients with PCOS were randomized to receive either oral simvastatin, 20 mg/d (n = 32), or placebo (n = 32) in a prospective, double-blind, randomized clinical trial (NCT 005-75601) in parallel with controlled ovarian hyperstimulation for IVF. All patients were determined to be at average risk for cardiovascular disease, based on high-sensitivity C-reactive protein (hsCRP) measurement at entry. After an 8-week treatment interval concluding at periovulatory human chorionic gonadotropin administration, selected clinical and laboratory parameters were measured. Mean serum total testosterone level decreased by 25% in the simvastatin group, compared to a 10% reduction in the placebo group (P < 0.001). A trend of lower serum luteinizing hormone levels was noted in experimental and control groups (29% vs 22%, respectively), although this difference was not significant (P > 0.05). Neither fasting insulin nor quantitative insulin sensitivity check index were significantly impacted by simvastatin (P > 0.05). As expected, total cholesterol was not modified among placebo patients but was significantly reduced after simvastatin (P = 0.001). In addition, hsCRP and vascular cell adhesion protein-1 were both significantly lower after simvastatin therapy compared to controls (P ≤ 0.005 for both). At study completion, no important change in body mass index was observed in either group (P ≥ 0.60). Although oocyte maturation, fertilization, and clinical pregnancy rates were all higher after simvastatin, none of these improvements were statistically significant. This report presents data from the first prospective, randomized, placebo-controlled clinical investigation of simvastatin in the setting of PCOS and IVF. Simvastatin seems to be compatible with gonadotropin therapy for IVF and can

  5. Effects of metformin administration on plasma gonadotropin levels in women with infertility, with an in vitro study of the direct effects on the pituitary gonadotrophs.

    PubMed

    Oride, Aki; Kanasaki, Haruhiko; Purwana, Indri N; Miyazaki, Kohji

    2010-09-01

    Changes in LH and FSH levels were evaluated before and after metformin administration. In all 25 patients, plasma LH levels were significantly reduced after 3 months of metformin administration (500-1,500 mg/day). When patients were classified into a PCOS group (n = 12) or a non-PCOS group (n = 13), the reduction in LH levels only remained significant in the PCOS group. Plasma FSH levels were unchanged following metformin treatment when all patients were considered collectively and when patients were classified based on PCOS. LH/FSH ratio was significantly reduced only in the PCOS group. To examine the direct effect of metformin on gonadotropin-secreting cells, gonadotroph cell line, LbetaT2 was used for in vitro studies. Treatment of LbetaT2 cells with metformin modified neither the LHbeta nor the FSHbeta subunit promoter activity. The GnRH-induced LHbeta promoter activity was not modulated in the presence of metformin. In contrast, GnRH-induced FSHbeta promoter activity was significantly potentiated in the presence of metformin. Our results suggest that metformin does indeed modulate the basal level of LH and the LH/FSH ratio, albeit indirectly, particularly in the patients with PCOS. Additionally our results suggest that metformin does directly regulate FSH gene expression.

  6. Involvement of pituitary gonadotropins, gonadal steroids and breeding season in sex change of protogynous dusky grouper, Epinephelus marginatus (Teleostei: Serranidae), induced by a non-steroidal aromatase inhibitor.

    PubMed

    Garcia, Carlos Eduardo de O; Araújo, Bruno C; Mello, Paulo H; Narcizo, Amanda de M; Rodrigues-Filho, Jandyr A; Medrado, Andreone T; Zampieri, Ricardo A; Floeter-Winter, Lucile M; Moreira, Renata Guimarães

    2013-10-01

    Two experiments were performed using the aromatase inhibitor (AI) letrozole (100mg/kg) to promote sex change, from female-to-male, in protogynous dusky grouper. One experiment was performed during the breeding season (spring) and the other at the end of the breeding season (summer). During the spring, AI promoted sex change after 9 weeks and the sperm produced was able to fertilize grouper oocytes. During the summer, the sex change was incomplete; intersex individuals were present and sperm was not released by any of the animals. Sex changed gonads had a lamellar architecture; cysts of spermatocytes and spermatozoa in the lumen of the germinal compartment. In the spring, after 4 weeks, 11ketotestosterone (11KT) levels were higher in the AI than in control fish, and after 9 weeks, coincident with semen release, testosterone levels increased in the AI group, while 11KT returned to the initial levels. Estradiol (E2) levels remained unchanged during the experimental period. Instead of decreasing throughout the period, as in control group, 17 α-OH progesterone levels did not change in the AI-treated fish, resulting in higher values after 9 weeks when compared with control fish. fshβ and lhβ gene expression in the AI animals were lower compared with control fish after 9 weeks. The use of AI was effective to obtain functional males during the breeding season. The increase in androgens, modulated by gonadotropins, triggered the sex change, enabling the development of male germ cells, whereas a decrease in E2 levels was not required to change sex in dusky grouper. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Effects of gonadotropin-releasing hormone administration on the pituitary-gonadal axis in male and female dogs before and after gonadectomy.

    PubMed

    de Gier, J; Buijtels, J J C W M; Albers-Wolthers, C H J; Oei, C H Y; Kooistra, H S; Okkens, A C

    2012-03-15

    GnRH-stimulation tests were performed in 14 female and 14 male client-owned dogs of several breeds, before and 4 to 5 mo after gonadectomy. The aim of the study was to obtain more insight into the pituitary-gonadal axis in intact and neutered dogs and to establish reference values. Basal plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations were increased significantly after gonadectomy in both bitches and male dogs. In both males and females ranges of the basal plasma FSH concentrations, before and after gonadectomy, did not overlap as opposed to the overlap in ranges of the basal plasma LH concentrations. Before gonadectomy basal plasma LH concentrations were lower and basal plasma FSH concentrations were higher in bitches than in male dogs. After gonadectomy these basal values did not differ significantly. GnRH administration before gonadectomy resulted in an increase in plasma LH and FSH concentrations in both genders. GnRH administration after gonadectomy produced an increase only in plasma LH concentrations in both genders, and a just significant increase in plasma FSH in castrated male dogs. GnRH administration before gonadectomy resulted in a significant increase in plasma testosterone concentration in both genders. In males ranges of basal and GnRH-stimulated plasma testosterone concentrations before and after gonadectomy did not overlap. Basal plasma estradiol concentrations were significantly higher in intact males than in castrated males and their ranges did not overlap. The basal estradiol concentrations in bitches before and after ovariectomy were not significantly different. At 120 min after GnRH administration, ranges of plasma estradiol concentration of intact and ovariectomized bitches no longer overlapped. In conclusion, basal plasma FSH concentration appears to be more reliable than basal plasma LH concentration for verification of neuter status in both male and female dogs. The basal plasma testosterone

  8. Neuroendocrine regulation of gonadotropin secretion in seasonally breeding birds

    PubMed Central

    Ubuka, Takayoshi; Bentley, George E.; Tsutsui, Kazuyoshi

    2013-01-01

    Seasonally breeding birds detect environmental signals, such as light, temperature, food availability, and presence of mates to time reproduction. Hypothalamic neurons integrate external and internal signals, and regulate reproduction by releasing neurohormones to the pituitary gland. The pituitary gland synthesizes and releases gonadotropins which in turn act on the gonads to stimulate gametogenesis and sex steroid secretion. Accordingly, how gonadotropin secretion is controlled by the hypothalamus is key to our understanding of the mechanisms of seasonal reproduction. A hypothalamic neuropeptide, gonadotropin-releasing hormone (GnRH), activates reproduction by stimulating gonadotropin synthesis and release. Another hypothalamic neuropeptide, gonadotropin-inhibitory hormone (GnIH), inhibits gonadotropin synthesis and release directly by acting on the pituitary gland or indirectly by decreasing the activity of GnRH neurons. Therefore, the next step to understand seasonal reproduction is to investigate how the activities of GnRH and GnIH neurons in the hypothalamus and their receptors in the pituitary gland are regulated by external and internal signals. It is possible that locally-produced triiodothyronine resulting from the action of type 2 iodothyronine deiodinase on thyroxine stimulates the release of gonadotropins, perhaps by action on GnRH neurons. The function of GnRH neurons is also regulated by transcription of the GnRH gene. Melatonin, a nocturnal hormone, stimulates the synthesis and release of GnIH and GnIH may therefore regulate a daily rhythm of gonadotropin secretion. GnIH may also temporally suppress gonadotropin secretion when environmental conditions are unfavorable. Environmental and social milieus fluctuate seasonally in the wild. Accordingly, complex interactions of various neuronal and hormonal systems need to be considered if we are to understand the mechanisms underlying seasonal reproduction. PMID:23531789

  9. Animal models for aberrations of gonadotropin action.

    PubMed

    Peltoketo, Hellevi; Zhang, Fu-Ping; Rulli, Susana B

    2011-12-01

    During the last two decades a large number of genetically modified mouse lines with altered gonadotropin action have been generated. These mouse lines fall into three categories: the lack-of-function mice, gain-of-function mice, and the mice generated by breeding the abovementioned lines with other disease model lines. The mouse strains lacking gonadotropin action have elucidated the necessity of the pituitary hormones in pubertal development and function of gonads, and revealed the processes from the original genetic defect to the pathological phenotype such as hypo- or hypergonadotropic hypogonadism. Conversely, the strains of the second group depict consequences of chronic gonadotropin action. The lines vary from those expressing constitutively active receptors and those secreting follicle-stimulating hormone (FSH) with slowly increasing amounts to those producing human choriogonadotropin (hCG), amount of which corresponds to 2000-fold luteinizing hormone (LH)/hCG biological activity. Accordingly, the phenotypes diverge from mild anomalies and enhanced fertility to disrupted gametogenesis, but eventually chronic, enhanced and non-pulsatile action of both FSH and LH leads to female and male infertility and/or hyper- and neoplasias in most of the gonadotropin gain-of-function mice. Elevated gonadotropin levels also alter the function of several extra-gonadal tissues either directly or indirectly via increased sex steroid production. These effects include promotion of tumorigenesis in tissues such as the pituitary, mammary and adrenal glands. Finally, the crossbreedings of the current mouse strains with other disease models are likely to uncover the contribution of gonadotropins in novel biological systems, as exemplified by the recent crossbreed of LHCG receptor deficient mice with Alzheimer disease mice.

  10. Pituitary Disorders

    MedlinePlus

    ... of other glands in the body. With pituitary disorders, you often have too much or too little ... one of your hormones. Injuries can cause pituitary disorders, but the most common cause is a pituitary ...

  11. Genetically modified mouse models addressing gonadotropin function.

    PubMed

    Ratner, Laura D; Rulli, Susana B; Huhtaniemi, Ilpo T

    2014-03-01

    The development of genetically modified animals has been useful to understand the mechanisms involved in the regulation of the gonadotropin function. It is well known that alterations in the secretion of a single hormone is capable of producing profound reproductive abnormalities. Human chorionic gonadotropin (hCG) is a glycoprotein hormone normally secreted by the human placenta, and structurally and functionally it is related to pituitary LH. LH and hCG bind to the same LH/hCG receptor, and hCG is often used as an analog of LH to boost gonadotropin action. There are many physiological and pathological conditions where LH/hCG levels and actions are elevated. In order to understand how elevated LH/hCG levels may impact on the hypothalamic-pituitary-gonadal axis we have developed a transgenic mouse model with chronic hCG hypersecretion. Female mice develop many gonadal and extragonadal phenotypes including obesity, infertility, hyperprolactinemia, and pituitary and mammary gland tumors. This article summarizes recent findings on the mechanisms involved in pituitary gland tumorigenesis and hyperprolactinemia in the female mice hypersecreting hCG, in particular the relationship of progesterone with the hyperprolactinemic condition of the model. In addition, we describe the role of hyperprolactinemia as the main cause of infertility and the phenotypic abnormalities in these mice, and the use of dopamine agonists bromocriptine and cabergoline to normalize these conditions. Copyright © 2014 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  12. Arg-Phe-amide-related peptides influence gonadotropin-releasing hormone neurons

    PubMed Central

    Kelestimur, Haluk; Kacar, Emine; Uzun, Aysegul; Ozcan, Mete; Kutlu, Selim

    2013-01-01

    The hypothalamic Arg-Phe-amide-related peptides, gonadotropin-inhibitory hormone and orthologous mammalian peptides of Arg-Phe-amide, may be important regulators of the hypothalamus-pituitary-gonadal reproductive axis. These peptides may modulate the effects of kisspeptins because they are presently recognized as the most potent activators of the hypothalamus-pituitary-gonadal axis. However, their effects on gonadotropin-releasing hormone neurons have not been investigated. In the current study, the GT1–7 cell line-expressing gonadotropin-releasing hormone was used as a model to explore the effects of Arg-Pheamide-related peptides on kisspeptin activation. Intracellular calcium concentration was quantified using the calcium-sensitive dye, fura-2 acetoxymethyl ester. Gonadotropin-releasing hormone released into the medium was detected via enzyme-linked immunosorbent assay. Results showed that 100 nmol/L kisspeptin-10 significantly increased gonadotropin-releasing hormone levels (at 120 minutes of exposure) and intracellular calcium concentrations. Co-treatment of kisspeptin with 1 μmol/L gonadotropin-inhibitory hormone or 1 μmol/L Arg-Phe-amide-related peptide-1 significantly attenuated levels of kisspeptin-induced gonadotropin-releasing hormone but did not affect kisspeptin-induced elevations of intracellular calcium concentration. Overall, the results suggest that gonadotropin-inhibitory hormone and Arg-Phe-amide-related peptide-1 may have inhibitory effects on kisspeptin-activated gonadotropin-releasing hormone neurons independent of the calcium signaling pathway. PMID:25206468

  13. Arg-Phe-amide-related peptides influence gonadotropin-releasing hormone neurons.

    PubMed

    Kelestimur, Haluk; Kacar, Emine; Uzun, Aysegul; Ozcan, Mete; Kutlu, Selim

    2013-06-25

    The hypothalamic Arg-Phe-amide-related peptides, gonadotropin-inhibitory hormone and orthologous mammalian peptides of Arg-Phe-amide, may be important regulators of the hypothalamus-pituitary-gonadal reproductive axis. These peptides may modulate the effects of kisspeptins because they are presently recognized as the most potent activators of the hypothalamus-pituitary-gonadal axis. However, their effects on gonadotropin-releasing hormone neurons have not been investigated. In the current study, the GT1-7 cell line-expressing gonadotropin-releasing hormone was used as a model to explore the effects of Arg-Pheamide-related peptides on kisspeptin activation. Intracellular calcium concentration was quantified using the calcium-sensitive dye, fura-2 acetoxymethyl ester. Gonadotropin-releasing hormone released into the medium was detected via enzyme-linked immunosorbent assay. Results showed that 100 nmol/L kisspeptin-10 significantly increased gonadotropin-releasing hormone levels (at 120 minutes of exposure) and intracellular calcium concentrations. Co-treatment of kisspeptin with 1 μmol/L gonadotropin-inhibitory hormone or 1 μmol/L Arg-Phe-amide-related peptide-1 significantly attenuated levels of kisspeptin-induced gonadotropin-releasing hormone but did not affect kisspeptin-induced elevations of intracellular calcium concentration. Overall, the results suggest that gonadotropin-inhibitory hormone and Arg-Phe-amide-related peptide-1 may have inhibitory effects on kisspeptin-activated gonadotropin-releasing hormone neurons independent of the calcium signaling pathway.

  14. Gonadotropin-releasing hormone analogs: Understanding advantages and limitations.

    PubMed

    Kumar, Pratap; Sharma, Alok

    2014-07-01

    Pituitary stimulation with pulsatile gonadotropin-releasing hormone (GnRH) analogs induces both follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Pituitary gonadotropin secretions are blocked upon desensitization when a continuous GnRH stimulus is provided by means of an agonist or when the pituitary receptors are occupied with a competitive antagonist. GnRH antagonists were not available originally; therefore, prolonged daily injections of agonist with its desensitizing effect were used. Today, single- and multiple-dose injectable antagonists are also available to block the LH surge and thus to cause desensitization. This review provides an overview of the use of GnRH analogs which is potent therapeutic agents that are considerably useful in a variety of clinical indications from the past to the future with some limitations. These indications include management of endometriosis, uterine leiomyomas, hirsutism, dysfunctional uterine bleeding, premenstrual syndrome, assisted reproduction, and some hormone-dependent tumours, other than ovulation induction.

  15. Withholding gonadotropins until human chorionic gonadotropin administration.

    PubMed

    Abdallah, Rony; Kligman, Isaac; Davis, Owen; Rosenwaks, Zev

    2010-11-01

    Withholding gonadotropins in women who exhibit high estradiol responses before follicles reach full maturation is called "coasting." Coasting, or suspending gonadotropin administration, can be an effective strategy for decreasing the risk of ovarian hyperstimulation syndrome (OHSS) while reducing cancelation rates. In in vitro fertilization cycles, mechanistically it is believed that withholding gonadotropins starves smaller follicles, induces apoptosis, and decreases the potential for these follicles to elaborate vascular endothelial growth factor, a known mediator of OHSS. It is generally accepted that coasting should be initiated when the estradiol (E₂) level is >3000 pg/mL in the setting of immature follicles. The human chorionic gonadotropin (hCG) trigger should be administered when the E₂ level subsequently drops to a "safe" level. Cycle cancellation should be considered if, after 3 to 4 days of coasting, the E₂ level remains excessively elevated. Oocyte retrieval may also be cancelled if the E₂ level on the day after hCG trigger drops precipitously. In gonadotropin-releasing hormone agonist (GnRHa)-based protocols, one can consider withholding GnRHa administration if the E₂ level continues to increase after a few days of coasting. Current data seem to show that the coasting period is short and/or is less likely to be required in GnRH-antagonist protocols as compared with GnRHa-based protocols. Large randomized control trials are still needed to establish the relative efficacy of coasting versus embryo cryopreservation in the context of OHSS prevention.

  16. Gonadotrope-specific deletion of Dicer results in severely suppressed gonadotropins and fertility defects.

    PubMed

    Wang, Huizhen; Graham, Ian; Hastings, Richard; Gunewardena, Sumedha; Brinkmeier, Michelle L; Conn, P Michael; Camper, Sally A; Kumar, T Rajendra

    2015-01-30

    Pituitary gonadotropins follicle-stimulating hormone and luteinizing hormone are heterodimeric glycoproteins expressed in gonadotropes. They act on gonads and promote their development and functions including steroidogenesis and gametogenesis. Although transcriptional regulation of gonadotropin subunits has been well studied, the post-transcriptional regulation of gonadotropin subunits is not well understood. To test if microRNAs regulate the hormone-specific gonadotropin β subunits in vivo, we deleted Dicer in gonadotropes by a Cre-lox genetic approach. We found that many of the DICER-dependent microRNAs, predicted in silico to bind gonadotropin β subunit mRNAs, were suppressed in purified gonadotropes of mutant mice. Loss of DICER-dependent microRNAs in gonadotropes resulted in profound suppression of gonadotropin-β subunit proteins and, consequently, the heterodimeric hormone secretion. In addition to suppression of basal levels, interestingly, the post-gonadectomy-induced rise in pituitary gonadotropin synthesis and secretion were both abolished in mutants, indicating a defective gonadal negative feedback control. Furthermore, mutants lacking Dicer in gonadotropes displayed severely reduced fertility and were rescued with exogenous hormones confirming that the fertility defects were secondary to suppressed gonadotropins. Our studies reveal that DICER-dependent microRNAs are essential for gonadotropin homeostasis and fertility in mice. Our studies also implicate microRNAs in gonadal feedback control of gonadotropin synthesis and secretion. Thus, DICER-dependent microRNAs confer a new layer of transcriptional and post-transcriptional regulation in gonadotropes to orchestrate the hypothalamus-pituitary-gonadal axis physiology. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Gonadotrope-specific Deletion of Dicer Results in Severely Suppressed Gonadotropins and Fertility Defects*

    PubMed Central

    Wang, Huizhen; Graham, Ian; Hastings, Richard; Gunewardena, Sumedha; Brinkmeier, Michelle L.; Conn, P. Michael; Camper, Sally A.; Kumar, T. Rajendra

    2015-01-01

    Pituitary gonadotropins follicle-stimulating hormone and luteinizing hormone are heterodimeric glycoproteins expressed in gonadotropes. They act on gonads and promote their development and functions including steroidogenesis and gametogenesis. Although transcriptional regulation of gonadotropin subunits has been well studied, the post-transcriptional regulation of gonadotropin subunits is not well understood. To test if microRNAs regulate the hormone-specific gonadotropin β subunits in vivo, we deleted Dicer in gonadotropes by a Cre-lox genetic approach. We found that many of the DICER-dependent microRNAs, predicted in silico to bind gonadotropin β subunit mRNAs, were suppressed in purified gonadotropes of mutant mice. Loss of DICER-dependent microRNAs in gonadotropes resulted in profound suppression of gonadotropin-β subunit proteins and, consequently, the heterodimeric hormone secretion. In addition to suppression of basal levels, interestingly, the post-gonadectomy-induced rise in pituitary gonadotropin synthesis and secretion were both abolished in mutants, indicating a defective gonadal negative feedback control. Furthermore, mutants lacking Dicer in gonadotropes displayed severely reduced fertility and were rescued with exogenous hormones confirming that the fertility defects were secondary to suppressed gonadotropins. Our studies reveal that DICER-dependent microRNAs are essential for gonadotropin homeostasis and fertility in mice. Our studies also implicate microRNAs in gonadal feedback control of gonadotropin synthesis and secretion. Thus, DICER-dependent microRNAs confer a new layer of transcriptional and post-transcriptional regulation in gonadotropes to orchestrate the hypothalamus-pituitary-gonadal axis physiology. PMID:25525274

  18. Leptin and the pituitary.

    PubMed

    Sone, M; Osamura, R Y

    2001-01-01

    -CSF) receptor, and the leukemia inhibitory factor (LIF) receptor. The leptin receptor is known to have at least six existing isoforms (Ob-Ra, b, c, d, e, f) from the difference in splicing. (Homozygote Mutation of Leptin and Leptin Receptor :Hormone Secretion Disorders) The point mutation of ob/ob mouse and the splicing mutation of db/db mouse show remarkable obesity and hyperphagia. These obesity models show a reproduction disorder with both the male and the female, and they develop with homozygote. The cause is thought to be the gonadotropin secretory abnormality in pituitary. Three family lines report the cases of this deficiency, and it is considered that the secretory abnormality in pituitary develops into hypogonadotropic. These patients show low value in plasma FSHbeta (follicle stimulating hormone-beta and LHbeta (luteinizing hormone-beta which are produced from pituitary, and the plasma GnRH (gonadotropin releasing hormone) level is also low. Furthermore, the leptin receptor deficient family line was reported in 1998, in which case only the homozygote developed. The plasma leptin concentration of normal human is about 8.0 ng/ml, and this case with leptin receptor deficiency has high value of 500-700 ng/ml, which is the equivalent to the db/db mouse. (Role of Leptin in Hypothalamus-Pituitary-Periphery Function) The role of leptin which regulates pituitary hormones suggests the promotion the GHRH (growth hormone releasing hormone) secretion in hypothalamus-pituitary axis, with the possibility of the rise in secretion of GH (growth hormone) in pituitary, i.e. effects of icv (intracerebroventricular) infusion of leptin has spontaneously stimulated GHRH, which promotes GH secretion in the normal rats. On the other hand, topical treatment of GH3 (derived from a rat pituitary GH-secreting cell line) with leptin directly inhibits cell proliferation. The obesity model animals (ob/ob, db/db, fa/fa) have equally plump body compared to the normal models, which shows signs of

  19. Therapeutic uses of gonadotropin-releasing hormone analogs.

    PubMed

    Andreyko, J L; Marshall, L A; Dumesic, D A; Jaffe, R B

    1987-01-01

    Since the discovery and synthesis of gonadotropin-releasing hormone (GnRH) in 1971, numerous long-acting agonistic and antagonistic analogs have been synthesized. Agonistic analogs were found to desensitize pituitary GnRH receptors with chronic use, resulting in decreased gonadotropin secretion and a hypogonadal state. These analogs are being investigated as potential contraceptives and in the treatment of several conditions in which decreased gonadal steroid production is desired. Substantial progress has been made in these areas. The purpose of this review is to provide the clinician with data regarding the potential clinical utility of this class of peptides.

  20. Effect of gonadotropin secretion rate on the radiosensitivity of the rat luteinizing hormone-releasing hormone neuron and gonadotroph

    SciTech Connect

    Winterer, J.; Barnes, K.M.; Lichter, A.S.; Deluca, A.M.; Loriaux, D.L.; Cutler, G.B. Jr.

    1988-03-01

    To test the hypothesis that the functional state of hypothalamic LHRH neurons and pituitary gonadotrophs might alter their radiosensitivity, we determined the experimental conditions under which the gonadotropin response to castration could be impaired by a single dose of cranial irradiation. Single doses of cranial irradiation greater than 2000 rads were lethal to unshielded rats. Shielding of the oropharynx and esophagus allowed the animals to survive doses up to 5000 rads. Doses between 2000 and 5000 rads had no effect on basal gonadotropin levels for as long as 3 months after irradiation. Irradiation caused a dose- and time-dependent impairment, however, in the gonadotropin response to castration. Impairment of the gonadotropin levels of castrate animals occurred in animals that were irradiated either before or after castration. However, rats irradiated in the castrate state showed a decreased susceptibility to irradiation damage. Additionally, stimulation of the pituitary by LHRH agonist (LHRHa) 3 h before irradiation significantly reduced the impairment of gonadotropin secretion 12-20 weeks after irradiation (P less than 0.05). Thus, increased functional activity of the rat hypothalamus or pituitary at the time of irradiation, induced by either castration or acute LHRHa administration, was associated with some protection against the gonadotropin-lowering effect of irradiation. Based upon these data, we hypothesize that stimulation of gonadotropin secretion at the time of therapeutic cranial irradiation in humans might protect against subsequent impairment of gonadotropin secretion.

  1. Dose-response characteristics of neonatal exposure to genistein on pituitary responsiveness to gonadotropin releasing hormone and volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) in postpubertal castrated female rats.

    PubMed

    Faber, K A; Hughes, C L

    1993-01-01

    Estrogen exposure during critical periods of development promotes androgenization of the brain, which is reflected in altered morphology, behavior, and cyclic hormone secretion in females. Previous work in our laboratory demonstrated that neonatal female rats injected with pharmaceutical or naturally occurring estrogens had decreased GnRH-induced LH secretion and increased volume of the SDN-POA as 42 day castrates. The current experiment defines the dose-response characteristics of neonatal exposure to the isoflavonoid phytoestrogen genistein (G) on pituitary sensitivity to GnRH and SDN-POA volume. Litters of rat pups received subcutaneous injections of either corn oil, 1, 10, 100, 200, 400, 500, or 1000 micrograms of G on days 1 to 10 of life. The litters were ovariectomized and weaned on day 21. On day 42 blood was drawn from right atrial catheters immediately prior to, 5, 10, 15, and 30 min following a single injection of 50 ng/kg of GnRH. Only the 10 micrograms dose of G was associated with increased pituitary response to GnRH, while progressive increases in exposure levels of G were associated with decreasing LH secretion. The SDN-POA volume was increased in only the 500 micrograms and 1000 micrograms exposure groups compared to controls. The results confirm that low doses of G have nonandrogenizing, pituitary-sensitizing effects, while higher doses of G mimic the more typical effects of estrogens. The use of both morphologic and physiologic end points more completely defines the reproductive consequences of environmental estrogen exposure during critical periods of CNS development.

  2. Targeted Pituitary Overexpression of Pituitary Adenylate-Cyclase Activating Polypeptide Alters Postnatal Sexual Maturation in Male Mice

    PubMed Central

    Yang, Rong Q.; Winters, Stephen J.

    2012-01-01

    The neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) is present in high concentrations within the hypothalamus, suggesting that it may be a hypophysiotropic factor, whereas pituitary expression suggests a paracrine function. PACAP stimulates gonadotropin secretion and enhances GnRH responsiveness. PACAP increases gonadotropin α-subunit (αGSU), lengthens LHβ, but reduces FSHβ mRNA levels in adult pituitary cell cultures in part by increasing follistatin. PACAP stimulates LH secretion in rats; however, acceptance of PACAP as a regulator of reproduction has been limited by a paucity of in vivo studies. We created a transgenic mouse model of pituitary PACAP overexpression using the αGSU subunit promoter. Real-time PCR was used to evaluate PACAP, follistatin, GnRH receptor, and the gonadotropin subunit mRNA in male transgenic and wild-type mice of various ages. Transgenic mice had greater than 1000-fold higher levels of pituitary PACAP mRNA; and immunocytochemistry, Western blot, and ELISA analyses confirmed high peptide levels. FSH, LH, and testosterone levels were significantly suppressed, and the timing of puberty was substantially delayed in PACAP transgenic mice in which gonadotropin subunit and GnRH receptor mRNA levels were reduced and pituitary follistatin expression was increased. Microarray analyses revealed 1229 of 45102 probes were significantly (P < 0.01) different in pituitaries from PACAP transgenic mice, of which 83 genes were at least 2-fold different. Genes involved in small molecule biochemistry, cancer, and reproductive system diseases were the top associated networks. The GnRH signaling pathway was the top canonical pathway affected by pituitary PACAP excess. These experiments provide the first evidence that PACAP affects gonadotropin expression and sexual maturation in vivo. PMID:22315445

  3. Regulation of tonic gonadotropin release in prepubertal female hamsters

    SciTech Connect

    Smith, S.G.; Matt, K.S.; Prestowitz, W.F.; Stetson, M.H.

    1982-04-01

    Basal serum gonadotropin levels were monitored weekly in female hamsters from birth to 10 weeks of age. Hamsters raised on three different photoperiods presented uniform pre- and postpubertal patterns of serum LH and FSH, suggesting that gonadotropin release in the young hamster occurs independently of ambient photoperiod. In all groups, serum LH levels increased gradually in animals up to 4 weeks of age, after which levels plateaued at 50--100 ng/ml. Serum FSH was markedly elevated in 2- and 3-week-old hamsters (800--1200 ng/ml), but remained at 200--400 ng/ml in all other groups. We next examined the change in the responsiveness of the pituitary to exogenous gonadotropin-releasing hormone (GnRH) challenge. Female hamsters 2 days of age failed to respond to any dose (0.025--1000 ng) of GnRH, while 10-day old females responded in typical dose-dependent fashion. GnRH-stimulated LH release first occurred in 6-day-old hamsters and was maximal by day 9, whereas FSH release first occurred on day 8 and was maximal by day 9. The prepubertal pattern of gonadotropin release can, in part, be explained on the basis of the development of pituitary GnRH sensitivity, which occurs independently of photoperiod.

  4. Pituitary-testicular responsiveness in male hypogonadotropic hypogonadism.

    PubMed Central

    Weinstein, R L; Reitz, R E

    1974-01-01

    An isolated deficiency of pituitary gonadotropins was demonstrated in six 46 XY males, 22 to 36 years of age, with and without anosmia. Undetectable or low levels of serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) clearly separated hypogonadotropic from normal adult males. Chronic (8-12 wk) administration of clomiphene citrate caused no increase in serum FSH or LH in gonadotropin-deficient subjects. However, the administration of synthetic luteinizing hormone releasing factor (LRF) resulted in the appearance of serum LH and, to a lesser degree, serum FSH in three subjects tested. While levels of plasma testosterone were significantly lower in gonadotropin-deficient subjects, plasma androstenedione and dehydroepiandrosterone were in a range similar to that of age-matched normal men. Treatment with human chorionic gonadotropin (HCG) increased levels of plasma testosterone to normal adult male values in all gonadotropin-deficient subjects. Cessation of treatment with HCG resulted in the return of plasma testosterone to low, pretreatment levels. That HCG therapy with resultant normal levels of plasma testosterone may somehow stimulate endogenous gonadotropin secretion in gonadotropin-deficient subjects was not evident. The adult male levels of serum FSH and LH after LRF, and plasma testosterone after HCG, confirm pituitary and Leydig cell responsiveness in these subjects. Images PMID:11344554

  5. Pituitary apoplexy.

    PubMed

    Briet, Claire; Salenave, Sylvie; Chanson, Philippe

    2015-03-01

    Pituitary apoplexy (PA) is a rare clinical syndrome caused by sudden hemorrhaging and/or infarction of the pituitary gland, generally within a pituitary adenoma. The main symptom is sudden-onset severe headache, associated with visual disorders or ocular palsy. Corticotropic deficiency may be life-threatening if left untreated. Computed tomography (CT) or MRI confirms the diagnosis by revealing a pituitary tumor with hemorrhagic and/or necrotic components. PA used to be considered a neurosurgical emergency but a conservative approach is increasingly used in selected patients, as it yields similar outcomes. Glucocorticoid treatment must always be started immediately after onset. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. New insights regarding glucocorticoids, stress and gonadotropin suppression.

    PubMed

    Breen, Kellie M; Karsch, Fred J

    2006-07-01

    This review highlights our recent work investigating the inhibitory effects of acute, physiologic stress-like increases in cortisol on reproductive neuroendocrine activity in sheep, the mechanisms responsible for this suppression, and the relevance of enhanced glucocorticoid secretion to stress-induced inhibition of gonadotropin secretion in this species. Initial studies established that cortisol rapidly suppresses pulsatile luteinizing hormone secretion. In ovariectomized ewes, this inhibition reflects the reduction of pituitary responsiveness to gonadotropin-releasing hormone mediated by the type II glucocorticoid receptor, rather than the suppression in hypothalamic gonadotropin-releasing hormone release. Studies in ovary-intact ewes, however, uncovered an alternative mode of cortisol action. During the follicular phase of the estrous cycle, cortisol reduces luteinizing hormone pulse frequency, most likely via the inhibition of gonadotropin-releasing hormone pulsatility. Recent preliminary evidence in ovariectomized ewes demonstrates increased cortisol secretion is essential for disruption of pulsatile luteinizing hormone secretion in response to a psychosocial stress. Taken together, our observations reveal diverse inhibitory actions of cortisol on gonadotropin secretion and that this glucocorticoid is not only sufficient, but necessary for suppression of reproductive neuroendocrine activity in response to certain types of stress.

  7. Gonadotropin-inhibitory hormone inhibits gonadal development and maintenance by decreasing gonadotropin synthesis and release in male quail.

    PubMed

    Ubuka, Takayoshi; Ukena, Kazuyoshi; Sharp, Peter J; Bentley, George E; Tsutsui, Kazuyoshi

    2006-03-01

    Until recently, any neuropeptide that directly inhibits gonadotropin secretion had not been identified. We recently identified a novel hypothalamic dodecapeptide that directly inhibits gonadotropin release in quail and termed it gonadotropin-inhibitory hormone (GnIH). The action of GnIH on the inhibition of gonadotropin release is mediated by a novel G protein-coupled receptor in the quail pituitary. This new gonadotropin inhibitory system is considered to be a widespread property of birds and provides us with an unprecedented opportunity to study the regulation of avian reproduction from an entirely novel standpoint. To understand the physiological role(s) of GnIH in avian reproduction, we investigated GnIH actions on gonadal development and maintenance in male quail. Continuous administration of GnIH to mature birds via osmotic pumps for 2 wk decreased the expressions of gonadotropin common alpha and LHbeta subunit mRNAs in a dose-dependent manner. Plasma LH and testosterone concentrations were also decreased dose dependently. Furthermore, administration of GnIH to mature birds induced testicular apoptosis and decreased spermatogenic activity in the testis. In immature birds, daily administration of GnIH for 2 wk suppressed normal testicular growth and rise in plasma testosterone concentrations. An inhibition of juvenile molt also occurred after GnIH administration. These results indicate that GnIH inhibits gonadal development and maintenance through the decrease in gonadotropin synthesis and release. GnIH may explain the phenomenon of photoperiod-induced gonadal regression before an observable decline in hypothalamic GnRH in quail. To our knowledge, GnIH is the first identified hypothalamic neuropeptide inhibiting reproductive function in any vertebrate class.

  8. Pituitary Tumors

    MedlinePlus

    ... pituitary is the "master control gland" - it makes hormones that affect growth and the functions of other glands in the body. Pituitary tumors are common, but often they don't cause health ... tumor produces hormones and disrupts the balance of hormones in your ...

  9. Pituitary gigantism.

    PubMed Central

    Lu, P W; Silink, M; Johnston, I; Cowell, C T; Jimenez, M

    1992-01-01

    A case of pituitary gigantism resulting from a pituitary adenoma which secreted growth hormone is described. The patient was successfully treated by surgery, which led to the normalisation of endogenous growth hormone secretion. An acceptable final height was achieved with high dose intramuscular testosterone treatment. Images Figure 1 PMID:1520009

  10. Effect of short-term and prolonged stress on the biosynthesis of gonadotropin-releasing hormone (GnRH) and GnRH receptor (GnRHR) in the hypothalamus and GnRHR in the pituitary of ewes during various physiological states.

    PubMed

    Ciechanowska, M; Łapot, M; Antkowiak, B; Mateusiak, K; Paruszewska, E; Malewski, T; Paluch, M; Przekop, F

    2016-11-01

    Using an ELISA assay, the levels of GnRH and GnRHR were analysed in the preoptic area (POA), anterior (AH) and ventromedial hypothalamus (VM), stalk/median eminence (SME); and GnRHR in the anterior pituitary gland (AP) of non-breeding and breeding sheep subjected to short-term or prolonged stress. The ELISA study was supplemented with an analysis of plasma LH concentration. Short-term footshock stimulation significantly increased GnRH levels in hypothalamus in both seasons. Prolonged stress elevated or decreased GnRH concentrations in the POA and the VM, respectively during anoestrus, and lowered GnRH amount in the POA-hypothalamus of follicular-phase sheep. An up-regulation of GnRHR levels was noted in both, anoestrous and follicular-phase animals. In the non-breeding period, a prolonged stress procedure increased GnRHR biosynthesis in the VM and decreased it in the SME and AP, while in the breeding time the quantities of GnRHR were significantly lower in the whole hypothalamus. In follicular-phase ewes the fluctuations of GnRH and GnRHR levels under short-term and prolonged stress were reflected in the changes of LH secretion, suggesting the existence of a direct relationship between GnRH and GnRH-R biosynthesis and GnRH/LH release in this period. The study showed that stress was capable of modulating the biosynthesis of GnRH and GnRHR; the pattern of changes was dependent upon the animal's physiological state and on the time course of stressor application. The obtained results indicate that the disturbances of gonadotropin secretion under stress conditions in sheep may be due to a dysfunction of GnRH and GnRHR biosynthetic pathways. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Dual pathways of calcium entry in spike and plateau phases of luteinizing hormone release from chicken pituitary cells: sequential activation of receptor-operated and voltage-sensitive calcium channels by gonadotropin-releasing hormone

    SciTech Connect

    Davidson, J.S.; Wakefield, I.K.; King, J.A.; Mulligan, G.P.; Millar, R.P.

    1988-04-01

    It has previously been shown that, in pituitary gonadotrope cells, the initial rise in cytosolic Ca2+ induced by GnRH is due to a Ca2+ mobilization from intracellular stores. This raises the possibility that the initial transient spike phase of LH release might be fully or partially independent of extracellular Ca2+. We have therefore characterized the extracellular Ca2+ requirements, and the sensitivity to Ca2+ channel blockers, of the spike and plateau phases of secretion separately. In the absence of extracellular Ca2+ the spike and plateau phases were inhibited by 65 +/- 4% and 106 +/- 3%, respectively. Both phases exhibited a similar dependence on concentration of extracellular Ca2+. However, voltage-sensitive Ca2+ channel blockers D600 and nifedipine had a negligible effect on the spike phase, while inhibiting the plateau phase by approximately 50%. In contrast, ruthenium red, Gd3+ ions, and Co2+ ions inhibited both spike and plateau phases to a similar extent as removal of extracellular Ca2+. A fraction (35 +/- 4%) of spike phase release was resistant to removal of extracellular Ca2+. This fraction was abolished after calcium depletion of the cells by preincubation with EGTA in the presence of calcium ionophore A23187, indicating that it depends on intracellular Ca2+ stores. Neither absence of extracellular Ca2+, nor the presence of ruthenium red or Gd3+ prevented mobilization of 45Ca2+ from intracellular stores by GnRH. We conclude that mobilization of intracellular stored Ca2+ is insufficient by itself to account for full spike phase LH release.

  12. Evaluation of Feasibility for a Case-Control Study of Pituitary-Ovarian Function in Premenopausal Women With Breast Cancer

    DTIC Science & Technology

    2006-07-01

    case-control study that uses gonadotropin releasing hormone (GnRH) agonist stimulation tests to compare pituitary -ovarian function in premenopausal women...in responsiveness of ovarian hormones to gonadotropin releasing hormone (GnRH) stimulation in healthy premenopausal women. GnRH stimulation was...determine the safety and feasibility of conducting a case-control study that uses gonadotropin releasing hormone (GnRH) stimulation tests to evaluate

  13. Extracellular signal-regulated kinase mediates gonadotropin subunit gene expression and LH release responses to endogenous gonadotropin-releasing hormones in goldfish.

    PubMed

    Klausen, Christian; Booth, Morgan; Habibi, Hamid R; Chang, John P

    2008-08-01

    The possible involvement of extracellular signal-regulated kinase (ERK) in mediating the stimulatory actions of two endogenous goldfish gonadotropin-releasing hormones (salmon (s)GnRH and chicken (c)GnRH-II) on gonadotropin synthesis and secretion was examined. Western blot analysis revealed the presence of ERK and phosphorylated (p)ERK in goldfish brain, pituitary, liver, ovary, testis and muscle tissue extracts, as well as extracts of dispersed goldfish pituitary cells and HeLa cells. Interestingly, a third ERK-like immunoreactive band of higher molecular mass was detected in goldfish tissue and pituitary cell extracts in addition to the ERK1-p44- and ERK2-p42-like immunoreactive bands. Incubation of primary cultures of goldfish pituitary cells with either a PKC-activating 4beta-phorbol ester (TPA) or a synthetic diacylglycerol, but not a 4alpha-phorbol ester, elevated the ratio of pERK/total (t)ERK for all three ERK isoforms. The stimulatory effects of TPA were attenuated by the PKC inhibitor GF109203X and the MEK inhibitor PD98059. sGnRH and cGnRH-II also elevated the ratio of pERK/tERK for all three ERK isoforms, in a time-, dose- and PD98059-dependent manner. In addition, treatment with PD98059 reduced the sGnRH-, cGnRH-II- and TPA-induced increases in gonadotropin subunit mRNA levels in Northern blot studies and sGnRH- and cGnRH-II-elicited LH release in cell column perifusion studies with goldfish pituitary cells. These results indicate that GnRH and PKC can activate ERK through MEK in goldfish pituitary cells. More importantly, the present study suggests that GnRH-induced gonadotropin subunit gene expression and LH release involve MEK/ERK signaling in goldfish.

  14. Pituitary abscess.

    PubMed

    Al Salman, Jameela Mohammed; Al Agha, Rawan Al Muataz Billa; Helmy, Mohamed

    2017-06-08

    Pituitary abscess is an uncommon pituitary lesion. Its clinical diagnosis can be difficult to distinguish from other pituitary lesions. This pathology is characterised by vague symptoms of headaches, generalised tiredness and hypopituitarism manifestations. A history of recent meningitis, paranasal sinusitis or head surgery can be a suggestive of the source of infection.A 20-year-old man was admitted to neurosurgery department with complain of headache, fatigue, polyuria, polydipsia, blurred vision and sexual dysfunction. MRI of the head revealed a suprasellar mass that was centrally hyperintense lesion on T2-weighted images with peripheral hypointensity and isointense centrally on T1 images with peripheral hyperintensity images. Treatment of this lesion pituitary abscess was surgical drainage of the pituitary area through a trans-sphenoidal approach and broad spectrum antibiotic therapy with ceftriaxone, metronidazole and vancomycin for 6 weeks. The patient continues to have pituitary insufficiency and treated with oral hydrocortisone.Although pituitary abscess is a rare condition, it should always be kept in mind when evaluating a patient with hypopituitarism. After the diagnosis, the surgery and antibiotics should be commenced rapidly. The outcome is usually good with proper treatment. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. Gonadotropin-inhibitory hormone (GnIH): discovery, progress and prospect

    PubMed Central

    Tsutsui, Kazuyoshi; Ubuka, Takayoshi; Bentley, George E.; Kriegsfeld, Lance J.

    2012-01-01

    A hypothalamic neuropeptide, gonadotropin-releasing hormone (GnRH), is the primary factor regulating gonadotropin secretion. An inhibitory hypothalamic neuropeptide for gonadotropin secretion was, until recently, unknown, although gonadal sex steroids and inhibin can modulate gonadotropin secretion. Findings from the last decade, however, indicate that GnRH is not the sole hypothalamic regulatory neuropeptide of vertebrate reproduction, with gonadotropin-inhibitory hormone (GnIH) playing a key role in the inhibition of reproduction. GnIH was originally identified in birds and subsequently in mammals and other vertebrates. GnIH acts on the pituitary and on GnRH neurons in the hypothalamus via a novel G protein-coupled receptor (GPR147). GnIH decreases gonadotropin synthesis and release, inhibiting gonadal development and maintenance. Such a down-regulation of the hypothalamo-pituitary-gonadal (HPG) axis may be conserved across vertebrates. Recent evidence further indicates that GnIH operates at the level of the gonads as an autocrine/paracrine regulator of steroidogenesis and gametogenesis. More recent evidence suggests that GnIH also acts both upstream of the GnRH system and at the level of the gonads to appropriately regulate reproductive activity across the seasons and during times of stress. The discovery of GnIH has fundamentally changed our understanding of hypothalamic control of reproduction. This review summarizes the discovery, progress and prospect of GnIH, a key regulator of vertebrate reproduction. PMID:22391238

  16. Dioxin Silences Gonadotropin Expression in Perinatal Pups by Inducing Histone Deacetylases

    PubMed Central

    Takeda, Tomoki; Fujii, Misaki; Taura, Junki; Ishii, Yuji; Yamada, Hideyuki

    2012-01-01

    Maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes the impairment of reproduction and development in the pups. Our previous studies have revealed that maternal treatment with TCDD attenuates the fetal production of pituitary gonadotropins (luteinizing hormone (LH) and follicle-stimulating hormone) at gestational day (GD) 20, leading to the impairment of sexual behavior in adulthood. However, the mechanism underlying such a reduction has remained unknown until now. When pregnant rats at GD15 were given an oral dose of TCDD (1 μg/kg), the testicular expression of steroidogenic proteins was reduced between GD20 and postnatal days (PND) 2. In accordance with this, the pituitary expression of gonadotropin β-subunit and serum gonadotropin were also attenuated from GD20 to PND0 in a pup-specific fashion. To identify the target genes linked to a fetal reduction in gonadotropin β-subunit, we performed a DNA microarray analysis using the fetal pituitary and its regulatory organ, the hypothalamus. The results obtained showed that TCDD induced histone deacetylases (HDACs) in the fetal pituitary. In support with this, TCDD markedly deacetylated histones H3 and H4 twined around the promoter of the fetal LHβ gene. This effect was fetus- and LHβ-specific, and this was not observed in the maternal pituitary or for other pituitary hormone genes. Finally, an LHβ reduction caused by TCDD was completely restored by maternal co-treatment with valproic acid, an HDAC inhibitor. These results strongly suggest that the increased deacetylation of histone owing to HDAC induction plays a critical role in the TCDD-induced reduction in LHβ in the fetal pituitary. PMID:22493514

  17. [Stimulation test of the adenohypophysis with arginine, gonadotropin-releasing hormone (GRH), and thyrotropin-releasing hormone (TRH) in 45, XO patients with Turner's syndrome (author's transl)].

    PubMed

    Rudolf, K; Kyank, H; Göretzlehner, G; Kunkel, S

    1980-01-01

    Pituitary stimulation tests with arginine, gonadotropin-releasing hormone (GRH) and thyrotropin-releasing hormone (TRH) were performed in five 45, XO patients with Turner's syndrome. Their ages ranged from 12--17 years. Serum levels of LH, FSH, PRL, HGH, and TSH were measured by RIA. The hypothalamo-pituitary system appeared normal in the patients with Turner's syndrome.

  18. 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

  19. Gonadotropin-releasing hormone stimulates prolactin release from lactotrophs in photoperiodic species through a gonadotropin-independent mechanism.

    PubMed

    Henderson, Helen L; Hodson, David J; Gregory, Susan J; Townsend, Julie; Tortonese, Domingo J

    2008-02-01

    Previous studies have provided evidence for a paracrine interaction between pituitary gonadotrophs and lactotrophs. Here, we show that GnRH is able to stimulate prolactin (PRL) release in ovine primary pituitary cultures. This effect was observed during the breeding season (BS), but not during the nonbreeding season (NBS), and was abolished by the application of bromocriptine, a specific dopamine agonist. Interestingly, GnRH gained the ability to stimulate PRL release in NBS cultures following treatment with bromocriptine. In contrast, thyrotropin-releasing hormone, a potent secretagogue of PRL, stimulated PRL release during both the BS and NBS and significantly enhanced the PRL response to GnRH during the BS. These results provide evidence for a photoperiodically modulated functional interaction between the GnRH/gonadotropic and prolactin axes in the pituitary gland of a short day breeder. Moreover, the stimulation of PRL release by GnRH was shown not to be mediated by the gonadotropins, since immunocytochemical, Western blotting, and PCR studies failed to detect pituitary LH or FSH receptor protein and mRNA expressions. Similarly, no gonadotropin receptor expression was observed in the pituitary gland of the horse, a long day breeder. In contrast, S100 protein, a marker of folliculostellate cells, which are known to participate in paracrine mechanisms within this tissue, was detected throughout the pituitaries of both these seasonal breeders. Therefore, an alternative gonadotroph secretory product, a direct effect of GnRH on the lactotroph, or another cell type, such as the folliculostellate cell, may be involved in the PRL response to GnRH in these species.

  20. 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 ...

  1. Pituitary tumor

    MedlinePlus

    ... enough of its hormones. This condition is called hypopituitarism . The causes of pituitary tumors are unknown. Some ... Cyst Endocrine glands Gigantism Growth hormone test Hyperthyroidism Hypopituitarism Multiple endocrine neoplasia (MEN) I Prolactin blood test ...

  2. Pituitary Apoplexy due to Pituitary Adenoma Infarction

    PubMed Central

    Kim, Joo Pyung; Kim, Sung Bum; Lim, Young Jin

    2008-01-01

    Cause of pituitary apoplexy has been known as hemorrhage, hemorrhagic infarction or infarction of pituitary adenoma or adjacent tissues of pituitary gland. However, pituitary apoplexy caused by pure infarction of pituitary adenoma has been rarely reported. Here, we present the two cases pituitary apoplexies caused by pituitary adenoma infarction that were confirmed by transsphenoidal approach (TSA) and pathologic reports. Pathologic report of first case revealed total tumor infarction of a nonfunctioning pituitary macroadenoma and second case partial tumor infarction of ACTH secreting pituitary macroadenoma. Patients with pituitary apoplexy which was caused by pituitary adenoma infarction unrelated to hemorrhage or hemorrhagic infarction showed good response to TSA treatment. Further study on the predisposing factors of pituitary apoplexy and the mechanism of infarction in pituitary adenoma is necessary. PMID:19096606

  3. Pituitary Apoplexy due to Pituitary Adenoma Infarction.

    PubMed

    Kim, Joo Pyung; Park, Bong Jin; Kim, Sung Bum; Lim, Young Jin

    2008-05-01

    Cause of pituitary apoplexy has been known as hemorrhage, hemorrhagic infarction or infarction of pituitary adenoma or adjacent tissues of pituitary gland. However, pituitary apoplexy caused by pure infarction of pituitary adenoma has been rarely reported. Here, we present the two cases pituitary apoplexies caused by pituitary adenoma infarction that were confirmed by transsphenoidal approach (TSA) and pathologic reports. Pathologic report of first case revealed total tumor infarction of a nonfunctioning pituitary macroadenoma and second case partial tumor infarction of ACTH secreting pituitary macroadenoma. Patients with pituitary apoplexy which was caused by pituitary adenoma infarction unrelated to hemorrhage or hemorrhagic infarction showed good response to TSA treatment. Further study on the predisposing factors of pituitary apoplexy and the mechanism of infarction in pituitary adenoma is necessary.

  4. [Pituitary apoplexy].

    PubMed

    Comuñas, F; Al-Ghanem, R; Calatayud Maldonado, V

    2003-12-01

    Pituitary apoplexy is an infrequent complication of pituitary adenomas, caused by hemorrhagic or ischemic infarction in the tumor, with typical clinical presentation: severe headache of sudden onset, visual disturbances, sleep tendency or comma. Along the last ten years we have treated eight patients with pituitary apoplexy. The diagnostic was clinically established in all of them. Seven cases complained of severe headache and vomiting. Eight patients reported visual disturbances. In one case low level of consciousness and meningeal irritation were the only findings. In six cases the apoplexy was the first pituitary adenoma manifestation. MRI and CT studies demonstrated the pituitary stroke in seven patients. Surgical trans-sphenoidal decompression was performed in seven patients, requiring urgent management in only one case. All patients experienced a marked visual improvement, but there was no amelioration of endocrine preoperative disturbances in any case. We conclude that quick diagnosis, early onset of hormonal therapy and urgent or delayed trans-sphenoidal surgery, depending on clinical manifestations, constitute the principies of the appropriate treatment of pituitary apoplexy.

  5. Pituitary apoplexy

    PubMed Central

    Ranabir, Salam; Baruah, Manash P.

    2011-01-01

    Pituitary apoplexy is rare endocrine emergency which can occur due to infarction or haemorrhage of pituitary gland. This disorder most often involves a pituitary adenoma. Occasionally it may be the first manifestation of an underlying adenoma. There is conflicting data regarding which type of pituitary adenoma is prone for apoplexy. Some studies showed predominance of non-functional adenomas while some other studies showed a higher prevalence in functioning adenomas amongst which prolactinoma have the highest risk. Although pituitary apoplexy can occur without any precipitating factor in most cases, there are some well recognizable risk factors such as hypertension, medications, major surgeries, coagulopathies either primary or following medications or infection, head injury, radiation or dynamic testing of the pituitary. Patients usually present with headache, vomiting, altered sensorium, visual defect and/or endocrine dysfunction. Hemodynamic instability may be result from adrenocorticotrophic hormone deficiency. Imaging with either CT scan or MRI should be performed in suspected cases. Intravenous fluid and hydrocortisone should be administered after collection of sample for baseline hormonal evaluation. Earlier studies used to advocate urgent decompression of the lesion but more recent studies favor conservative approach for most cases with surgery reserved for those with deteriorating level of consciousness or increasing visual defect. The visual and endocrine outcomes are almost similar with either surgery or conservative management. Once the acute phase is over, patient should be re-evaluated for hormonal deficiencies. PMID:22029023

  6. Pituitary apoplexy.

    PubMed

    Ranabir, Salam; Baruah, Manash P

    2011-09-01

    Pituitary apoplexy is rare endocrine emergency which can occur due to infarction or haemorrhage of pituitary gland. This disorder most often involves a pituitary adenoma. Occasionally it may be the first manifestation of an underlying adenoma. There is conflicting data regarding which type of pituitary adenoma is prone for apoplexy. Some studies showed predominance of non-functional adenomas while some other studies showed a higher prevalence in functioning adenomas amongst which prolactinoma have the highest risk. Although pituitary apoplexy can occur without any precipitating factor in most cases, there are some well recognizable risk factors such as hypertension, medications, major surgeries, coagulopathies either primary or following medications or infection, head injury, radiation or dynamic testing of the pituitary. Patients usually present with headache, vomiting, altered sensorium, visual defect and/or endocrine dysfunction. Hemodynamic instability may be result from adrenocorticotrophic hormone deficiency. Imaging with either CT scan or MRI should be performed in suspected cases. Intravenous fluid and hydrocortisone should be administered after collection of sample for baseline hormonal evaluation. Earlier studies used to advocate urgent decompression of the lesion but more recent studies favor conservative approach for most cases with surgery reserved for those with deteriorating level of consciousness or increasing visual defect. The visual and endocrine outcomes are almost similar with either surgery or conservative management. Once the acute phase is over, patient should be re-evaluated for hormonal deficiencies.

  7. The hagfish pituitary gland and its putative adenohypophysial hormones.

    PubMed

    Nozaki, Masumi

    2008-10-01

    The pituitary gland is present in all vertebrates, from agnathans (jawless fishes) to mammals, but not in invertebrates. Hagfishes, which lack both jaws and vertebrae, are considered the most primitive vertebrate known, living or extinct. Accordingly, studies on hagfishes are indispensable for understanding the origin and evolution of the pituitary hormones. Nevertheless, little is known about the hagfish adenohypophysial hormones. Our recent immunohistochemical and lectin histochemical studies have revealed that gonadotropin (GTH), adrenocorticotropin (ACTH), and growth hormone (GH) are present in the hagfish pituitary gland. This review summarizes the latest data regarding the hagfish adenohypophysial hormones from an evolutionary point of view.

  8. 21 CFR 522.1079 - Serum gonadotropin and chorionic gonadotropin.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Serum gonadotropin and chorionic gonadotropin. 522.1079 Section 522.1079 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM...

  9. 21 CFR 522.1079 - Serum gonadotropin and chorionic gonadotropin.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Serum gonadotropin and chorionic gonadotropin. 522.1079 Section 522.1079 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM...

  10. 21 CFR 522.1079 - Serum gonadotropin and chorionic gonadotropin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Serum gonadotropin and chorionic gonadotropin. 522.1079 Section 522.1079 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM...

  11. 21 CFR 522.1079 - Serum gonadotropin and chorionic gonadotropin.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Serum gonadotropin and chorionic gonadotropin. 522.1079 Section 522.1079 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM...

  12. 21 CFR 522.1079 - Serum gonadotropin and chorionic gonadotropin.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Serum gonadotropin and chorionic gonadotropin. 522.1079 Section 522.1079 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM...

  13. Advances in recombinant gonadotropin production for use in bovine superovulation.

    PubMed

    Hesser, M W; Morris, J C; Gibbons, J R

    2011-10-01

    Bovine ovarian hyperstimulation is a process that currently relies on pituitary-derived follicle stimulating hormone (FSH) to facilitate the maturation of multiple follicles to achieve dominance and eventual ovulation. The prevalence of this process, also called superovulation, has more than doubled in the past 10 years, but the efficiency of recovered transferable embryos has remained low at ~6 per collection. The use of pituitary-derived products presents other problems including contamination from other hormones, inconsistencies within and among batches, and the possibility of the spread of disease-transmitting agents. Recombinant gonadotropins have been engineered to yield varieties of FSH and luteinizing hormone from a myriad of heterologous hosts with the resulting products demonstrating various levels of biological activity. Research has also been devoted to alternative delivery methods to reduce the frequency of injections required in current superovulatory protocols. Together, recombinant gonadotropins and alternative delivery approaches potentially provide an economical alternative to the use of pituitary-derived products. © 2011 Blackwell Verlag GmbH.

  14. 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.

  15. Binding sites for gonadotropins in human postmenopausal ovaries

    SciTech Connect

    Nakano, R.; Shima, K.; Yamoto, M.; Kobayashi, M.; Nishimori, K.; Hiraoka, J.

    1989-02-01

    The binding of human LH and human FSH to postmenopausal ovarian tissue from 21 patients with cervical carcinoma was analyzed. The binding sites for FSH and LH were demonstrated in postmenopausal ovarian tissue. The surface-binding sites for gonadotropins were localized in the cells of cortical stroma of the postmenopausal ovary. In addition, diffuse cytoplasmic staining of endogenous estrogen and 3 beta-hydroxysteroid dehydrogenase activity were detected immunohistochemically and histochemically in the cells of the cortical stroma. Electron microscopic study also suggested steroidogenic function in the cells of the cortical stroma. The results of the present study suggest that postmenopausal ovaries contain specific binding sites for pituitary gonadotropins and play a role in ovarian steroidogenesis.

  16. Benzodiazepines and anterior pituitary function.

    PubMed

    Arvat, E; Giordano, R; Grottoli, S; Ghigo, E

    2002-09-01

    Benzodiazepines (BDZ) are one of the most prescribed classes of drugs because of their marked anxiolytic, anticonvulsant, muscle relaxant and hypnotic effects. The pharmacological actions of BDZ depend on the activation of 2 specific receptors. The central BDZ receptor, present in several areas of the central nervous system (CNS), is a component of the GABA-A receptor, the activation of which increases GABAergic neurotransmission and is followed by remarkable neuroendocrine effects. The peripheral benzodiazepine receptors (PBR), structurally and functionally different from the GABA-A receptor, have been shown in peripheral tissues but also in the CNS, in both neurones and glial cells, and in the pituitary gland. BDZ receptors bind to a family of natural peptides called endozepines, firstly isolated from neurons and glial cells in the brain and then in several peripheral tissues as well. Endozepines modulate several central and peripheral biological activities, including some neuroendocrine functions and synthetic BDZ are likely to mimic them, at least partially. BZD, especially alprazolam (AL), possess a clear inhibitory influence on the activity of the HPA axis in both animals and humans. This effect seems to be mediated at the hypothalamic and/or suprahypothalamic level via suppression of CRH. The strong negative influence of AL on hypothalamicpituitary-adrenal (HPA) axis agrees with its peculiar efficacy in the treatment of panic disorders and depression. BZD have also been shown to increase GH secretion via mechanisms mediated at the hypothalamic or supra-hypothalamic level, though a pituitary action cannot be ruled out. Besides the impact on HPA and somatotrope function, BDZ also significantly affect the secretion of other pituitary hormones, such as gonadotropins and PRL, probably acting through GABAergic mediation in the hypothalamus and/or in the pituitary gland. In all, BDZ are likely to represent a useful tool to investigate GABAergic activity and clarify

  17. Pituitary Carcinoma

    PubMed Central

    Cusimano, Michael D.; Ohori, Paul; Martinez, A. Julio; Jungreis, Charles; Wright, Donald C.

    1994-01-01

    The presence of distant metastases may be asymptomatic in patients who present with symptoms and signs due to the local mass effects of an invasive pituitary adenoma. A case of pituitary carcinoma in a 54-year-old man who presented with widespread asymptomatic distant metastases 12 years after initial diagnosis is reviewed. The long course and asymptomatic metastases suggested a relatively slow-growing malignancy. The factors that played a role in the pathogenesis of the metastasis are unknown. A review of the literature on pituitary carcinoma suggests that accurate diagnosis and a multidisciplinary approach to management of such lesions emphasizing surgery, radiotherapy, and hormonal manipulation may provide these patients with the longest and best quality of survival. ImagesFigure 1Figure 2Figure 3p48-bFigure 4Figure 5Figure 6 PMID:17170926

  18. Pituitary deficiencies.

    PubMed

    Greco, Deborah S

    2012-02-01

    Diabetes insipidus, arising from damage to or congenital abnormalities of the neurohypophysis, is the most common pituitary deficiency in animals. Hypopituitarism and isolated growth hormone or thyrotropin deficiency may result in growth abnormalities in puppies and kittens. In addition, treatment of associated hormone deficiencies, such as hypothyroidism and hypoadrenocorticism, in patients with panhypopituitarism is vital to restore adequate growth in dwarfed animals. Secondary hypoadrenocorticism is an uncommon clinical entity; however differentiation of primary versus secondary adrenal insufficiency is of utmost importance in determining optimal therapy. This article will focus on the pathogenesis, diagnosis and treatment of hormone deficiencies of the pituitary gland and neurohypophysis. Copyright © 2012. Published by Elsevier Inc.

  19. 21 CFR 556.304 - Gonadotropin.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... residues of total gonadotropins (human chorionic gonadotropin and pregnant mare serum gonadotropin) is 42... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gonadotropin. 556.304 Section 556.304 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL...

  20. 21 CFR 556.304 - Gonadotropin.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... residues of total gonadotropins (human chorionic gonadotropin and pregnant mare serum gonadotropin) is 42... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gonadotropin. 556.304 Section 556.304 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL...

  1. Thymulin gene therapy prevents the reduction in circulating gonadotropins induced by thymulin deficiency in mice

    PubMed Central

    Reggiani, Paula C.; Vesenbeckh, Silvan M.; Pléau, Jean M.; Sosa, Yolanda E.; Cónsole, Gloria M.; Schade, Rüdiger; Henklein, Peter; Dardenne, Mireille

    2009-01-01

    Integrity of the thymus during perinatal life is necessary for a proper maturation of the pituitary-gonadal axis in mice and other mammalian species. Thus congenitally athymic (nude) female mice show significantly reduced levels of circulating gonadotropins, a fact that seems to be causally related to a number of reproductive derangements described in these mutants. Interestingly, a number of in vitro studies suggest that the thymic peptide thymulin may be involved in thymus-pituitary communication. To determine the consequences of low serum thymulin in otherwise normal animals, we induced short (8 days)- and long (33 days)-term thymulin deficiency in C57BL/6 mice by neonatally injecting (intraperitoneally) an anti-thymulin serum and assessed their circulating gonadotropin levels at puberty and thereafter. Control mice received an irrelevant antiserum. Gonadotropins were measured by radioimmunoassay and thymulin by bioassay. Both long- and short-term serum thymulin immunoneutralization resulted in a significant reduction in the serum levels of gonadotropins at 33 and 45 days of age. Subsequently, we injected (intramuscularly) an adenoviral vector harboring a synthetic DNA sequence (5′-ATGCAAGCCAAATCTCAAGGTGGATCCAACTAGTAG-3′) encoding a biologically active analog of thymulin, methionine-FTS, in newborn nude mice (which are thymulin deficient) and measured circulating gonadotropin levels when the animals reached 52 days of age. It was observed that neonatal thymulin gene therapy in the athymic mice restored their serum thymulin levels and prevented the reduction in circulating gonadotropin levels that typically emerges in these mutants after puberty. Our results indicate that thymulin plays a relevant physiological role in the thymus-pituitary-gonadal axis. PMID:17389714

  2. Gonadotropins Regulate Rat Testicular Tight Junctions in Vivo

    PubMed Central

    McCabe, Mark J.; Tarulli, Gerard A.; Meachem, Sarah J.; Robertson, David M.; Smooker, Peter M.; Stanton, Peter G.

    2010-01-01

    Sertoli cell tight junctions (TJs) are an essential component of the blood-testis barrier required for spermatogenesis; however, the role of gonadotropins in their maintenance is unknown. This study aimed to investigate the effect of gonadotropin suppression and short-term replacement on TJ function and TJ protein (occludin and claudin-11) expression and localization, in an adult rat model in vivo. Rats (n = 10/group) received the GnRH antagonist, acyline, for 7 wk to suppress gonadotropins. Three groups then received for 7 d: 1) human recombinant FSH, 2) human chorionic gonadotropin (hCG) and rat FSH antibody (to study testicular androgen stimulation alone), and 3) hCG alone (to study testicular androgen and pituitary FSH production). TJ proteins were assessed by real-time PCR, Western blot analysis, and immunohistochemistry, whereas TJ function was assessed with a biotin permeation tracer. Acyline treatment significantly reduced testis weights, serum androgens, LH and FSH, and adluminal germ cells (pachytene spermatocyte, round and elongating spermatids). In contrast to controls, acyline induced seminiferous tubule permeability to biotin, loss of tubule lumens, and loss of occludin, but redistribution of claudin-11, immunostaining. Short-term hormone replacement stimulated significant recoveries in adluminal germ cell numbers. In hCG ± FSH antibody-treated rats, occludin and claudin-11 protein relocalized at the TJ, but such relocalization was minimal with FSH alone. Tubule lumens also reappeared, but most tubules remained permeable to biotin tracer, despite the presence of occludin. It is concluded that gonadotropins maintain Sertoli cell TJs in the adult rat via a mechanism that includes the localization of occludin and claudin-11 at functional TJs. PMID:20357222

  3. Gonadotropins regulate rat testicular tight junctions in vivo.

    PubMed

    McCabe, Mark J; Tarulli, Gerard A; Meachem, Sarah J; Robertson, David M; Smooker, Peter M; Stanton, Peter G

    2010-06-01

    Sertoli cell tight junctions (TJs) are an essential component of the blood-testis barrier required for spermatogenesis; however, the role of gonadotropins in their maintenance is unknown. This study aimed to investigate the effect of gonadotropin suppression and short-term replacement on TJ function and TJ protein (occludin and claudin-11) expression and localization, in an adult rat model in vivo. Rats (n = 10/group) received the GnRH antagonist, acyline, for 7 wk to suppress gonadotropins. Three groups then received for 7 d: 1) human recombinant FSH, 2) human chorionic gonadotropin (hCG) and rat FSH antibody (to study testicular androgen stimulation alone), and 3) hCG alone (to study testicular androgen and pituitary FSH production). TJ proteins were assessed by real-time PCR, Western blot analysis, and immunohistochemistry, whereas TJ function was assessed with a biotin permeation tracer. Acyline treatment significantly reduced testis weights, serum androgens, LH and FSH, and adluminal germ cells (pachytene spermatocyte, round and elongating spermatids). In contrast to controls, acyline induced seminiferous tubule permeability to biotin, loss of tubule lumens, and loss of occludin, but redistribution of claudin-11, immunostaining. Short-term hormone replacement stimulated significant recoveries in adluminal germ cell numbers. In hCG +/- FSH antibody-treated rats, occludin and claudin-11 protein relocalized at the TJ, but such relocalization was minimal with FSH alone. Tubule lumens also reappeared, but most tubules remained permeable to biotin tracer, despite the presence of occludin. It is concluded that gonadotropins maintain Sertoli cell TJs in the adult rat via a mechanism that includes the localization of occludin and claudin-11 at functional TJs.

  4. [Macroprolactinemia associated with pituitary macroadenoma: treatment with quinagolide].

    PubMed

    Lakatos, Gergely; Szücs, Nikolette; Kender, Zoltán; Czirják, Sándor; Rácz, Károly

    2010-06-27

    According to current concept, macroprolactin is biologically inactive and, therefore, its accumulation in serum has little, if any, pathological significance. Authors present the history of a 80-year-old man who proved to have, among other associated disorders, an intra- and parasellar pituitary tumor measuring 21x12x12 mm in size which was revealed by pituitary MRI. His hormonal evaluation indicated a marked hyperprolactinemia mainly due to macroprolactinemia (total prolactin, 514 ng/ml; reference range, 1.6-10.7 ng/ml; macroprolactin 436 ng/ml, monomer prolactin 78.2 ng/ml). Tests for function of the pituitary-thyroid axis showed a mild subclinical primary hypothyroidism. The function of the pituitary-adrenal axis was normal, and other hormonal tests revealed low-normal serum gonadotropins and decreased testosterone level, whereas serum insulin-like growth factor I was normal. Although the majority of current guidelines state that dopamine-agonist treatment which is successfully used in prolactin-producing pituitary tumors and in other hyperprolactinemic disorders is unnecessary in patients with macroprolactinemia, the authors introduced a dopamine-agonist, quinagolide. During prolonged treatment, plasma prolactin returned close to the upper limit of normal (12.3 ng/ml) and 9 months after the beginning of treatment pituitary MRI showed a remarkable shrinkage of the pituitary tumor. Authors propose that in this patient the pituitary tumor secreted macroprolactin, and they recommend a treatment trial with dopamine-agonist in pituitary macroadenomas associated with macroprolactinemia.

  5. A rare case of type 1 diabetes mellitus with pituitary hypoplasia.

    PubMed

    Pinto, Jostol; Sudeep, K; Venkatesha, B M

    2014-01-01

    Growth failure and pubertal abnormalities are not uncommon in chronic uncontrolled metabolic diseases like diabetes mellitus. We present a young girl with uncontrolled type 1 diabetes mellitus, who presented with short stature and primary amenorrhea, and on evaluation was found to have anterior pituitary hypoplasia. In addition to uncontrolled diabetes mellitus, she presented with early onset growth failure and lack of spontaneous secondary sexual characteristics. She had central hypothyroidism and inappropriately normal gonadotropin levels. However her serum cortisol levels were normal. MRI of the sellar-suprasellar region revealed a small anterior pituitary gland with thinning of the pituitary stalk consistent with pituitary hypoplasia. While uncontrolled type 1 diabetes itself may cause growth retardation and pubertal abnormalities, this girl had coexisting pituitary maldevelopment - a rare co-existence of two major illnesses of unrelated etiologies. The partial pituitary hormonal deficiency, which spared the hypothalamo-pituitary-adrenal axis, may be due to a transcription factor defect.

  6. What Are Pituitary Tumors?

    MedlinePlus

    ... testicles. Prolactin causes milk production in the female breast. Its function in men is not known. Posterior pituitary The smaller, back part of the pituitary gland, known as the posterior pituitary, is really an ...

  7. Electrical synapses connect a network of gonadotropin releasing hormone neurons in a cichlid fish

    PubMed Central

    Ma, Yunyong; Hu, Caroline K.; Huguenard, John R.; Fernald, Russell D.

    2015-01-01

    Initiating and regulating vertebrate reproduction requires pulsatile release of gonadotropin-releasing hormone (GnRH1) from the hypothalamus. Coordinated GnRH1 release, not simply elevated absolute levels, effects the release of pituitary gonadotropins that drive steroid production in the gonads. However, the mechanisms underlying synchronization of GnRH1 neurons are unknown. Control of synchronicity by gap junctions between GnRH1 neurons has been proposed but not previously found. We recorded simultaneously from pairs of transgenically labeled GnRH1 neurons in adult male Astatotilapia burtoni cichlid fish. We report that GnRH1 neurons are strongly and uniformly interconnected by electrical synapses that can drive spiking in connected cells and can be reversibly blocked by meclofenamic acid. Our results suggest that electrical synapses could promote coordinated spike firing in a cellular assemblage of GnRH1 neurons to produce the pulsatile output necessary for activation of the pituitary and reproduction. PMID:25775522

  8. Hypothalamic-pituitary-gonadal endocrine system in the hagfish.

    PubMed

    Nozaki, Masumi

    2013-12-30

    The hypothalamic-pituitary system is considered to be a seminal event that emerged prior to or during the differentiation of the ancestral agnathans (jawless vertebrates). Hagfishes as one of the only two extant members of the class of agnathans are considered the most primitive vertebrates known, living or extinct. Accordingly, studies on their reproduction are important for understanding the evolution and phylogenetic aspects of the vertebrate reproductive endocrine system. In gnathostomes (jawed vertebrates), the hormones of the hypothalamus and pituitary have been extensively studied and shown to have well-defined roles in the control of reproduction. In hagfish, it was thought that they did not have the same neuroendocrine control of reproduction as gnathostomes, since it was not clear whether the hagfish pituitary gland contained tropic hormones of any kind. This review highlights the recent findings of the hypothalamic-pituitary-gonadal endocrine system in the hagfish. In contrast to gnathostomes that have two gonadotropins (GTH: luteinizing hormone and follicle-stimulating hormone), only one pituitary GTH has been identified in the hagfish. Immunohistochemical and functional studies confirmed that this hagfish GTH was significantly correlated with the developmental stages of the gonads and showed the presence of a steroid (estradiol) feedback system at the hypothalamic-pituitary levels. Moreover, while the identity of hypothalamic gonadotropin-releasing hormone (GnRH) has not been determined, immunoreactive (ir) GnRH has been shown in the hagfish brain including seasonal changes of ir-GnRH corresponding to gonadal reproductive stages. In addition, a hagfish PQRFamide peptide was identified and shown to stimulate the expression of hagfish GTHβ mRNA in the hagfish pituitary. These findings provide evidence that there are neuroendocrine-pituitary hormones that share common structure and functional features compared to later evolved vertebrates.

  9. Hypothalamic-Pituitary-Gonadal Endocrine System in the Hagfish

    PubMed Central

    Nozaki, Masumi

    2013-01-01

    The hypothalamic-pituitary system is considered to be a seminal event that emerged prior to or during the differentiation of the ancestral agnathans (jawless vertebrates). Hagfishes as one of the only two extant members of the class of agnathans are considered the most primitive vertebrates known, living or extinct. Accordingly, studies on their reproduction are important for understanding the evolution and phylogenetic aspects of the vertebrate reproductive endocrine system. In gnathostomes (jawed vertebrates), the hormones of the hypothalamus and pituitary have been extensively studied and shown to have well-defined roles in the control of reproduction. In hagfish, it was thought that they did not have the same neuroendocrine control of reproduction as gnathostomes, since it was not clear whether the hagfish pituitary gland contained tropic hormones of any kind. This review highlights the recent findings of the hypothalamic-pituitary-gonadal endocrine system in the hagfish. In contrast to gnathostomes that have two gonadotropins (GTH: luteinizing hormone and follicle-stimulating hormone), only one pituitary GTH has been identified in the hagfish. Immunohistochemical and functional studies confirmed that this hagfish GTH was significantly correlated with the developmental stages of the gonads and showed the presence of a steroid (estradiol) feedback system at the hypothalamic-pituitary levels. Moreover, while the identity of hypothalamic gonadotropin-releasing hormone (GnRH) has not been determined, immunoreactive (ir) GnRH has been shown in the hagfish brain including seasonal changes of ir-GnRH corresponding to gonadal reproductive stages. In addition, a hagfish PQRFamide peptide was identified and shown to stimulate the expression of hagfish GTHβ mRNA in the hagfish pituitary. These findings provide evidence that there are neuroendocrine-pituitary hormones that share common structure and functional features compared to later evolved vertebrates. PMID:24416029

  10. Rapid enlargement of an intracranial germ cell tumor after gonadotropin hormone therapy.

    PubMed

    Sasagawa, Yasuo; Tachibana, Osamu; Nakagawa, Athushi; Nakada, Satoko; Nojima, Takayuki; Koya, Daisuke; Iizuka, Hideaki

    2016-09-01

    We report a case of an intracranial germ cell tumor (iGCT) that showed rapid enlargement after human chorionic gonadotropin (hCG) hormone therapy for pituitary hypogonadism. A 16-year-old boy presented with headache and was diagnosed with a suprasellar tumor. He was initially observed without surgery. Intranasal desmopressin therapy was started for central diabetes insipidus, but there was no change in the tumor size on MRI. The diagnosis of the tumor remained unknown for 4years. Levels of serum gonadotropin hormones (follicle-stimulating and luteinizing hormone) and testosterone progressively decreased, and the patient developed pituitary hypogonadism and complained about his undeveloped beard, lack of underarm hair, and erectile dysfunction. Intramuscular gonadotropin injection (hCG 5000U×2/week) was started at age 20. Eight months after the first gonadotropin injection, the MRI showed tumor growth with vivid enhancement. Craniotomy was performed and the tumor was partially resected. The histological diagnosis was immature teratoma. After surgery, the patient was treated with 5 cycles of chemotherapy with carboplatin and etoposide. He also received radiation therapy of 50Gy (20Gy tumor bed and 30Gy whole ventricles) to the residual tumor, after which the tumor decreased in size. We postulate that iGCT may be at risk of progression during hCG hormone therapy. Thus, careful monitoring is required for a patient with iGCT who receives this therapy.

  11. Effect of nutrition during calfhood and peripubertal period on serum metabolic hormones, gonadotropins and testosterone concentrations, and on sexual development in bulls.

    PubMed

    Brito, Leonardo F C; Barth, Albert D; Rawlings, Norm C; Wilde, Randal E; Crews, Denny H; Mir, Priya S; Kastelic, John P

    2007-07-01

    The objective of the present study was to characterize the effects of nutrition on circulating concentrations of metabolic hormones, gonadotropins, and testosterone during sexual development in bulls. Nutrition regulated the hypothalamus-pituitary-testes axis through effects on the GnRH pulse generator in the hypothalamus and through direct effects on the testes. Pituitary function (gonadotropin secretion after GnRH challenge) was not affected by nutrition. However, nutrition affected LH pulse frequency and basal LH concentration during the early gonadotropin rise (10-26 weeks of age). There were close temporal associations between changes in insulin-like growth factor-I (IGF-I) concentrations and changes in LH pulse frequency, suggesting a role for IGF-I in regulating the early gonadotropin rise in bulls. The peripubertal increase in testosterone concentration was delayed in bulls with lesser serum IGF-I concentrations (low nutrition), suggesting a role for IGF-I in regulating Leydig cell function. Serum IGF-I concentrations accounted for 72 and 67% of the variation in scrotal circumference and paired-testes volume, respectively (at any given age), indicating that IGF-I may regulate testicular growth. Bulls with a more sustained elevated LH pulse frequency during the early gonadotropin rise (high nutrition) had greater testicular mass at 70 weeks of age relative to the control group (medium nutrition), despite no differences in metabolic hormone concentrations after 26 weeks of age. Therefore, gonadotropin-independent mechanism regulating testicular growth might be dependent on previous gonadotropin milieu.

  12. Possible role of PACAP and its PAC1 receptor in the differential regulation of pituitary LHbeta- and FSHbeta-subunit gene expression by pulsatile GnRH stimulation.

    PubMed

    Kanasaki, Haruhiko; Purwana, Indri N; Miyazaki, Kohji

    2013-02-01

    The pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), are mainly under the control of hypothalamic gonadotropin-releasing hormone (GnRH), which regulates male and female gonadal function. GnRH is released in a pulsatile manner from the hypothalamus, and the frequency of GnRH pulses determines the dominance of output of LH and FSH from pituitary gonadotrophs. That is, more rapid pulses of GnRH preferentially increase synthesis and secretion of LH, whereas FSH is preferentially stimulated by slower GnRH pulses. The detailed mechanisms underlying this phenomenon remain unknown. Pituitary adenylate cyclase-activating polypeptide (PACAP) was originally identified as a hypothalamic activator of cAMP production in pituitary cells. PACAP is produced within the pituitary gonadotroph as well as in the central nervous system. PACAP stimulates gonadotropin alpha-, LHbeta-, and FSHbeta-subunits as well as receptors for GnRH in the pituitary gonadotropin-secreting cells. In addition, its own receptor, PACAP type I receptor (PAC1R), is also regulated by PACAP in gonadotrophs. GnRH stimulates expression of PACAP as well as PAC1R, and lower frequencies of GnRH pulses preferentially increase PACAP and PAC1R expression in gonadotrophs. Increasing concentrations of PACAP further increase the levels of gonadotropin subunit and that increasing amounts of PAC1R in gonadotrophs potentiates the effects of PACAP or GnRH on gonadotropin subunit expression. In addition, we have observed that GnRH-increased FSHbeta-subunit expression was prevented in the presence of PAC1R antagonist. These observations suggest the involvement of locally produced PACAP and its PAC1R in the differential regulation of specific gonadotropin subunit expression by pulsatile GnRH stimulation. Here, we review the possible involvement of PACAP and its PAC1R in gonadotropin control on the basis of our observations with gonadotroph cell lines.

  13. Mechanisms for pituitary tumorigenesis: the plastic pituitary

    PubMed Central

    Melmed, Shlomo

    2003-01-01

    The anterior pituitary gland integrates the repertoire of hormonal signals controlling thyroid, adrenal, reproductive, and growth functions. The gland responds to complex central and peripheral signals by trophic hormone secretion and by undergoing reversible plastic changes in cell growth leading to hyperplasia, involution, or benign adenomas arising from functional pituitary cells. Discussed herein are the mechanisms underlying hereditary pituitary hypoplasia, reversible pituitary hyperplasia, excess hormone production, and tumor initiation and promotion associated with normal and abnormal pituitary differentiation in health and disease. PMID:14660734

  14. Effects of a gonadotropin-releasing hormone antagonist on gonadotropin levels in Masu salmon and Sockeye salmon.

    PubMed

    Amano, Masafumi; Ikuta, Kazumasa; Kitamura, Shoji

    2007-09-01

    The salmon gonadotropin-releasing hormone (sGnRH) is considered to be involved in gonadal maturation via gonadotropin (GTH) secretion in salmonid fishes. However, there is no direct evidence for endogenous sGnRH-stimulated GTH secretion in salmonids. In this study, to clarify whether endogenous sGnRH stimulates GTH secretion, we examined the effects of the mammalian GnRH (mGnRH) antagonist [Ac-Delta(3)-Pro(1), 4FD-Phe(2), D-Trp(3,6)]-mGnRH on luteinizing hormone (LH) levels in 0-year-old masu salmon Oncorhynchus masou and sockeye salmon Oncorhynchus nerka. First, the effects of the GnRH antagonist on LH release were examined in 0-year-old precocious male masu salmon. GnRH antagonist treatment for 3 hr significantly inhibited an increase in plasma LH levels that was artificially induced by exogenous sGnRH administration, indicating that the GnRH antagonist is effective in inhibiting LH release from the pituitary. Subsequently, we examined the effect of the GnRH antagonist on LH synthesis in 0-year-old immature sockeye salmon that were pretreated with exogenous testosterone for 42 days to increase the pituitary LH contents; the testosterone treatment did not affect the plasma LH levels. GnRH antagonist treatment slightly but significantly inhibited an increase in the testosterone-stimulated pituitary LH content levels. However, no significant differences in the plasma LH levels were observed between the GnRH antagonist-treated and control groups. These results suggest that endogenous sGnRH is involved in LH secretion in salmonid fishes.

  15. Evaluation of Feasibility for a Case-Control Study of Pituitary-Ovarian Function in Premenopausal Women with Breast Cancer

    DTIC Science & Technology

    2005-07-01

    feasibility of a case-control study that uses gonadotropin releasing hormone (GnRH) stimulation tests to evaluate sensitivity of the hypothalamic...determine the safety and feasibility of conducting a case-control study that uses gonadotropin releasing hormone (GnHR) stimulation tests to evaluate...women. The full-scale study will determine if: 1) the anterior pituitary of pre-menopausal women with breast cancer secretes more luteinizing hormone (LH

  16. Prolactin messenger ribonucleic acid concentrations throughout the ovine estrous cycle: Assessment relative to prolactin serum and pituitary amounts

    SciTech Connect

    Landefeld, T.; Roulia, V.; Bagnell, T.; Ballard, T.; Levitan, I. )

    1991-01-01

    Prolactin (PRL) mRNA concentrations were assessed by nucleic acid hybridization assays in pituitaries of ewes representing the defined stages of the ovine estrous cycle. Concomitantly, pituitary and serum PRL concentrations were measured in these ewes using radioimmunoassays. It was observed that PRL serum, pituitary and mRNA concentrations tended to increase near the time of the gonadotropin preovulatory surge, particularly between 24 hrs before behavioral estrus to 5 hours after estrus. However, the changes in PRL mRNA, serum and pituitary concentrations were shown not to be statistically significant. These data suggest that PRL production during the sheep estrous cycle is maintained without dramatic changes in synthesis or secretion.

  17. Gonadotropin excretion and body composition.

    PubMed

    Penny, R; Goldstein, I P; Frasier, S D

    1978-02-01

    Urinary follicle stimulating hormone (FSH) and luteinizing hormone (LH) excretion was correlated with calculated total body water (TBW) and body fat (BF) in 140 normal girls and 142 normal boys, ages 3 to 16 years. In girls, there was a significant increase in gonadotropin excretion at the time of a significant increase in BF as a percent of body weight and decrease in TBW as a percent of body weight. Pubertal changes in body composition were seen in girls at the same chronological age and stage of puberty as increased gonadotropin excretion. Similar findings were observed in boys. Pubertal changes in body composition (an increase in TBW as a percent of body weight and decrease of BF as a percent of body weight) accompanied significantly increased gonadotropin excretion. Both developmental changes were seen at the same chronological age and stage of puberty. Our findings are consistent with the hypothesis that characteristic changes in body composition as well as the other hallmarks of puberty, including menarche in girls, result from increased gonadotropin and gonadal steroid secretion. They do not support the hypothesis that changes of body composition trigger increased hypothalamic function and hormone secretion leading to the subsequent events of puberty.

  18. Gonadotropin-inhibitory hormone (GnIH) in the amphibian brain and its relationship with the gonadotropin releasing hormone (GnRH) system: An overview.

    PubMed

    Jadhao, Arun G; Pinelli, Claudia; D'Aniello, Biagio; Tsutsui, Kazuyoshi

    2017-01-01

    It is well known that the hypothalamic neuropeptide gonadotropin-releasing hormone (GnRH) plays an important role as a primary factor regulating gonadotropin secretion in reproductive processes in vertebrates. The discovery of the presence of a gonadotropin-inhibitory hormone (GnIH) in the brains of birds has further contributed to our understanding of the reproduction control by the brain. GnIH plays a key role in inhibition of reproduction and acts on the pituitary gland and GnRH neurons via a novel G protein-coupled receptor (GPR147). GnIH decreases gonadotropin synthesis and release, thus inhibiting gonadal development and maintenance. The GnRH and GnIH neuronal peptidergic systems are well reported in mammals and birds, but limited information is available regarding their presence and localization in the brains of other vertebrate species, such as reptiles, amphibians and fishes. The aim of this review is to compile and update information on the localization of GnRH and GnIH neuronal systems, with a particular focus on amphibians, summarizing the neuroanatomical distribution of GnIH and GnRH and emphasizing the discovery of GnIH based on RFamide peptides and GnIH orthologous peptides found in other vertebrates and their functional significance.

  19. Androgens Mediate Sex-Dependent Gonadotropin Expression During Late Prenatal Development in the Mouse.

    PubMed

    Kreisman, Michael J; Song, Christopher I; Yip, Kathleen; Natale, Bryony V; Natale, David R; Breen, Kellie M

    2017-09-01

    Central organization of the hypothalamic-pituitary-gonadal axis is initiated during fetal life. At this critical time, gonadal hormones mediate sex-specific development of the hypothalamic-pituitary axis, which then dictates reproductive physiology and behavior in adulthood. Although studies have investigated the effects of prenatal androgens on central factors influencing gonadotropin-releasing hormone (GnRH) release, the impact of fetal androgens on gonadotrope function has been overlooked. In the current study, we demonstrated that gonadotropin gene expression and protein production were robustly elevated in female mice compared with males during late fetal development and that this sex difference was dependent on fetal androgens. Treatment of dams from embryonic day (E)15.5 to E17.5 with testosterone, dihydrotestosterone (DHT), or the androgen antagonist flutamide eliminated the sex difference at E18.5. Specifically, flutamide relieved the suppression in male gene expression, elevating the level to that of females, whereas testosterone or DHT attenuated female gene expression to male levels. The gonadotrope population is equivalent in males and females, and gonadotropic cells in both sexes express androgen receptors, suggesting that androgen-dependent transcriptional regulation can occur in these cells in either sex. Studies using mouse models lacking GnRH signaling show that GnRH is necessary for enhanced gonadotropin expression in females and is therefore required to observe the sex difference. Collectively, these data suggest that circuits controlling GnRH input to the fetal pituitary are unrestrained in females yet robustly inhibited in males via circulating androgens and demonstrate plasticity in gonadotropin synthesis and secretion in both sexes depending on the androgen milieu during late prenatal development. Copyright © 2017 Endocrine Society.

  20. Pyrrolidon carboxypeptidase activities in the hypothalamus-pituitary-thyroid and hypothalamus-pituitary-ovary axes of rats with mammary gland cancer induced by N-methyl nitrosourea.

    PubMed

    Carrera, M P; Ramírez-Expósito, M J; Valenzuela, M T; García, M J; Mayas, M D; Arias de Saavedra, J M; Sánchez, R; Pérez, M C; Martínez-Martos, J M

    2005-02-01

    Pyrrolidon carboxypeptidase is an omega-peptidase that hydrolyses N-terminal pyroglutamyl residues from biologically active peptides such as gonadotropin-releasing and thyrotrophin-releasing hormones. We previously described a decrease in both rat and human pyrrolidon carboxypeptidase activity with breast cancer, suggesting that gonadotropin-releasing hormone may be an important local intracrine, autocrine and/or paracrine hormonal factor in the pathogenesis of breast cancer while playing a role in the tumoral process. However, the other susceptible substrate of pyrrolidon carboxypeptidase, thyrotrophin-releasing hormone, may also be modified with breast cancer, supporting an association between breast cancer and thyroid disorders. The present work analyses soluble and membrane-bound pyrrolidon carboxypeptidase activities in the hypothalamus-pituitary-thyroid and hypothalamus-pituitary-ovary axes in N-methyl nitrosourea-induced breast cancer in rats. Our aim was to determine the possible relationship between gonadotropin-releasing hormone and thyrotrophin-releasing hormone regulation through pyrrolidon carboxypeptidase activity. We propose that pyrrolidon carboxypeptidase activity dysregulation at various local and systemic levels may participate in the initiation, promotion and progression of breast cancer induced in rat by N-methyl nitrosourea through the increase in gonadotropin-releasing hormone. Since pyrrolidon carboxypeptidase activity also acts on thyrotrophin-releasing hormone, the dysregulation of this enzyme's activity could indirectly affect hypothalamus-pituitary-thyroid axis function, and thus potentially represent a link between the diseases of thyroid and breast cancer.

  1. Expression of a Gonadotropin-Releasing Hormone Receptor-Simian Virus 40 T-Antigen Transgene Has Sex-Specific Effects on the Reproductive Axis

    PubMed Central

    Jeong, Kyeong-Hoon; Gill, John C.; Nosé, Vania; Parlow, Albert F.; Carroll, Rona S.; Kaiser, Ursula B.

    2009-01-01

    The GnRH receptor (GnRHR) responds to pulsatile GnRH signals to coordinate pituitary gonadotropin synthesis and secretion. Previously, a 1.2-kb fragment of the 5′-flanking region isolated from the mouse GnRHR gene was shown to target expression to pituitary gonadotropes in vivo. The 1.2-kb gene promoter fused to the simian virus 40 large T antigen (TAg) was used to generate transgenic mice that form gonadotrope-derived pituitary tumors at 4–5 months of age. Transgenic female mice have hypogonadotropic hypogonadism, infantile gonads, and are infertile throughout their life span, whereas males remain reproductively intact until their tumors become large. We hypothesized that the targeted TAg expression causes a sex-specific disruption of the reproductive axis at the level of the pituitary gland. To test this hypothesis, we characterized the pituitary gonadotropin β-subunit and TAg expression patterns, and measured plasma gonadotropin and gonadal steroid levels in female and male mice before and after pituitary tumor development. TAg expression was observed in transgenic females and males 15 d of age, before tumor development. Interestingly, and in contrast to the transgenic males, pituitary LHβ and FSHβ subunit protein levels, and plasma LH and FSH levels, were reduced in transgenic females. Reproductive organs in transgenic female mice remained underdeveloped but were normal in transgenic males. We conclude that the expression of the TAg transgene driven by the GnRHR gene promoter results in female-specific infertility due to disruption of gonadotropin production and secretion even before tumor development. PMID:19282386

  2. Targeting Gonadotropins: An Alternative Option for Alzheimer Disease Treatment

    PubMed Central

    Casadesus, Gemma; Puig, Emma Ramiro; Webber, Kate M.; Atwood, Craig S.; Escuer, Margarida Castell; Bowen, Richard L.; Perry, George; Smith, Mark A.

    2006-01-01

    Recent evidence indicates that, alongside oxidative stress, dysregulation of the cell cycle in neurons susceptible to degeneration in Alzheimer disease may play a crucial role in the initiation of the disease. As such, the role of reproductive hormones, which are closely associated with the cell cycle both during development and after birth, may be of key import. While estrogen has been the primary focus, the protective effects of hormone replacement therapy on cognition and dementia only during a “crucial period” led us to expand the study of hormonal influences to other members of the hypothalamic pituitary axis. Specifically, in this review, we focus on luteinizing hormone, which is not only increased in the sera of patients with Alzheimer disease but, like estrogen, is modulated by hormone replacement therapy and also influences cognitive behavior and pathogenic processing in animal models of the disease. Targeting gonadotropins may be a useful treatment strategy for disease targeting multiple pleiotropic downstream consequences. PMID:17047306

  3. Seasonal and stress related changes in plasma gonadotropins, sex steroids, and corticosterone in the bullfrog, Rana catesbeiana.

    PubMed

    Licht, P; McCreery, B R; Barnes, R; Pang, R

    1983-04-01

    expectation of pituitary--gonadal relationships. Levels of plasma gonadotropins and steroids did not show the reciprocal relationship expected from a simple negative feed-back between gonadal and pituitary secretion, nor did changes in gonadotropins and gonadal activities show the consistent positive correlation expected from a direct dependence of gonadal function on circulating gonadotropins. In females, plasma T, but not E, correlated with ovarian growth. Plasma T in females reached much higher levels than in males, but DHT was higher in males. Androgens were generally elevated during the period of sexual activity in males, but absolute levels did not correlate well with individual differences in sexual behavior. Thus, seasonal changes in testicular and ovarian activities cannot be accounted for solely by seasonal cycles in circulating gonadotropin levels.

  4. Pituitary Somatostatin Receptor Signaling

    PubMed Central

    Ben-Shlomo, Anat; Melmed, Shlomo

    2010-01-01

    Somatostatin (SRIF) is a major regulator of pituitary function, mostly inhibiting hormone secretion and to a lesser extent pituitary cell growth. Five SRIF receptor subtypes (SSTR1–5) are ubiquitously expressed G-protein coupled receptors. In the pituitary, SSTR1, SSTR2, SSTR3 and SSTR5 are expressed, with SSTR2 and SSTR5 predominating. As new SRIF-analogs have recently been introduced for treatment of pituitary disease, we evaluate the current knowledge of cell-specific pituitary SRIF receptor signaling and highlight areas of future research for comprehensive understanding of these mechanisms. Elucidating pituitary SRIF receptor signaling enables understanding of pituitary hormone secretion and cell growth, and also points to future therapeutic development for pituitary disorders. PMID:20149677

  5. CT of pituitary abscess

    SciTech Connect

    Fong, T.C.; Johns, R.D.; Long, M.; Myles, S.T.

    1985-06-01

    Pituitary abscess is a rare condition, with only 50 cases reported in the literature. Of those, 29 cases were well documented for analysis. Preoperative diagnosis of pituitary abscess is difficult. The computed tomographic (CT) appearance of pituitary abscess was first described in 1983; the abscess was depicted by axial images with coronal reconstruction. The authors recently encountered a case of pituitary abscess documented by direct coronal CT of the sella turcica.

  6. Clinical uses of gonadotropin-releasing hormone analogues.

    PubMed Central

    Casper, R F

    1991-01-01

    Gonadotropin-releasing hormone (Gn-RH) analogues are synthetic derivatives of the native hypothalamic peptide with alterations in their chemical structure that result in changes in biologic activity. Several Gn-RH agonists are available for clinical use, and all act through the same mechanism: first to stimulate and then to inhibit gonadotropin and gonadal steroid secretion by downregulating the pituitary Gn-RN receptors. This review should provide clinicians with a working knowledge of the physiologic and pharmacokinetic features of Gn-RH agonists. Although over 2000 articles concerning Gn-RH analogues have been published I chose to review only those that were the first to report a novel clinical application. Gn-RH agonists have proved to be extremely efficacious in treating gonadal steroid-dependent problems such as endometriosis, uterine leiomyoma, precocious puberty and prostate and breast cancers, and they have resulted in very few side effects. Long-term use may, however, lead to skeletal calcium loss in women as a consequence of hypoestrogenism. Further research is needed to prevent this and maintain clinical efficacy. PMID:1986827

  7. Pituitary lymphoma developing within pituitary adenoma.

    PubMed

    Morita, Ken; Nakamura, Fumihiko; Kamikubo, Yasuhiko; Mizuno, Naoaki; Miyauchi, Masashi; Yamamoto, Go; Nannya, Yasuhito; Ichikawa, Motoshi; Kurokawa, Mineo

    2012-06-01

    Lymphoma occurring in the pituitary gland is an exceedingly infrequent event. Here, we describe a case of pituitary lymphoma complicating recurrent pituitary adenoma. A 56-year-old male with a history of pituitary adenoma was diagnosed with diffuse large B-cell lymphoma (DLBCL) of the left ocular adnexa, which was successfully treated by standard chemotherapy and local radiotherapy. Eight months later, he complained of diplopia and bitemporal hemianopia. Brain magnetic resonance imaging detected a suprasellar tumor. Transsphenoidal biopsy of the mass was performed, and histopathological examination revealed DLBCL admixed with pituitary adenoma. On a review of the literature, we found that pituitary lymphoma developing within adenoma is a recurrent phenomenon. The composite tumor is likely to be characterized by suprasellar involvement and presentation of visual disturbances. Moreover, in the present case, the suprasellar tumor remained visible after autologous peripheral stem cell transplant, likely due to the residual pituitary adenoma. We therefore recommend that refractory pituitary lymphoma should be vigorously biopsied in search of possibly underlying adenoma.

  8. Pituitary tumor apoplexy.

    PubMed

    Chang, Claudia V; Felicio, Andre C; Toscanini, Andrea Cecilia; Teixeira, Manoel Jacobsen; Cunha-Neto, Malebranche Berardo Carneiro da

    2009-06-01

    Pituitary tumor apoplexy is a medical emergency due to acute infarction or hemorrhage in the pituitary gland. In this review, the authors discuss the sellar anatomy, the pituitary gland and adenomas' vascularization and the general aspects of the syndrome such as its ethiopatogenesis, predisposing factors, clinical features, treatment and prognosis.

  9. Structure-function relationship of gonadotropins

    SciTech Connect

    Bellet, D.; Bidart, J.M.

    1989-01-01

    In this book, investigators highlight progress recently made in research on the structure-function relationship of gonadotropins. The contributors provide coverage of major breakthroughs such as the cloning of the ovarian receptor for lutropin and choriogonadotropin, the elucidation of the structure of this receptor, and the first crystallographic studies of human chorionic gonadotropin. The book also describes significant advances in the epitope mapping of gonadotropins, the immunochemical and biochemical study of their structure, the examination of regulatory processes involved in subunit association, and the elucidation of the complex mechanisms responsible for regulation and expression of gonadotropin genes.

  10. Evidence for a gonadotropin from nonpregnant subjects that has physical, immunological, and biological similarities to human chorionic gonadotropin.

    PubMed Central

    Chen, H C; Hodgen, G D; Matsuura, S; Lin, L J; Gross, E; Reichert, L E; Birken, S; Canfield, R E; Ross, G T

    1976-01-01

    Substances from urinary extracts of normal, nonpregnant subjects and human pituitary gonadotropin preparations were found to react similarly to human chorionic gonadotropin (hCG) in a radioimmunoassay system that is highly specific for hCG and without crossreactivity to human luteinizing hormone (hLH). The antiserum was produced in a rabbit immunized with a bovine albumin conjugate of the unique carboxyl-terminal peptide (residues 123-145) isolated from a tryptic digest of the reduced, S-carboxymethylated hCGbeta subunit. The antibody recognition site on the peptide was found to reside on the last 15 amino acid residues of the carboxyl-terminal peptide, as evidenced by the competitive binding activities against 125I-labeled hCG of a series of peptides chemically synthesized according to the carboxyl-terminal sequence of HCGbeta. In order to elucidate the nature of the crossreacting substance in urinary extracts, a human postmenopausal urinary preparation (Pergonal) and a kaolin-acetone extract of urine from a patient with Klinefelter's syndrome were subjected to gel chromatography on Sephadex G-100. The results indicate that fractions showing immunocrossreactivity with the antiserum to hCGbeta-carboxyl-terminal peptide coeluted with 125I-labeled hCG which was separated distinctly from hLH. The same fractions from this postmenopausal urinary gonadotropin preparation exhibited in vitro biological activity proportional to the immunocrossreactivity of the hCG-specific antiserum. Concentration of postmenopausal women's urine by acetone precipitation retained approximately five times more immunoreactivity per unit volume than kaolin-acetone extraction, when assayed with the antiserum to hCGbeta-carboxyl-terminal peptide. PMID:60763

  11. Direct evidence of estrogen modulation of pituitary sensitivity to luteinizing hormone-releasing factor during the menstrual cycle.

    PubMed Central

    Wang, C F; Yen, S S

    1975-01-01

    To delineate the role of estradiol in the augmented pituitary gonadotropin responsiveness to synthetic luteinizing hormone releasing factor (LRF) seen during high-estrogen phases of the ovulatory cycles (late follicular and midluteal phases), the anti-estrogenic effect of clomiphene citrate (Clomid) on pituitary response to LRF was evaluated during different phases of the ovulatory cycle. Clomid administration (100 mg/day times 5 days) completely negates the augmented gonadotropin responses to LRF (150 mug) during late follicular and midluteal phases observed during the control studies. Thus, a quantitatively and qualitatively similar pituitary sensitivity to LRF during three distinct phases of the menstrual cycle was induced by Clomid treatment that resembles the LRF responsiveness of themale pituitary. The present study demonstrates the pituitary component of the estrogen-induced changes in the sensitivity to LRF. From this and previous data, we conclude that the increases of estradiol secretion associated with the follicular maturation and corpus luteum formation represent a major component of the feedback signal in the modulation of cyclic gonadotropin release occasioned in a large measure by the augmented pituitary sensitivity to LRF. PMID:1088908

  12. 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.

  13. Expression of the long-chain fatty acid receptor GPR120 in the gonadotropes of the mouse anterior pituitary gland.

    PubMed

    Moriyama, Ryutaro; Deura, Chikaya; Imoto, Shingo; Nose, Kazuhiro; Fukushima, Nobuyuki

    2015-01-01

    G-protein-coupled receptor 120 (GPR120) has been known to be a receptor of long-chain fatty acids. Here, we investigated GPR120 expression in the mouse pituitary gland via real-time PCR, in situ hybridization, and immunohistochemistry. GPR120 mRNA was abundantly expressed in the pituitary gland of ad-lib fed animals. In situ hybridization and immunohistochemistry revealed GPR120 expression in the gonadotropes of the anterior pituitary gland, but not in thyrotropes, somatotropes, lactotropes, corticotropes, melanotropes, and the posterior pituitary gland. Furthermore, 24 h of fasting induced an increase in GPR120 mRNA expression in the pituitary gland. These results demonstrate that GPR120 in mouse pituitary gonadotropes is upregulated by fasting and that it may play a role in controlling gonadotropin secretion.

  14. Gonadotropin and estrogen responses in freshwater turtle (Chrysemys picta) from Cape Cod, Massachusetts.

    PubMed

    Kitana, Noppadon; Khonsue, Wichase; Won, Seung Jae; Lance, Valentine A; Callard, Ian P

    2006-10-01

    As a result of chemical waste disposal on the Massachusetts Military Reservation, a Superfund site on Cape Cod, MA, contaminated groundwater plumes have formed. These plumes are of concern due to the widespread use of groundwater wells as a drinking water source by the local population. Prior observations on a sentinel species Chrysemys picta field-trapped from ponds on Cape Cod suggested deficits in reproductive processes including lower levels of vitellogenin, estradiol-17beta, oviduct weights, and oocyte numbers in females and lower testicular weight and sperm count in males. Possible loci in the hypothalamic-pituitary-gonadal-liver axis at which xenobiotics may act were determined in turtles trapped from Moody Pond (a test site) and Washburn Pond (a reference site). Specifically, gonadotropin and estrogen responses were assessed using plasma steroids and vitellogenin as markers. Basal vitellogenin levels were significantly lower in Moody Pond females; however, vitellogenin responses to estradiol-17beta were the same in both groups, indicating a normal hepatic response to estrogen. In contrast, estradiol-17beta secretion was not stimulated by gonadotropin in Moody Pond females, compared to Washburn animals. Basal plasma testosterone and the response to gonadotropin in males were similar, although steroid levels in Moody Pond animals were slower to return to baseline after gonadotropin injection. The results suggest that a low-level mixture of xenobiotic contaminants may interfere with the steroid metabolic pathways in turtles exposed to the test site, but not the reference site, environment.

  15. Structural and Functional Divergence of Gonadotropin-Inhibitory Hormone from Jawless Fish to Mammals

    PubMed Central

    Ogawa, Satoshi; Parhar, Ishwar S.

    2014-01-01

    Gonadotropin-inhibitory hormone (GnIH) was discovered as a novel hypothalamic peptide that inhibits gonadotropin release in the quail. The presence of GnIH-homologous peptides and its receptors (GnIHRs) have been demonstrated in various vertebrate species including teleosts, suggesting that the GnIH-GnIHR family is evolutionarily conserved. In avian and mammalian brain, GnIH neurons are localized in the hypothalamic nuclei and their neural projections are widely distributed. GnIH acts on the pituitary and gonadotropin-releasing hormone neurons to inhibit reproductive functions by decreasing gonadotropin release and synthesis. In addition, GnIH-GnIHR signaling is regulated by various factors, such as environmental cues and stress. However, the function of fish GnIH orthologs remains inconclusive because the physiological properties of fish GnIH peptides are debatable. This review summarizes the current research progress in GnIH-GnIHR signaling and their physiological functions in vertebrates with special emphasis on non-mammalian vertebrate species. PMID:25386165

  16. Neurology of the pituitary.

    PubMed

    Samarasinghe, Shanika; Emanuele, Mary Ann; Mazhari, Alaleh

    2014-01-01

    The anterior pituitary hormones are essential for reproduction, growth, metabolic homeostasis, stress response, and adaptation to changes in the external environment. Each pituitary hormone is secreted in a distinctive pulsatile manner reflecting its regulation by the central nervous system through a complex interaction between hypothalamic neuroendocrine pathways, feedback effects from peripheral target gland hormones, and intrapituitary mechanisms. While the most common cause of a pituitary mass is an adenoma, the differential diagnosis is broad and includes pituitary hyperplasia, lymphocytic hypophysitis, craniopharyngioma among others. Patients with pituitary adenomas can be asymptomatic or present with symptoms due to mass effect, pituitary hormone dysfunction, or both. Prolactinomas represent 40% of pituitary adenomas, the majority of which are microadenomas. Hyperfunction of growth hormone and ACTH are far less common, while TSH-producing tumors are exceedingly rare. Hypopituitarism in patients with pituitary adenomas can be partial or complete. The clinical picture will depend on the type, degree, and rapidity of onset of pituitary hormone deficiency. An MRI specifically focused on the sellar region is the imaging modality of choice to detect pituitary pathology. Management of pituitary tumors ranges from observation of nonfunctioning microadenomas through medical, surgical, and radiotherapeutic approaches dependent on tumor type, function, size, and invasiveness. © 2014 Elsevier B.V. All rights reserved.

  17. Effect of feed restriction during calfhood on serum concentrations of metabolic hormones, gonadotropins, testosterone, and on sexual development in bulls.

    PubMed

    Brito, L F C; Barth, A D; Rawlings, N C; Wilde, R E; Crews, D H; Boisclair, Y R; Ehrhardt, R A; Kastelic, J P

    2007-07-01

    The objective of the present study was to evaluate the effects offeed restriction during calfhood on serum concentrations of metabolic hormones, gonadotropins, and testosterone, and on sexual development in bulls. Eight beef bull calves received a control diet from 10 to 70 weeks of age. An additional 16 calves had restricted feed (75% of control) from 10 to 26 weeks of age (calfhood), followed by either control or high nutrition (n=8/group) during the peripubertal period until 70 weeks of age. Restricted feed during calfhood inhibited the hypothalamic GnRH pulse generator, reduced the pituitary response to GnRH, impaired testicular steroidogenesis, delayed puberty, and reduced testicular weight at 70 weeks of age, regardless of the nutrition during the peripubertal period. Restricted feed reduced serum IGF-I concentrations, but concentrations of leptin, insulin, and GH were not affected. In conclusion, restricted feed during calfhood impaired sexual development in bulls due to adverse effects on every level of the hypothalamus-pituitary-gonad axis and these effects were not overcome by supplemental feeding during the peripubertal period. Furthermore, based on temporal associations, the effects of restricted feed on the hypothalamus-pituitary-gonad axis might be mediated by serum IGF-I concentrations. These results supported the hypotheses that the pattern of LH secretion during the early gonadotropin rise during calfhood is the main determinant of age of puberty in bulls and that gonadotropin-independent mechanisms involved in testicular growth during the peripubertal period are affected by previous LH exposure.

  18. Fox Tales: Regulation of Gonadotropin Gene Expression by Forkhead Transcription Factors

    PubMed Central

    Thackray, Varykina G.

    2013-01-01

    Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are produced by pituitary gonadotrope cells and are required for steroidogenesis, the maturation of ovarian follicles, ovulation, and spermatogenesis. Synthesis of LH and FSH is tightly regulated by a complex network of signaling pathways activated by hormones including gonadotropin-releasing hormone, activin and sex steroids. Members of the forkhead box (FOX) transcription factor family have been shown to act as important regulators of development, homeostasis and reproduction. In this review, we focus on the role of four specific FOX factors (FOXD1, FOXL2, FOXO1 and FOXP3) in gonadotropin hormone production and discuss our current understanding of the molecular function of these factors derived from studies in mouse genetic and cell culture models. PMID:24099863

  19. Monoclonal antibodies to gonadotropin subunits

    SciTech Connect

    Ehrlich, P.H.; Moyle, W.R.; Canfield, R.E.

    1985-01-01

    The production of monoclonal antibodies to peptide hormones, with their unifocal binding sites, can provide tools for understanding hormone structure and function. The paper focuses on techniques that are important for the study of monoclonal antibodies to chorionic gonadotropin (hCG), including hybridoma production, methods of screening for desired clones, properties of the monoclonal antibodies, effect of antibodies on hormone-receptor interaction, inhibition of binding of radiolabeled hCG, inhibition of hCG induced steroidogenesis, determination of relative orientation of epitopes, and synergistic actions of monoclonal antibodies to hCG.

  20. Hirsutism, virilism, polycystic ovarian disease, and the steroid-gonadotropin-feedback system: a career retrospective

    PubMed Central

    2012-01-01

    This career retrospective describes how the initial work on the mechanism of hormone action provided the tools for the study of hirsutism, virilism, and polycystic ovarian disease. After excessive ovarian and or adrenal androgen secretion in polycystic ovarian disease had been established, the question whether the disease was genetic or acquired, methods to manage hirsutism and methods for the induction of ovulation were addressed. Recognizing that steroid gonadotropin feedback was an important regulatory factor, initial studies were done on the secretion of LH and FSH in the ovulatory cycle. This was followed by the study of basic mechanisms of steroid-gonadotropin feedback system, using castration and steroid replacement and the events surrounding the natural onset of puberty. Studies in ovariectomized rats showed that progesterone was a pivotal enhancer of estrogen-induced gonadotropin release, thus accounting for the preovulatory gonadotropin surge. The effects of progesterone were manifested by depletion of the occupied estrogen receptors of the anterior pituitary, release of hypothalamic LHRH, and inhibition of enzymes that degrade LHRH. Progesterone also promoted the synthesis of FSH in the pituitary. The 3α,5α-reduced metabolite of progesterone brought about selective LH release and acted using the GABAA receptor system. The 5α-reduced metabolite of progesterone brought about selective FSH release; the ability of progesterone to bring about FSH release was dependent on its 5α-reduction. The GnRH neuron does not have steroid receptors; the steroid effect was shown to be mediated through the excitatory amino acid glutamate, which in turn stimulated nitric oxide. These observations led to the replacement of the long-accepted belief that ovarian steroids acted directly on the GnRH neuron by the novel concept that the steroid feedback effect was exerted at the glutamatergic neuron, which in turn regulated the GnRH neuron. The neuroprotective effects of

  1. Hirsutism, virilism, polycystic ovarian disease, and the steroid-gonadotropin-feedback system: a career retrospective.

    PubMed

    Mahesh, Virendra B

    2012-01-01

    This career retrospective describes how the initial work on the mechanism of hormone action provided the tools for the study of hirsutism, virilism, and polycystic ovarian disease. After excessive ovarian and or adrenal androgen secretion in polycystic ovarian disease had been established, the question whether the disease was genetic or acquired, methods to manage hirsutism and methods for the induction of ovulation were addressed. Recognizing that steroid gonadotropin feedback was an important regulatory factor, initial studies were done on the secretion of LH and FSH in the ovulatory cycle. This was followed by the study of basic mechanisms of steroid-gonadotropin feedback system, using castration and steroid replacement and the events surrounding the natural onset of puberty. Studies in ovariectomized rats showed that progesterone was a pivotal enhancer of estrogen-induced gonadotropin release, thus accounting for the preovulatory gonadotropin surge. The effects of progesterone were manifested by depletion of the occupied estrogen receptors of the anterior pituitary, release of hypothalamic LHRH, and inhibition of enzymes that degrade LHRH. Progesterone also promoted the synthesis of FSH in the pituitary. The 3α,5α-reduced metabolite of progesterone brought about selective LH release and acted using the GABA(A) receptor system. The 5α-reduced metabolite of progesterone brought about selective FSH release; the ability of progesterone to bring about FSH release was dependent on its 5α-reduction. The GnRH neuron does not have steroid receptors; the steroid effect was shown to be mediated through the excitatory amino acid glutamate, which in turn stimulated nitric oxide. These observations led to the replacement of the long-accepted belief that ovarian steroids acted directly on the GnRH neuron by the novel concept that the steroid feedback effect was exerted at the glutamatergic neuron, which in turn regulated the GnRH neuron. The neuroprotective effects of

  2. Quantitative bioassays for measuring biologically functional gonadotropins based on eel gonadotropic receptors.

    PubMed

    Minegishi, Y; Dirks, R P; de Wijze, D L; Brittijn, S A; Burgerhout, E; Spaink, H P; van den Thillart, G E E J M

    2012-08-01

    Significant declines in eel stocks have been noted in many parts of the world. Because eel aquaculture is dependent on wild-caught juveniles, there is a need to achieve artificial reproduction. Adult eel maturation is currently induced by repeated injections of purified gonadotropin (human chorionic gonadotropin [hCG]) or pituitary extract. Thus the determination of the biological efficacy and quantification of internal levels of gonadotropic hormones is important for optimizing artificial reproduction protocols. To quantify the plasma levels of biologically functional gonadotropic hormones, we developed a bioassay for luteinizing hormone (LH) and follicle-stimulating hormone (FSH) based on the stable expression of receptors in HEK293 cells of the Japanese eel Anguilla japonica LH (ajLHR) and the European eel Anguilla anguilla FSH (aaFSHR), respectively. Such cells also contain a firefly luciferase reporter gene driven by a cAMP-responsive element (CRE-Luc). We found that the obtained stable cells, with ajLHR, responded linearly to a more than 100,000-fold concentration range of hCG diluted in saline. The cells with aaFSHR showed a linear response to a 1000-fold concentration range of salmon pituitary extract mixed with saline. The biological functionality of the LH and FSH bioassays was validated using hCG, human FSH, and pituitary extracts from salmon, carp and eel. Since the toxins in eel plasma damaged the HEK293 cells, the protocol was adapted to selectively inactivate the toxins by heating at 37°C for 24h. This process successfully enabled the monitoring of hormone levels in blood plasma sampled from hCG-injected eels. In this paper, we describe the development of gonadotropin bioassays that will be useful for improving reproduction protocols in eel aquaculture.

  3. Maternal exposure to dioxin disrupts gonadotropin production in fetal rats and imprints defects in sexual behavior.

    PubMed

    Takeda, Tomoki; Matsumoto, Yuki; Koga, Takayuki; Mutoh, Junpei; Nishimura, Yoshio; Shimazoe, Takao; Ishii, Yuji; Ishida, Takumi; Yamada, Hideyuki

    2009-06-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related substances are a class of environmental pollutants with suspected toxic effects on reproductive and developmental processes. This study investigated a hypothesis that maternal exposure to TCDD damages gonadotropin-regulated steroidogenesis in fetal gonads to imprint defects in sexual behavior as well as the maturation of gonadal tissues. Oral administration of 1 microg/kg TCDD to pregnant Wistar rats at gestational day (GD) 15 attenuated the expression of luteinizing hormone (LH), a regulator of gonadal steroidogenesis, in the pituitaries of male and female fetuses at GD20. TCDD treatment also reduced the fetal expression of testicular and ovarian steroidogenic proteins, including steroidogenic acute-regulatory protein. These changes in pituitary and gonadal proteins were fetus-specific, and this seems not to be because of the greater delivery of TCDD to the brain of fetuses than adults. This is because a reduction in LH production was not reproduced even although TCDD was administered intraventricularly to adult rats. Direct supplementation of equine chorionic gonadotropin (eCG), an LH-mimicking hormone, to TCDD-exposed fetuses at GD17 restored the reduced expression of gonadal steroidogenic proteins. Maternal exposure to TCDD delayed the development of gonadal tissues in male and female pups and impaired their sexual behavior. However, eCG treatment at the fetal stage again restored not only tissue maturation but also many of the behavioral defects that occurred at adulthood. These results demonstrate that TCDD disrupts steroidogenesis in fetuses by targeting pituitary gonadotropin production and imprints demasculinization in males and defeminization in females in terms of their copulatory behavior.

  4. Molecular and expression characterization of three gonadotropin subunits common alpha, FSHbeta and LHbeta in groupers.

    PubMed

    Li, Chuang-Ju; Zhou, Li; Wang, Yang; Hong, Yun-Han; Gui, Jian-Fang

    2005-04-15

    A SMART cDNA plasmid library was constructed from protogyous greasy grouper (Epinephelus coioides) pituitary, and the full-length cDNAs of three gonadotropin (GTH) subunits common alpha, FSHbeta and LHbeta were cloned and sequenced from the library. The nucleotide sequences of common alpha, FSHbeta and LHbeta subunit cDNAs are 647, 594 and 574 bp in length, and encode for mature peptides of 94, 99 and 115 aa, respectively. High homology was observed by amino acid sequence alignment and identity comparison of the grouper mature peptides of common alpha, FSHbeta and LHbeta with that of other fishes. Phylogenetic tree analyses of the three GTH mature subunits revealed similar phylogeny relationships among the studied fish species. Three polyclonal antibodies were prepared from the in vitro expressed common alpha, FSHbeta and LHbeta mature proteins, respectively. Western blot analysis and immunofluoresence localization were performed on two typical stages of ovarian development stages in red-spotted grouper. Significant differences in protein expression levels of three gonadotropin subunits were revealed between the two ovarian development stages. In the individuals with resting ovary, common alpha was almost not detected in pituitaries, and FSHbeta and LHbeta expression levels were very low. While in the individuals with developing ovary, the expression of all three gonadotropin subunits reached to a high level. Immunofluoresence localization indicated that the grouper FSHbeta cells mainly distributed in the middle area of PPD, while the LHbeta cells distributed more widely, including in the area similar to the FSHbeta cells and at the external periphery of pituitary near to the PI side. The common alpha might be expressed in both FSHbeta and LHbeta cells. Double immunofluoresence localization further demonstrated FSHbeta and LHbeta expression in distinct cells in the PPD area, although the FSHbeta and LHbeta cells were detected in the identical area of PPD.

  5. Ovulation induction with pulsatile gonadotropin-releasing hormone (GnRH) or gonadotropins in a case of hypothalamic amenorrhea and diabetes insipidus.

    PubMed

    Georgopoulos, N A; Markou, K B; Pappas, A P; Protonatariou, A; Vagenakis, G A; Sykiotis, G P; Dimopoulos, P A; Tzingounis, V A

    2001-12-01

    Hypothalamic amenorrhea is a treatable cause of infertility. Our patient was presented with secondary amenorrhea and diabetes insipidus. Cortisol and prolactin responded normally to a combined insulin tolerance test (ITT) and thyrotropin-releasing hormone (TRH) challenge, while thyroid-stimulating hormone (TSH) response to TRH was diminished, and no response of growth hormone to ITT was detected. Both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels increased following gonadotropin-releasing hormone (GnRH) challenge. No response of LH to clomiphene citrate challenge was detected. Magnetic resonance imaging findings demonstrated a midline mass occupying the inferior hypothalamus, with posterior lobe not visible and thickened pituitary stalk. Ovulation induction was carried out first with combined human menopausal gonadotropins (hMG/LH/FSH) (150 IU/day) and afterwards with pulsatile GnRH (150 ng/kg/pulse). Ovulation was achieved with both pulsatile GnRH and combine gonadotropin therapy. Slightly better results were achieved with the pulsatile GnRH treatment.

  6. Strength-duration characteristics of estrogen effects on gonadotropin response to gonadotropin-releasing hormone in women. I. Effects of varying duration of estradiol administration.

    PubMed

    Keye, W R; Jaffe, R B

    1975-12-01

    This study was designed to investigate the effects of increased serum concentrations of estradiol of varying durations upon the gonadotropin responses to synthetic gonadotropin-releasing hormone (GnRH or LRF). Beginning at 8:00 PM on the first day of the menstrual cycle, subjects received im injections of estradiol benzoate (E2B), 5 mug/kg initially, followed by 2.5 mug/kg every 12 h for a total of 3, 5, 7, 9, or 11 injections. Twelve h after the last E2B injection, or 36, 60, 84, 108, or 132 h after the first injection of E2B (2 subjects at each time interval), each subject received 100 mug GnRH, iv. In addition, each subject received 100 mug GnRH iv during one of the seven days of the antecedent (control) menstrual cycle during which no exogenous estradiol was administered. When GnRH was infused 36 h after the initiation of E2B pretreatment, there was no significant LH or FSH increase. In contrast, LH and FSH responses were augmented and prolonged when compared with control cycles when GnRH was administered at 84, 108, or 132 h. At 60 h, responses of LH were augmented, although not to as great a degree. FSH responses were not augmented at 60 h. Expressed as maximal increase from baseline, gonadotropin responses following E2B were 1 1/2 to 9 times those achieved during control cycles (without E2B). Since mean serum estradiol concentrations at 36 h (185.9 +/- 20.0), when gonadotropin responses were absent, were similar to those at 60 (157.7 +/- 31.6), 84 (186.2 +/- 38.1), 108 (181.3 +/- 46.7), and 132 h (128.0 +/- 43.0 pg/ml), when responses were augmented, these results support the concept that the modulating effect of estradiol on pituitary response is dependent upon the duration of exposure of the hypothalamic-pituitary system to increased concentrations of estradiol. It is probable that the duration of the late follicular phase rise in serum estradiol is responsible, at least in part, for the augmented gonadotropin response seen at midcycle.

  7. TSH secreting pituitary adenoma.

    PubMed

    Jha, S; Kumar, S

    2009-07-01

    Thyrotropin (TSH) secreting pituitary adenomas are a very rare cause of hyperthyroidism. They typically present with signs and symptoms of hyperthyroidism and rarely can be asymptomatic. TSH secreting tumors account for 1 percent of all pituitary adenoma. They are a rare cause of thyrotoxicosis in which adenomas completely or partially lose feedback regulation of thyroid hormones and lead to sustained stimulation of thyroid gland. The most definitive treatment of thyrotropin (TSH)-secreting pituitary adenomas is transsphenoidal removal of tumor after restoring euthyroidism. We report a case of pituitary adenoma associated with elevated serum free thyroid hormones and non-suppressed TSH levels.

  8. Differential regulation of gonadotropins (FSH and LH) and growth hormone (GH) by neuroendocrine, endocrine, and paracrine factors in the zebrafish--an in vitro approach.

    PubMed

    Lin, Sze-Wah; Ge, Wei

    2009-01-15

    Recently, zebrafish has quickly risen as a model species for functional analysis of the brain-pituitary-gonad axis. However, one of the hurdles for such work in this popular model organism is the small size of its pituitary gland, which makes it difficult to investigate the regulation of pituitary hormone expression and secretion in vitro. To provide a solution to this problem and demonstrate the value of zebrafish in reproductive endocrinology, the present study was undertaken to establish a primary pituitary cell culture followed by investigating the regulation of FSHbeta (fshb), LHbeta (lhb), and GH (gh) expression by a variety of neuroendocrine, endocrine, and paracrine factors. All the factors examined influenced the expression of fshb, lhb, and ghin vitro except epidermal growth factor (EGF) despite the expression of its receptor egfr in the pituitary. Acting in a similar manner, gonadal steroids (estradiol and testosterone) stimulated both fshb and lhb, but had no effect on gh. In contrast, all other factors tested (gonadotropin-releasing hormone, GnRH; pituitary adenylate cyclase-activating polypeptide, PACAP; activin/follistatin, and insulin-like growth factor I, IGF-I) exhibited distinct effects on the expression of the three target genes studied, suggesting roles for these factors in the differential regulation of two gonadotropins and growth hormone and therefore the gonadotrophic and somatotrophic axes.

  9. Letrozole, Gonadotropin, or Clomiphene for Unexplained Infertility.

    PubMed

    Diamond, Michael P; Legro, Richard S; Coutifaris, Christos; Alvero, Ruben; Robinson, Randal D; Casson, Peter; Christman, Gregory M; Ager, Joel; Huang, Hao; Hansen, Karl R; Baker, Valerie; Usadi, Rebecca; Seungdamrong, Aimee; Bates, G Wright; Rosen, R Mitchell; Haisenleder, Daniel; Krawetz, Stephen A; Barnhart, Kurt; Trussell, J C; Ohl, Dana; Jin, Yufeng; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping

    2015-09-24

    The standard therapy for women with unexplained infertility is gonadotropin or clomiphene citrate. Ovarian stimulation with letrozole has been proposed to reduce multiple gestations while maintaining live birth rates. We enrolled couples with unexplained infertility in a multicenter, randomized trial. Ovulatory women 18 to 40 years of age with at least one patent fallopian tube were randomly assigned to ovarian stimulation (up to four cycles) with gonadotropin (301 women), clomiphene (300), or letrozole (299). The primary outcome was the rate of multiple gestations among women with clinical pregnancies. After treatment with gonadotropin, clomiphene, or letrozole, clinical pregnancies occurred in 35.5%, 28.3%, and 22.4% of cycles, and live birth in 32.2%, 23.3%, and 18.7%, respectively; pregnancy rates with letrozole were significantly lower than the rates with standard therapy (gonadotropin or clomiphene) (P=0.003) or gonadotropin alone (P<0.001) but not with clomiphene alone (P=0.10). Among ongoing pregnancies with fetal heart activity, the multiple gestation rate with letrozole (9 of 67 pregnancies, 13%) did not differ significantly from the rate with gonadotropin or clomiphene (42 of 192, 22%; P=0.15) or clomiphene alone (8 of 85, 9%; P=0.44) but was lower than the rate with gonadotropin alone (34 of 107, 32%; P=0.006). All multiple gestations in the clomiphene and letrozole groups were twins, whereas gonadotropin treatment resulted in 24 twin and 10 triplet gestations. There were no significant differences among groups in the frequencies of congenital anomalies or major fetal and neonatal complications. In women with unexplained infertility, ovarian stimulation with letrozole resulted in a significantly lower frequency of multiple gestation but also a lower frequency of live birth, as compared with gonadotropin but not as compared with clomiphene. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01044862.).

  10. Comparative aspects of GnRH-Stimulated signal transduction in the vertebrate pituitary - Contributions from teleost model systems.

    PubMed

    Chang, John P; Pemberton, Joshua G

    2017-06-03

    Gonadotropin-releasing hormone (GnRH) is a major regulator of reproduction through actions on pituitary gonadotropin release and synthesis. Although it is often thought that pituitary cells are exposed to only one GnRH, multiple GnRH forms are delivered to the pituitary of teleost fishes; interestingly this can include the cGnRH-II form usually thought to be non-hypophysiotropic. GnRHs can regulate other pituitary cell-types, both directly as well as indirectly, and multiple GnRH receptors (GnRHRs) may also be expressed in the pituitary, and even within a single pituitary cell-type. Literature on the differential actions of native GnRH isoforms in primary pituitary cells is largely derived from teleost fishes. This review will outline the diversity and complexity of GnRH-GnRHR signal transduction found within vertebrate gonadotropes as well as extra-gonadotropic sites with special emphasis on comparative studies from fish models. The implications that GnRHR transduction mechanisms are GnRH isoform-, function-, and cell-specific are also discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Plasma prolactin changes during the administration of human menopausal gonadotropins in nonovulatory women.

    PubMed

    Kemmann, E; GEMZELL, C A; Beinert, W C; Beling, C B; Jones, J R

    1977-09-15

    Plasma prolactin concentrations were determined in 16 nonovulatory women during treatment with human meonpausal gonadotropins (hMG). In eight patients with initially normal prolactin levels of less than 20 ng. per milliliter, a significant rise was noted at the end of hMG administration, this is thought to be a response to increased endogenous estrogen concentrations. A similar rise in plasma prolactin levels was seen in some but not all of the eight patients with initially elevated "basal" prolactin concentrations. Three of these hyperprolactinemic patients had radiographic evidence of a pituitary lesion--either a pituitary adenoma or a "microadenoma"--but the variance in prolactin response could not be explained on this basis. The two groups of normo- and hyper-prolactinemic patients showed no significant difference in the required dosage and duration or hMG treatment, plasma estradiol-17 beta response, and ovulatory and pregnancy outcome.

  12. Testicular enlargement in a patient with a FSH-secreting pituitary adenoma.

    PubMed

    Dahlqvist, Per; Koskinen, Lars-Owe D; Brännström, Thomas; Hägg, Erik

    2010-04-01

    Clinically non-functional pituitary adenomas are often derived from gonadotropin producing cells. However, gonadotropinomas causing elevated serum levels of follicle-stimulating hormone (FSH) and clinical signs of FSH hypersecretion are very rarely described. Our patient, a 56-year-old man, was referred to our clinic with signs of hypogonadism. Magnetic resonance imaging (MRI) and biochemical examinations showed a large pituitary adenoma and excessive levels of serum FSH. Clinical examination and ultrasound measurement revealed bilaterally enlarged testes. After pituitary surgery, serum FSH levels normalized and there was a decrease in testicular volume. This case suggests that supraphysiological levels of FSH from a gonadotropinoma can cause a clinically observable effect, i.e. testicular enlargement. This is in line with experimental studies showing biological effect of FSH from pituitary adenomas and previous occasional reports of ovarian hyperstimulation and testicular enlargement in patients with FSH-secreting gonadotropinomas.

  13. Effects of gonadoliberin analogue triptorelin on the pituitary-testicular complex in neonatal rats.

    PubMed

    Dygalo, N N; Shemenkova, T V; Kalinina, T S; Shishkina, G T

    2014-02-01

    Triptorelin, a synthetic analogue of neurohormone gonadoliberin (gonadotropin-releasing hormone, GnRH) administered daily to rats on postnatal days 5-7 suppressed the expression of GnRH receptor in the pituitary gland, but did not change functioning of the pituitary-testicular complex. Administration of triptorelin on postnatal days 12-14 (i.e. during the formation of pulsatile pattern of GnRH secretion and increasing levels of its mRNA receptor in the pituitary gland) had no effect on receptor expression, but increased the levels of luteinizing hormone mRNA in the pituitary gland and the weight of testes. At that time, blood levels of testosterone were lowered, which indicated disturbed pulsatile pattern of GnRH secretion.

  14. The control of reproductive physiology and behavior by gonadotropin-inhibitory hormone

    PubMed Central

    Ubuka, Takayoshi; McGuire, Nicolette L.; Calisi, Rebecca M.; Perfito, Nicole; Bentley, George E.

    2008-01-01

    Gonadotropin-releasing hormone (GnRH) controls the reproductive physiology and behavior of vertebrates by stimulating synthesis and release of gonadotropin from the pituitary gland. In 2000, another hypothalamic neuropeptide, gonadotropin-inhibitory hormone (GnIH), was discovered in quail and found to be an inhibiting factor for gonadotropin release. GnIH homologs are present in the brains of vertebrates, including birds, mammals, amphibians, and fish. These peptides, categorized as RF amide-related peptides (RFRPs), possess a characteristic LPXRF-amide (X = L or Q) motif at their C-termini. GnIH/RFRP precursor mRNA encodes a polypeptide that is possibly cleaved into three mature peptides in birds and two in mammals. The names of these peptides are GnIH, GnIH-related peptide-1 (GnIH-RP-1) and GnIH-RP-2 in birds, and RFRP-1 and RFRP-3 in mammals. GnIH/RFRP is synthesized in neurons of the paraventricular nucleus of the hypothalamus in birds and the dorsomedial hypothalamic area in mammals. GnIH neurons project to the median eminence, thus providing a functional neuroanatomical infrastructure to regulate anterior pituitary function. In quail, GnIH inhibits gonadal activity by decreasing synthesis and release of gonadotropin. The widespread distribution of GnIH/RFRP immunoreactive fibers in all animals tested suggests various actions within the brain. In accordance, GnIH/RFRP receptor mRNA is also expressed widely in the brain and the pituitary. GnIH/RFRP immunoreactive axon terminals are in probable contact with GnRH neurons in birds and mammals, and we recently demonstrated expression of GnIH receptor mRNA in GnRH-I and GnRH-II neurons in European starlings. Thus, GnIH/RFRP may also inhibit gonadotropin synthesis and release by inhibiting GnRH neurons in addition to having direct actions on the pituitary gland. Intracerebroventricular administration of GnIH/RFRP further inhibits reproductive behaviors in songbirds and rodents, possibly via direct actions on the Gn

  15. Pituitary Apoplexy Mimicking Meningitis

    PubMed Central

    Oh, Keun; Kim, Jang-Hee; Choi, Jin-Wook; Kang, Jae-Kyu

    2013-01-01

    Pituitary apoplexy is a rare but life-threatening disorder. Clinical presentation of this condition includes severe headaches, impaired consciousness, fever, visual disturbance, and variable ocular paresis. The clinical presentation of meningeal irritation is very rare. Nonetheless, if present and associated with fever, pituitary apoplexy may be misdiagnosed as a meningitis. We experienced a case of pituitary apoplexy masquerading as a meningitis. A 42-year-old man presented with meningitis associated symptoms and initial imaging studies did not show evidence of intra-lesional hemorrhage in the pituitary mass. However, a follow-up imaging after neurological deterioration revealed pituitary apoplexy. Hereby, we report our case with a review of literatures. PMID:24904903

  16. FOXO1 is regulated by insulin and IGF1 in pituitary gonadotropes.

    PubMed

    Skarra, Danalea V; Thackray, Varykina G

    2015-04-15

    The FOXO1 transcription factor is important for multiple aspects of reproductive function. We previously reported that FOXO1 functions as a repressor of gonadotropin hormone synthesis, but how FOXO1 is regulated in pituitary gonadotropes is unknown. The growth factors, insulin and insulin-like growth factor I (IGF1), function as key regulators of cell proliferation, metabolism and apoptosis in multiple cell types through the PI3K/AKT signaling pathway. In this study, we found that insulin and IGF1 signaling in gonadotropes induced FOXO1 phosphorylation through the PI3K/AKT pathway in immortalized and primary cells, resulting in FOXO1 relocation from the nucleus to the cytoplasm. Furthermore, insulin administration in vivo induced phosphorylation of FOXO1 and AKT in the pituitary. Thus, insulin and IGF1 act as negative regulators of FOXO1 activity and may serve to fine-tune gonadotropin expression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. FOXO1 is Regulated by Insulin and IGF1 in Pituitary Gonadotropes

    PubMed Central

    Skarra, Danalea V.; Thackray, Varykina G.

    2015-01-01

    The FOXO1 transcription factor is important for multiple aspects of reproductive function. We previously reported that FOXO1 functions as a repressor of gonadotropin hormone synthesis, but how FOXO1 is regulated in pituitary gonadotropes is unknown. The growth factors, insulin and insulin-like growth factor I (IGF1) function as key regulators of cell proliferation, metabolism and apoptosis in multiple cell types through the PI3K/AKT signaling pathway. In this study, we found that insulin and IGF1 signaling in gonadotropes induced FOXO1 phosphorylation through the PI3K/AKT pathway in immortalized and primary cells, resulting in FOXO1 relocation from the nucleus to the cytoplasm. Furthermore, insulin administration in vivo induced phosphorylation of FOXO1 and AKT in the pituitary. Thus, insulin and IGF1 act as negative regulators of FOXO1 activity and may serve to fine-tune gonadotropin expression. PMID:25676570

  18. Hypothalamic pituitary disorders expressed by galactorrhea. A dynamic evaluation.

    PubMed

    Perez-Lopez, F R

    1975-11-01

    Physiologic and pathologic production of milk involves complex relations between the mammary glands, hormones, and the central nervous system. In all the galactorrhea syndromes there is a functional or mechanical problem at the pituitary level, with abnormal secretion or reserve of prolactin secretion. Stimulatory agents of prolactin, like thyrotropin releasing hormone (TRH), chlorpromazine, amnio acids, and insulin, can be helpful in the study of the hypothalamic pituitary functional reserve, while the osmotic tests seem to provide a clear distinction between functional and tumoral causes. The inhibitory agents of prolactin secretion, L-dopa and CB 154, permit the study of the negative control of the hormone. In addition, CB 154 appears to be an effective treatment for functional galactorrhea. Hyperprolactinemia appears to exert an inhibitory influence on gonadotropins. Clomiphene, acting on the hypothalamus, and LHRH, acting on the gonadotropes, permit the assessment of the gonadotropic hypothalamic-hypophyseal axis.

  19. Provocative stimulation of the hypothalamic-pituitary-testicular axis in men with spinal cord injury.

    PubMed

    Bauman, W A; La Fountaine, M F; Cirnigliaro, C M; Kirshblum, S C; Spungen, A M

    2016-11-01

    Prospective study. To determine the integrity of the hypothalamic-pituitary-testicular axis in healthy men with spinal cord injury (SCI). Thirty healthy men with chronic SCI (37±10 years) and thirty-eight able-bodied (AB) controls (36±10 years) participated. Gonadotropin-releasing hormone (GnRH; 100 μg IV) was administered to determine gonadotropin release, and human chorionic gonadotropin (hCG; 4000 IU IM) was administered to determine testosterone (T) secretion. Responses to stimulation were categorized as 'responder' or 'non-responder' by clinical criteria. Single factor ANOVA with repeated measures was performed to identify group differences. The proportion of responders to pituitary GnRH stimulation was similar in the SCI group (22 subjects (73%) for the follicular-stimulating hormone (FSH) and 23 subjects (76%) for the luteinizing hormone (LH) to that of the AB group. The SCI-responder group had an increased FSH response after stimulation compared with the AB-responder group (P<0.05). The SCI-responder group had a greater LH area under the curve to GnRH stimulation than the AB-responder group (P=0.06). The peak FSH response was at 60 min and the peak LH response at 30 min, regardless of group designation. All groups had similar increases in serum T concentration to hCG stimulation. The pituitary response to stimulation in healthy men with SCI revealed an augmented FSH response; LH response only trended higher. The testicular response to provocative stimulation was similar in hypogonadal and eugondal subjects and in GnRH responders and non-responders. These findings suggest a lack of hypothalamic drive of pituitary gonadotropin release in healthy people with chronic SCI.

  20. Blood, pituitary, and brain renin-angiotensin systems and regulation of secretion of anterior pituitary gland.

    PubMed

    Ganong, W F

    1993-07-01

    In addition to increasing blood pressure, stimulating aldosterone and vasopressin secretion, and increasing water intake, angiotensin II affects the secretion of anterior pituitary hormones. Some of these effects are direct. There are angiotensin II receptors on lactotropes and corticotropes in rats, and there may be receptors on thyrotropes and other secretory cells. Circulating angiotensin II reaches these receptors, but angiotensin II is almost certainly generated locally by the pituitary renin-angiotensin system as well. There are also indirect effects produced by the effects of brain angiotensin II on the secretion of hypophyseotropic hormones. In the anterior pituitary of the rat, the gonadotropes contain renin, angiotensin II, and some angiotensin-converting enzyme. There is debate about whether these cells also contain small amounts of angiotensinogen, but most of the angiotensinogen is produced by a separate population of cells and appears to pass in a paracrine fashion to the gonadotropes. An analogous situation exists in the brain. Neurons contain angiotensin II and probably renin, but most angiotensin-converting enzyme is located elsewhere and angiotensinogen is primarily if not solely produced by astrocytes. Angiotensin II causes secretion of prolactin and adrenocorticotropic hormone (ACTH) when added to pituitary cells in vitro. Paracrine regulation of prolactin secretion by angiotensin II from the gonadotropes may occur in vitro under certain circumstances, but the effects of peripheral angiotensin II on ACTH secretion appear to be mediated via the brain and corticotropin-releasing hormone (CRH). In the brain, there is good evidence that locally generated angiotensin II causes release of norepinephrine that in turn stimulates gonadotropin-releasing hormone-secreting neurons, increasing circulating luteinizing hormone. In addition, there is evidence that angiotensin II acts in the arcuate nuclei to increase the secretion of dopamine into the portal

  1. Gonadotropin-releasing hormone: regulation of the GnRH gene.

    PubMed

    Lee, Vien H Y; Lee, Leo T O; Chow, Billy K C

    2008-11-01

    As the key regulator of reproduction, gonadotropin-releasing hormone (GnRH) is released by neurons in the hypothalamus, and transported via the hypothalamo-hypophyseal portal circulation to the anterior pituitary to trigger gonadotropin release for gonadal steroidogenesis and gametogenesis. To achieve appropriate reproductive function, mammals have precise regulatory mechanisms; one of these is the control of GnRH synthesis and release. In the past, the scarcity of GnRH neurons and their widespread distribution in the brain hindered the study of GnRH gene expression. Until recently, the development of GnRH-expressing cell lines with properties similar to those of in vivo GnRH neurons and also transgenic mice facilitated GnRH gene regulation research. This minireview provides a summary of the molecular mechanisms for the control of GnRH-I and GnRH-II gene expression. These include basal transcription regulation, which involves essential cis-acting elements in the GnRH-I and GnRH-II promoters and interacting transcription factors, and also feedback control by gonadotropins and gonadal sex steroids. Other physiological stimuli, e.g. insulin and melatonin, will also be discussed.

  2. Pituitary gland and pregnancy.

    PubMed

    Foyouzi, Nastaran; Frisbaek, Yr; Norwitz, Errol R

    2004-12-01

    The hypothalamic-pituitary-adrenal axis is central to mammalian reproductive function, including conception, pregnancy maintenance, parturition, and breastfeeding. Pregnancy is associated with substantial physiologic changes within this endocrine axis to meet the demands of pregnancy, which include support of the fetus (volume support, nutritional and oxygen supply, clearance of fetal waste), protection of the fetus (from starvation, drugs, toxins), preparation of the uterus for labor, and protection of the mother from potential cardiovascular injury at delivery. This article reviews the anatomy, embryology, and physiology of the pituitary. The effect of pregnancy on pituitary structure and function, in health and disease, also is discussed.

  3. Incidental pituitary macroadenomas.

    PubMed

    Chacko, A G; Chandy, M J

    1992-01-01

    Five cases of incidentally detected pituitary macroadenomas are described. All five had suprasellar extensions, but none had visual field defects as tested by computed perimetry. One patient had sellar changes seen on an X-ray film taken following a head injury, while the others were detected by computed tomography performed for seizures, stroke and meningitis. Four patients underwent trans-sphenoidal surgery for suprasellar extensions with or without hypopituitarism, while one was managed conservatively as he had normal visual fields and pituitary function and there was a spontaneous decrease in size of the adenoma. The management of such incidental pituitary macroadenomas is discussed.

  4. Pituitary Colloid Cyst

    PubMed Central

    Guduk, Mustafa; Sun, Halil Ibrahim; Sav, Murat Aydin; Berkman, Zafer

    2017-01-01

    Abstract Colloid cysts appear most commonly in the third ventricle, their occurrence in the sellar region is uncommon. The authors report a female patient with a pituitary colloid cyst. She was diagnosed incidentally with a sellar lesion by a routine paranasal computed tomography examination performed for planning of a dental implant surgery. Radiologic examinations revealed a pituitary lesion that was removed by transnasal transsphenoidal route. Her pathologic examination revealed that the lesion was a colloid cyst. Although rare, colloid cysts should be considered in the differential diagnosis of pituitary lesions PMID:27792102

  5. Evaluation of pituitary function after infectious meningitis in childhood.

    PubMed

    Giavoli, Claudia; Tagliabue, Claudia; Profka, Eriselda; Senatore, Laura; Bergamaschi, Silvia; Rodari, Giulia; Spada, Anna; Beck-Peccoz, Paolo; Esposito, Susanna

    2014-10-06

    A number of studies of adults have shown that pituitary deficiencies can develop in a considerable proportion of subjects during the acute phase of meningitis or years after the infection has disappeared. The results of the very few studies of the impact of pediatric meningitis on hypothalamic-pituitary function are conflicting. In order to determine the incidence of pituitary dysfunction in children with central nervous system infection, we evaluated pituitary function and anthropometric parameters in 19 children with meningitis of different etiologies (15 males; mean age ± standard deviation [SD] at pituitary evaluation, 5.9 ± 4.0 years; mean time from the acute event ± SD, 18 ± 10 months). All of the subjects had a normal stature and growth velocity for their age and gender, and none of them was obese. On the basis of Tanner's reference charts, 17 subjects (13 boys and all four girls) were pre-pubertal; two boys were in Tanner stage 2. None of the subjects had central hypothyroidism. All of the patients had normal serum of insulin growth factor (IGF)-I and prolactin. Their sex steroid and gonadotropin levels were concordant with their age and pubertal status. Early morning urine osmolality and serum electrolyte levels showed no signs of diabetes insipidus. All of the patients had normal plasma adrenocorticotropic hormone (ACTH) levels. Peak cortisol responses to the standard dose Synacthen test (SDST) were normal in all cases. The results showed that hypopituitarism following infectious meningitis appears to be infrequent in childhood and children's pituitary glands seem to be less vulnerable to damage than those of adults.

  6. High prevalence rate of pituitary incidentaloma: is it associated with the age-related decline of the sex hormones levels?

    PubMed

    Kastelan, Darko; Korsic, Mirko

    2007-01-01

    Incidental pituitary adenoma is the common finding during brain imaging. According to multistep model of pituitary tumourigenesis genetic alterations provide the initiating event that transforms cells while hormones play a role in promoting cell proliferation. Development of pituitary adenoma in a case of excessive hypophysiotrophic hormones production or reduced feedback suppression by target gland hormones emphasizes the importance of hormonal stimulation in pituitary tumourigenesis. Pituitary hyperplasia has been reported in pregnancy, hypothyroidism and conditions such as CRH or GHRH hypersecretion. Moreover, recent study reported one case of gonadotroph macroadenoma and two cases of gonadotroph cells hyperplasia in patients with Klinefelter syndrome probably due to protracted stimulation of gonadotroph cells because of lack of androgen feedback. Significant changes of the hypothalamic-pituitary-gonadal axis occurred with aging. In females, after menopause, estradiol level decreases by 35-fold and estrone level by 20-fold that results in increased gonadotropins levels. Similarly, FSH, but not LH, level is increased with advancing age in men, too, although the age-related difference in the level is less in comparison with women. Regarding these data, we hypothesised that high prevalence rate of pituitary incidentaloma in the elderly is associated with age-related decline in sex hormones levels and subsequent lack of feedback suppression leading to permanent gonadotrophs stimulation which is the crucial step in the pituitary tumour development. According to previously mentioned multistep model of pituitary tumourigenesis, incidentaloma will develop only in persons with already present intrinsic pituitary cell defects. However, further studies have to answer the questions of whether the incidence of pituitary tumours is more frequent in elderly, whether women with late onset menopause or those taking long-term hormone replacement therapy have lower rate of

  7. Determination of human chorionic gonadotropin.

    PubMed

    Stenman, Ulf-Håkan; Alfthan, Henrik

    2013-12-01

    Determination of human chorionic gonadotropin (hCG) is used for diagnosis and monitoring of pregnancy, pregnancy related disorders, for trophoblastic and some nontrophoblastic tumors. In addition, hCG is determined for doping control in males. Assay of hCG is complicated by the occurrence of different molecular forms, which are detected to various degrees by different assays. The main form of hCG in circulation and in patients with trophoblastic tumors is intact heterodimeric hCG. The free β subunit (hCGβ) is a minor form in plasma in both conditions, but it may be the major form aggressive trophoblastic cancer. Therefore, assays measuring hCG and hCGβ together are mainly used for diagnosis of pregnancy and trophoblastic diseases. When excreted into urine, most of hCG (and hCGβ) is broken down to the core fragment of hCGβ (hCGβcf), which is the main immunoreactive form of hCG in urine during pregnancy. Specific determination of hCGβ is of value in screening for Down's syndrome and diagnosis of nontrophoblastic cancer. hCGbcf is of limited utility but it is important because it may disturb assay of hCG in pregnancy.

  8. Stages of Pituitary Tumors

    MedlinePlus

    ... type 1 (MEN1) syndrome . Carney complex . Isolated familial acromegaly . Signs of a pituitary tumor include problems with ... cause: Headache. Some loss of vision. In adults, acromegaly (growth of the bones in the face, hands, ...

  9. Social regulation of the brain-pituitary-gonadal axis.

    PubMed Central

    Francis, R C; Soma, K; Fernald, R D

    1993-01-01

    Reproduction in vertebrates is regulated by the hypothalamic-pituitary-gonadal axis via neural and hormonal feedback. This axis is also subject to exogenous influences, particularly social signals. In the African cichlid fish Haplochromis burtoni, gonadal development in males is socially regulated. A small fraction of the males, which are brightly colored, maintain territories and aggressively dominate inconspicuously colored nonterritorial males. Here we show through manipulation of the social and endocrine environment that changes in social status and gonadal state are accompanied by soma size changes in a population of gonadotropin-releasing hormone-containing neurons in the ventral forebrain. In territorial males, these cells are significantly larger than in nonterritorial males. When an animal switches from being territorial to nonterritorial through a change in social situation, these cells shrink; in animals that change from nonterritorial to territorial status, the cells enlarge. These gonadotropin-releasing hormone-containing cells project to the pituitary and are ultimately responsible for regulating gonadal growth. This mechanism of socially induced cell size change provides the potential for relatively quick adaptive changes in the neuron-endocrine system without nerve cell addition or death. Since the structure of this regulatory axis is conserved among all vertebrates, other species with socially modulated reproductive physiology may exhibit a similar form of physiological regulation. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8356086

  10. Prenatal Exposure to Low Doses of Bisphenol A Increases Pituitary Proliferation and Gonadotroph Number in Female Mice Offspring at Birth1

    PubMed Central

    Brannick, Katherine E.; Craig, Zelieann R.; Himes, Ashley D.; Peretz, Jackye R.; Wang, Wei; Flaws, Jodi A.; Raetzman, Lori T.

    2012-01-01

    ABSTRACT The pituitary gland is composed of hormone-producing cells essential for homeostasis and reproduction. Pituitary cells are sensitive to endocrine feedback in the adult and can have altered hormonal secretion from exposure to the endocrine disruptor bisphenol A (BPA). BPA is a prevalent plasticizer used in food and beverage containers, leading to widespread human exposure. Although prenatal exposure to BPA can impact reproductive function in the adult, the effects of BPA on the developing pituitary are unknown. We hypothesized that prenatal exposure to low doses of BPA impacts gonadotroph cell number or parameters of hormone synthesis. To test this, pregnant mice were administered 0.5 μg/kg/day of BPA, 50 μg/kg/day of BPA, or vehicle beginning on Embryonic Day 10.5. At parturition, pituitaries from female offspring exposed in utero to either dose of BPA had increased proliferation, as assessed by mKi67 mRNA levels and immunohistochemistry. Coincidently, gonadotroph number also increased in treated females. However, we observed a dichotomy between mRNA levels of Lhb and Fshb. Female mice exposed to 0.5 μg/kg/day BPA had increased mRNA levels of gonadotropins and the gonadotropin-receptor hormone (GNRH) receptor (Gnrhr), which mediates GNRH regulation of gonadotropin production and release. In contrast, mice treated with 50 μg/kg/day of BPA had decreased gonadotropin mRNA levels, Gnrhr and Nr5a1, a transcription factor required for gonadotroph differentiation. No other pituitary hormones were altered on the day of birth in response to in utero BPA exposure, and male pituitaries showed no change in the parameters tested. Collectively, these results show that prenatal exposure to BPA affects pituitary gonadotroph development in females. PMID:22875908

  11. Separation of gonadotropic fractions with different species specificities from tuna pituitaries

    SciTech Connect

    Ando, H.; Ishii, S.

    1988-05-01

    Eight different gonadotropic glycoprotein fractions were separated from the acetone-dried powder of yellow fin tuna pituitary glands by successive chromatographies on Superose 12 for gel filtration and Mono Q for anion exchange using the Pharmacia fast protein liquid chromatography system. This was preceded by preliminary separations using an ammonium sulfate precipitation method and affinity chromatography on concanavalin A-Sepharose. For biological characterization, we employed two radioreceptor assay systems, one using goby testis plasma membranes and silver carp GTH as the receptor and radioligand, respectively, and the other using testis plasma membranes of the yellow fin tuna and gonadotropin of the same species, respectively. We also employed two testicular cyclic AMP accumulation bioassay methods in vitro, one with the goby testis and the other with the mackerel testis. The least acidic fraction after Mono Q was further separated into four subfractions by rechromatography with Mono Q. They were strongly active in the tuna and mackerel assays but almost inactive in the goby assays. They were referred to as tuna-type tuna gonadotropin. In contrast, the most acidic fraction obtained after the first Mono Q was active in the goby assays but almost inactive in the tuna and mackerel assays. It was referred to as goby-type tuna gonadotropin. The intermediate fractions were active on both assays and are considered to be mixtures of tuna-type and goby-type gonadotropins. The reason for the presence of gonadotropin inactive to homologous species is discussed from the evolutionary viewpoint.

  12. Chorionic gonadotropin and its receptor are both expressed in human retina, possible implications in normal and pathological conditions.

    PubMed

    Dukic-Stefanovic, Sladjana; Walther, Jan; Wosch, Sebastian; Zimmermann, Gerolf; Wiedemann, Peter; Alexander, Henry; Claudepierre, Thomas

    2012-01-01

    Extra-gonadal role of gonadotropins has been re-evaluated over the last 20 years. In addition to pituitary secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH), the CNS has been clearly identified as a source of hCG acting locally to influence behaviour. Here we demonstrated that human retina is producing this gonadotropin that acts as a neuroactive molecule. Müller glial and retinal pigmented epithelial (RPE) cells are producing hCG that may affects neighbour cells expressing its receptor, namely cone photoreceptors. It was previously described that amacrine and retinal ganglion (RGC) cells are targets of the gonadotropin releasing hormone that control the secretion of all gonadotropins. Therefore our findings suggest that a complex neuroendocrine circuit exists in the retina, involving hCG secreting cells (glial and RPE), hCG targets (photoreceptors) and hCG-release controlling cells (amacrine and RGC). The exact physiological functions of this circuit have still to be identified, but the proliferation of photoreceptor-derived tumor induced by hCG demonstrated the need to control this neuroendocrine loop.

  13. Giant necrotic pituitary apoplexy.

    PubMed

    Fanous, Andrew A; Quigley, Edward P; Chin, Steven S; Couldwell, William T

    2013-10-01

    Apoplexy of the pituitary gland is a rare complication of pituitary adenomas, involving hemorrhage with or without necrosis within the tumor. This condition may be either asymptomatic or may present with severe headache, visual impairment, ophthalmoplegia, and pituitary failure. Transsphenoidal surgery is the treatment of choice, and early intervention is usually required to ensure reversal of visual impairment. Reports of pituitary apoplectic lesions exceeding 60.0mm in diameter are very rare. A 39-year-old man with long-standing history of nasal congestion, decreased libido and infertility presented with a sudden onset of severe headache and diplopia. MRI of the head demonstrated a massive skull base lesion of 70.0 × 60.0 × 25.0mm, compatible with a giant pituitary macroadenoma. The lesion failed to enhance after administration of a contrast agent, suggesting complete necrotic apoplexy. Urgent surgical decompression was performed, and the lesion was resected via a transnasal transsphenoidal approach. Pathological analysis revealed evidence of necrotic pituitary apoplexy. At the 2 month follow-up, the patient had near-complete to complete resolution of his visual impairment. To the authors' knowledge, this report is unique as the patient demonstrated complete necrotic apoplexy and it underlines the diagnostic dilemma in such a case. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Extragonadal actions of chorionic gonadotropin

    PubMed Central

    Banerjee, Prajna

    2011-01-01

    The primary embryonic signal in primates is chorionic gonadotropin (CG, designated hCG in humans), that is classically associated with corpus luteum rescue and progesterone production. However, research over the past decade has revealed the presence of the hCG receptor in a variety of extragonadal tissues. Additionally, discoveries of the multiple variants of hCG, namely, native hCG, hyperglycosylated hCG (hyp-hCG) and the β-subunit of the hyperglycosylated hCG (hCG-free β) has established a role for extragonadal actions of hCG. For the initiation and maintenance of pregnancy, hCG mediates multiple placental, uterine and fetal functions. Some of these include development of syncytiotrophoblast cells, mitotic growth and differentiation of the endometrium, localized suppression of the maternal immune system, modulation of uterine morphology and gene expression and coordination of intricate signal transduction between the endometrium. Recurrent pregnancy loss, preeclampsia and endometriosis are associated with altered responses of hCG, all of which have a detrimental effect on pregnancy. A role for hyp-hCG in mediating the development of both trophoblastic and non-trophoblastic tumors has also been suggested. Other significant non-gonadal applications of hCG include predicting preeclampsia, determining the risk of Down’s syndrome and gestational trophoblastic disease, along with relaxing myometrial contractility and preventing recurrent miscarriages. Presence of hCG free-β in serum of cancer patients enables its usage as a diagnostic tumor marker. Thus, the extragonadal functions of hCG encompasses a wide spectrum of applications and is an open area for continued investigation. PMID:21845366

  15. Pituitary Apoplexy Following Mitral Valvuloplasty

    PubMed Central

    Kim, Young Ha; Son, Dong Wuk; Cha, Seung Heon

    2015-01-01

    Pituitary apoplexy is a rare but potentially life-threatening clinical syndrome caused by the sudden enlargement of a pituitary adenoma secondary to hemorrhage or infarction. Pituitary apoplexy after cardiac surgery is a very rare perioperative complication. Factors associated with open heart surgery that may lead to pituitary apoplexy include hemodynamic instability during cardiopulmonary bypass and systemic heparinization. We report a case of pituitary apoplexy after mitral valvuloplasty with cardiopulmonary bypass. After early pituitary tumor resection and hormonal replacement therapy, the patient made a full recovery. PMID:25932297

  16. Development of a homologous radioimmunoassay for red seabream follicle stimulating hormone and regulation of gonadotropins by GnRH in red seabream, Pagrus major.

    PubMed

    Okuzawa, Koichi; Kazeto, Yukinori; Uji, Susumu; Yamaguchi, Toshiya; Tanaka, Hideki; Nyuji, Mitsuo; Gen, Koichiro

    2016-12-01

    Using a recombinant chimeric single-chain follicle stimulating hormone (FSH), we established a radioimmunoassay (RIA) for red seabream (Pagrus major) FSH (pmFSH) which became a powerful tool for studying reproductive physiology. We studied the profiles in plasma and pituitary concentrations of FSH and luteinizing hormone (LH) during sexual maturation. A pre-established RIA for red seabream LH was used for the LH measurements. The regulation of FSH and LH secretion from the pituitary was investigated using a gonadotropin-releasing hormone analog (GnRHa) in vivo and in vitro. Marked differences in plasma and pituitary FSH levels were observed between males and females; pituitary FSH content in males was much higher than that in females during all seasons, and plasma FSH levels in males were high during the spawning season, whereas those in females were unchanged. In contrast, plasma and pituitary levels of LH were elevated before and during the spawning season in males and females. Injecting or implanting (cholesterol pellet) a GnRHa into adult and juvenile red seabream resulted in significant increases in plasma LH concentrations; however, no significant change was observed in plasma FSH. Moreover, GnRHa stimulated only LH secretion in an in vitro experiment using dispersed pituitary cells. The discrete FSH and LH secretion profiles revealed suggest differential roles for the two gonadotropins during red seabream gametogenesis. In addition, the marked difference in pituitary FSH levels in males and females suggests the relative significance of FSH in male reproduction. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Inhibition of follicular development induced by chronic unpredictable stress is associated with growth and differentiation factor 9 and gonadotropin in mice.

    PubMed

    Wu, Li-Min; Liu, Yu-Sheng; Tong, Xian-Hong; Shen, Ni; Jin, Ren-Tao; Han, Hui; Hu, Mei-Hong; Wang, Wei; Zhou, Gui-Xiang

    2012-04-01

    Chronic psychosocial stress negatively affects ovarian function. Ovarian follicular development is regulated by both pituitary-derived gonadotropins and intraovarian regulatory factors. To date, the suppressive effects of chronic stress on the ovary have been observed to be manifested mainly as an inhibition of gonadotropin release. It is not clear whether there are any other intraovarian regulatory mechanisms involved in this process. Growth and differentiation factor 9 (GDF9) is an important, oocyte-specific paracrine regulator required for follicular development. In this study, the chronic unpredictable mild stress model was used to produce psychosocial stress in mice. The number of different developmental stages of follicles was counted on ovarian sections stained with hematoxylin and eosin. Real-time PCR and Western blotting were used to detect the mRNA and protein levels, respectively, of GDF9. The results show that chronic unpredictable stress inhibits follicular development, increases follicular atresia, and suppresses GDF9 expression. Exogenous gonadotropin treatment partly restores the repressed antral follicular development, but has no effect on the repressed secondary follicular development associated with chronic stress. Treatment with recombinant GDF9 restores secondary follicular development. Cotreatments with GDF9 and gonadotropins restore both secondary and antral follicular development in stressed mice. These findings demonstrate that inhibition of follicular development induced by chronic unpredictable stress is associated with GDF9 and gonadotropin.

  18. Pituitary apoplexy: a rare complication of leuprolide therapy in prostate cancer treatment.

    PubMed

    Tanios, Georges; Mungo, Nicolas Andrews; Kapila, Aaysha; Bajaj, Kailash

    2017-07-14

    Gonadotropin-releasing hormone agonists, used widely in the treatment of metastatic prostate cancer and hormone receptor-positive breast cancer, are associated with a rare but potentially fatal outcome of pituitary apoplexy (PA). An 85-year-old man presented with sudden onset of headache, left eye pain, sensitivity to light, nausea and vomiting. The symptoms started 4 hours after initiation of leuprolide therapy for treatment of recently diagnosed metastatic prostate carcinoma. Radiological imaging of the brain demonstrated a heterogeneously enlarged pituitary gland measuring 19×16×13 mm and T1-hyperintense signal compatible with pituitary haemorrhage. Hormone function tests were indicative of panhypopituitarism, confirming the diagnosis of PA. Due to age, the patient was started on hormonal replacement therapy and eventually symptoms improved. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. Activation of GABA B receptors in the anterior pituitary inhibits prolactin and luteinizing hormone secretion.

    PubMed

    Lux-Lantos, V; Rey, E; Libertun, C

    1992-11-01

    Previous work from our laboratory showed that baclofen could lower serum prolactin (PRL) levels acting at the central nervous system. The present experiments were designed to evaluate whether the gamma-aminobutyric acid B agonist was also effective in inhibiting hormone release at the pituitary level. In monolayer cultures of adenohypophyseal dispersed cells, baclofen inhibited basal PRL secretion after 1 or 2 h of incubation. This inhibition was significantly abolished by three antagonists: phaclofen, 3-aminopropyl-phosphonic acid and 4-aminobutylphosphonic acid. Furthermore, baclofen inhibited the thyrotropin-releasing hormone-induced PRL release in a concentration-dependent manner. With regard to gonadotropin secretion, baclofen was unable to modify basal luteinizing hormone (LH) secretion, but significantly inhibited the LH-releasing hormone-induced LH release. These results show that baclofen, in addition to its central neuroendocrine effects, inhibits pituitary hormone secretion, under basal and/or stimulated conditions, by direct action at the pituitary level.

  20. Effects of shortened photoperiod on gonadotropin-releasing hormone, gonadotropin, and vitellogenin gene expression associated with ovarian maturation in rainbow trout.

    PubMed

    Choi, Sungchang; Lee, Cheul Ho; Park, Woodong; Kim, Dae-Jung; Sohn, Young Chang

    2010-01-01

    Reproductive activities of salmonids are synchronized by changes in photoperiod, which control the endocrine system via the brain-pituitary-gonadal axis. Gonadotropin-releasing hormone (GnRH) in the brain regulates synthesis and release of the pituitary gonadotropins (GTHs; FSH and LH). FSH and LH in turn stimulate the production of sex steroids for oocyte growth and maturation-Inducing steroid hormones for oocyte maturation and ovulation, respectively, in female salmonids. To clarify effects of long-term photoperiod manipulations on the reproductive activity of salmonids from early recrudescence to ovulation, we Investigated the gene expression profiles of GnRH, GTHs, and vitellogenin (VTG), and plasma sex steroids in female rainbow trout (Oncorhynchus mykiss). In addition, the percentages of eyed embryos and hatched alevins were examined together with the number of ovulated eggs to evaluate the effects of photoperiod regimes on egg quality. During late summer, the mRNA levels of GnRHs, GTHalpha, and LHbeta, and the plasma level of a maturational steroid (17alpha,20beta-dihydroxy-4-pregnen-3-one; 17,20beta-P) were significantly elevated by a gradually shortened photoperiod under constant temperature, in accordance with accelerated sexual maturation. The percentages of eyed embryos and hatched alevins from fish ovulated in August were comparable to those of control fish observed in December. These results clearly indicate that syntheses of GnRHs, LH, VTG, and 17,20beta-P are effectively accelerated by a programmed long-short photoperiod regime in early recrudescent female rainbow trout, without a marked deterioration in egg quality.

  1. Gonadotropin-releasing hormone mRNA and gonadotropin beta-subunit mRNA expression in the adult female rat exposed to ethanol in utero.

    PubMed

    Wilson, M E; Marshall, M T; Bollnow, M R; McGivern, R F; Handa, R J

    1995-10-01

    Previous studies have demonstrated that exposure of female rats to ethanol in utero results in long-term deficits in reproductive function, including a delayed onset of puberty and an early onset of acyclicity. In the present studies, we determined if changes in reproduction are correlated with changes in gonadotropin-releasing hormone (GnRH) mRNA expression in the brain or gonadotropin subunit mRNA expression in the anterior pituitary gland. We used in situ hybridization histochemical techniques to examine the density of GnRH mRNA and the distribution of GnRH mRNA-containing cells in the basal forebrain, and reverse transcription-polymerase chain reaction (RT-PCR) to quantitate the beta-subunit mRNA of luteinizing hormone (LH beta) and follicle-stimulating hormone (FSH beta) in the anterior pituitary gland of adult (3 months of age) fetal alcohol-exposed (FAE) female rats. For GnRH mRNA measurements, animals were gonadectomized 4 days before use. Three groups of animals were examined. FAE females were derived from pregnant dams fed a liquid diet containing 35% ethanol-derived calories from gestational day 14 until parturition. Dams of control animals were either pair-fed (PF) an isocaloric diet with sucrose substituted for ethanol or maintained on normal laboratory rat chow [chow-fed (CF)]. Serial blood samples taken by indwelling right atrial cannulae demonstrated significantly smaller pulses of LH (p < 0.05) and FSH (p < 0.05) in ovariectomized FAE females at 3 months of age, compared with PF and CF controls. Distribution of GnRH mRNA-containing cells was mapped throughout the forebrain, and the number of autoradiographic silver grains/cell was determined.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Pulsatile GnRH Therapy May Restore Hypothalamus-Pituitary-Testis Axis Function in Patients With Congenital Combined Pituitary Hormone Deficiency: A Prospective, Self-Controlled Trial.

    PubMed

    Zheng, Junjie; Mao, Jiangfeng; Xu, Hongli; Wang, Xi; Huang, Bingkun; Liu, Zhaoxiang; Cui, Mingxuan; Xiong, Shuyu; Ma, Wanlu; Min, Le; Kaiser, Ursula B; Nie, Min; Wu, Xueyan

    2017-07-01

    The effectiveness of pulsatile gonadotropin-releasing hormone (GnRH) therapy in patients with congenital combined pituitary hormone deficiency (CCPHD) has not been investigated because of the limited number of patients, as well as these patients' presumed pituitary hypoplasia, poor gonadotrophic cell reserve, and impaired gonadotrophic response to GnRH. To assess the pituitary response to pulsatile GnRH therapy in men with CCPHD. Prospective, self-controlled, 3-month clinical trial. University endocrine clinic. Men with hypogonadotropic hypogonadism caused by CCPHD. Pulsatile GnRH was administered subcutaneously for 3 months. Primary endpoints were total serum testosterone, testicular volume, and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Secondary endpoints included occurrence of spermatogenesis. A total of 40 men with CCPHD completed the study. Of these, 60% (24 of 40) showed a good response to pulsatile GnRH treatment (response group). At 3 months, their LH and FSH levels increased to within the normal range and their testosterone levels increased to 8.67 ± 4.83 nmol/L. Of the patients in the response group, 33.3% (8 of 24) of them achieved spermatogenesis. The remaining 40% (16 of 40) of patients had a poor response to pulsatile GnRH treatment. Magnetic resonance imaging (MRI) did not reveal any correlation between pituitary response and pituitary height and/or integrity of the pituitary stalk. This study suggests that gonadotrophs in patients with CCPHD can exist and be functional-even with MRI evidence of pituitary hypoplasia or dysplasia. Pulsatile GnRH therapy restored pituitary-testis axis function in 60% of patients with CCPHD. These results may directly guide the clinical therapeutic choice.

  3. Molecular Characterization of Three Gonadotropin Subunits and Their Expression Patterns during Ovarian Maturation in Cynoglossus semilaevis

    PubMed Central

    Shi, Bao; Liu, Xuezhou; Xu, Yongjiang; Wang, Shanshan

    2015-01-01

    The endocrine regulation of reproduction in a multiple spawning flatfish with an ovary of asynchronous development remains largely unknown. The objectives of this study were to monitor changes in mRNA expression patterns of three gonadotropin hormone (GTH) subunits (FSHβ, LHβ and CGα) and plasma GTH levels during ovarian maturation of half-smooth tongue sole Cynoglossus semilaevis. Cloning and sequence analysis revealed that the cDNAs of FSHβ, LHβ and CGα were 541, 670 and 685 bp in length, and encode for peptides of 130, 158 and 127 amino acids, respectively. The number of cysteine residues and potential N-linked glycosylation sites of the flatfish GTHs were conserved among teleosts. However, the primary structure of GTHs in Pleuronectiformes appeared to be highly divergent. The FSHβ transcriptional level in the pituitary remained high during the vitellogenic stage while plasma levels of FSH peaked and oocyte development was stimulated. The LHβ expression in the pituitary and ovary reached the maximum level during oocyte maturation stages when the plasma levels of LH peaked. The brain GTHs were expressed at the different ovarian stages. These results suggested that FSH and LH may simultaneously regulate ovarian development and maturation through the brain-pituitary-ovary axis endocrine system in tongue sole. PMID:25633101

  4. [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.

  5. Glycoprotein hormone in the pituitary of hagfish and its evolutionary implications.

    PubMed

    Uchida, Katsuhisa; Moriyama, Shunsuke; Sower, Stacia A; Nozaki, Masumi

    2013-02-01

    The pituitary gland is present in all vertebrates, from agnathans (jawless vertebrates) to mammals, but not in invertebrates. Reproduction in gnathostomes (jawed vertebrates) is controlled by two pituitary gonadotropins (GTHs), luteinizing hormone and follicle-stimulating hormone, which are part of the pituitary glycoprotein hormone (GPH) family. Hagfishes, which lack both jaws and vertebrae, are considered the most primitive vertebrate known, living or extinct. Accordingly, they are of particular importance in understanding the evolution of the pituitary GPHs and their functions related to vertebrate reproduction. Nevertheless, key elements of the reproductive endocrine system in hagfish have yet to be elucidated. Our current report has revealed the first identification of a functional GPH composed of two subunits that possess gonadotropic action at the pituitary of brown hagfish. It seems most likely that an ancestral GPH gave rise to only one GTH in hagfish pituitary and that multiplicity of GPHs arose later during the early evolution of gnathostomes. This paper briefly summarizes the latest findings on the hagfish GPH from an evolutionary point of view.

  6. Androgen responsiveness of the pituitary gonadotrope cell line LbetaT2.

    PubMed

    Lawson, M A; Li, D; Glidewell-Kenney, C A; López, F J

    2001-09-01

    Androgens have a profound effect on the hypothalamic-pituitary axis by reducing the synthesis and release of the pituitary gonadotropin LH. The effect on LH is partly a consequence of a direct, steroid-dependent action on pituitary function. Although androgen action has been well studied in vivo, in vitro cell models of androgen action on pituitary gonadotropes have been scarce. Recently, an LH-expressing cell line, LbetaT2, was generated by tumorigenesis targeted to the LH-producing cells of the mouse pituitary. The purpose of these studies was to determine the presence of androgen receptor (AR) and establish its function in this cell line. RT-PCR analysis indicated that the LbetaT2 cell line expresses AR mRNA. Transient transfection assays, using the mouse mammary tumor virus (MMTV) promoter, showed that a functional AR is also present. Testosterone (TEST), dihydrotestosterone (DHT), 7alpha-methyl-19-nortestosterone (MENT), and fluoxymesterone (FLUOXY) increased reporter gene activity in the rank order of potencies MENT>DHT> TEST>FLUOXY. Additionally, activation of MMTV promoter activity by DHT in LbetaT2 cells was diminished by the AR antagonists casodex and 2-hydroxy-flutamide, indicating that the effects of DHT are mediated through AR. In summary, these studies showed that the LbetaT2 cell line is a useful model for the evaluation and molecular characterization of androgen action in pituitary gonadotropes.

  7. The Characteristics of Incidental Pituitary Microadenomas in 120 Korean Forensic Autopsy Cases

    PubMed Central

    Kim, Jang-Hee; Seo, Jung-Seok; Lee, Bong-Woo; Lee, Sang-Young; Jeon, Seok-Hoon

    2007-01-01

    To investigate the characteristics of incidental pituitary microadenomas, we examined 120 pituitary glands from Korean forensic autopsy cases, from which eight tumors were identified (incidence 6.7%). The average age of the affected subjects was 50 yr (range: 33-96 yr) with a female predominance. The maximum diameters of the tumors ranged from 0.4 to 5.4 mm (mean: 2.8 mm). Immunohistochemical analysis of pituitary hormones revealed three growth hormone-secreting adenomas, one prolactin-producing adenoma, one gonadotropin-producing adenoma, one plurihormonal adenoma, and two null cell adenomas. MIB-1 staining for Ki-67 antigen showed no positive expression. The microvessel density (MVD) of the pituitary microadenomas ranged from 2.3 to 11.6% (mean: 5.3%) and was significantly lower than that of nonneoplastic pituitary glands (11.9-20.1%, mean: 14.8%). Our study provides reference data on incidental pituitary microadenomas in the Korean population. PMID:17923757

  8. Experimental and computational study of inter- and intra- species specificity of gonadotropins for various gonadotropin receptors.

    PubMed

    Aizen, Joseph; Kowalsman, Noga; Kobayashi, Makito; Hollander, Lian; Sohn, Young Chang; Yoshizaki, Goro; Niv, Masha Y; Levavi-Sivan, Berta

    2012-11-25

    The gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and their receptors play critical roles in vertebrate reproduction. In order to study intra- and interspecies ligand promiscuity of gonadotropins, COS-7 cells were transiently transfected with one of the gonadotropin receptor genes, FSHR or LHR, and tested for activation by gonadotropins from representative fish orders: Aquilliformes (eel; e), Salmoniformes (trout; tr), and Perciformes (tilapia; ta), and of mammalian origin: porcine (p), bovine (b) and human (h). The study reveals complex relations between the gonadotropin hormones and their receptors. Each gonadotropin activated its own cognate receptor. However, taLHR was also activated by hCG and eLHR was activated by hFSH, hCG, and trFSH. For FSHR, the only cross-reactivity detected was for hFSHR, which was activated by pFSH and bFSH. These findings are of great interest and applicability in the context of activation of various GTHRs by their ligands and by ligands from other vertebrates. Analysis of the three-dimensional models of the structures highlights the importance of residues outside of the currently established hormone-receptor interface region. In addition, the interface residues in taFSHR and the effect of exon duplication, which causes an insert in the LRR domain, are suggested to affect the interaction and binding of taFSH.

  9. 21 CFR 556.304 - Gonadotropin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.304 Gonadotropin. (a) Acceptable daily intake (ADI). The ADI for...

  10. 21 CFR 556.304 - Gonadotropin.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.304 Gonadotropin. (a) Acceptable daily intake (ADI). The ADI for...

  11. 21 CFR 556.304 - Gonadotropin.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.304 Gonadotropin. (a) Acceptable daily intake (ADI). The ADI for...

  12. 21 CFR 522.1081 - Chorionic gonadotropin.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Chorionic gonadotropin. 522.1081 Section 522.1081 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS §...

  13. 21 CFR 522.1081 - Chorionic gonadotropin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Chorionic gonadotropin. 522.1081 Section 522.1081 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS §...

  14. 21 CFR 522.1081 - Chorionic gonadotropin.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Chorionic gonadotropin. 522.1081 Section 522.1081 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS §...

  15. 21 CFR 522.1081 - Chorionic gonadotropin.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Chorionic gonadotropin. 522.1081 Section 522.1081 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS §...

  16. 21 CFR 522.1081 - Chorionic gonadotropin.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Chorionic gonadotropin. 522.1081 Section 522.1081 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS §...

  17. Cloning of the elk TSH beta-subunit cDNA and seasonal expression of the pituitary glycoprotein hormone genes.

    PubMed

    Clark, Rena J; Furlan, Michael A; Chedrese, P Jorge

    2005-06-01

    We report the elk (Cervus elaphus) thyroid stimulating hormone (TSH) beta-subunit cDNA cloning, nucleotide and deduced amino acid sequences. The TSH beta-subunit cDNA was obtained by RT-PCR of polyadenylated pituitary RNA. The deduced elk TSH beta-subunit peptide chain shares between 93 to 99% sequence similarities with the reported TSH beta-subunit of a sub-set of related species. The TSH beta-subunit gene is expressed in the elk pituitary gland as a mature transcript of approximately 600 bases, which corresponds to the size of the mRNA expressed in the sheep pituitary gland. Seasonal expression of the pituitary gonadotropin genes was investigated by Northern blot analyses. Samples of elk pituitary glands collected during the breeding season showed elevated steady state levels of common alpha-subunit and FSH and LH beta-subunit gene expression, consistent with the seasonal reproductive cycling of this species. Samples collected before the breeding season demonstrated decreased expression of the gonadotropin genes. TSH, which is not directly tied to reproduction, had similar levels of expression, regardless of the animal's reproductive status.

  18. What Are the Key Statistics about Pituitary Tumors?

    MedlinePlus

    ... Tumors About Pituitary Tumors What Are the Key Statistics About Pituitary Tumors? About 10,000 pituitary tumors ... What Are Pituitary Tumors? What Are the Key Statistics About Pituitary Tumors? What’s New in Pituitary Tumor ...

  19. Pituitary apoplexy in an adrenocorticotropin-producing pituitary macroadenoma.

    PubMed

    Sahin, Serap Baydur; Cetinkalp, S; Erdogan, M; Cavdar, U; Duygulu, G; Saygili, F; Yilmaz, C; Ozgen, A G

    2010-10-01

    Adrenocorticotropin (ACTH) producing macroadenomas and pituitary apoplexy are unusual in Cushing' s disease. A 20-year-old man who had been diagnosed Cushing' s disease 2 months ago, presented with sudden headache, nausea, and vomiting. His serum cortisol level was 0.4 μg/dl and ACTH level was 23.9 pg/ml. Magnetic resonance imaging of the pituitary gland disclosed a hemorrhage in the pituitary macroadenoma (22×19 mm). He was treated with IV methylprednisolone immediately and then the symptoms were relieved within the first day of the treatment. The hemorrhagic lesion was resected by transsphenoidal surgery successfully. Impaired secretion of pituitary hormones may be seen after the pituitary apoplexy. We communicate a case with pituitary apoplexy of an ACTH secreting pituitary macroadenoma, causing acute glucocorticoid insufficiency.

  20. Diagnosis and treatment of pituitary adenomas.

    PubMed

    Chanson, P; Salenave, S

    2004-12-01

    Pituitary tumors cause symptoms by secreting hormones (prolactin, PRL, responsible for amenorrhea-galactorrhea in women and decreased libido in men; growth hormone, GH, responsible for acromegaly; adrenocorticotropic hormone, ACTH, responsible for Cushing's syndrome; thyroid-stimulating hormone, TSH, responsible for hyperthyroidism), depressing the secretion of hormones (hypopituitarism), or by mass-related effects (headaches, visual field abnormalities...). All patients with pituitary tumors should be evaluated for gonadal, thyroid and adrenal function as well as PRL and GH secretion. Specific stimulation and suppression tests for pituitary hormones are performed in selected situations for detecting the type of hypersecretion or the response to treatment. Imaging procedures (mainly magnetic resonance imaging, MRI, nowadays) determine the presence, size and extent of the lesion. The classification of pituitary tumors is based on the staining properties of the cell cytoplasm viewed by light microscopy and immunocytochemistry revealing the secretory pattern of the adenoma. Treatment of pituitary adenomas consists of surgery (performed in more than 99% of cases via a transphenoidal route) and radiotherapy, generally fractionated or, in selected cases, using stereotactic techniques such as gamma-knife. The availability of medical treatment (dopamine, DA, agonists, somatostatin analogs, GH-receptor antagonists...) has profoundly modified the indications of radiotherapy, drugs being now generally used as a second-line treatment, after surgery (or even as first-line treatment). Based on the results of the different treatment modalities for each type of pituitary adenoma, recommendations will be proposed. They may be summarized as follows. For treatment of GH-secreting adenomas, trans-sphenoidal surgery is the first-line therapy except when the macroadenoma is giant or if surgery is contra-indicated; postoperative radiation therapy (fractionated, or by gamma-knife) is

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. Gonadotropins in the Russian Sturgeon: Their Role in Steroid Secretion and the Effect of Hormonal Treatment on Their Secretion.

    PubMed

    Yom-Din, Svetlana; Hollander-Cohen, Lian; Aizen, Joseph; Boehm, Benjamin; Shpilman, Michal; Golan, Matan; Hurvitz, Avshalom; Degani, Gad; Levavi-Sivan, Berta

    2016-01-01

    In the reproduction process of male and female fish, pituitary derived gonadotropins (GTHs) play a key role. To be able to specifically investigate certain functions of Luteinizing (LH) and Follicle stimulating hormone (FSH) in Russian sturgeon (Acipenser gueldenstaedtii; st), we produced recombinant variants of the hormones using the yeast Pichia pastoris as a protein production system. We accomplished to create in vitro biologically active heterodimeric glycoproteins consisting of two associated α- and β-subunits in sufficient quantities. Three dimensional modelling of both GTHs was conducted in order to study the differences between the two GTHs. Antibodies were produced against the unique β-subunit of each of the GTHs, in order to be used for immunohistochemical analysis and to develop an ELISA for blood and pituitary hormone quantification. This detection technique revealed the specific localization of the LH and FSH cells in the sturgeon pituitary and pointed out that both cell types are present in substantially higher numbers in mature males and females, compared to immature fish. With the newly attained option to prevent cross-contamination when investigating on the effects of GTH administration, we compared the steroidogeneic response (estradiol and 11-Keto testosterone (11-KT) in female and males, respectively) of recombinant stLH, stFSH, and carp pituitary extract in male and female sturgeon gonads at different developmental stages. Finally, we injected commercially available gonadotropin releasing hormones analog (GnRH) to mature females, and found a moderate effect on the development of ovarian follicles. Application of only testosterone (T) resulted in a significant increase in circulating levels of 11-KT whereas the combination of GnRH + T did not affect steroid levels at all. The response pattern for estradiol demonstrated a similar situation. FSH levels showed significant increases when GnRH + T was administered, while no changes were present in

  6. Gonadotropins in the Russian Sturgeon: Their Role in Steroid Secretion and the Effect of Hormonal Treatment on Their Secretion

    PubMed Central

    Yom-Din, Svetlana; Hollander-Cohen, Lian; Aizen, Joseph; Boehm, Benjamin; Shpilman, Michal; Golan, Matan; Hurvitz, Avshalom; Degani, Gad; Levavi-Sivan, Berta

    2016-01-01

    In the reproduction process of male and female fish, pituitary derived gonadotropins (GTHs) play a key role. To be able to specifically investigate certain functions of Luteinizing (LH) and Follicle stimulating hormone (FSH) in Russian sturgeon (Acipenser gueldenstaedtii; st), we produced recombinant variants of the hormones using the yeast Pichia pastoris as a protein production system. We accomplished to create in vitro biologically active heterodimeric glycoproteins consisting of two associated α- and β-subunits in sufficient quantities. Three dimensional modelling of both GTHs was conducted in order to study the differences between the two GTHs. Antibodies were produced against the unique β-subunit of each of the GTHs, in order to be used for immunohistochemical analysis and to develop an ELISA for blood and pituitary hormone quantification. This detection technique revealed the specific localization of the LH and FSH cells in the sturgeon pituitary and pointed out that both cell types are present in substantially higher numbers in mature males and females, compared to immature fish. With the newly attained option to prevent cross-contamination when investigating on the effects of GTH administration, we compared the steroidogeneic response (estradiol and 11-Keto testosterone (11-KT) in female and males, respectively) of recombinant stLH, stFSH, and carp pituitary extract in male and female sturgeon gonads at different developmental stages. Finally, we injected commercially available gonadotropin releasing hormones analog (GnRH) to mature females, and found a moderate effect on the development of ovarian follicles. Application of only testosterone (T) resulted in a significant increase in circulating levels of 11-KT whereas the combination of GnRH + T did not affect steroid levels at all. The response pattern for estradiol demonstrated a similar situation. FSH levels showed significant increases when GnRH + T was administered, while no changes were present in

  7. [Thyrotropin-secreting pituitary adenomas].

    PubMed

    Caron, Philippe

    2009-01-01

    TSH-secreting pituitary adenomas represent 0.5 to 1% of all pituitary adenomas. They are recognized with increasing frequency due to the measurement of TSH level in patients with hyperthyroidism, the ultra sensitive TSH assays and the improvement in pituitary imaging. Patients present mild or moderate signs of hyperthyroidism. Hormonal evaluation shows increased free thyroid hormone concentration with detectable, normal or increased serum TSH level, raising the differential diagnosis with pituitary resistance to thyroid hormone syndrome. Magnetic resonance imaging reveals pituitary adenomas in most patients. Transphenoidal surgery remains the treatment of choice in patients with TSH-secreting pituitary microadenomas, while long-acting somatostatin analogs seem to be an alternative medical treatment to surgery in patients with macroadenomas or invasive pituitary tumors.

  8. The pituitary gland in patients with Langerhans cell histiocytosis: a clinical and radiological evaluation.

    PubMed

    Kurtulmus, Neslihan; Mert, Meral; Tanakol, Refik; Yarman, Sema

    2015-04-01

    Langerhans cell histiocytosis (LCH) is a rare disease in which the most common endocrine manifestation is diabetes insipidus (DI). Data on anterior pituitary function in patients with LCH are limited. Thus, the present study investigated anterior pituitary function in LCH patients with DI via the evaluation of clinical and radiological findings at disease onset and during follow-up. The present study retrospectively evaluated nine patients with LCH (five males and four females). All diagnoses of LCH were made following histological and/or immunophenotypic analyses of tissue biopsies, bronchoalveolar lavage, or cerebrospinal fluid (CSF). Basal and, if necessary, dynamic pituitary function tests were used to assess anterior pituitary function, and magnetic resonance imaging (MRI) scans were used to image the pituitary. The LCH treatment modality was based on organ involvement. The mean age at onset of DI was 27.6 years (range 15-60 years). One patient (11%) exhibited single organ involvement, while eight patients (89%) displayed multisystem organ involvement. On admittance, one patient had hypogonadotropic hypogonadism, one patient exhibited panhypopituitarism [hypogonadotropic hypogonadism, central hypothyroidism, hypocortisolism, and growth hormone (GH) deficiency], and four patients (44%) displayed hyperprolactinemia. The MRI data revealed infundibular enlargement in seven patients (78%), a thalamic mass in one patient (11%), and the absence of the bright spot in all patients. A single patient (11%) showed a mass in the pons that had a partially empty sella. The patients were treated with radiation therapy (RT), chemotherapy (CT), or a combination of both (RT+CT) and were followed up for a median of 91.8 months (range 2-318 months). Seven patients were assessed during the follow-up period, of whom four patients (57.1%) developed anterior pituitary hormone deficiency, three (43%) were diagnosed with GH deficiency, and one (14%) exhibited gonadotropin deficiency

  9. Gonadotropin-releasing hormone receptor system: modulatory role in aging and neurodegeneration

    PubMed Central

    Wang, Liyun; Chadwick, Wayne; Park, Soo-Sung; Zhou, Yu; Silver, Nathan; Martin, Bronwen; Maudsley, Stuart

    2010-01-01

    Receptors for hormones of the hypothalamic-pituitary-gonadal axis are expressed throughout the brain. Age-related decline in gonadal reproductive hormones cause imbalances of this axis and many hormones in this axis have been functionally linked to neurodegenerative pathophysiology. Gonadotropin-releasing hormone (GnRH) plays a vital role in both central and peripheral reproductive regulation. GnRH has historically been known as a pituitary hormone; however, in the past few years, interest has been raised in GnRH actions at non-pituitary peripheral targets. GnRH ligands and receptors are found throughout the brain where they may act to control multiple higher functions such as learning and memory function and feeding behavior. The actions of GnRH in mammals are mediated by the activation of a unique rhodopsin-like G protein-coupled receptor that does not possess a cytoplasmic carboxyl terminal sequence. Activation of this receptor appears to mediate a wide variety of signaling mechanisms that show diversity in different tissues. Epidemiological support for a role of GnRH in central functions is evidenced by a reduction in neurodegenerative disease after GnRH agonist therapy. It has previously been considered that these effects were not via direct GnRH action in the brain, however recent data has pointed to a direct central action of these ligands outside the pituitary. We have therefore summarized the evidence supporting a central direct role of GnRH ligands and receptors in controlling central nervous physiology and pathophysiology. PMID:20632963

  10. Reproductive axis function and gonadotropin microheterogeneity in a male rat model of diet-induced obesity.

    PubMed

    Olivares, Aleida; Méndez, Juan Pablo; Zambrano, Elena; Cárdenas, Mario; Tovar, Armando; Perera-Marín, Gerardo; Ulloa-Aguirre, Alfredo

    2010-04-01

    Obesity causes complex metabolic and endocrine changes that may lead to adverse outcomes, including hypogonadism. We herein studied the reproductive axis function in male rats under a high-fat diet and analyzed the impact of changes in glycosylation of pituitary LH on the bioactivity of this gonadotropin. Rats were fed with a diet enriched in saturated fat (20% of total calories) and euthanized on days 90 or 180 of diet. Long-term (180 days), high-fat feeding rats exhibited a metabolic profile compatible with insulin resistance and metabolic syndrome; they concomitantly showed decreased intrapituitary and serum LH concentrations, low serum testosterone levels, and elevated serum 17beta-estradiol concentrations. A fall in biological to immunological ratio of intrapituitary LH was detected in 180 days control diet-treated rats but not in high-fat-fed animals, as assessed by a homologous in vitro bioassay. Chromatofocusing of pituitary extracts yielded multiple LH charge isoforms; a trend towards decreased abundance of more basic isoforms (pH 9.99-9.0) was apparent in rats fed with the control diet for 180 days but not in those that were fed the diet enriched in saturated fat. It is concluded that long-term high-fat feeding alters the function of the pituitary-testicular axis, resulting in hypogonadotropic hypogonadism. The alterations in LH function found in these animals might be subserved by changes in hypothalamic GnRH output and/or sustained gonadotrope exposure to an altered sex steroid hormone milieu, representing a distinctly different regulatory mechanism whereby the pituitary attempts to counterbalance the effects of long-term obesity on reproductive function. (c) 2009 Elsevier Inc. All rights reserved.

  11. Expression of gonadotropin-releasing hormone receptor in cerebral cortical neurons of embryos and adult rats.

    PubMed

    Quintanar, J Luis; Salinas, Eva; González, Rodolfo

    2007-01-03

    Mammalian gonadotropin-releasing hormone (GnRH) was initially isolated from hypothalamus and its receptor from anterior pituitary, although extrapituitary GnRH receptors have been reported. The aim of the present study was to investigate whether GnRH receptor and its mRNA are expressed in cerebral cortical neurons of rat embryos and adult rats using immunohistochemical and reverse transcriptase polymerase chain reaction (RT-PCR) techniques. The immunohistochemistry and RT-PCR analysis showed expression of GnRH receptor and presence of its mRNA, in both cerebral cortical neurons of rat embryos and cerebral cortical tissues of adult rats. Additional experiments showed a decrease in the receptor mRNA expression when cultured neurons of rat embryos were treated with GnRH. It is possible that the presence of GnRH receptors in cortical neurons of rat may be involved in other physiological roles such as neurohormone or neuromodulator.

  12. Resistance to growth hormone releasing hormone and gonadotropins in Albright's hereditary osteodystrophy.

    PubMed

    Mantovani, Giovanna; Spada, Anna

    2006-05-01

    Heterozygous inactivating mutations in the Gs alpha gene cause Albright's hereditary osteo-dystrophy (AHO). Consistent with the observation that only maternally inherited mutations lead to resistance to hormone action (pseudohypoparathyroidism type Ia [PHP-Ia), recent studies have provided evidence for a predominant maternal origin of Gs alpha transcripts in endocrine organs, such as thyroid, gonad and pituitary. Accordingly, patients with PHP-Ia display variable degrees of resistance to parathyroid hormone (PTH), thyroid stimulating hormone (TSH), gonadotropins and growth hormone (GH) releasing hormone (GHRH). Although the incidence and the clinical and biochemical characteristics of PTH and TSH resistance have been widely investigated and described, the cause and significance of the reproductive dysfunction in AHO is still poorly understood. The clinical finding of alterations of GH secretion in these patients was described for the first time only 2 years ago. The present report briefly reviews the literature focusing on the actual knowledge about these last two subjects.

  13. IGF-I levels reflect hypopituitarism severity in adults with pituitary dysfunction.

    PubMed

    Tirosh, Amit; Toledano, Yoel; Masri-Iraqi, Hiba; Eizenberg, Yoav; Tzvetov, Gloria; Hirsch, Dania; Benbassat, Carlos; Robenshtok, Eyal; Shimon, Ilan

    2016-08-01

    To evaluate the utility of Insulin-like growth factor I (IGF-I) standard deviation score (SDS) as a surrogate marker of severity of hypopituitarism in adults with pituitary pathology. We performed a retrospective data analysis, including 269 consecutive patients with pituitary disease attending a tertiary endocrine clinic in 1990-2015. The medical files were reviewed for the complete pituitary hormone profile, including IGF-I, and clinical data. Age-adjusted assay reference ranges of IGF-I were used to calculate IGF-I SDS for each patient. The main outcome measures were positive and negative predictive values of low and high IGF-I SDS, respectively, for the various pituitary hormone deficiencies. IGF-I SDS correlated negatively with the number of altered pituitary axes (p < 0.001). Gonadotropin was affected in 76.6 % of cases, followed by thyrotropin (58.4 %), corticotropin (49.1 %), and prolactin (22.7 %). Positive and negative predictive values yielded a clear trend for the probability of low/high IGF-I SDS for all affected pituitary axes. Rates of diabetes insipidus correlated with IGF-I SDS values both for the full study population, and specifically for patients with non-functioning pituitary adenomas. IGF-I SDS can be used to evaluate the somatotroph function, as a valid substitute to absolute IGF-I levels. Moreover, IGF-I SDS predicted the extent of hypopituitarism in adults with pituitary disease, and thus can serve as a marker of hypopituitarism severity.

  14. Fasting and glucose effects on pituitary leptin expression. Is leptin a local signal for nutrient status?

    PubMed Central

    Crane, Christopher; Akhter, Noor; Johnson, Brandy W.; Iruthayanathan, Mary; Syed, Farhan; Kudo, Akihiko; Zhou, Yi-Hong; Childs, Gwen V.

    2007-01-01

    Leptin, a potent anorexigenic hormone is found in the anterior pituitary. The aim of this study was to determine if and how pituitary leptin-bearing cells were regulated by nutritional status. Male rats showed 64% reductions in pituitary leptin mRNA, but not serum leptin, 24 h after fasting, accompanied by significant 30-50% reductions in growth hormone (GH), prolactin, luteinizing hormone (LH), and 70-80% reductions in target cells for gonadotropin releasing hormone (GnRH) or growth hormone releasing hormone (GHRH). There was a 2—fold increase in corticotropes. Subsets (22%) of pituitary cells co-expressed leptin and GH and <5% co-expressed leptin and LH, prolactin, TSH, or ACTH. Fasting resulted in significant 55-75% losses in cells with leptin proteins or mRNA and GH or LH. To determine if restoration of serum glucose could rescue leptin, LH and GH, additional fasted rats were given 10% glucose water for 24 h. Restoring serum glucose in fasted rats resulted in pituitary cell populations with normal levels of leptin, GH, and LH cells. Similarly, LH and GH cells were restored, in vitro, after populations from fasted rats were treated for as little as 1 h in 10-100 pg/ml leptin. These correlative changes in pituitary leptin, LH and GH, coupled with leptin’s rapid restoration of GH and LH, in vitro, suggest that pituitary leptin may signal nutritional changes. Collectively, the findings suggest that pituitary leptin expression could be coupled to glucose sensors like glucokinase, to facilitate rapid responses by the neuroendocrine system to nutritional cues. PMID:17595338

  15. Specific gonadotropin binding to Pseudomonas maltophilia.

    PubMed

    Richert, N D; Ryan, R J

    1977-03-01

    Binding of 125I-labeled human chorionic gonadotropin to Pseudomonas maltophilia is dependent on time, temperature, and pH and the binding to this procaryotic species is hormone-specific and saturable. The equilibrium dissociation constant is 2.3 X 10(-9) M. There are no cooperative interactions between binding sites (Hill coefficient, 1.05). The number of sites is estimaated as 240 fmol/100 mug of protein. NaCl and KCl, at concentrations from 1 to 10 mM, have no effect on binding. Divalent cations (Mg2+ and Ca2+) and 1 mM EDTA inhibit hormone binding. Binding is destroyed by heat or by treatment with Pronase of alpha-chymotrypsin and is increased by phospholipase C. Binding of the labeled gonadotropin is not observed with other gram-negative organisms--e.g., Escherichia coli, Pseudomonas testosteroni, Pseudomonas aeruginosa, Enterobacter aerogenes, or Enterobacter cloacae.

  16. Schistocephalus solidus infections increase gonadotropins and gonadotropin releasing hormone (GnRH3) mRNA levels in the three-spined stickleback, Gasterosteus aculeatus.

    PubMed

    Shao, Yi Ta; Tseng, Yung Che; Trombley, Susanne; Hwang, Pung Pung; Schmitz, Monika; Borg, Bertil

    2012-09-01

    Parasites often impair the reproduction of their hosts, one well known case being the cestode Schistocephalus solidus which is a common parasite in three-spined sticklebacks, Gasterosteus aculeatus. One of the possible ways that this could be exerted is by suppression on the brain-pituitary-gonadal (BPG) axis. In this study, mRNA levels of FSH-β and LH-β and of GnRH2 (cGnRH II) and GnRH3 (sGnRH) were measured via Q-PCR in infected and uninfected fish sampled from the field a few weeks before the onset of breeding. The pituitary mRNA levels of both FSH-β and LH-β were higher in infected males than in uninfected males. Also in females, FSH-β mRNA levels were higher in infected individuals than in others, whereas there was no significant difference found in LH-β expression. Brain mRNA levels of GnRH3 were higher in infected fish than in uninfected fish in both sexes, but no difference was found in GnRH2 mRNA levels. Thus, infection by S. solidus was able to alter the expressions not only of gonadotropins (GtHs), but also of GnRH which has not been observed previously. However, the effects are opposite to what should be expected if the parasite suppressed reproduction via actions on the brain-pituitary level. The gonads are perhaps more likely to be impaired by the parasites in other ways, and changed feedbacks on the BPG axis could then lead to the increases in GtHs and GnRH. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  17. 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.

  18. TERT Expression in Pituitary Adenomas.

    PubMed

    Can, Nuray; Çelik, Mehmet; Bülbül, Buket Yilmaz; Süt, Necdet; Özyilmaz, Filiz; Aytürk, Semra; Güldiken, Sibel; Sarikaş, Nurtaç; Puyan, Fulya Öz; Yalta, Tülin Deniz; Kutlu, Ali Kemal

    2017-01-01

    Although pituitary adenomas have benign histomorphological features, some of them may present in an aggressive manner. To predict the behaviour of these tumours, telomerase reverse transcriptase (TERT) activity in pituitary adenomas has been the subject of a few studies with contradictory results. This study aims to investigate whether immunohistochemical expression of TERT differs in neoplastic and nonneoplastic pituitary tissues and aims to investigate whether TERT expression is related to clinicopathological features of pituitary adenomas. The study included 48 patients who had been diagnosed with pituitary adenomas and had clinical follow-ups. Nonneoplastic pituitary tissues were obtained from autopsy specimens (n=20). Immunohistochemistry for TERT antibody was performed. Both the nuclear and cytoplasmic expression of TERT antibody was noted, and total combined TERT staining was evaluated according to nuclear and cytoplasmic stainings. TERT expression did not differ between neoplastic and nonneoplastic pituitary tissues. Neither total (combined nuclear and cytoplasmic) TERT nor nuclear TERT expression revealed any statistically significant relationship with any of the clinicopathological features. Higher cytoplasmic TERT expression was observed in adenomas with recurrence than adenomas without recurrence (p=0.035). This study introduces the notion that immunohistochemical expression of TERT does not differ in neoplastic and nonneoplastic pituitary tissues. Pituitary adenomas with cytoplasmic immunohistochemical expression of TERT have significantly higher rates of recurrence. Further studies, including combined methods of immunohistochemistry and molecular analyses in larger groups, may reveal applicable results for the clinical significance of TERT in pituitary adenomas.

  19. Molecular, cellular, morphological, physiological and behavioral aspects of gonadotropin-inhibitory hormone.

    PubMed

    Ubuka, Takayoshi; Son, You Lee; Tsutsui, Kazuyoshi

    2016-02-01

    Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic neuropeptide that was isolated from the brains of Japanese quail in 2000, which inhibited luteinizing hormone release from the anterior pituitary gland. Here, we summarize the following fifteen years of researches that investigated on the mechanism of GnIH actions at molecular, cellular, morphological, physiological, and behavioral levels. The unique molecular structure of GnIH peptide is in its LPXRFamide (X=L or Q) motif at its C-terminal. The primary receptor for GnIH is GPR147. The cell signaling pathway triggered by GnIH is initiated by inhibiting adenylate cyclase and decreasing cAMP production in the target cell. GnIH neurons regulate not only gonadotropin synthesis and release in the pituitary, but also regulate various neurons in the brain, such as GnRH1, GnRH2, dopamine, POMC, NPY, orexin, MCH, CRH, oxytocin, and kisspeptin neurons. GnIH and GPR147 are also expressed in gonads and they may regulate steroidogenesis and germ cell maturation in an autocrine/paracrine manner. GnIH regulates reproductive development and activity. In female mammals, GnIH may regulate estrous or menstrual cycle. GnIH is also involved in the regulation of seasonal reproduction, but GnIH may finely tune reproductive activities in the breeding seasons. It is involved in stress responses not only in the brain but also in gonads. GnIH may inhibit male socio-sexual behavior by stimulating the activity of cytochrome P450 aromatase in the brain and stimulates feeding behavior by modulating the activities of hypothalamic and central amygdala neurons. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Emergence of an Ancestral Glycoprotein Hormone in the Pituitary of the Sea Lamprey, a Basal Vertebrate.

    PubMed

    Sower, Stacia A; Decatur, Wayne A; Hausken, Krist N; Marquis, Timothy J; Barton, Shannon L; Gargan, James; Freamat, Mihael; Wilmot, Michael; Hollander, Lian; Hall, Jeffrey A; Nozaki, Masumi; Shpilman, Michal; Levavi-Sivan, Berta

    2015-08-01

    The gnathostome (jawed vertebrates) classical pituitary glycoprotein hormones, FSH, LH, and TSH, consist of a common α-subunit (GpA1) and unique β-subunits (Gpβ1, -2, and -3), whereas a recently identified pituitary glycoprotein hormone, thyrostimulin, consists of GpA2 and GpB5. This paper reports the identification, expression, and function of an ancestral, nonclassical, pituitary heterodimeric glycoprotein hormone (GpH) consisting of the thyrostimulin A2 subunit with the classical β-subunit in the sea lamprey, Petromyzon marinus, a jawless basal vertebrate. Lamprey (l) GpA2, and lGpHβ were shown to form a heterodimer by coimmunoprecipitation of lGpA2 with FLAG-tagged lGpHβ after the overexpression in transiently transfected COS7 cells using a bipromoter vector. Dual-label fluorescent in situ hybridization and immunohistochemistry showed the coexpression of individual subunits in the proximal pars distalis of the pituitary. GnRH-III (1μΜ) significantly increased the expression of lGpHβ and lGpA2 in in vitro pituitary culture. Recombinant lamprey GpH was constructed by tethering the N terminal of lGpA2 to the C terminal of lGpHβ with a linker region composed of six histidine residues followed by three glycine-serine repeats. This recombinant lamprey GpH activated the lamprey glycoprotein hormone receptor I as measured by increased cAMP/luciferase activity. These data are the first to demonstrate a functional, unique glycoprotein heterodimer that is not found in any other vertebrate. These data suggest an intermediate stage of the structure-function of the gonadotropin/thyroid-stimulating hormone in a basal vertebrate, leading to the emergence of the highly specialized gonadotropin hormones and thyroid stimulating hormones in gnathostomes.

  1. Whole brain-pituitary in vitro preparation of the transgenic medaka (Oryzias latipes) as a tool for analyzing the differential regulatory mechanisms of LH and FSH release.

    PubMed

    Karigo, Tomomi; Aikawa, Masato; Kondo, Chika; Abe, Hideki; Kanda, Shinji; Oka, Yoshitaka

    2014-02-01

    Two types of gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), are important pituitary hormones for sexual maturation and reproduction, and both of them are centrally regulated by gonadotropin-releasing hormone (GnRH) from the hypothalamus. In mammals, these two gonadotropins are secreted from a single type of gonadotrope. The mechanisms of differential regulation by GnRH of the release of two types of gonadotropins with different secretory profiles are still unknown. In teleosts, however, LH and FSH are secreted from separate cellular populations, unlike in mammals. This feature makes them useful for studying the regulatory mechanisms of LH and FSH secretions independently. Here, we generated transgenic medaka lines that express Ca(2+) indicator protein, inverse-pericam, specifically in the LH or FSH cells. We performed cell-type-specific Ca(2+) imaging of LH and FSH cells, respectively, using the whole brain-pituitary preparations of these transgenic fish in which all neural circuits and GnRH neuronal projection to the pituitary are kept intact. LH and FSH cells showed different Ca(2+) responses to GnRH. The results suggest differential regulation mechanisms for LH and FSH release by GnRH. Moreover, we also succeeded in detecting the effect on LH cells of endogenous GnRH peptide, which was released by electrical stimulation of the axons of GnRH1 neurons. Thus, our newly developed experimental model system using the whole brain-pituitary in vitro preparation of the transgenic medaka is a powerful tool for analyzing the differential regulatory mechanisms of the release of LH and FSH by multisynaptic neural inputs to the pituitary.

  2. Gonadotropin Pulsatllity in FemaIe Long Distance Runners

    DTIC Science & Technology

    1986-10-24

    8 in Ovarian Follicles 3. Development of the Endometrium 10 B. Gonadotropin Regulation During the 11 Menstrual Cycle 1. overvrew of Gonadotropin...changes in gonadotropin and ovarian steroids throughout the cycle. The development of the ovarian follicle and endometrium are also shown. ’ j...3. Development of the Endometrium During menstruation, bleeding occurs due to a sloughing off of the endometrium from the previous menstrual cycle

  3. Pituitary tumours: inflammatory and granulomatous expansive lesions of the pituitary.

    PubMed

    Carpinteri, R; Patelli, I; Casanueva, F F; Giustina, A

    2009-10-01

    Inflammatory and granulomatous diseases of the pituitary are rare causes of sellar masses. Lymphocytic hypophysitis is the most relevant of these disorders, and it is characterised by autoimmune pathogenesis with focal or diffuse inflammatory infiltration and varying degrees of pituitary gland destruction. Endocrine symptoms may include partial or total hypopituitarism, with adrenocorticotropic hormone (ACTH) deficiency being the earliest and most frequent alteration. Pituitary abscess is a rare but potentially life-threatening disease and, in 30-50% of patients, anterior pituitary hormone deficiencies or central diabetes insipidus (DI) at onset may be observed: the earliest manifestation being growth hormone deficiency (GHD), followed by follicle-stimulating hormone (FSH)/luteinising hormone (LH), thyroid-stimulating hormone (TSH) and ACTH deficiencies. Fungal infections of the pituitary are also very rare and include aspergillosis and coccidioidomycosis. Concerning pituitary involvement in systemic diseases, in sarcoidosis endocrine complications are rare, but the hypothalamus and pituitary are the glands most commonly affected. DI is reported in approximately 25-33 % of all neurosarcoidosis cases and is the most frequently observed endocrine disorder. Hyperprolactinaemia and anterior pituitary deficiencies may also occur. Rarely, partial or global anterior pituitary dysfunction may be present also in Wegener's granulomatosis, either at onset or in the course of the disease, resulting in deficiency of one or more of the pituitary axes. Other forms of granulomatous pituitary lesions include idiopathic giant cell granulomatous hypophysitis, Takayasu's disease, Cogan's syndrome and Crohn's disease. The hypotalamic-pituitary system is involved mainly in children with Langerhans' cells histiocytosis who develop DI, which is the most common endocrine manifestation. Anterior pituitary dysfunction is found more rarely and is almost invariably associated with DI

  4. Multidisciplinary Management of Pituitary Apoplexy.

    PubMed

    Albani, Adriana; Ferraù, Francesco; Angileri, Filippo Flavio; Esposito, Felice; Granata, Francesca; Ferreri, Felicia; Cannavò, Salvatore

    2016-01-01

    Pituitary apoplexy is a rare clinical syndrome due to ischemic or haemorrhagic necrosis of the pituitary gland which complicates 2-12% of pituitary tumours, especially nonfunctioning adenomas. In many cases, it results in severe neurological, ophthalmological, and endocrinological consequences and may require prompt surgical decompression. Pituitary apoplexy represents a rare medical emergency that necessitates a multidisciplinary approach. Modalities of treatment and times of intervention are still largely debated. Therefore, the management of patients with pituitary apoplexy is often empirically individualized and clinical outcome is inevitably related to the multidisciplinary team's skills and experience. This review aims to highlight the importance of a multidisciplinary approach in the management of pituitary apoplexy and to discuss modalities of presentation, treatment, and times of intervention.

  5. Multidisciplinary Management of Pituitary Apoplexy

    PubMed Central

    Albani, Adriana; Angileri, Filippo Flavio; Esposito, Felice; Granata, Francesca; Ferreri, Felicia; Cannavò, Salvatore

    2016-01-01

    Pituitary apoplexy is a rare clinical syndrome due to ischemic or haemorrhagic necrosis of the pituitary gland which complicates 2–12% of pituitary tumours, especially nonfunctioning adenomas. In many cases, it results in severe neurological, ophthalmological, and endocrinological consequences and may require prompt surgical decompression. Pituitary apoplexy represents a rare medical emergency that necessitates a multidisciplinary approach. Modalities of treatment and times of intervention are still largely debated. Therefore, the management of patients with pituitary apoplexy is often empirically individualized and clinical outcome is inevitably related to the multidisciplinary team's skills and experience. This review aims to highlight the importance of a multidisciplinary approach in the management of pituitary apoplexy and to discuss modalities of presentation, treatment, and times of intervention. PMID:28074095

  6. Demonstration of reserved anterior pituitary function among patients with amenorrhea after postpartum hemorrhage.

    PubMed

    Huang, Y Y; Ting, M K; Hsu, B R; Tsai, J S

    2000-04-01

    To demonstrate the residual pituitary function of patients with Sheehan's syndrome years after the obstetric complication, 14 patients with postpartum hemorrhage followed by secondary amenorrhea and agalactia were included in this review. Due to their unfamiliarity with the clinical symptoms, these patients did not receive pretreatment hormonal therapy. The mean age at their last delivery was 29 years (range 21-38 years). The mean duration between postpartum hemorrhage and the subsequent clinical manifestations leading to the endocrine investigation was 18 years (range 1-33 years). Eight patients presented with symptoms of severe hyponatremia (serum sodium less than 125 mmol/l) more than 16 years (mean 23 +/- 10) after the occurrence of postpartum hemorrhage. The electrolyte abnormality was primarily due to adrenal dysfunction. Seven out of 14 patients had normal basal luteinizing hormone (LH) levels and adequate LH responses to gonadotropin releasing hormone stimulation. Administration of thyrotropin releasing hormone provoked thyrotropin release and/or prolactin secretion in four cases. The manifestation of clinical hypopituitarism and the degree of empty sella on computed tomography scanning did not accurately indicate the secreting ability of the pituitary in patients with Sheehan's syndrome. Although all the patients had amenorrhea, the gonadotropic functions of the pituitary still remain in some patients. Various degrees of other pituitary functions can also been demonstrated even several decades after the occurrence of obstetric complications. Our data suggest that the amenorrhea of Sheehan's patients is not simply due to a dysfunction of the pituitary gonadotrophs.

  7. The pituitary gland under infrared light - in search of a representative spectrum for homogeneous regions.

    PubMed

    Banas, A; Banas, K; Furgal-Borzych, A; Kwiatek, W M; Pawlicki, B; Breese, M B H

    2015-04-07

    The pituitary gland is a small but vital organ in the human body. It is located at the base of the brain and is often described as the master gland due to its multiple functions. The pituitary gland secretes and stores hormones, such as the thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), growth hormone (hGH), prolactin, gonadotropins, and luteinizing hormones, as well as the antidiuretic hormone (ADH). A proper diagnosis of pituitary disorders is of utmost importance as this organ participates in regulating a variety of body functions. Typical histopathological analysis provides much valuable information, but it gives no insight into the biochemical background of the changes that occur within the gland. One approach that could be used to evaluate the biochemistry of tissue sections obtained from pituitary disorders is Fourier Transform Infra-Red (FTIR) spectromicroscopy. In order to collect diagnostically valuable information large areas of tissue must be investigated. This work focuses on obtaining a unique and representative FTIR spectrum characteristic of one type of cell architecture within a sample. The idea presented is based on using hierarchical cluster analysis (HCA) for data evaluation to search for uniform patterns within samples from the perspective of FTIR spectra. The results obtained demonstrate that FTIR spectromicroscopy, combined with proper statistical evaluation, can be treated as a complementary method for histopathological analysis and ipso facto can increase the sensitivity and specificity for detecting various disorders not only for the pituitary gland, but also for other human tissues.

  8. The hypothalamic-pituitary axis in men and women with chronic kidney disease.

    PubMed

    Holley, Jean L

    2004-10-01

    Although the precise abnormalities that lead to failure of the hypothalamic-pituitary-gonadal axis in men and women with chronic kidney disease (CKD) and end-stage renal disease (ESRD) remains undefined, evidence exists for defects in both the hypothalamus and the pituitary. The lack of appropriate cyclic release of gonadotropin-releasing hormone (GnRH) by the hypothalamus leads to loss of normal pulsatile luteinizing hormone (LH) release by the pituitary, which results in impaired ovulation in women and reduced testosterone and sperm production in men. The cause of impaired cyclic release of GnRH is unclear, but hyperprolactinemia, elevated endorphins, and high levels of GnRH and LH caused by reduced clearance may contribute. Perturbations of the hypothalamic-pituitary-gonadaotropin axis in CKD lead to high rates of infertility, dysfunctional uterine bleeding, and impaired puberty in children. Only through additional study of the complex effects of CKD on the hypothalamic-pituitary-gonadal axis will the precise abnormalities in hormonal control of reproduction be explained.

  9. Risk factor for pituitary dysfunction in children and adolescents with Rathke's cleft cysts

    PubMed Central

    Lim, Han Hyuk

    2010-01-01

    Purpose This study evaluated the clinical manifestations of and risk factors for pituitary insufficiency in children and adolescents with Rathke's cleft cysts. Methods Forty-four patients with Rathke's cleft cysts younger than 19 years who visited Seoul National University Children's Hospital between January 1995 and September 2009 were enrolled. Rathke's cleft cysts were confirmed histologically through an operation in 15 patients and by brain magnetic resonance imaging (MRI) in 29 patients. The clinical, hormonal, and imaging features were reviewed retrospectively. Results The clinical presentation of symptomatic patients was as follows: headache (65%), endocrinopathy (61%), and visual disturbance (19%). Endocrinopathy included central precocious puberty (18%), diabetes insipidus (14%), general weakness (11%), and decreased growth velocity (7%). After surgery, hyperprolactinemia resolved in all patients, but growth hormone insufficiency, hypothyroidism, and diabetes insipidus did not improve. Pituitary insufficiency except gonadotropin abnormality correlated significantly with severe headache, visual disturbance, general weakness, and cystic size. Suprasellar extension of cysts and high signals in the T2-weighted image on brain MRI were related to hypothyroidism, hypocortisolism, and diabetes insipidus. Multivariable linear regression analysis showed that only general weakness was a risk factor for pituitary insufficiency (R2=0.549). Conclusion General weakness is a risk factor for pituitary insufficiency in patients with Rathke's cleft cysts. When a patient with a Rathke's cleft cyst complains of general weakness, the clinician should evaluate pituitary function and consider surgical treatment. PMID:21189952

  10. SIADH following pituitary adenoma apoplexy.

    PubMed

    Ebner, Florian Heinrich; Hauser, Till K; Honegger, Juergen

    2010-04-01

    The rare case of a patient with SIADH following pituitary adenoma apoplexy is reported. Since apoplexy did not exert any mass effect on surrounding structures, the patient was treated conservatively and the anterior pituitary gland insufficiency has been substituted adequately. Seven days after the apoplexy the patient again showed low serum-Na(+) levels despite cortisol substitution. Diagnosis of SIADH was made. It is essential to be aware of this rare syndrome in patients with pituitary adenoma apoplexy.

  11. Endoscopic surgery of pituitary tumors.

    PubMed

    Dhepnorrarat, Rataphol Chris; Ang, Beng Ti; Sethi, Dharambir Singh

    2011-08-01

    Endoscopic pituitary surgery has been gaining wide acceptance as the first-line treatment of most functional pituitary adenomas. This technique has many advantages over traditional procedures, and growing evidence supports its use for endocrine control of functioning tumors. This article reviews data on the different modalities of treatment of functioning pituitary adenomas and compares the results. Endoscopic pituitary surgery controls tumor growth and endocrinopathy as well as or better than other treatment modalities. Complication rates are low and patient recovery is fast. Furthermore, surgery provides a means of achieving prompt decompression of neurologic structures and endocrine remission.

  12. Triple jeopardy in the pituitary.

    PubMed

    Goh, Kian-Peng; Lee, Hwei-Yee; Rajasoorya, Raja C

    2008-01-01

    Aggressive pituitary tumors are rare the pathogenesis is not well established. The development of pituitary tumor after apoplexy has also been rarely reported. We describe the sequential development of Cushing's disease, apoplexy and aggressive pituitary tumor in the same patient. A 31-year old male presented with eutopic ACTH dependent Cushing's syndrome which failed initial pituitary surgery. He underwent subsequent bilateral adrenalectomy for control of hypercortisolism. An episode of pituitary apoplexy then occurred which was followed by the development of a null-cell pituitary tumor. This second tumor exhibited an aggressive behavior with invasion into the surrounding structures and systemic spread clinically. This case provides important evidence for the hypotheses of the pathogenesis of aggressive pituitary tumors which could have arisen from surviving adenoma cells following apoplexy or as a de novo development of pituitary carcinoma from cells which were not part of the original adenoma. This is the first report of a transformation of Cushing's disease to an aggressive and invasive null cell tumor after pituitary irradiation, apoplexy and surgery.

  13. Gene Therapy for Pituitary Tumors

    PubMed Central

    Seilicovich, Adriana; Pisera, Daniel; Sciascia, Sandra A.; Candolfi, Marianela; Puntel, Mariana; Xiong, Weidong; Jaita, Gabriela; Castro, Maria G.

    2009-01-01

    Pituitary tumors are the most common primary intracranial neoplasms. Although most pituitary tumors are considered typically benign, others can cause severe and progressive disease. The principal aims of pituitary tumor treatment are the elimination or reduction of the tumor mass, normalization of hormone secretion and preservation of remaining pituitary function. In spite of major advances in the therapy of pituitary tumors, for some of the most difficult tumors, current therapies that include medical, surgical and radiotherapeutic methods are often unsatisfactory and there is a need to develop new treatment strategies. Gene therapy, which uses nucleic acids as drugs, has emerged as an attractive therapeutic option for the treatment of pituitary tumors that do not respond to classical treatment strategies if the patients become intolerant to the therapy. The development of animal models for pituitary tumors and hormone hypersecretion has proven to be critical for the implementation of novel treatment strategies and gene therapy approaches. Preclinical trials using several gene therapy approaches for the treatment of anterior pituitary diseases have been successfully implemented. Several issues need to be addressed before clinical implementation becomes a reality, including the development of more effective and safer viral vectors, uncovering novel therapeutic targets and development of targeted expression of therapeutic transgenes. With the development of efficient gene delivery vectors allowing long-term transgene expression with minimal toxicity, gene therapy will become one of the most promising approaches for treating pituitary adenomas. PMID:16457646

  14. Anti-Müllerian hormone: a new actor of sexual dimorphism in pituitary gonadotrope activity before puberty

    PubMed Central

    Garrel, Ghislaine; Racine, Chrystèle; L’Hôte, David; Denoyelle, Chantal; Guigon, Céline J.; di Clemente, Nathalie; Cohen-Tannoudji, Joëlle

    2016-01-01

    Anti-Müllerian hormone (AMH) contributes to male sexual differentiation and acts on gonads of both sexes. Identification of AMH receptivity in both pituitary and brain has led to the intriguing idea that AMH participates to the hypothalamic-pituitary control of reproduction, however in vivo experimental evidence is still lacking. We show that AMH stimulates secretion and pituitary gene expression of the gonadotropin FSH in vivo in rats. AMH action is sex-dependent, being restricted to females and occurring before puberty. Accordingly, we report higher levels of pituitary AMH receptor transcripts in immature females. We show that AMH is functionally coupled to the Smad pathway in LβT2 gonadotrope cells and dose-dependently increases Fshb transcript levels. Furthermore, AMH was shown to establish complex interrelations with canonical FSH regulators as it cooperates with activin to induce Fshb expression whereas it reduces BMP2 action. We report that GnRH interferes with AMH by decreasing AMH receptivity in vivo in females. Moreover, AMH specifically regulates FSH and not LH, indicating that AMH is a factor contributing to the differential regulation of gonadotropins. Overall, our study uncovers a new role for AMH in regulating gonadotrope function and suggests that AMH participates in the postnatal elevation of FSH secretion in females. PMID:27030385

  15. Cocaine- and amphetamine-regulated transcript peptide in the rat anterior pituitary gland is localized in gonadotrophs and suppresses prolactin secretion.

    PubMed

    Kuriyama, Genshin; Takekoshi, Susumu; Tojo, Katsuyoshi; Nakai, Yoshikatsu; Kuhar, Michael J; Osamura, R Yoshiyuki

    2004-05-01

    Cocaine- and amphetamine-regulated transcript (CART) mRNA and CART peptide are abundant in the hypothalamic nuclei that control anterior pituitary function. CART peptide has also been localized in the anterior pituitary gland itself, although its role in pituitary function has not as yet been elucidated. In the present study, we investigated the localization and function of CART peptide in the anterior pituitary gland. Immunohistochemical observations revealed that CART peptide colocalized with FSH and LH in gonadotroph cells but that it was absent from the other hormone-producing cells. Immunoelectronmicroscopy suggested that CART peptide and gonadotropin were colocalized in the same secretory granules. CART peptide suppressed prolactin release from dispersed anterior pituitary cells 15 min after its addition into the media [basal production, 234.9 +/- 14.6 ng/ml vs. CART 55-102 peptide 100 nm, 125.0 +/- 18.2 ng/ml (P < 0.01, n = 5)]. Prolactin release was suppressed by CART in a dose-related manner; on the other hand, CART peptide did not affect the secretion of other anterior pituitary hormones. CART peptide synthesis by these cells was elevated 15 min after the addition of leptin to the media (100 nm), as determined by immunoblotting, but LHRH (10 nm) did not significantly affect CART peptide expression. These findings suggest that CART synthesis in the anterior pituitary may be stimulated by leptin and that CART peptide may play a role in the regulation of anterior pituitary hormone secretion in the rat.

  16. The role of gonadotropin-releasing hormone antagonists in in vitro fertilization.

    PubMed

    Diedrich, K; Ludwig, M; Felberbaum, R E

    2001-09-01

    Gonadotropin-releasing hormone (GnRH)-antagonists can suppress the pituitary hormone secretion completely within a few hours, allowing the avoidance of premature luteinization within controlled ovarian hyperstimulation (COH) for assisted reproductive technologies (ART) by midcycle administration. Two different protocols were described, which were widely used in COH in several phase II and III studies as well as in clinical practice since the GnRH-antagonists Cetrorelix (Cetrotidesound recording copyright sign; Serono International S.A., Geneva, Switzerland) and Ganirelix (Orgalutansound recording copyright sign, Antagonsound recording copyright sign; Organon, Oss, The Netherlands) are available on the market. Cetrorelix was applied in single- and multiple-dose protocols; Ganirelix was used until now only according to the multiple-dose protocol. Fertilization rates of >60% as well as clinical pregnancy rates of about 30% per transfer sound most promising. Estradiol secretion is not compromised by the GnRH-antagonists using recombinant follicle-stimulating hormone (FSH) for COH. The incidence of a premature leutinizing hormone (LH) surge is far below 2% while the pituitary response remains preserved, allowing the induction of ovulation by GnRH or GnRH-agonists. However, luteal phase support remains mandatory. The incidence of severe ovarian hyperstimulation syndrome (OHSS) seems to be lower under antagonist treatment than in the long agonistic protocol. Treatment time is significantly shortened. Without any doubt GnRH-antagonists have the potential to become the new standard for controlled ovarian hyperstimulation.

  17. Gonadal development and gonadotropin gene expression during puberty in cultured chub mackerel (Scomber japonicus).

    PubMed

    Nyuji, Mitsuo; Kodama, Ryoko; Kato, Keitaro; Yamamoto, Shinji; Yamaguchi, Akihiko; Matsuyama, Michiya

    2014-06-01

    Understanding puberty is important for establishing aquaculture in fish. In this study, we analyzed the timing and completion of pubertal development along with changes in pituitary gonadotropin genes (fshb and lhb) in cultured chub mackerel (Scomber japonicus). At 45 days post-hatching (dph), gonadal sex differentiation was observed. The onset of puberty occurred at 192 dph in females with the start of vitellogenesis, whereas it occurred at 164 dph in males, with the beginning of spermatogenesis (proliferation and differentiation of germ cells). The completion of puberty was at 326 dph in females when vitellogenesis completed, and it was at 338 dph in males during spermiation. All fish sampled during the spawning season completed pubertal development. In the pituitary of female fish, fshb expression was activated during early secondary growth and was maintained high throughout vitellogenesis, whereas lhb expression was highest at the completion of vitellogenesis. In male fish, fshb and lhb expression were activated from the onset of spermatogenesis and further activated during late pubertal development; fshb remained high between late spermatogenesis and spermiation, whereas lhb was highest during spermiation.

  18. [Gonadotroph pituitary adenomas].

    PubMed

    Chanson, P

    2000-09-01

    Initially, the distinction between "functional" and "non-functional" adenomas was a purely clinical notion. A "non-secreting" adenoma was not considered to cause acromegaly nor Cushing's syndrome nor amenorrhea-galactorrhea syndrome. The term "chromophobe adenoma" has been used since the advent Herlant tetrachrome. More recently immunocytochemistry methods have demonstrated that most of the "clinically non functional" adenomas (chromophobe with classical histology) are actually gonadotrophin secreting adenomas or gonadotroph adenomas. Due to progress in immunocytochemistry applied to operated adenomas, it is now known that gonadotroph tumors account for 15 to 20% of all pituitary adenomas. Gonadotroph adenomas are monoclonal but their pathogenesis, unlike somatotroph adenomas causing acromegaly and despite numerous molecular studies, remains unknown. Gonadotroph adenomas are most always discovered in patients presenting a pituitary syndrome (half to three-quarters consult for a visual field disorder). Pituitary imaging almost always demonstrates a macroadenoma: two-thirds of the macroadenomas are enclosed. Anterior pituitary insufficiency is much more frequent than gonad hyperstimulation whether testicular (macro-orchidia) or ovarian (ovarian hyperstimulation similar to that observed in ovulation induction). A careful analysis of hormone assay results shows that baseline concentrations of gonadotrophin or their free sub-units is elevated in 30 to 50% of cases (especially FSH in men, and the free a sub-unit in premenopausal women). Dynamic tests contribute little to diagnosis: the GnRH test is positive in 75 to 100% of cases, the TRH test in 60 to 70% for FSH (or alpha) and when there is already a baseline hypersecretion of FSH (or a) in 20 to 30% of the cases for the LH when the baseline LH concentration is high. The immunocytochemistry of gonadotroph adenomas is slightly different from that of other adenomas: generally, only 5 to 10% of the cells, grouped in

  19. Testosterone production in response to exogenous gonadotropin releasing hormone (GnRH challenge) depends on social environment and color polymorphism.

    PubMed

    Cain, Kristal E; Pryke, Sarah R

    2017-04-01

    Testosterone is an important mediator of behavior, morphology and physiology. A cascade of signals regulates the amount of testosterone (T) circulating in the plasma; in response to stimulus the hypothalamus releases gonadotropin-releasing hormone (GnRH), which triggers secretion of gonadotropins from the pituitary, stimulating the synthesis and release of T from the gonads. Previous work has shown that changes to the social environment can alter circulating T-levels, which may have important fitness consequences, but it is currently unclear whether these changes are due to alterations in the signal from the brain, or changes in the ability of the pituitary and gonads to respond to this signal. Further, the strength and direction of response to a changing environment may differ according to life-history strategy. Species with genetically determined alternative strategies offer a pathway for examining these differences. Here we use a finch with a genetically determined polymorphism, the Gouldian finch (Erythrura gouldiae), to determine whether T-levels change in response to social environment. We also use injections of GnRH to determine whether these changes are due to alterations in the ability of the pituitary and gonads to respond to this signal. We found that social environment (presence of females) had a rapid effect on male circulating T-levels, and that this difference was reflected in responsiveness to GnRH. We observed no overall morph differences in T-levels, but we did observe morph differences in the pattern of T secretion across environments, and morph differences in the repeatability of T-levels across time and environment. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Gonadotropin Surge-inhibiting/attenuating Factors: A Review of Current Evidence, Potential Applications, and Future Directions for Research

    PubMed Central

    VEGA, MARIO G.; ZAREK, SHVETHA M.; BHAGWAT, MEDHA; SEGARS, JAMES H.

    2016-01-01

    SUMMARY Animal studies in the 1980s suggested the existence of an ovarian hormone, termed gonadotropin surge-inhibiting/attenuating factor (GnSIF/AF), that modulates pituitary secretion of luteinizing hormone (LH). Given the importance of identifying regulatory factors of the hypothalamic-pituitary-ovarian axis and the accumulating data suggesting its existence, we conducted a comprehensive literature search using PubMed, Web of Science, Scopus, and Embase to identify articles related to GnSIF/AF. The search generated 161 publications, of which 97 were included in this study. Several attempts have been made to identify and characterize this hormone and several candidates have been identified, but the protein sequences of these putative GnSIF/AF factors differ widely from one study to another. In addition, while the RF-amide RFRP-3 is known foremost as a neuropeptide, some research supports an ovarian origin for this non-steroidal hormone, thereby suggesting a role for RFRP-3 either as a co-modulator of GnSIF/AF or as a gonadotropin-inhibiting factor in the hypothalamus (GnIH). Discovery of the KNDy neurons that modulate GnRH secretion, on the other hand, further encourages the search for substance(s) that modulate their activity and that indirectly affect LH secretion and the hypothalamic-pituitary-ovarian axis. While it has remained an elusive hormone, GnSIF/AF holds many potential applications for contraception, in vitro fertilization, and/or cancer as well as for understanding polycystic ovary syndrome, metabolic diseases, and/or pubertal development. In this review, we rigorously examine the available evidence regarding the existence of GnSIF/AF, previous attempts at its identification, limitations to its discovery, future directions of research, and potential clinical applications. PMID:25581424

  1. Pituitary gland imaging and outcome.

    PubMed

    Di Iorgi, Natascia; Morana, Giovanni; Gallizia, Anna Lisa; Maghnie, Mohamad

    2012-01-01

    Magnetic resonance imaging (MRI) allows a detailed and precise anatomical study of the pituitary gland by differentiating between the anterior and posterior pituitary lobes. The identification of posterior pituitary hyperintensity, now considered a marker of neurohypophyseal functional integrity, has been the most striking advance for the diagnosis and understanding of anterior and posterior pituitary diseases. The advent of MRI has in fact led to a significant improvement in the understanding of the pathogenesis of disorders that affect the hypothalamo-pituitary area. Today, there is convincing evidence to support the hypothesis that marked MRI differences in pituitary morphology indicate a diverse range of disorders which affect the organogenesis and function of the anterior pituitary gland with different prognoses. Furthermore, the association of extrapituitary malformations accurately defined by MRI has supported a better definition of several conditions linked to pituitary hormone deficiencies and midline defects. MRI is a very informative procedure that should be used to support a diagnosis of hypopituitarism. It is useful in clinical management, because it helps endocrinologists determine which patients to target for further molecular studies and genetic counselling, which ones to screen for additional hormone deficits, and which ones may need growth hormone replacement into adult life.

  2. Paradoxical consequence of human chorionic gonadotropin misuse.

    PubMed

    Pektezel, Mehmet Yasir; Bas, Demet Funda; Topcuoglu, Mehmet Akif; Arsava, Ethem Murat

    2015-01-01

    Recombinant human chorionic gonadotropin (hCG) is commonly misused as a weight reducing or performance enhancing agent but is associated with increased risk of thromboembolic events. A 29-year-old female with a history of obesity was admitted to our center with a diagnosis of ischemic stroke. Etiologic workup revealed a large patent foramen ovale and history of recent use of hCG as part of a weight loss regimen. This report highlights the potential complications of hCG therapy, particularly when used for unapproved indications and without medical supervision.

  3. [Gonadotropin levels and spermatogenesis in infertile patients].

    PubMed

    Scarselli, G; DID, S

    1976-06-01

    165 STERILE MALE PATIENTS UNDERWENT SEMEN EXAMINATIONS AND SERUM GONADOTROPINS DOSAGE. In 47 of these patients a testicular biopsy was preformed. The results of the statistical analysis showed a significant correlation between the sperm count and the FSH in addition to a close and precise relation between the initial stages of the spermatogenesis and FSH. No correlation was found to exist in regard to the LH. The Authors finally showed their interpertation of such data, with the possibility of different prognosis in subjects having severe oligozoospermia, but with a bioptic picture which did or did not present damage at the spermatid maturation stage.

  4. [Impact of gonadotropins in women suffering from cancer].

    PubMed

    Valdelièvre, Constance; Sonigo, Charlotte; Comtet, Marjorie; Simon, Cynthia; Eskenazi, Sarah; Grynberg, Michaël

    2016-03-01

    The role of gonadotropins in the genesis of malignant diseases, in particular gynecologic cancers, is still controversial. The production of ovarian steroids, as a consequence of FSH and LH actions, may constitute a bias to draw reliable conclusions. Over the past decades, the use of exogenous gonadotropins has markedly increased in cancer patients, candidates for fertility preservation, and in survivors facing infertility as a consequence of gonadotoxic treatments. In gynecologic cancers, high serum estradiol levels may be problematic and can therefore be overcome by specific protocols of ovarian stimulation. However, exogenous gonadotropin administration in cancer patients should systematically be included in a multidisciplinary approach. The present article discusses the possible role of gonadotropins as tumorigenic factors and the use of exogenous gonadotropins in females suffering from cancer.

  5. 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

  6. [Micropump infusion of gonadorelin in the treatment of hypogonadotropic hypogonadism in patients with pituitary stalk interruption syndrome: cases analysis and literature review].

    PubMed

    Shao, Wei-min; Bai, Wen-jun; Chen, Yi-min; Liu, Lei; Wang, Yu-jie

    2014-08-18

    Two cases of hypogonadotropic hypogonadism caused by pituitary stalk interruption syndrome treated by pulse infusion of gonadorelin via micropump were reported, and their clinical features and the treatment process of pulse infusion of gonadorelin via micropump summarized. Both of the 2 patients were presented primarily with hypogonadotropic hypogonadism. After the treatment with pulse infusion of gonadorelin via micropump, their syndrome of androgen deficiency improved and the gonadotropin levels promoted at the end of 12 weeks' follow-up. Pulse infusion of gonadorelin via micropump is an alternative to treat hypogonadotropic hypogonadism caused by pituitary stalk interruption syndrome.

  7. Modeling the brain-pituitary-gonad axis in salmon

    SciTech Connect

    Kim, Jonghan; Hayton, William L.; Schultz, Irv R.

    2006-08-24

    To better understand the complexity of the brain-pituitary-gonad axis (BPG) in fish, we developed a biologically based pharmacodynamic model capable of accurately predicting the normal functioning of the BPG axis in salmon. This first-generation model consisted of a set of 13 equations whose formulation was guided by published values for plasma concentrations of pituitary- (FSH, LH) and ovary- (estradiol, 17a,20b-dihydroxy-4-pregnene-3-one) derived hormones measured in Coho salmon over an annual spawning period. In addition, the model incorporated pertinent features of previously published mammalian models and indirect response pharmacodynamic models. Model-based equations include a description of gonadotropin releasing hormone (GnRH) synthesis and release from the hypothalamus, which is controlled by environmental variables such as photoperiod and water temperature. GnRH stimulated the biosynthesis of mRNA for FSH and LH, which were also influenced by estradiol concentration in plasma. The level of estradiol in the plasma was regulated by the oocytes, which moved along a maturation progression. Estradiol was synthesized at a basal rate and as oocytes matured, stimulation of its biosynthesis occurred. The BPG model can be integrated with toxico-genomic, -proteomic data, allowing linkage between molecular based biomarkers and reproduction in fish.

  8. Gonadotropin-releasing hormone in the ovary.

    PubMed

    Metallinou, Chryssa; Asimakopoulos, Byron; Schröer, Andreas; Nikolettos, Nikos

    2007-12-01

    Gonadotropin-releasing hormone (GnRH) plays a pivotal role in the physiology of reproduction in mammals. GnRH acts by binding to the GnRH receptor (GnRHR). In humans, only 1 conventional GnRH receptor subtype (type I GnRH receptor) has been found. In the human genome, 2 forms of GnRH have been identified, GnRH-I (mammal GnRH) and GnRH-II (chicken GnRH II). Both forms and their common receptor are expressed, apart from the hypothalamus, in various compartments of the human ovary. Gonadal steroids, gonadotropins, and GnRH itself controls the regulation of the GnRH/GnRHR system gene expression in the human ovary. The 2 types of GnRH acting paracrinally/autocrinally influence ovarian steroidogenesis, decrease the proliferation, and induce apoptosis of ovarian cells. In this review, the biology of GnRH/GnRHR system in humans, the potential roles of GnRH, and the direct effects of GnRH analogues in ovarian cells are discussed.

  9. Pituitary dysfunction in traumatic brain injury: Is evaluation in the acute phase worthwhile?

    PubMed Central

    Dalwadi, Pradip P.; Bhagwat, Nikhil M.; Tayde, Parimal S.; Joshi, Ameya S.; Varthakavi, Premlata K.

    2017-01-01

    Introduction: Traumatic brain injury (TBI) is an under-recognized cause of hypopituitarism. According to recent data, it could be more frequent than previously known. However, there is a scarcity of data in Indian population. Aims: The main aim of the study was to determine the prevalence of pituitary hormone deficiencies in the acute phase of TBI. The secondary objectives were to correlate the severity of trauma with basal hormone levels and to determine whether initial hormone deficiencies predict mortality. Subjects and Methods: Forty-nine TBI patients (41 men and 8 women) were included in this study. Pituitary functions were evaluated within 24 h of admission. Results: Gonadotropin deficiency was found in 65.3% patient while 46.9% had low insulin-like growth factor-1, 12.24% had cortisol level <7 mcg/dl. Cortisol and prolactin level were positively correlated with the severity of TBI suggestive of stress response. Free triiodothyronine (fT3) and free thyroxine were significantly lower in patients with increasing severity of tuberculosis. Logistic regression analysis revealed that mortality after TBI was unrelated to the basal pituitary hormone levels except low T3 level, which was found to be positively related to mortality. Conclusions: Pituitary dysfunction is common after TBI and the most commonly affected axes are growth hormone and gonadotropin axis. Low fT3 correlates best with mortality. During the acute phase of TBI, at least an assessment of cortisol is vital as undetected cortisol deficiency can be life-threatening PMID:28217503

  10. Nesfatin-1 regulates the hypothalamo-pituitary-ovarian axis of fish.

    PubMed

    Gonzalez, Ronald; Shepperd, Erin; Thiruppugazh, Vetri; Lohan, Sneha; Grey, Caleb L; Chang, John P; Unniappan, Suraj

    2012-10-01

    Nesfatin-1 is an anorexigen in goldfish. In the present study, we provide novel data indicating the presence and regulatory effects of nesfatin-1 on the hypothalamo-pituitary-ovarian (HPO) axis of goldfish. Nucleobindin-2 (NUCB2)/nesfatin-1-like immunoreactive (ir) cells are present in the hypothalamus and in the pituitary, suggesting a hypophysiotropic role for nesfatin-1. NUCB2/nesfatin-1-like ir cells colocalize gonadotropin-releasing hormone (GnRH) in the nucleus lateralis tuberis posterioris and the nucleus anterior tuberis of the goldfish hypothalamus. The presence of nesfatin-1 with GnRH in these two nuclei implicated in pituitary hormone release suggests a role for nesfatin-1 on gonadotropin secretion. A single i.p. injection of synthetic goldfish nesfatin-1 (50 ng/g body wt) resulted in an acute decrease (∼75%) in the expression of hypothalamic chicken GnRH-II and salmon GnRH mRNAs at 15 min postinjection in goldfish. Meanwhile, pituitary luteinizing hormone (LH) beta and follicle-stimulating hormone beta mRNAs were also inhibited (∼80%), but only at 60 min postinjection. Nesfatin-1 administration also resulted in a significant reduction (∼60%) in serum LH levels at 60 min postadministration. Nesfatin-1-like immunoreactivity was also found in the follicle cells, but not the oocytes, in zebrafish and goldfish ovaries. Incubation of zebrafish follicles with nesfatin-1 resulted in a significant reduction in basal germinal vesicle breakdown (∼50%) during the oocyte maturation. In addition, nesfatin-1 also attenuated the stimulatory effects of maturation-inducing hormone on germinal vesicle breakdown. Together, the current results indicate that nesfatin-1 is a metabolic hormone with an inhibitory tone on fish reproduction. Nesfatin-1 appears to elicit this suppressive effect through actions on all three tissues in the fish HPO axis.

  11. Electrotonic Coupling in the Pituitary Supports the Hypothalamic-Pituitary-Gonadal Axis in a Sex Specific Manner

    PubMed Central

    Göngrich, Christina; García-González, Diego; Le Magueresse, Corentin; Roth, Lena C.; Watanabe, Yasuhito; Burks, Deborah J.; Grinevich, Valery; Monyer, Hannah

    2016-01-01

    Gap junctions are present in many cell types throughout the animal kingdom and allow fast intercellular electrical and chemical communication between neighboring cells. Connexin-36 (Cx36), the major neuronal gap junction protein, synchronizes cellular activity in the brain, but also in other organs. Here we identify a sex-specific role for Cx36 within the hypothalamic-pituitary-gonadal (HPG) axis at the level of the anterior pituitary gland (AP). We show that Cx36 is expressed in gonadotropes of the AP sustaining their synchronous activity. Cx36 ablation affects the entire downstream HPG axis in females, but not in males. We demonstrate that Cx36-mediated coupling between gonadotropes in the AP supports gonadotropin-releasing hormone-induced secretion of luteinizing hormone. Furthermore, we provide evidence for negative feedback regulation of Cx36 expression in the AP by estradiol. We thus, conclude that hormonally-controlled plasticity of gap junction communication at the level of the AP constitutes an additional mechanism affecting female reproduction. PMID:27587994

  12. Gonadotropin and kisspeptin gene expression, but not GnRH, are impaired in cFOS deficient mice

    PubMed Central

    Xie, Changchuan; Jonak, Carrie R.; Kauffman, Alexander S.; Coss, Djurdjica

    2015-01-01

    cFOS is a pleiotropic transcription factor, which binds to the AP1 site in the promoter of target genes. In the pituitary gonadotropes, cFOS mediates induction of FSHβ and GnRH receptor genes. Herein, we analyzed reproductive function in the cFOS-deficient mice to determine its role in vivo. In the pituitary cFOS is necessary for gonadotropin subunit expression, while TSHβ is unaffected. Additionally, cFOS null animals have the same sex-steroid levels, although gametogenesis is impeded. In the brain, cFOS is not necessary for GnRH neuronal migration, axon targeting, cell number, or mRNA levels. Conversely, cFOS nulls, particularly females, have decreased Kiss1 neuron numbers and lower Kiss1 mRNA levels. Collectively, our novel findings suggest that cFOS plays a cell-specific role at multiple levels of the hypothalamic–pituitary–gonadal axis, affecting gonadotropes but not thyrotropes in the pituitary, and kisspeptin neurons but not GnRH neurons in the hypothalamus, thereby contributing to the overall control of reproduction. PMID:25958044

  13. A Combined Anterior Pituitary Stimulation Test: Experience With 285 Individuals

    PubMed Central

    Elias, Alan N.; Valenta, Lubomir J.

    1987-01-01

    A pituitary reserve test was performed in 285 individuals. Eighteen were healthy volunteers without any endocrine disease, 25 suffered from a presumed hypothalamic abnormality, 22 from hypopituitarism, 10 from acromegaly, 65 from the amenorrhea-galactorrhea syndrome, 2 from Nelson's syndrome, 32 from borderline primary hypothyroidism, 15 from borderline hyperthyroidism, 20 were on chronic levothyroxine therapy for primary hypothyroidism, and 15 had severe uncorrected primary hypothyroidism. Sixteen postmenopausal women were also included, as well as 15 patients with idiopathic ovarian failure and six with ovarian dysgenesis. Twelve male patients with hypergonadotropic and 12 with hypogonadotropic hypogonadism were also examined. The pituitary reserve test consisted of intravenous administration of a mixture of the thyrotropin-releasing hormone (TRH), gonadotropin-releasing hormone (GnRH), and regular insulin. The following tests were obtained prior to the injection only (time 0): serum thyroxine (T4), tri-iodothyronine (T3), T3 resin uptake or thyroxine-binding globulin, total and free testosterone in men, estradiol and progesterone in women, and sex hormone binding globulin. At times 0, 20, 30, and 60 minutes, serum concentrations of the following compounds were obtained: glucose, adrenocorticotropic hormone, cortisol, growth hormone, prolactin, thyroid-stimulating hormone, luteinizing hormone, and follicle-stimulating hormone. Normal responses were established in a large number of cases. More or less typical patterns were demonstrated in the above-listed disease categories. Poor correlations between basal and stimulated values were observed, which emphasizes the diagnostic importance of the stimulation test. Maximum data were obtained using a combined test that has negligible morbidity, may be performed within an hour in an outpatient setting, and which examines the anterior pituitary function in a comprehensive fashion. PMID:3121862

  14. The expanding role of recombinant gonadotropins in assisted reproduction.

    PubMed

    Adams, T E; Boime, I

    2008-07-01

    Using recombinant gonadotropins for assisted reproduction of domestic species is still in its infancy. Yet, the purity, potency and pathogen-free nature of recombinant gonadotropins make them attractive alternatives to tissue-derived gonadotropic agents. In this study, the authors summarize the work to date using recombinant gonadotropins to enhance the - fertility of domestic animals and they discussed their recent studies examining the biopotency of single chain analogues of human gonadotropins. In these studies, single chain analogues of follicle stimulating hormone (Fc alpha), chorionic gonadotropin (CG beta alpha) or a gonadotropin construct with dual activity (FcCG beta alpha) were administered to sheep pre-treated with antisera directed against GnRH. Ovulation was induced 3 days after analogue administration using hCG (1000 IU, iv). Although Fc alpha or CG beta alpha alone induced only modest oestradiol production during the pre-hCG period, serum concentrations of oestradiol were markedly increased (p < 0.05) 3 days after administration of FcCG beta alpha or the Fc alpha + CG beta alpha combination. Final ovarian weight was significantly increased (p < 0.05) in animals receiving Fc alpha, Fc alpha + CG beta alpha or FcCG beta alpha. Collectively, these observations demonstrate that the single chain analogues of the human gonadotropins are active in sheep.

  15. Successful quadruplet pregnancy following ovulation induced with human menopausal gonadotropin and human chorionic gonadotropin.

    PubMed

    Lauersen, N H; Buchman, M; Beling, C G

    1974-01-01

    A case report of a quadruplet pregnancy that followed the induction of ovulation by human chorionic gonadotropin and human menopausal gonadotropin is presented. Examination revealed 4 separate placentas, indicating development from 4 different ova. The infants all did well at term, with no signs of respiratory distress syndrome, and have developed normally. Early diagnosis by ultrasonography and complete early bedrest are important for fetal survival. Hospitalization at Week 27-28 of pregnancy is essential, and a complete, competent staff able to handle high-risk patients should be available. Intravenous ethanol infusion is useful during early labor. The patient must be carefully observed for postpartum hemorrhage and should be followed in the recovery room for 24 hours.

  16. Pituitary transcription factor Prop-1 stimulates porcine follicle-stimulating hormone beta subunit gene expression.

    PubMed

    Aikawa, Satoko; Kato, Takako; Susa, Takao; Tomizawa, Kyoko; Ogawa, Satoshi; Kato, Yukio

    2004-11-12

    Molecular cloning of the transcription factor that modulates the expression of porcine follicle-stimulating hormone beta subunit (FSHbeta) gene was performed by the yeast one-hybrid cloning system using the -852/-746 upstream region (Fd2) as a bait sequence. We eventually cloned a pituitary transcription factor, Prop-1, which has been identified as an upstream transcription factor of Pit-1 gene. Binding ability of Prop-1 to the bait sequence was confirmed using recombinant Prop-1, and the binding property was investigated by DNase I footprinting, revealing that Prop-1 certainly bound to the large AT-rich region throughout the Fd2. Co-transfection of Prop-1 expression vector together with a reporter gene fused with Fd2 in CHO cells demonstrated an attractive stimulation of reporter gene expression. Immunohistochemistry of adult porcine pituitary confirmed the colocalization of the Prop-1 and FSHbeta subunit. This study is the first to report that Prop-1 participates in the regulation of FSHbeta gene. The present finding will provide new insights into the development of pituitary cell lineage and combined pituitary hormone deficiency (CPHD), since why the defect of Prop-1 causes CPHD including gonadotropins (FSH and LH) has yet to be clarified.

  17. Pituitary dysfunction after traumatic brain injury: are there definitive data in children?

    PubMed

    Casano-Sancho, Paula

    2016-11-21

    In the past decade, several studies in adults and children have described the risk of pituitary dysfunction after traumatic brain injury (TBI). As a result, an international consensus statement recommended follow-up on the survivors. This paper reviews published studies regarding hypopituitarism after TBI in children and compares their results. The prevalence of hypopituitarism ranges from 5% to 57%. Growth hormone (GH) and ACTH deficiency are the most common, followed by gonadotropins and thyroid-stimulating hormone. Paediatric studies have failed to identify risk factors for developing hypopituitarism, and therefore we have no tools to restrict screening in severe TBI. In addition, the present review highlights the lack of a unified follow-up and the fact that unrecognised pituitary dysfunction is frequent in paediatric population. The effect of hormonal replacement in patient recovery is important enough to consider baseline screening and reassessment between 6 and 12 months after TBI. Medical community should be aware of the risk of pituitary dysfunction in these patients, given the high prevalence of endocrine dysfunction already reported in the studies. Longer prospective studies are needed to uncover the natural course of pituitary dysfunction, and new studies should be designed to test the benefit of hormonal replacement in metabolic, cognitive and functional outcome in these patients.

  18. Identification of spectrin as a calmodulin-binding component in the pituitary gonadotrope

    SciTech Connect

    Wooge, C.H.

    1989-01-01

    Gonadotropin releasing hormone (GnRH) is a hypothalamic decapeptide which stimulates the release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the pituitary. Ca{sup 2+} fulfills the requirements of a second messenger for this system. Inhibition of calmodulin will inhibit GnRH stimulated LH release. The aim of the present studies has been to identify the locus of action of calmodulin within the pituitary. By use of an {sup 125}I-calmodulin gel overlayer assay, five major Ca{sup 2+}-dependent {sup 125}I-calmodulin labelled components of subunit M{sub r} > 205,000; 200,000; 135,000; 60,000; and 52,000 have been identified. This labeling was found to be phenothiazine-sensitive. Ca{sup 2+}-independent binding that was observed appears to be due to hydrophobic interactions of calmodulin with acid-soluble proteins, principally histones. Subcellular fractionation revealed that the Ca{sup 2+}-dependent calmodulin-binding components are localized primarily in the cytosolic fraction. Separation of dispersed anterior pituitary cells through a linear Metrizamide gradient yielded gonadotrope-enriched fractions, which were found to contain all five {sup 125}I-calmodulin binding components corresponding to the major bands in the pituitary homogenate. The calmodulin-binding component levels do not appear to be differentially regulated by steroids. The calmodulin binding component with a M{sub r} > 205,000 has been identified as spectrin. Spectrin-like immunoreactivity and {sup 125}I-calmodulin-binding activity in pituitary tissue homogenates co-migrated in various percentage acrylamide gels with avian erythrocyte spectrin. Spectrin was detected in a gonadotrope-enriched fraction by immunoblotting, and confirmed in gonadotropes by indirect immunofluorescence of cultured pituitary cells in which spectrin- and LH-immunoreactivity co-localized.

  19. Gonadotrope and thyrotrope development in the human and mouse anterior pituitary gland.

    PubMed

    Pope, Caroline; McNeilly, Judy R; Coutts, Shiona; Millar, Mike; Anderson, Richard A; McNeilly, Alan S

    2006-09-01

    Genes and orthologous intrinsic and extrinsic factors critical for embryonic pituitary gonadotrope and thyrotrope cell differentiation have been identified mainly in rodents, but data on the human are very limited. In human fetal pituitaries examined between 14 and 19 weeks of gestation using immunofluorescent confocal microscopy, we found that most fetal gonadotropes expressed alpha-GSU, LHbeta, and FSHbeta gonadotropin subunits while almost no cells expressed alpha-GSU and LHbeta alone. Gonadotropes expressing alpha-GSU and FSHbeta only were detected in both male and female pituitaries, increasing in proportion to total gonadotropes in both males and females from 14 (approximately 4.5%) to 19 weeks (approximately 16.5%) with a peak in males of 45.5% compared with females of 16.5% at 17 weeks of gestation. When FSHbeta or LHbeta genes were expressed, gonadotropes were non-dividing. This profile of human fetal gonadotrope development differs from the current mouse model. Furthermore, while expression of alpha-GSU appears to be the lead protein in gonadotropes, in thyrotropes which ultimately express alpha-GSU with TSHbeta, we observed that most if not all thyrotropes were TSHbeta-positive but alpha-GSU-negative until around 19 weeks in human, and e15 in mouse, fetal pituitaries. Furthermore, the TSHbeta-only thyrotropes were dividing, and TSHbeta rather than alpha-GSU was the lead protein in thyrotrope development. Thus, while biologically active dimeric FSH and LH can be produced by the human fetal pituitary by 14 weeks, dimeric biologically active TSH will only be produced from around 17 weeks of gestation. The mechanism(s) responsible for the different molecular regulation of alpha-GSU gene expression in gonadotropes and thyrotropes in the developing human fetal pituitary now requires investigation.

  20. A Novel Model for Development, Organization, and Function of Gonadotropes in Fish Pituitary

    PubMed Central

    Golan, Matan; Biran, Jakob; Levavi-Sivan, Berta

    2014-01-01

    The gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are key regulators of the reproductive axis in vertebrates. Despite the high popularity of zebrafish as a model organism for studying reproductive functions, to date no transgenic zebrafish with labeled gonadotropes have been introduced. Using gonadotropin regulatory elements from tilapia, we generated two transgenic zebrafish lines with labeled gonadotropes. The tilapia and zebrafish regulatory sequences were highly divergent but several conserved elements allowed the tilapia promoters to correctly drive the transgenes in zebrafish pituitaries. FSH cells reacted to stimulation with gonadotropin releasing hormone by proliferating and showing increased transgene fluorescence, whereas estrogen exposure caused a decrease in cell number and transgene fluorescence. Transgene fluorescence reflected the expression pattern of the endogenous fshb gene. Ontogenetic expression of the transgenes followed typical patterns, with FSH cells appearing early in development, and LH cells appearing later and increasing dramatically in number with the onset of puberty. Our transgenic lines provide a powerful tool for investigating the development, anatomy, and function of the reproductive axis in lower vertebrates. PMID:25379037

  1. Neuromuscular Involvement in Pituitary Gigantism

    PubMed Central

    Lewis, P. D.

    1972-01-01

    Investigation of two pituitary giants complaining of severe muscular weakness showed a peripheral neuropathy in both cases. Histological appearances suggestive of myopathy were also present in one case. PMID:4337949

  2. Treatment Option Overview (Pituitary Tumors)

    MedlinePlus

    ... type 1 (MEN1) syndrome . Carney complex . Isolated familial acromegaly . Signs of a pituitary tumor include problems with ... cause: Headache. Some loss of vision. In adults, acromegaly (growth of the bones in the face, hands, ...

  3. General Information about Pituitary Tumors

    MedlinePlus

    ... type 1 (MEN1) syndrome . Carney complex . Isolated familial acromegaly . Signs of a pituitary tumor include problems with ... cause: Headache. Some loss of vision. In adults, acromegaly (growth of the bones in the face, hands, ...

  4. Treatment Options for Pituitary Tumors

    MedlinePlus

    ... type 1 (MEN1) syndrome . Carney complex . Isolated familial acromegaly . Signs of a pituitary tumor include problems with ... cause: Headache. Some loss of vision. In adults, acromegaly (growth of the bones in the face, hands, ...

  5. 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

  6. Leptin influences histidine dipeptides and nitric oxide release from anterior pituitary cells of sheep in vitro.

    PubMed

    Kosior-Korzecka, U; Ducci, M; Martelli, F; Bobowiec, R

    2008-12-01

    Our previous results show that leptin, as well as nitric oxide (NO) and some antioxidants (histidine dipeptides - HDP) change the secretion of gonadotrophins from ovine adenohypophysis cells in vitro. NO and HDP are produced by pituitary and can modulate gonadotropin secretion by autocrine action. It is possible that these compounds mediate leptin influence on gonadotropin secretion. Therefore, the objective of the present study was to analyse leptin effect on NO and HDP (3-metyl-L-histidine, carnosine and anserine) release from ovine pituitary in vitro. Adenohypophysis cells were cultured in McCoy 5A medium with GnRH (4 x 10(-9) M) and 10(-10)-10(-5) M/l of leptin, respectively. Next, the media for analysis of NO (Griess method) and HDP (HPLC) were collected. Leptin in concentration of 10(-8)-10(-6) M/l caused a significant augmentation in NO in the culture medium, whereas in the dose of 10(-5) M/l reduced (P< or =0.05) NO release. The level of 3-metyl-L-histidine and anserine, but not carnosine, was significantly lower in the culture with 10(-8)-10(-7) M/l of leptin. Taking into account that 10(-8)-10(-7) M/l leptin stimulates LH and FSH secretion, as show in our previous study, it is possible that this effect in ewes is mediated by augmented release of NO and reduction of HDP level.

  7. Quadruple Injection of Hypothalamic Peptides to Evaluate Pituitary Function in Normal Subjects

    PubMed Central

    Kaltenborn, K. C.; Jubiz, William

    1985-01-01

    A single intravenous injection of four hypothalamic releasing hormones—corticotropin-, growth hormone-, gonadotropin- and thyrotropin-releasing hormones—was administered to normal subjects. Except for the plasma adrenocorticotropic hormone (ACTH) level, a statistically significant increase in all anterior pituitary hormone levels occurred. Transient flushing was the only consistent side effect. In the same persons, results were compared with those obtained with insulin-induced hypoglycemia and a single-dose overnight metyrapone test. Growth hormone and cortisol responses to insulin-induced hypoglycemia were similar but prolactin increment was less than that obtained by the peptide injection. ACTH increments from both tests were substantially less than those obtained by the overnight metyrapone test. We conclude that pituitary function can be effectively studied in normal subjects by the combination of a metyrapone test with a triple bolus of growth hormone-, thytropin- and gonadotropin-releasing hormones, but not by a quadruple bolus of the hypothalamic peptides. Compared with insulin-induced hypoglycemia, this approach yields more information with fewer side effects. PMID:3919507

  8. Quadruple injection of hypothalamic peptides to evaluate pituitary function in normal subjects.

    PubMed

    Kaltenborn, K C; Jubiz, W

    1985-01-01

    A single intravenous injection of four hypothalamic releasing hormones-corticotropin-, growth hormone-, gonadotropin- and thyrotropin-releasing hormones-was administered to normal subjects. Except for the plasma adrenocorticotropic hormone (ACTH) level, a statistically significant increase in all anterior pituitary hormone levels occurred. Transient flushing was the only consistent side effect. In the same persons, results were compared with those obtained with insulin-induced hypoglycemia and a single-dose overnight metyrapone test. Growth hormone and cortisol responses to insulin-induced hypoglycemia were similar but prolactin increment was less than that obtained by the peptide injection. ACTH increments from both tests were substantially less than those obtained by the overnight metyrapone test. We conclude that pituitary function can be effectively studied in normal subjects by the combination of a metyrapone test with a triple bolus of growth hormone-, thytropin- and gonadotropin-releasing hormones, but not by a quadruple bolus of the hypothalamic peptides. Compared with insulin-induced hypoglycemia, this approach yields more information with fewer side effects.

  9. Precipitating factors in pituitary apoplexy

    PubMed Central

    Biousse, V; Newman, N; Oyesiku, N

    2001-01-01

    Pituitary apoplexy is a rare but life threatening condition caused by sudden haemorrhage or infarction of the pituitary gland. Potential precipitating factors in the occurrence of acute pituitary apoplexy in 30 consecutive patients were identified and compared with the clinical characteristics and outcome of patients with and without associated factors. Six patients had a previously known pituitary adenoma. All patients complained of severe headaches, associated with neuro-ophthalmological symptoms and signs in 83% and altered mental status in 30%. Potential risk factors were identified in nine patients (30%). When there was an associated factor, the clinical presentation was no different than in patients without such factors although altered mental status may be more frequent in patients with associated diseases. In these patients, the visual prognosis was worse and the diagnosis was more difficult to establish. Acute pituitary apoplexy is unpredictable and should be considered in any patient with abrupt neuro-ophthalmological deterioration associated with headache. Patients with pituitary apoplexy often have an associated disease that confounds recognition and treatment despite a typical presentation.

 PMID:11561045

  10. A history of pituitary pathology.

    PubMed

    Asa, Sylvia L; Mete, Ozgur

    2014-03-01

    The history of pituitary pathology is a long one that dates back to biblical times, but the last 25 years have represented an era of "coming of age." The role of the pituitary in health and disease was the subject of many studies over the last century. With the development of electron microscopy, immunoassays, and immunohistochemistry, the functional alterations associated with pituitary disease have been clarified. The additional information provided by molecular genetic studies has allowed progress in understanding the pathogenesis of pituitary disorders. Nevertheless, many questions remain to be answered. For example, pathologists cannot morphologically distinguish locally aggressive adenomas from carcinomas when tumor is confined to the sella. Sadly, basal cell carcinoma, the most common carcinoma of skin, usually causes less morbidity than pituitary adenomas, which occur in almost 20 % of the general population, can cause significant illness and even death, and yet are still classified as benign. The opportunity to increase awareness of the impact of these common lesions on quality of life is the current challenge for physicians and patients. We anticipate that ongoing multidisciplinary approaches to pituitary disease research will offer new insights into diseases arising from this fascinating organ.

  11. Molecular characterization and functional analysis of pituitary GnRH receptor in a commercial scombroid fish, chub mackerel (Scomber japonicus).

    PubMed

    Lumayno, Sanny David Pacheco; Ohga, Hirofumi; Selvaraj, Sethu; Nyuji, Mitsuo; Yamaguchi, Akihiko; Matsuyama, Michiya

    2017-01-30

    The gonadotropin-releasing hormone (GnRH) is essential during pubertal onset, for its regulation of the synthesis and release of pituitary gonadotropins. Its action is mediated by GnRH receptors (GnRHRs) in the pituitary gonadotrophs. Our previous study demonstrated that the chub mackerel brain expresses three GnRH forms (gnrh1, gnrh2, and gnrh3), and that only GnRH1 neurons innervate anterior pituitary regions. Furthermore, chub mackerel gnrh1 mRNA exhibited a significant increase at pubertal onset. The present study aimed to isolate the functional GnRHR form involved in chub mackerel puberty. The open reading frame of our cloned receptor encodes 428 amino acids and contains seven transmembrane domains. Phylogenetic analysis also indicated clustering with other teleost-type IIB GnRHRs, mainly those involved in reproduction. Reporter gene assay results showed that all four synthetic peptides (GnRH1, GnRH2, GnRH3, and GnRH analogue) bind to the cloned receptor. Three deduced GnRH ligands stimulated luteinizing hormone (LH) release from cultured pituitary cells in vitro. Receptor gene expression was mainly detected in the pituitary and showed an increasing trend in the developing gonadal stages of both sexes during the pubertal process; this process was synchronous with previous studies of follicle-stimulating hormone beta (fshβ) and lhβ gene expression in chub mackerel. These results suggest that the cloned receptor is likely involved in the regulation of pubertal onset in this species. Therefore, we have designated the receptor cmGnRHR1.

  12. Steroidogenic Acute Regulatory Protein (StAR): Evidence of Gonadotropin-Induced Steroidogenesis in Alzheimer Disease

    PubMed Central

    Webber, Kate M; Stocco, Douglas M; Casadesus, Gemma; Bowen, Richard L; Atwood, Craig S; Previll, Laura A; Harris, Peggy LR; Zhu, Xiongwei; Perry, George; Smith, Mark A

    2006-01-01

    Background Alzheimer disease (AD) is clinically characterized by progressive memory loss, impairments in behavior, language and visual-spatial skills and ultimately, death. Epidemiological data reporting the predisposition of women to AD has led to a number of lines of evidence suggesting that age-related changes in hormones of the hypothalamic-pituitary-gonadal (HPG) axis following reproductive senescence, may contribute to the etiology of AD. Recent studies from our group and others have reported not only increases in circulating gonadotropins, namely luteinizing hormone (LH) in individuals with AD compared with control individuals, but also significant elevations of LH in vulnerable neuronal populations in individuals with AD compared to control cases as well as the highest density of gonadotropin receptors in the brain are found within the hippocampus, a region devastated in AD. However, while LH is higher in AD patients, the downstream consequences of this are incompletely understood. To begin to examine this issue, here, we examined the expression levels of steroidogenic acute regulatory (StAR) protein, which regulates the first key event in steroidogenesis, namely, the transport of cholesterol into the mitochondria, and is regulated by LH through the cyclic AMP second messenger pathway, in AD and control brain tissue. Results Our data revealed that StAR protein was markedly increased in both the cytoplasm of hippocampal pyramidal neurons as well as in the cytoplasm of other non-neuronal cell types from AD brains when compared with age-matched controls. Importantly, and suggestive of a direct mechanistic link, StAR protein expression in AD brains colocalized with LH receptor expression. Conclusion Therefore, our findings suggest that LH is not only able to bind to its receptor and induce potentially pathogenic signaling in AD, but also that steroidogenic pathways regulated by LH may play a role in AD. PMID:17018137

  13. Modulation of gonadotropin secretion by Sertoli cell inhibin, LHRH, and sex steroids.

    PubMed

    Massicotte, J; Lagacé, L; Labrie, F; Dorrington, J H

    1984-10-01

    Sertoli cell culture media (SCM) from 10-, 20-, 30-, 35-, and 40-day-old male Wistar rats were assayed to determine the inhibin activity in anterior pituitary cells in culture. In agreement with previous data, SCM did not affect the luteinizing hormone (LH) spontaneous release at all ages studied, whereas it inhibited specifically follicle-stimulating hormone (FSH) spontaneous release by 40% for the 40-day-old rats. Younger animals (10-, 20-, and 30-day-old) showed a 60% inhibition of the FSH basal release. The inhibin activity was also different at all stages studied, the IC50 being markedly displaced to the right as the age increased, leading to a fivefold difference between 10- and 30- to 40-day-old rats. The same pattern was observed when the LH and FSH responses to 0.3 nM LH-releasing hormone (LHRH) were studied. SCM from 35-day-old rats did not alter total LH, whereas total FSH was markedly reduced, thus suggesting a reduced FSH synthesis in the presence of inhibin. SCM exerts an additive inhibitory effect with dihydrotestosterone on the LH response to LHRH, whereas it reverses the stimulatory effect of the androgen on spontaneous and LHRH-induced FSH release. Moreover, SCM reversed the stimulatory effect of 17 beta-estradiol on both spontaneous and LHRH-induced LH and FSH release, whereas the stimulatory effect of progesterone on FSH release was 50-80% inhibited. The present data show that inhibin activity of Sertoli cell origin can exert marked interactions with sex steroids in the control of gonadotropin secretion. These data also demonstrate that the inhibin component is an important factor in sexual maturation of the rat and that high FSH levels of 10-day-old rats could suggest a modulation by a nonandrogenic factor of gonadotropin secretion in developing rats.

  14. Galactorrhoea and pituitary mass: a typical prolactinoma?

    PubMed Central

    Brandle, M.; Schmid, C.

    2000-01-01

    A 21 year old woman presenting with galactorrhoea, hyperprolactinaemia, and a pituitary mass on magnetic resonance imaging (MRI) is described who was referred to us before planned pituitary surgery. Although a thorough history did not suggest hypothyroidism, laboratory studies revealed profound primary hypothyroidism. At that time, pituitary MRI showed homogeneous enlargement of the pituitary gland consistent with pituitary hyperplasia due to primary hypothyroidism. With thyroid hormone replacement therapy the galactorrhoea resolved, concentrations of prolactin and thyroid hormones returned to normal, and the pituitary shrunk to normal size within two months. This case illustrates that primary hypothyroidism can present only with galactorrhoea and pituitary mass, and should therefore be considered in the differential diagnosis of hyperprolactinaemia and pituitary enlargement. 


Keywords: primary hypothyroidism; galactorrhoea; pituitary mass PMID:10727570

  15. Gonadotropins in European sea bass: Endocrine roles and biotechnological applications.

    PubMed

    Mazón, María José; Molés, Gregorio; Rocha, Ana; Crespo, Berta; Lan-Chow-Wing, Olivier; Espigares, Felipe; Muñoz, Iciar; Felip, Alicia; Carrillo, Manuel; Zanuy, Silvia; Gómez, Ana

    2015-09-15

    Follicle stimulating hormone (Fsh) and luteinizing hormone (Lh) are central endocrine regulators of the gonadal function in vertebrates. They act through specific receptors located in certain cell types found in the gonads. In fish, the differential roles of these hormones are being progressively elucidated due to the development of suitable tools for their study. In European sea bass (Dicentrarchus labrax), isolation of the genes coding for the gonadotropin subunits and receptors allowed in first instance to conduct expression studies. Later, to overcome the limitation of using native hormones, recombinant dimeric gonadotropins, which show different functional characteristics depending on the cell system and DNA construct, were generated. In addition, single gonadotropin beta-subunits have been produced and used as antigens for antibody production. This approach has allowed the development of detection methods for native gonadotropins, with European sea bass being one of the few species where both gonadotropins can be detected in their native form. By administering recombinant gonadotropins to gonad tissues in vitro, we were able to study their effects on steroidogenesis and intracellular pathways. Their administration in vivo has also been tested for use in basic studies and as a biotechnological approach for hormone therapy and assisted reproduction strategies. In addition to the production of recombinant hormones, gene-based therapies using somatic gene transfer have been offered as an alternative. This approach has been tested in sea bass for gonadotropin delivery in vivo. The hormones produced by the genes injected were functional and have allowed studies on the action of gonadotropins in spermatogenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Effects of lamprey gonadotropin-releasing hormone-III on steroidogenesis and spermiation in male sea lampreys.

    PubMed

    Deragon, K L; Sower, S A

    1994-09-01

    The biological activities of lamprey gonadotropin-releasing hormone-III (GnRH-III) were determined in the adult male sea lamprey, Petromyzon marinus. One injection of lamprey GnRH-III at 0.1 or 0.2 microgram/g body wt stimulated plasma estradiol and progesterone levels in adult male sea lampreys undergoing final maturation. Four successive injections of lamprey GnRH-III at 0.1 microgram/g of lamprey GnRH-1 at 0.2 microgram/g induced spermiation in 78 or 30% of the lampreys, respectively, compared to 0% in controls by Day 16. In summary, lamprey GnRH-III is biologically active in stimulating the pituitary-gonadal axis in adult male lampreys.

  17. The ovary feels fine when paracrine and autocrine networks cooperate with gonadotropins in the regulation of folliculogenesis.

    PubMed

    Canipari, R; Cellini, V; Cecconi, S

    2012-01-01

    The production of a mature oocyte is the major function of the female gonad. This process depends on highly coordinated interplay between all the components of the ovarian follicle, i.e. the oocyte surrounded by epithelial-derived granulosa cells and mesenchymal- derived theca cells. Follicular growth and oocyte maturation are dependent primarily on pituitary-derived gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH). However, other bioactive molecules play an important role during this process. In fact, granulosa and theca cells as well as the oocytes are the site of synthesis and/or action of a number of locally-released factors that promote the complex regulation of follicular development. The elucidation of these factors is critical to understand ovarian physiology and pathology.

  18. 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.

  19. Microdose gonadotropin-releasing hormone agonist in the absence of exogenous gonadotropins is not sufficient to induce multiple follicle development.

    PubMed

    Chung, Karine; Fogle, Robin; Bendikson, Kristin; Christenson, Kamilee; Paulson, Richard

    2011-01-01

    Because the effectiveness of the "microdose flare" stimulation protocol often is attributed to the dramatic endogenous gonadotropin release induced by the GnRH agonist, the aim of this study was to determine whether use of microdose GnRH agonist alone could induce multiple ovarian follicle development in normal responders. Based on these data, the duration of gonadotropin rise is approximately 24 to 48 hours and is too brief to sustain continued multiple follicle growth.

  20. Comparative effects of diverse vertebrate gonadotropins on estradiol-17 beta formation in vitro in an immature rat Sertoli cell bioassay.

    PubMed

    Yu, J Y; Shen, S T; Yang, W H; Papkoff, H; Ishii, S

    1996-11-01

    The biopotencies of pituitary gonadotropins (GTHs) from various vertebrate classes were examined in an in vitro rat Sertoli cell bioassay which was previously established for mammalian follicle-stimulating hormones (FSHs). Potencies of the gonadotropins were determined by incubation of Sertoli cells obtained from 10-day-old rats, with increasing doses of GTHs, which resulted in dose-related and parallel estradiol-17 beta formation converted from added 19-hydroxy-androstenedione. In general, mammalian (human and ovine) FSHs were most potent, avian (chicken, turkey, and ostrich) FSHs were intermediate, and reptilian (snapping turtle) and amphibian (bullfrog) FSHs were the least potent. By contrast, mammalian and bullfrog luteinizing hormones (LHs) were inactive or negligibly active in this assay; avian LHs possessed one-fifth to one-half of the potency of the FSH preparations of the same species. The data suggest that the assay is specific for FSHs from mammalian and amphibian species and is relatively specific for FSHs from avian species. Both snapping turtle FSH and LH exhibited low and similar potencies in this bioassay. Black silver carp GTH was also active in this assay, although its potency was much lower. The present study has demonstrated that the immature rat Sertoli cell aromatase assay in vitro is useful for measurement of FSH contents in mammalian species and of FSH activity in diverse nonmammalian species. It also provides an approach for the investigation of structure-function relations of gonadotropin in diverse vertebrate species in relation to phylogenic patterns and specificity of hormone-receptor interaction. The findings from the present study imply that the binding sites of vertebrate FSHs share a certain degree of homology and that the binding sites of FSH receptors on Sertoli cells from immature rat have a relatively low degree of animal class specificity.

  1. Dissecting the Roles of Gonadotropin-Inhibitory Hormone in Mammals: Studies Using Pharmacological Tools and Genetically Modified Mouse Models

    PubMed Central

    Leon, Silvia; Tena-Sempere, Manuel

    2016-01-01

    Reproduction is essential for perpetuation of the species and, hence, is controlled by a sophisticated network of regulatory factors of central and peripheral origin that integrate at the hypothalamic–pituitary–gonadal (HPG) axis. Among the central regulators of reproduction, kisspeptins, as major stimulatory drivers of gonadotropin-releasing hormone (GnRH) neurosecretion, have drawn considerable interest in the last decade. However, the dynamic, if not cyclic (in the female), nature of reproductive function and the potency of kisspeptins and other stimulatory signals of the HPG axis make tenable the existence of counterbalance inhibitory mechanisms, which may keep stimulation at check and would allow adaptation of reproductive maturation and function to different endogenous and environmental conditions. In this context, discovery of the gonadotropin-inhibitory hormone (GnIH) in birds, and its mammalian homolog, RFRP, opened up the exciting possibility that this inhibitory signal might operate centrally to suppress, directly or indirectly, GnRH/gonadotropin secretion, thus reciprocally cooperating with other stimulatory inputs in the dynamic regulation of the reproductive hypothalamic–pituitary unit. After more than 15 years of active research, the role of GnIH/RFRP in the control of the HPG axis has been documented in different species. Yet, important aspects of the physiology of this system, especially regarding its relative importance and actual roles in the control of key facets of reproductive function, remain controversial. In the present work, we aim to provide a critical review of recent developments in this area, with special attention to studies in rodent models, using pharmacological tools and functional genomics. In doing so, we intend to endow the reader with an updated view of what is known (and what is not known) about the physiological role of GnIH/RFRP signaling in the control of mammalian reproduction. PMID:26779117

  2. The Regulation and Function of Fibroblast Growth Factor 8 and Its Function during Gonadotropin-Releasing Hormone Neuron Development

    PubMed Central

    Chung, Wilson C. J.; Linscott, Megan L.; Rodriguez, Karla M.; Stewart, Courtney E.

    2016-01-01

    Over the last few years, numerous studies solidified the hypothesis that fibroblast growth factor (FGF) signaling regulates neuroendocrine progenitor cell proliferation, fate specification, and cell survival and, therefore, is critical for the regulation and maintenance of homeostasis of the body. One important example that underscores the involvement of FGF signaling during neuroendocrine cell development is gonadotropin-releasing hormone (GnRH) neuron ontogenesis. Indeed, transgenic mice with reduced olfactory placode (OP) Fgf8 expression do not have GnRH neurons. This observation indicates the requirement of FGF8 signaling for the emergence of the GnRH neuronal system in the embryonic OP, the putative birth place of GnRH neurons. Mammalian reproductive success depends on the presence of GnRH neurons to stimulate gonadotropin secretion from the anterior pituitary, which activates gonadal steroidogenesis and gametogenesis. Together, these observations are critical for understanding the function of GnRH neurons and their control of the hypothalamus–pituitary–gonadal (HPG) axis to maintain fertility. Taken together, these studies illustrate that GnRH neuron emergence and hence HPG function is vulnerable to genomic and molecular signals that abnormally modify Fgf8 expression in the developing mouse OP. In this short review, we focus on research that is aimed at unraveling how androgen, all-trans retinoic acid, and how epigenetic factors modify control mouse OP Fgf8 transcription in the context of GnRH neuronal development and mammalian reproductive success. PMID:27656162

  3. Heterogeneous nuclear ribonucleoprotein A/B and G inhibits the transcription of gonadotropin-releasing-hormone 1

    PubMed Central

    Zhao, Sheng; Korzan, Wayne J.; Chen, Chun-Chun; Fernald, Russell D.

    2008-01-01

    Gonadotropin releasing hormone 1 (GnRH1) causes the release of gonadotropins from the pituitary to control reproduction. Here we report that two heterogeneous nuclear ribonucleoproteins (hnRNP-A/B and hnRNP-G) bind to the GnRH-I upstream promoter region in a cichlid fish, Astatotilapia burtoni. We identified these binding proteins using a newly developed homology based method of mass spectrometric peptide mapping. We show that both hnRNP-A/B and hnRNP-G co-localize with GnRH1 in the pre-optic area of the hypothalamus in the brain. We also demonstrated that these ribonucleoproteins exhibit similar binding capacity in vivo, using immortalized mouse GT1-7 cells where overexpression of either hnRNP-A/B or hnRNP-G significantly down-regulate GnRH1 mRNA levels in GT1-7 cells, suggesting that both act as repressors in GnRH1 transcriptional regulation. PMID:17920292

  4. Effect of improved nutrition during calfhood on serum metabolic hormones, gonadotropins, and testosterone concentrations, and on testicular development in bulls.

    PubMed

    Brito, Leonardo F C; Barth, Albert D; Rawlings, Norm C; Wilde, Randal E; Crews, Denny H; Mir, Priya S; Kastelic, John P

    2007-11-01

    The objective of the present study was to evaluate the effects of improved nutrition during calfhood on serum metabolic hormones, gonadotropins and testosterone concentrations, and on sexual development in bulls. Bulls received high (n=17) or control nutrition (n=16) diets from 10 to 30 week of age and the same control nutrition diet from 31 to 74 week of age. Improved nutrition during calfhood resulted in a more sustained period of elevated LH secretion (pulse frequency and total secretion in 10h) during the early gonadotropin rise. GnRH-stimulated LH secretion was not affected by diet, indicating that pituitary responsiveness was not altered; therefore, improved nutrition had direct effects on GnRH secretion by the hypothalamus. Insulin and insulin-like growth factor-I (IGF-I) concentrations were greater during calfhood in bulls receiving high nutrition, indicating that these metabolic hormones might be involved in regulating GnRH and LH secretion. Improved nutrition also resulted in increased testosterone secretion that was associated with greater circulating IGF-I concentrations, suggesting a role for this metabolic hormone in regulating Leydig cell number and function. Furthermore, improved nutrition during calfhood resulted in greater testicular weight and sperm production in mature bulls, indicating that increased LH secretion during calfhood, and increased IGF-I and testosterone concentrations during calfhood and peripubertal period were associated with greater testicular cell proliferation and enhanced function.

  5. Pituitary apoplexy within a macroprolactinoma.

    PubMed

    Watt, Alastair; Pobereskin, Louis; Vaidya, Bijay

    2008-11-01

    A 61-year-old lady was admitted to hospital with sepsis due to a urinary tract infection. Three days after admission, she suddenly started to have severe headache with visual disturbance and right third nerve palsy. Urgent magnetic resonance angiography excluded internal carotid artery aneurysm but showed a large lesion extending superiorly from the clivus towards the right cerebral peduncle, which was confirmed by a CT scan of the brain. The lesion was initially thought to be a primary or a metastatic brain tumor. CT scans of the thorax, abdomen and pelvis showed no evidence of metastatic disease. MRI scan revealed a huge pituitary adenoma containing hemorrhage. Subsequent pituitary function tests indicated a grossly elevated serum prolactin level and hypopituitarism. Magnetic resonance angiography of the head; CT scans of the brain, thorax, abdomen and pelvis; MRI scan of the pituitary gland; and baseline and dynamic anterior pituitary function testing. Pituitary apoplexy within a macroprolactinoma. Steroid replacement, careful control of fluid and electrolyte balance and conservative nonsurgical management with the dopamine agonist cabergoline resulted in resolution of the patient's headache, improvement of the third nerve palsy and subsequent normalization of the prolactin level, with reduction in size of the prolactinoma on MRI scan.

  6. Transcranial surgery for pituitary adenomas.

    PubMed

    Youssef, A Samy; Agazzi, Siviero; van Loveren, Harry R

    2005-07-01

    Although the transsphenoidal approach is the preferred approach to the vast majority of pituitary tumors with or without suprasellar extension, the transcranial approach remains a vital part of the neurosurgical armamentarium for 1 to 4% of these tumors. The transcranial approach is effective when resection becomes necessary for a portion of a pituitary macroadenoma that is judged to be inaccessible from the transsphenoidal route because of isolation by a narrow waist at the diaphragma sellae, containment within the cavernous sinus lateral to the carotid artery, projection anteriorly onto the planum sphenoidale, or projection laterally into the middle fossa. The application of a transcranial approach in these circumstances may still be mitigated by response to prolactin inhibition of prolactinomas, the frequent lack of necessity to remove asymptomatic nonsecretory adenomas from the cavernous sinus, and the lack of evidence that sustained chemical cures can be reliably achieved by removal of secretory adenomas (adrenocorticotropic hormone, growth hormone) from the cavernous sinus. Cranial base surgical techniques have refined the surgical approach to pituitary adenomas but have had less effect on actual surgical indications than anticipated. Because application of the transcranial approach to pituitary adenomas is and should be rare in clinical practice, it is useful to standardize the technique to a default mode with which the surgical team is most experienced and, therefore, most comfortable. Our default mode for transcranial pituitary surgery is the frontotemporal-orbitozygomatic approach.

  7. 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.

  8. The brain-pituitary-gonad axis in male teleosts, with special emphasis on flatfish (Pleuronectiformes).

    PubMed

    Weltzien, Finn-Arne; Andersson, Eva; Andersen, Øivind; Shalchian-Tabrizi, Kamran; Norberg, Birgitta

    2004-03-01

    The key component regulating vertebrate puberty and sexual maturation is the endocrine system primarily effectuated along the brain-pituitary-gonad (BPG) axis. By far most investigations on the teleost BPG axis have been performed on salmonids, carps, catfish and eels. Accordingly, earlier reviews on the BPG axis in teleosts have focused on these species, and mainly on females (e.g. 'Fish Physiology, vol. IXA. Reproduction (1983) pp. 97'; 'Proceedings of the Fourth International Symposium on the Reproductive Physiology of Fish. FishSymp91, Sheffield, UK, 1991, pp. 2'; 'Curr. Top. Dev. Biol. 30 (1995) pp. 103'; 'Rev. Fish Biol. Fish. 7 (1997) pp. 173'; 'Proceedings of the Sixth International Symposium on the Reproductive Physiology of Fish. John Grieg A/S, Bergen, Norway, 2000, pp. 211'). However, in recent years new data have emerged on the BPG axis in flatfish, especially at the level of the brain and pituitary. The evolutionarily advanced flatfishes are important model species both from an evolutionary point of view and also because many are candidates for aquaculture. The scope of this paper is to review the present status on the male teleost BPG axis, with an emphasis on flatfish. In doing so, we will first discuss the present understanding of the individual constituents of the axis in the best studied teleost models, and thereafter discuss available data on flatfish. Of the three constituents of the BPG axis, we will focus especially on the pituitary and gonadotropins. In addition to reviewing recent information on flatfish, we present some entirely new information on the phylogeny and molecular structure of teleost gonadotropins.

  9. Intraovarian expression of GnRH-1 and gonadotropin mRNA and protein levels in Siberian hamsters during the estrus cycle and photoperiod induced regression/recrudescence

    PubMed Central

    Shahed, Asha; Young, Kelly A.

    2010-01-01

    The hypothalamic-pituitary-gonadal (HPG) axis is the key reproductive regulator in vertebrates. While gonadotropin releasing hormone (GnRH), follicle stimulating (FSH), and luteinizing (LH) hormones are primarily produced in the hypothalamus and pituitary, they can be synthesized in the gonads, suggesting an intraovarian GnRH-gonadotropin axis. Because these hormones are critical for follicle maturation and steroidogenesis, we hypothesized that this intraovarian axis may be important in photoperiod-induced ovarian regression/recrudescence in seasonal breeders. Thus, we investigated GnRH-1 and gonadotropin mRNA and protein expression in Siberian hamster ovaries during (1) the estrous cycle; where ovaries from cycling long day hamsters (LD;16L:8D) were collected at proestrus, estrus, diestrus I, and diestrus II and (2) during photoperiod induced regression/ recrudescence; where ovaries were collected from hamsters exposed to 14wks of LD, short days (SD;8L:16D), or 8wks post-transfer to LD after 14wks SD (PT). GnRH-1, LHβ, FSHβ, and common α subunit mRNA expression was observed in cycling ovaries. GnRH-1 expression peaked at diestrus I compared to other stages (p<0.05). FSHβ and LHβ mRNA levels peaked at proestrus and diestrus I (p<0.05), with no change in the α subunit across the cycle (p>0.05). SD exposure decreased ovarian mass and plasma estradiol concentrations (p<0.05) and increased GnRH-1, LHβ, FSHβ, and α subunit mRNA expression as compared to LD and, except for LH, compared to PT (p<0.05). GnRH and gonadotropin protein was also dynamically expressed across the estrous cycle and photoperiod exposure. The presence of cycling intraovarian GnRH-1 and gonadotropin mRNA suggests that these hormones may be locally involved in ovarian maintenance during SD regression and/or could potentially serve to prime ovaries for rapid recrudescence. PMID:20955709

  10. [Treatment of pituitary adenoma].

    PubMed

    Chanson, P

    1998-12-12

    RECOMMENDED TREATMENTS: The different therapeutic strategies proposed for pituitary adenomas are relatively well-known thanks to numerous studies evaluating their effect on outcome. Unfortunately, large comparative clinical trials are difficult to construct due to the small number of cases of this rare condition. Therapeutic recommendations are thus generally based on the opinion of recognized experts. MICROADENOMA: Small (< 10 mm) prolactin-secreting adenomas should be treated surgically, generally by transsphenoidal adenomectomy, or medically by dopaminergic agonists: bromocriptin, quinagolide or cabergolin (the two latter drugs are more effective and better tolerated than their parent compound bromocriptin). MACROADENOMA: The expected success rate for surgical treatment of macroadenomas is low and dopaminergic agonists is generally recommended (including cases with visual impairment since the effect can be very rapid). Prolactin levels can be lowered and tumor volume reduced (in > 70% of cases). ACROMEGALY: Surgery is the firs intention treatment for acromegaly. In case of unsuccessful surgery (the criteria for "cure" are much more strict in 1998 than previously), somatostatin analog and/or hypothalamo-hypophyseal radiotherapy are recommended. Slow release formulations of somatostatin analogs can now be given by monthly (octreotide LP) or biweekly (lanreotide LP) injections. CUSHING'S DISEASE: Cure can be achieved in > 80% of cases with surgery, the first intention treatment of choice. If surgery is unsuccessful, radiotherapy can be proposed associated with anticortisol drugs (mitotane), if needed, while waiting for the late effect of radiotherapy. CLINICALLY SILENT ADENOMAS: Non-functional adenomas should be operated. Some propose adjuvant radiotherapy in all cases and others only if residual tissue persists post-operatively.

  11. Identification of a regulatory loop for the synthesis of neurosteroids: a steroidogenic acute regulatory protein-dependent mechanism involving hypothalamic-pituitary-gonadal axis receptors

    PubMed Central

    Meethal, Sivan Vadakkadath; Liu, Tianbing; Chan, Hsien W.; Ginsburg, Erika; Wilson, Andrea C.; Gray, Danielle N.; Bowen, Richard L.; Vonderhaar, Barbara K.; Atwood, Craig S.

    2009-01-01

    Brain sex steroids are derived from both peripheral (primarily gonadal) and local (neurosteroids) sources and are crucial for neurogenesis, neural differentiation and neural function. The mechanism(s) regulating the production of neurosteroids is not understood. To determine whether hypothalamic-pituitary-gonadal axis components previously detected in the extra-hypothalamic brain comprise a feedback loop to regulate neuro-sex steroid (NSS) production, we assessed dynamic changes in expression patterns of steroidogenic acute regulatory (StAR) protein, a key regulator of steroidogenesis, and key hypothalamic-pituitary-gonadal endocrine receptors, by modulating peripheral sex hormone levels in female mice. Ovariectomy (OVX; high serum gonadotropins, low serum sex steroids) had a differential effect on StAR protein levels in the extrahypothalamic brain; increasing the 30- and 32-kDa variants but decreasing the 37-kDa variant and is indicative of cholesterol transport into mitochondria for steroidogenesis. Treatment of OVX animals with E2,P4,or E2 + P4 for 3 days, which decreases OVX-induced increases in GnRH/gonadotropin production, reversed this pattern. Suppression of gonadotropin levels in OVX mice using the GnRH agonist leuprolide acetate inhibited the processing of the 37-kDa StAR protein into the 30-kDa StAR protein, confirming that the differential processing of brain StAR protein is regulated by gonadotropins. OVX dramatically suppressed extra-hypothalamic brain gonadotropin-releasing hormone 1 receptor expression, and was further suppressed in E2- or P4-treated OVX mice. Together, these data indicate the existence of endocrine and autocrine/paracrine feedback loops that regulate NSS synthesis. Further delineation of these feedback loops that regulate NSS production will aid in developing therapies to maintain brain sex steroid levels and cognition. PMID:19493163

  12. Evolutionary origin of the structure and function of gonadotropin-inhibitory hormone: insights from lampreys.

    PubMed

    Osugi, Tomohiro; Daukss, Dana; Gazda, Kristen; Ubuka, Takayoshi; Kosugi, Takayoshi; Nozaki, Masumi; Sower, Stacia A; Tsutsui, Kazuyoshi

    2012-05-01

    Gonadotropin (GTH)-inhibitory hormone (GnIH) is a novel hypothalamic neuropeptide that inhibits GTH secretion in mammals and birds by acting on gonadotropes and GnRH neurons within the hypothalamic-pituitary-gonadal axis. GnIH and its orthologs that have an LPXRFamide (X = L or Q) motif at the C terminus (LPXRFamide peptides) have been identified in representative species of gnathostomes. However, the identity of an LPXRFamide peptide had yet to be identified in agnathans, the most ancient lineage of vertebrates, leaving open the question of the evolutionary origin of GnIH and its ancestral function(s). In this study, we identified an LPXRFamide peptide gene encoding three peptides (LPXRFa-1a, LPXRFa-1b, and LPXRFa-2) from the brain of sea lamprey by synteny analysis and cDNA cloning, and the mature peptides by immunoaffinity purification and mass spectrometry. The expression of lamprey LPXRFamide peptide precursor mRNA was localized in the brain and gonad by RT-PCR and in the hypothalamus by in situ hybridization. Immunohistochemistry showed appositions of lamprey LPXRFamide peptide immunoreactive fibers in close proximity to GnRH-III neurons, suggesting that lamprey LPXRFamide peptides act on GnRH-III neurons. In addition, lamprey LPXRFa-2 stimulated the expression of lamprey GnRH-III protein in the hypothalamus and GTHβ mRNA expression in the pituitary. Synteny and phylogenetic analyses suggest that the LPXRFamide peptide gene diverged from a common ancestral gene likely through gene duplication in the basal vertebrates. These results suggest that one ancestral function of LPXRFamide peptides may be stimulatory compared with the inhibitory function seen in later-evolved vertebrates (birds and mammals).

  13. Gonadotropin releasing hormone in the primitive vertebrate family Myxinidae: reproductive neuroanatomy and evolutionary aspects.

    PubMed

    Sills, Eric Scott; Palermo, Gianpiero D

    2013-01-01

    The family Myxinidae embraces all hagfish species, and occupies an evolutionary niche intermediate between ancestral vertebrates and the gnathostomes (jawed vertebrates). Gonadotropin releasing hormone (GnRH) modulates neuroendocrine activity in vertebrates and works in the context of the hypothalamic-pituitary (H-P) axis. The appearance of this neuroendocrine axis marks one of the most crucial developmental achievements in vertebrate evolution, because it enabled further diversification in general growth, metabolism, osmoregulation and reproduction as jawed vertebrates evolved. GnRH studies in hagfish draw attention because such work may be considered as providing proxy data for similar investigations conducted upon long extinct species. Indeed, the fossil record reveals little anatomical difference between those hagfish living 300 million years ago and their modern descendants. Accordingly, the hagfish can offer important evolutionary lessons as they have some highly unusual characteristics not seen in any other vertebrate; they retain many representative features of an ancestral state from which all vertebrates originated. Indeed, because central control of reproduction is perhaps the most basic function of the vertebrate H-P axis, and given the importance of GnRH in this network, research on GnRH in hagfish can help elucidate the early evolution of the H-P system itself. Like all vertebrates, hagfish have a functional hypothalamic area and a pituitary gland, constituting a basic H-P axis. But what role does GnRH play in the reproductive system of this "living fossil"? How can understanding GnRH in hagfish help advance the knowledge of vertebrate neuroendocrinology? Here, information on neuroendocrine function and the role of GnRH specifically in this very basal vertebrate is reviewed.

  14. What Happens After Treatment for Pituitary Tumors?

    MedlinePlus

    ... adenomas. If you had a functional (hormone-making) pituitary adenoma, hormone measurements can often be done within days ... risk. Occasionally, people with large or fast-growing pituitary adenomas may be disabled or have their lives shortened ...

  15. Human Chorionic Gonadotropin and Breast Cancer

    PubMed Central

    Schüler-Toprak, Susanne; Treeck, Oliver; Ortmann, Olaf

    2017-01-01

    Breast cancer is well known as a malignancy being strongly influenced by female steroids. Pregnancy is a protective factor against breast cancer. Human chorionic gonadotropin (HCG) is a candidate hormone which could mediate this antitumoral effect of pregnancy. For this review article, all original research articles on the role of HCG in breast cancer were considered, which are listed in PubMed database and were written in English. The role of HCG in breast cancer seems to be a paradox. Placental heterodimeric HCG acts as a protective agent by imprinting a permanent genomic signature of the mammary gland determining a refractory condition to malignant transformation which is characterized by cellular differentiation, apoptosis and growth inhibition. On the other hand, ectopic expression of β-HCG in various cancer entities is associated with poor prognosis due to its tumor-promoting function. Placental HCG and ectopically expressed β-HCG exert opposite effects on breast tumorigenesis. Therefore, mimicking pregnancy by treatment with HCG is suggested as a strategy for breast cancer prevention, whereas targeting β-HCG expressing tumor cells seems to be an option for breast cancer therapy. PMID:28754015

  16. Gonadotropin subunits of the characiform Astyanax altiparanae: Molecular characterization, spatiotemporal expression and their possible role on female reproductive dysfunction in captivity.

    PubMed

    de Jesus, Lázaro Wender O; Bogerd, Jan; Vieceli, Felipe M; Branco, Giovana S; Camargo, Marília P; Cassel, Mônica; Moreira, Renata G; Yan, Chao Y I; Borella, Maria I

    2017-05-15

    To better understand the endocrine control of reproduction in Characiformes and the reproductive dysfunctions that commonly occur in migratory fish of this order when kept in captivity, we chose Astyanax altiparanae, which has asynchronous ovarian development and multiple spawning events, as model species. From A. altiparanae pituitary total RNA, we cloned the full-length cDNAs coding for the follicle-stimulating hormone β subunit (fshb), the luteinizing hormone β subunit (lhb), and the common gonadotropin α subunit (gpha). All three sequences showed the highest degree of amino acid identity with other homologous sequences from Siluriformes and Cypriniformes. Real-time, quantitative PCR analysis showed that gpha, fshb and lhb mRNAs were restricted to the pituitary gland. In situ hybridization and immunofluorescence, using specific-developed and characterized polyclonal antibodies, revealed that both gonadotropin β subunits mRNAs/proteins are expressed by distinct populations of gonadotropic cells in the proximal pars distalis. No marked variations for lhb transcripts levels were detected during the reproductive cycle, and 17α,20β-dihydroxy-4-pregnen-3-one plasma levels were also constant, suggesting that the reproductive dysfunction seen in A. altiparanae females in captivity are probably due to a lack of increase of Lh synthesis during spawning season. In contrast, fshb transcripts changed significantly during the reproductive cycle, although estradiol-17β (E2) levels remained constant during the experiment, possibly due to a differential regulation of E2 synthesis. Taken together, these data demonstrate the putative involvement of gonadotropin signaling on the impairment of the reproductive function in a migratory species when kept in captivity. Future experimental studies must be carried to clarify this hypothesis. All these data open the possibility for further basic and applied studies related to reproduction in this fish model. Copyright © 2016

  17. NR5A2 Regulates Lhb and Fshb Transcription in Gonadotrope-Like Cells In Vitro, but Is Dispensable for Gonadotropin Synthesis and Fertility In Vivo

    PubMed Central

    Fortin, Jérôme; Kumar, Vikas; Zhou, Xiang; Wang, Ying; Auwerx, Johan; Schoonjans, Kristina; Boehm, Ulrich; Boerboom, Derek; Bernard, Daniel J.

    2013-01-01

    Successful mammalian reproduction depends on proper synthesis of the pituitary-derived glycoprotein hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Several transcription factors cooperate to activate cell-specific and hormone-regulated expression of the gonadotropin beta subunits (Lhb and Fshb). Among these, NR5A1 (steroidogenic factor 1; SF1) has been shown to directly bind to the Lhb promoter, mediate basal and gonadotropin-releasing hormone (GnRH)-stimulated Lhb transcription, and possibly directly regulate Fshb expression. Recently, the closely-related NR5A2 was shown to activate the rat Lhb promoter in vitro. Here, we further characterized the role of NR5A2 in regulating gonadotropin synthesis. Ectopically expressed NR5A2 directly activated the murine Lhb promoter in a manner identical to that of NR5A1, whereas neither factor activated the murine Fshb promoter. In LβT2 gonadotrope-like cells, depletion of endogenous NR5A1 or NR5A2 impaired basal and GnRH-stimulated Lhb and Fshb transcription. To analyze the physiological role of NR5A2 in gonadotropes in vivo, we generated mice with a gonadotrope-specific deletion of Nr5a2. In contrast with our in vitro data, these mice had normal pituitary Lhb and Fshb expression and intact fertility. Together, our data establish that NR5A2 can act in a non-redundant manner to regulate Lhb and Fshb transcription in vitro, but is dispensable in vivo. PMID:23536856

  18. Testosterone enhances GABA and taurine but not N-methyl-D,L-aspartate stimulation of gonadotropin secretion in the goldfish: possible sex steroid feedback mechanisms.

    PubMed

    Trudeau, V L; Sloley, B D; Peter, R E

    1993-04-01

    The effects of gonadal steroids on GABA-, taurine (TAU)- and N-methyl-D,L-aspartate (NMA)-induced gonadotropin-II (GTH-II) release were investigated in male and female goldfish in vivo. In sexually regressed goldfish (both sexes mixed), intraperitoneal implantation for 5 to 10 days with solid Silastic pellets containing testosterone (100 micrograms/g), oestradiol (100 micrograms/g) or progesterone (100 micrograms/g) was previously shown to elevate serum sex steroid levels to values comparable to those in sexually mature animals, and to potentiate gonadotropin-releasing hormone-stimulated GTH-II release. In the present study, testosterone but not oestradiol or progesterone enhanced the stimulatory effects of exogenous GABA (100 micrograms/g) on GTH-II release in vivo. TAU (1 mg/g) stimulated GTH-II release in sexually regressed mixed sex and sexually recrudescent male goldfish, and both testosterone and oestradiol implantation enhanced GTH-II release induced by TAU. The glutamate agonist NMA (25 to 50 micrograms/g) was also found to stimulate GTH-II release; however it was relatively less effective in elevating serum GTH-II levels than GABA and TAU, and its effects were not modulated by sex steroid treatments. Pretreatment of goldfish with alpha-methyl-p-tyrosine to deplete brain and pituitary catecholamines did not affect NMA action on GTH-II release. Our results indicate that GABA, TAU and NMA are involved in the neuroendocrine regulation of GTH-II release in goldfish, and support the idea that testosterone participates in the positive feedback regulation of pituitary gonadotropin release in a non-mammalian vertebrate by enhancing GABA- and TAU-stimulated GTH release in vivo.

  19. Use of the immature rat uterotrophic assay for specific measurements of chorionic gonadotropins and follicle-stimulating hormones in vivo bioactivities.

    PubMed

    Lecompte, F; Harbeby, E; Cahoreau, C; Klett, D; Combarnous, Y

    2010-09-15

    The uterine weight growth stimulation by equine Chorionic Gonadotropin (eCG/PMSG) was found to occur at much lower eCG concentrations than ovarian growth. Human Chorionic Gonadotropin (hCG) which has only LH activity, was found to be as active as eCG in the uterotrophic assay whereas equine Luteinizing Hormone (eLH) which has dual LH+FSH activities like eCG, exhibited a much lower potency. In contrast to hCG, porcine and ovine LH as well as pFSH and oFSH exhibited no uterotrophic activity indicating that only gonadotropins with both LH activity and long half-lives are active alone in this assay. The FSH preparations were nevertheless found to trigger a dose-dependent response, but only in the presence of a subactive dose of hCG. The uterotrophic activity of hCG was found to be suppressed in ovariectomized immature rats and to be diminished after injection of GnRH antagonist suggesting an indirect pathway implicating the hypothalamo-pituitary complex. The data in this report together with the analysis of literature suggest that choriogonadotropins exert their stimulatory role on uterine growth by an indirect mechanism involving an increase in ovarian FSH receptors and FSH release by the pituitary. At the lowest concentrations of hCG, the increase in ovarian FSH receptors without endogenous FSH release is thought to be responsible for the sensitivity of the uterotrophic assay to exogenous FSHs. In conclusion, the immature rat uterotrophic assay is a sensitive and convenient assay for eCG and hCG as well as for FSHs in the presence of a sub-active dose of hCG.

  20. Cerebral ischaemia in pituitary apoplexy.

    PubMed

    Ahmed, Shahzada K; Semple, Patrick L

    2008-11-01

    Pituitary apoplexy is a potentially fatal condition that can have serious consequences even after successful treatment. One of the potential complications of this syndrome is occlusion of the internal carotid arteries, which causes cerebral ischaemia. This can occur through one of two mechanisms--direct compression of the artery or vasospasm caused by factors released from haemorrhagic or necrotic material. We illustrate two examples of cerebral ischaemia with pituitary apoplexy, one with compression and one with vasospasm, both ending in a successful resolution. In both, magnetic resonance imaging, angiography, and hormonal studies allow diagnosis, and urgent surgical decompression should be the treatment of choice. We review the literature and discuss the mechanisms.

  1. Pituitary function and morphology in Fabry disease.

    PubMed

    Maione, Luigi; Tortora, Fabio; Modica, Roberta; Ramundo, Valeria; Riccio, Eleonora; Daniele, Aurora; Belfiore, Maria Paola; Colao, Annamaria; Pisani, Antonio; Faggiano, Antongiulio

    2015-11-01

    Endocrine abnormalities are known to affect patients with Fabry disease (FD). Pituitary gland theoretically represents an ideal target for FD because of high vascularization and low proliferation rate. We explored pituitary morphology and function in a cohort of FD patients through a prospectic, monocentric study at an Academic Tertiary Center. The study population included 28 FD patients and 42 sex and age-matched normal subjects. The protocol included a contrast enhancement pituitary MRI, the assessment of pituitary hormones, anti-pituitary, and anti-hypothalamus antibodies. At pituitary MRI, an empty sella was found in 11 (39%) FD patients, and in 2 (5%) controls (p < 0.001). Pituitary volume was significantly smaller in FD than in controls (p < 0.001). Determinants of pituitary volume were age and alpha-galactosidase enzyme activity. Both parameters resulted independently correlated at multivariate analysis. Pituitary function was substantially preserved in FD patients. Empty sella is a common finding in patients with FD. The major prevalence in the elderly supports the hypothesis of a progressive pituitary shrinkage overtime. Pituitary function seems not to be impaired in FD. An endocrine workup with pituitary hormone assessment should be periodically performed in FD patients, who are already at risk of cardiovascular complications.

  2. Anterior pituitary gene expression with reproductive aging in the female rat.

    PubMed

    Zheng, Weiming; Jimenez-Linan, Mercedes; Rubin, Beverly S; Halvorson, Lisa M

    2007-06-01

    Although reproductive aging in women is classically attributed to loss of ovarian follicles, recent data have suggested that the entire hypothalamic-pituitary-ovarian axis undergoes functional changes with time. The aim of this study was to characterize age-related changes in pituitary gene expression for factors with known importance for gonadotroph function, including 1) steroid hormone receptors (Esr and Pgr), 2) orphan nuclear receptors [Nr5a1 (steroidogenic factor-1) and Nr5a2 (liver receptor homologue-1)], and 3) pituitary-derived polypeptides (activin, inhibin, and follistatin), as well as 4) gonadotropin subunits and 5) GnRH receptors. We chose to utilize a middle-aged rat model for these studies. Young (Y; 3-mo-old) and middle-aged (MA; 9- to 12-mo-old) rats were ovariectomized, primed with estradiol, and injected with progesterone to induce an LH surge. The mRNA levels for the gonadotropin subunits and GnRH receptors were decreased in middle-aged females relative to young animals. Nr5a1 and follistatin mRNA levels were significantly greater in Y versus MA animals following ovariectomy. Furthermore, steroid-induced regulation of these genes was lost in the MA animals. Regulation of the Nr5a2, Inhba, and Inhbb transcripts was also limited to the young animals. In contrast, there were no significant differences in the mRNA levels of Esr or Pgr family members between age groups at any time point. Although this in vivo model normalizes ovarian steroid levels, it does not control for potential differences in GnRH stimulation with aging. Therefore, in a second set of experiments, we used an in vitro perifusion system to compare the effects of pulsatile GnRH in the two age groups. Nr5a1 mRNA expression was greater in Y than MA animals and was significantly decreased by GnRH pulses in both age groups. Follistatin mRNA levels increased significantly with GnRH treatment in Y animals but were not significantly changed in the MA females. Taken together, these data

  3. The antigonadotropic action of testosterone but not 7alpha-methyl-19-nortestosterone is attenuated through the 5alpha-reductase pathway in the castrated male rat pituitary gland.

    PubMed

    Bandivdekar, A H; Karp, R; Sundaram, K; Kumar, N

    2000-01-01

    The enzyme 5alpha-reductase plays a significant role in the prostate to amplify the action of testosterone (T) by converting it to a more potent androgen, dihydrotestosterone (DHT). The role of 5alpha-reductase in the testosterone feedback inhibition of gonadotropin secretion from the pituitary has not been elucidated. Therefore, we investigated the role of 5alpha-reductase on T action in in vitro and in vivo models. Castration has been reported to increase the 5alpha-reductase activity in pituitary glands. Hence, the effect of castration duration on the conversion of T to DHT by pituitary homogenates and the responsiveness of pituitary monolayer cell cultures to gonadotropin-releasing hormone (GnRH) challenge exposure were investigated. Incubation of [3H]-T with pituitary homogenates showed that the conversion of T to 5alpha-reduced metabolites was two- to threefold greater in pituitaries from rats who had been castrated for 14 days compared with those castrated for 1 day. In addition, the GnRH-stimulated release of LH from monolayer cell cultures of pituitaries from rats castrated for 1 day was twofold greater, whereas that from rats castrated for 2 weeks was six- to sevenfold greater compared with basal luteinizing hormone (LH) release. Hence we used rats castrated for 2 weeks to elucidate the role of 5alpha-reductase in T feedback inhibition. The inhibitory effects of the androgens T, 19-nortestosterone (19-NT), and 7alpha-methyl-19-nortestosterone (MENT) at 3 different concentrations (10(-9), 10(-7), and 10(-5) mol/L) on GnRH-stimulated LH release from monolayer cell cultures of pituitaries from rats castrated for 2 weeks were examined. All 3 androgens showed dose-dependent inhibition of LH release. MENT showed the greatest inhibition, followed by 19-NT and T. In the presence of finasteride (a 5alpha-reductase inhibitor), the inhibition of LH released by T and 19-NT were significantly greater. The inhibitory effect of MENT, which does not undergo 5alpha

  4. Synchronous activation of gonadotropin-releasing hormone gene transcription and secretion by pulsatile kisspeptin stimulation

    PubMed Central

    Choe, Han Kyoung; Kim, Hee-Dae; Park, Sung Ho; Lee, Han-Woong; Park, Jae-Yong; Seong, Jae Young; Lightman, Stafford L.; Son, Gi Hoon; Kim, Kyungjin

    2013-01-01

    Pulsatile release of hypothalamic gonadotropin-releasing hormone (GnRH) is essential for pituitary gonadotrope function. Although the importance of pulsatile GnRH secretion has been recognized for several decades, the mechanisms underlying GnRH pulse generation in hypothalamic neural networks remain elusive. Here, we demonstrate the ultradian rhythm of GnRH gene transcription in single GnRH neurons using cultured hypothalamic slices prepared from transgenic mice expressing a GnRH promoter-driven destabilized luciferase reporter. Although GnRH promoter activity in each GnRH neuron exhibited an ultradian pattern of oscillations with a period of ∼10 h, GnRH neuronal cultures exhibited partially synchronized bursts of GnRH transcriptional activity at ∼2-h intervals. Surprisingly, pulsatile administration of kisspeptin, a potent GnRH secretagogue, evoked dramatic synchronous activation of GnRH gene transcription with robust stimulation of pulsatile GnRH secretion. We also addressed the issue of hierarchical interaction between the circadian and ultradian rhythms by using Bmal1-deficient mice with defective circadian clocks. The circadian molecular oscillator barely affected basal ultradian oscillation of GnRH transcription but was heavily involved in kisspeptin-evoked responses of GnRH neurons. In conclusion, we have clearly shown synchronous bursts of GnRH gene transcription in the hypothalamic GnRH neuronal population in association with episodic neurohormone secretion, thereby providing insight into GnRH pulse generation. PMID:23509283

  5. Gonadotropin-releasing hormone receptor in spinal cord neurons of embryos and adult rats.

    PubMed

    Quintanar, J Luis; Salinas, Eva; González, Rodolfo

    2009-09-11

    Mammalian gonadotropin-releasing hormone (GnRH) and its receptor have been found in the neuroendocrine reproductive axis. However, they can be localized in other extra-pituitary tissues as well including the central nervous system. The present study reports the expression of GnRH receptor and its mRNA in spinal cord neurons of rat embryos and adult rats, using immunohistochemistry and reverse transcriptase polymerase chain reaction (RT-PCR). Immunohistochemistry showed that the spinal cord neurons of rat embryos and adult rats expressed the GnRH receptor. The study of GnRH receptor mRNAs revealed that both cultured spinal cord neurons of rat embryos and adult rats expressed the GnRH receptor mRNA. Additional in vitro experiments showed that the expression of GnRH receptor mRNA was less in the spinal cord neurons exposed to GnRH compared to unexposed ones. These results raise the possibility that GnRH may play other roles independently from its participation in reproductive function.

  6. Changes of gonadotropin-releasing hormone receptor 2 during the anadromous spawning migration in Coilia nasus.

    PubMed

    Duan, Jin-Rong; Fang, Di-An; Zhang, Min-Ying; Liu, Kai; Zhou, Yan-Feng; Xu, Dong-Po; Xu, Pao; Li, Da-Peng

    2016-11-24

    An increase in the activity of the pituitary-gonad axis (PG-axis) and gonad development are essential for the onset of spawning migration in teleosts. In the fish Coilia nasus, gonad development and spawning migration up the Yangtze River occurs by the end of each summer. We hypothesized that gonadotropin releasing hormones receptor 2 (GnRH-R2), which together produce a signal that interacts with the PG-axis, may help to regulate spawning migration processes. In this regard, we (1) characterized the gonadosomatic index (GSI) in the anadromous fish C. nasus; (2) analyzed the GnRH-R2 mRNA expression levels in ovary and brain, and concentrations in the serum; and (3) identified the GnRH-R2 protein distribution in the brain and ovaries. We found strong relationships between all of these indices. The results indicate that GnRH-R2 could act together to promote spawning during the anadromous migration. There is some evidence that the GnRH-R2 gene expression levels and protein distributions change in association with the migratory behavior.

  7. Enzymatic tracer damage during the gonadotropin releasing hormone radioimmunoassay: analytical and immunological assessment

    SciTech Connect

    O'Conner, J.L.; Lapp, C.A.; Clary, A.R.

    1985-09-23

    Hypothalamic supernatants from 60 day female rats were fractionated from Sephadex G-200 columns. The radioimmunoassay (RIA) for gonadotropin releasing hormone (GnRH) detected an apparently cross-reacting high molecular weight substance. The substance caused apparent displacement of iodinated GnRH binding in dose response fashion; however, no biological activity was observed in pituitary cell cultures. In order to determine whether the depressed binding might be caused by enzymatic degradation of iodinated GnRH during the RIA incubation, iodinated GnRH was preincubated under RIA conditions with either buffer or increasing concentrations of the GnRH cross-reacting material. Aliquots were subjected to polyacrylamide gel electrophoresis (PAGE) and the gels slices counted. Identical aliquots were subsequently used as iodinated hormone in the RIA of known quantities of synthetic GnRH. Tracer damage during the RIA-like preincubation period was reflected in the subsequent PAGE studies as decreased counts per minute in the intact GnRH peak and in the RIA studies as over-estimated quantification of the GnRH standards. This report describes such damage during the GnRH RIA and the data misinterpretations which result. 30 references, 6 figures, 1 table.

  8. Hypothalamic neural systems controlling the female reproductive life cycle: Gonadotropin-releasing hormone, glutamate, and GABA

    PubMed Central

    Maffucci, Jacqueline A.; Gore, Andrea C.

    2009-01-01

    The hypothalamic-pituitary-gonadal (HPG) axis undergoes a number of changes throughout the reproductive life cycle that are responsible for the development, puberty, adulthood, and senescence of reproductive systems. This natural progression is dictated by the neural network controlling the hypothalamus including the cells that synthesize and release gonadotropin-releasing hormone (GnRH) and their regulatory neurotransmitters. Glutamate and GABA are the primary excitatory and inhibitory neurotransmitters in the central nervous system, and as such contribute a great deal to modulating this axis throughout the lifetime via their actions on receptors in the hypothalamus, both directly on GnRH neurons as well as indirectly though other hypothalamic neural networks. Interactions among GnRH neurons, glutamate, and GABA, including the regulation of GnRH gene and protein expression, hormone release, and modulation by estrogen, are critical to age-appropriate changes in reproductive function. Here, we present evidence for the modulation of GnRH neurosecretory cells by the balance of glutamate and GABA in the hypothalamus, and the functional consequences of these interactions on reproductive physiology across the life cycle. PMID:19349036

  9. Effects of leptin on FSH cells in the pituitary gland of Podarcis siculus.

    PubMed

    Ferrandino, Ida; Monaco, Antonio; Grimaldi, Maria Consiglio

    2015-03-01

    Leptin is the hormone synthesised by adipocytes, which plays an important role in regulating appetite and metabolism. In mammals, this pleiotropic hormone also plays a key role in controlling gonadotropin secretion by stimulatory hypothalamic and pituitary actions. However, little is known about leptin in lower vertebrates and particularly few studies are available on reptiles. In the present work, we analysed the action of recombinant human leptin on FSH cells in the pituitary gland of Podarcis siculus female lizards exposed to four different concentrations of the hormone. FSH cells showed a dose-dependent reaction. The data are indicative of the role played by leptin in modulating the cellular activity of such cells in the pituitary gland of P. siculus, similar to what was already reported in mammals. A functional receptor is evidently able to respond to leptin in this lizard, but further comparative studies are needed to understand the role of this hormone in ectothermic vertebrates. Copyright © 2015 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  10. The Recreational Drug Ecstasy Disrupts the Hypothalamic-Pituitary-Gonadal Reproductive Axis in Adult Male Rats

    PubMed Central

    Dickerson, Sarah M.; Walker, Deena M.; Reveron, Maria E.; Duvauchelle, Christine L.; Gore, Andrea C.

    2009-01-01

    Reproductive function involves an interaction of three regulatory levels: hypothalamus, pituitary, and gonad. The primary drive upon this system comes from hypothalamic gonadotropin-releasing hormone (GnRH) neurosecretory cells, which receive afferent inputs from other neurotransmitter systems in the central nervous system to result in the proper coordination of reproduction and the environment. Here, we hypothesized that the recreational drug ±-3,4-Methylenedioxymethamphetamine (MDMA; “ecstasy”), which acts through several of the neurotransmitter systems that affect GnRH neurons, suppresses the hypothalamic-pituitary-gonadal (HPG) reproductive axis of male rats. Adult male Sprague-Dawley rats self-administered saline or MDMA or saline either once (acute) or for 20 days (chronic), and were euthanized 7 days following last administration. We quantified hypothalamic GnRH mRNA, serum luteinizing hormone (LH) concentrations, and serum testosterone levels, as indices of hypothalamic, pituitary, and gonadal functions, respectively. The results indicate that the hypothalamic and gonadal levels of the HPG axis are significantly altered by MDMA, with GnRH mRNA and serum testosterone levels suppressed in rats administered MDMA compared to saline. Furthermore, our finding that hypothalamic GnRH mRNA levels are suppressed in the context of low testosterone concentrations suggests that the central GnRH neurosecretory system may be a primary target of inhibitory regulation by MDMA usage. PMID:18309234

  11. Clinically non-functioning pituitary adenomas: Pathogenic, diagnostic and therapeutic aspects.

    PubMed

    Mercado, Moises; Melgar, Virgilio; Salame, Latife; Cuenca, Dalia

    Clinically non-functioning pituitary adenomas (NFPAs) are among the most common tumors in the sellar region. These lesions do not cause a hormonal hypersecretion syndrome, and are therefore found incidentally (particularly microadenomas) or diagnosed based on compressive symptoms such as headache and visual field defects, as well as clinical signs of pituitary hormone deficiencies. Immunohistochemically, more than 45% of these adenomas stain for gonadotropins or their subunits and are therefore called gonadotropinomas, while 30% of them show no immunostaining for any hormone and are known as null cell adenomas. The diagnostic approach to NFPAs should include visual field examination, an assessment of the integrity of all anterior pituitary hormone systems, and magnetic resonance imaging of the sellar region to define tumor size and extension. The treatment of choice is transsphenoidal resection of the adenoma, which in many instances cannot be completely accomplished. The recurrence rate after surgery may be up to 30%. Persistent or recurrent adenomas are usually treated with radiation therapy. In a small proportion of these cases, drug treatment with dopamine agonists and, to a lesser extent, somatostatin analogs may achieve reduction or at least stabilization of the tumor. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Pituitary apoplexy associated with cabergoline therapy.

    PubMed

    Chng, Edwin; Dalan, Rinkoo

    2013-12-01

    Pituitary apoplexy is a rare medical emergency which results from hemorrhage or infarction in the pituitary gland. One of the predisposing factors is treatment with dopamine agonists, especially bromocriptine. We report a 20-year-old Chinese man with prolactinoma who developed pituitary apoplexy 6 weeks after initiation of cabergoline. He was treated conservatively with supportive therapy, and recovered well with no loss of pituitary function. A literature search was conducted and a review of the reported patients with pituitary apoplexy during treatment with dopamine agonists is discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Imaging diagnosis: pituitary apoplexy in a cat.

    PubMed

    Beltran, Elsa; Dennis, Ruth; Foote, Alastair; De Risio, Luisa; Matiasek, Lara

    2012-01-01

    A 7-year-old male neutered domestic short-haired cat had depression for 5 months and acute blindness. A lesion at the level of the rostral and middle cranial fossae was suspected. A large pituitary mass compressing the optic chiasm was detected in magnetic resonance images and there was also evidence of recent intratumoral hemorrhage, leading to a diagnosis of pituitary apoplexy; these findings were confirmed at postmortem examination. Pituitary apoplexy is a clinical syndrome characterized by acute neurologic signs related to hemorrhagic infarction within a pituitary tumor. Pituitary apoplexy should be considered in patients with acute onset of blindness and altered mental status. © 2012 Veterinary Radiology & Ultrasound.

  14. Idiopathic granulomatous hypophysitis presenting as pituitary apoplexy.

    PubMed

    Husain, Qasim; Zouzias, Alexandros; Kanumuri, Vivek V; Eloy, Jean Anderson; Liu, James K

    2014-03-01

    Idiopathic granulomatous hypophysitis (IGH) is an extremely rare chronic inflammatory lesion of the pituitary gland. This condition typically presents with chronic onset of headache and slow development of visual deficits. Pituitary apoplexy is a clinical syndrome characterized by sudden onset of headache, vision loss, opthalmoplegia, and signs of meningeal irritation. Although IGH has been previously described in the literature, its presentation as clinical pituitary apoplexy is novel. We report, to our knowledge, the first patient with IGH manifesting as clinical pituitary apoplexy. Physicians involved in the treatment of pituitary disease should be aware of this rare entity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Pituitary gigantism: Causes and clinical characteristics.

    PubMed

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

    2015-12-01

    Acromegaly and pituitary gigantism are very rare conditions resulting from excessive secretion of growth hormone (GH), usually by a pituitary adenoma. Pituitary gigantism occurs when GH excess overlaps with the period of rapid linear growth during childhood and adolescence. Until recently, its etiology and clinical characteristics have been poorly understood. Genetic and genomic causes have been identified in recent years that explain about half of cases of pituitary gigantism. We describe these recent discoveries and focus on some important settings in which gigantism can occur, including familial isolated pituitary adenomas (FIPA) and the newly described X-linked acrogigantism (X-LAG) syndrome.

  16. Treatment situation of male hypogonadotropic hypogonadism in pediatrics and proposal of testosterone and gonadotropins replacement therapy protocols

    PubMed Central

    Sato, Naoko; Hasegawa, Tomonobu; Hasegawa, Yukihiro; Arisaka, Osamu; Ozono, Keiichi; Amemiya, Shin; Kikuchi, Toru; Tanaka, Hiroyuki; Harada, Shohei; Miyata, Ichiro; Tanaka, Toshiaki

    2015-01-01

    Abstract Male hypogonadotropic hypogonadism (MHH), a disorder associated with infertility, is treated with testosterone replacement therapy (TRT) and/or gonadotropins replacement therapy (GRT) (TRT and GRT, together with HRT hormone replacement therapy). In Japan, guidelines have been set for treatment during adolescence. Due to the risk of rapid maturation of bone age, low doses of testosterone or gonadotropins have been used. However, the optimal timing and methods of therapeutic intervention have not yet been established. The objective of this study was to investigate the current situation of treatment for children with MHH in Japan and to review a primary survey involving councilors of the Japanese Society for Pediatric Endocrinology and a secondary survey obtained from 26 facilities conducting HRT. The subjects were 55 patients with MHH who reached their adult height after HRT. The breakdown of the patients is as follows: 7 patients with Kallmann syndrome, 6 patients with isolated gonadotropin deficiency, 18 patients with acquired hypopituitarism due to intracranial and pituitary tumor, 22 patients with classical idiopathic hypopituitarism due to breech delivery, and 2 patients with CHARGE syndrome. The mean age at the start of HRT was 15.7 yrs and mean height was 157.2 cm. The mean age at reaching adult height was 19.4 yrs, and the mean adult height was 171.0 cm. The starting age of HRT was later than the normal pubertal age and showed a significant negative correlation with pubertal height gain, but it showed no correlation with adult height. As for spermatogenesis, 76% of the above patients treated with hCG-rFSH combined therapy showed positive results, though ranging in levels; impaired spermatogenesis was observed in some with congenital MHH, and favorable spermatogenesis was observed in all with acquired MHH. From the above, we propose the establishment of a treatment protocol for the start low-dose testosterone or low-dose gonadotropins by dividing

  17. Presenting Symptoms of Pituitary Apoplexy.

    PubMed

    Pyrgelis, Efstratios-Stylianos; Mavridis, Ioannis; Meliou, Maria

    2017-04-24

    The classical term "pituitary apoplexy" (PA) describes a clinical syndrome usually characterized by abrupt onset of headache accompanied by neurologic and/or endocrinologic deterioration due to sudden expansion of a mass within the sella turcica as a result of hemorrhage or infarction within a pituitary tumor and adjacent pituitary gland. PA is a medical emergency and a difficult diagnosis to establish. Thus this article reviews the presenting symptoms of PA patients to help clinicians recognize or at least suspect this critical condition early on. PA commonly occurs in the setting of a preexisting adenoma, and several patients are unaware of its existence prior to the onset of apoplexy symptoms, which are mainly of a neurologic, ophthalmologic, and endocrinologic nature. Neurologic symptoms include sudden-onset severe headache and other symptoms of subarachnoid hemorrhage, symptoms from compression of the cavernous sinus contents, nausea/vomiting, impaired consciousness, and symptoms of meningeal irritation. Ophthalmologic symptoms include visual field defects, visual loss, diplopia, and ophthalmoplegia. Endocrinologic disturbances include pituitary adenoma symptoms, cortisol deficiency, panhypopituitarism, diabetes insipidus, and syndrome of inappropriate secretion of antidiuretic hormone. Magnetic resonance imaging is the imaging method of choice to aid the PA diagnosis. Its differential diagnoses include cerebrovascular accidents, infectious diseases, and other causes of endocrinologic imbalance. Transsphenoidal surgery is the treatment of choice, especially if there are associated visual abnormalities and ophthalmoplegia. Clinicians should be aware of the presenting symptoms because early diagnosis may reduce the morbidity and mortality of this neurosurgical emergency. Georg Thieme Verlag KG Stuttgart · New York.

  18. Adenohypophysitis in rat pituitary allografts

    PubMed Central

    Rotondo, Fabio; Quintanar-Stephano, Andres; Asa, Sylvia L; Lombardero, Matilde; Berczi, Istvan; Scheithauer, Bernd W; Horvath, Eva; Kovacs, Kalman

    2010-01-01

    The histological, immunohistochemical and ultrastructural alterations in 81 pituitary allografts from Lewis rats transplanted beneath the renal capsule of Wistar rats were investigated. Intrasellar pituitaries of rats bearing allografts were also examined. Recipient rats were sacrificed at various time points after transplantation. Two days after transplantation, the central portion of the allografts demonstrated ischaemic necrosis. A week later, massive mononuclear cell infiltrates consisting primarily of lymphocytes and to a lesser extent, macrophages, plasma cells and granulocytes became prominent. At about three to four weeks after transplantation, the mononuclear cell infiltrate diminished; the surviving adenohypophysial cells, mainly prolactin (PRL) cells, increased in number and necrosis was replaced by connective tissue. No histological changes were noted in the intrasellar pituitaries of rats bearing allografts. Immunohistochemistry demonstrated that the surviving adenohypophysial cells were mainly PRL-producing cells. Electron microscopy revealed adenohypophysial cell destruction, a spectrum of inflammatory cells and, in late phase, accumulation of fibroblasts and collagen fibres. PRL cells were the prominent cell types; they increased in number. It appears that pituitary allografts are ‘foreign’ and evoke an immune response, suggesting that they may be used as an experimental animal model for morphological investigation of the development and progression of adenohypophysitis, a rare disease occurring mainly in young women often associated with pregnancy. PMID:20586813

  19. How Are Pituitary Tumors Diagnosed?

    MedlinePlus

    ... for another reason may detect a pituitary tumor. Magnetic resonance imaging (MRI) scan MRI scans use radio waves and strong magnets to create ... vein to improve the quality of the image. MRI scans are very helpful in looking at the brain ...

  20. Developmental abnormalities of the posterior pituitary gland.

    PubMed

    di Iorgi, Natascia; Secco, Andrea; Napoli, Flavia; Calandra, Erika; Rossi, Andrea; Maghnie, Mohamad

    2009-01-01

    While the molecular mechanisms of anterior pituitary development are now better understood than in the past, both in animals and in humans, little is known about the mechanisms regulating posterior pituitary development. The posterior pituitary gland is formed by the evagination of neural tissue from the floor of the third ventricle. It consists of the distal axons of the hypothalamic magnocellular neurones that shape the neurohypophysis. After its downward migration, it is encapsulated together with the ascending ectodermal cells of Rathke's pouch which form the anterior pituitary. By the end of the first trimester, this development is completed and vasopressin and oxytocin can be detected in neurohypophyseal tissue. Abnormal posterior pituitary migration such as the ectopic posterior pituitary lobe appearing at the level of median eminence or along the pituitary stalk have been reported in idiopathic GH deficiency or in subjects with HESX1, LHX4 and SOX3 gene mutations. Another intriguing feature of abnormal posterior pituitary development involves genetic forms of posterior pituitary neurodegeneration that have been reported in autosomal-dominant central diabetes insipidus and Wolfram disease. Defining the phenotype of the posterior pituitary gland can have significant clinical implications for management and counseling, as well as providing considerable insight into normal and abnormal mechanisms of posterior pituitary development in humans.

  1. Pituitary apoplexy presenting with anorexia and hyponatraemia

    PubMed Central

    Sasaki, Yosuke; Nakata, Kenji; Suzuki, Kenichi; Ando, Yasuyo

    2015-01-01

    Pituitary apoplexy, a syndrome caused by haemorrhage into the pituitary gland, typically manifests as sudden severe headache, visual symptoms and hypopituitarism, including adrenal insufficiency. We report a case of a 65-year-old man with adrenal insufficiency due to pituitary apoplexy presenting with anorexia following temporal headache and diagnosed through evaluation for hyponatraemia. MRI focusing on the pituitary gland helped to confirm the diagnosis. Our experience serves as a useful reminder of this atypical presentation of pituitary apoplexy, also known as ‘subclinical pituitary apoplexy,’ and underscores the importance of careful evaluation for hyponatraemia using serial urine osmolality, which is useful to distinguish hypovolaemic hyponatraemia from euvolaemic hyponatraemia. Clinicians should consider pituitary apoplexy as a differential diagnosis in cases of anorexia, loss of energy or hyponatraemia, following headache even when the patient is lacking classical symptoms such as severe headache or visual symptoms. PMID:25858941

  2. Pituitary apoplexy presenting with anorexia and hyponatraemia.

    PubMed

    Sasaki, Yosuke; Nakata, Kenji; Suzuki, Kenichi; Ando, Yasuyo

    2015-04-09

    Pituitary apoplexy, a syndrome caused by haemorrhage into the pituitary gland, typically manifests as sudden severe headache, visual symptoms and hypopituitarism, including adrenal insufficiency. We report a case of a 65-year-old man with adrenal insufficiency due to pituitary apoplexy presenting with anorexia following temporal headache and diagnosed through evaluation for hyponatraemia. MRI focusing on the pituitary gland helped to confirm the diagnosis. Our experience serves as a useful reminder of this atypical presentation of pituitary apoplexy, also known as 'subclinical pituitary apoplexy,' and underscores the importance of careful evaluation for hyponatraemia using serial urine osmolality, which is useful to distinguish hypovolaemic hyponatraemia from euvolaemic hyponatraemia. Clinicians should consider pituitary apoplexy as a differential diagnosis in cases of anorexia, loss of energy or hyponatraemia, following headache even when the patient is lacking classical symptoms such as severe headache or visual symptoms.

  3. Molecular regulation of hypothalamus-pituitary-gonads axis in males.

    PubMed

    Jin, Jia-Min; Yang, Wan-Xi

    2014-11-01

    The hypothalamic-pituitary-gonadal axis (HPG) plays vital roles in reproduction and steroid hormone production in both sexes. The focus of this review is upon gene structures, receptor structures and the signaling pathways of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The hormones' functions in reproduction as well as consequences resulting from mutations are also summarized. Specific characteristics of hormones such as the pulsatile secretions of GnRH are also covered. The different regulators of the HPG axis are introduced including kisspeptin, activin, inhibin, follistatin, androgens and estrogen. This review includes not only their basic information, but also their unique function in the HPG axis. Here we view the HPG axis as a whole, so relations between ligands and receptors are well described crossing different levels of the HPG axis. Hormone interactions and transformations are also considered. The major information of this article is depicted in three figures summarizing the current discoveries on the HPG axis. This article systematically introduces the basic knowledge of the HPG axis and provides information of the current advances relating to reproductive hormones. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Biologically Active Chorionic Gonadotropin: Synthesis by the Human Fetus

    NASA Astrophysics Data System (ADS)

    McGregor, W. G.; Kuhn, R. W.; Jaffe, R. B.

    1983-04-01

    The kidney, and to a slight extent the liver, of human fetuses were found to synthesize and secrete the α subunit common to glycoprotein hormones. Fetal lung and muscle did not synthesize this protein. Since fetal kidney and liver were previously found to synthesize β chorionic gonadotropin, their ability to synthesize bioactive chorionic gonadotropin was also determined. The newly synthesized hormone bound to mouse Leydig cells and elicited a biological response: namely, the synthesis of testosterone. These results suggest that the human fetus may participate in metabolic homeostasis during its development.

  5. Pregnant mare's serum gonadotropin. III. Hemispaying and the reversal of the antifertility faculty of pregnant mare's serum gonadotropin.

    PubMed

    Chatterjee, A; Pal, A K; Gupta, T

    1977-10-01

    A single injection of 10 IU of pregnant mare's serum gonadotropin (PMSG) on day 5 of pregancy caused wastage of the fetoplacental unit by day 16 of pregnancy. Semispaying, which seems to subtract approximately 50% of the ovarian steroid contribution, at 24, 48, and 72 hours following the PMSG schedule prevented the antifertility faculty of the hormone preparation. However, hemicastration at 96 hours following the gonadotropin regimen was found to be ineffective, and 100% of the test animals showed complete termination of pregnancy. Experimental data collectively tempt us to propose that an estrogen excess, particularly of follicular origin in both ovaries, is essential for more than 72 hours following gonadotropin sensitization before the antifertility faculty of PMSG can be demonstrated.

  6. Testicular Steroidogenesis and Locomotor Activity Are Regulated by Gonadotropin-Inhibitory Hormone in Male European Sea Bass

    PubMed Central

    Paullada-Salmerón, José A.; Cowan, Mairi; Aliaga-Guerrero, María; López-Olmeda, José F.; Mañanós, Evaristo L.; Zanuy, Silvia

    2016-01-01

    Gonadotropin-inhibitory hormone (GnIH) is a neurohormone that suppresses reproduction by acting at both the brain and pituitary levels. In addition to the brain, GnIH may also be produced in gonads and can regulate steroidogenesis and gametogenesis. However, the function of GnIH in gonadal physiology has received little attention in fish. The main objective of this study was to evaluate the effects of peripheral sbGnih-1 and sbGnih-2 implants on gonadal development and steroidogenesis during the reproductive cycle of male sea bass (Dicentrarchus labrax). Both Gnihs decreased testosterone (T) and 11-ketotestosterone (11-KT) plasma levels in November and December (early- and mid-spermatogenesis) but did not affect plasma levels of the progestin 17,20β-dihydroxy-4-pregnen-3-one (DHP). In February (spermiation), fish treated with sbGnih-1 and sbGnih-2 exhibited testicles with abundant type A spermatogonia and partial spermatogenesis. In addition, we determined the effects of peripheral Gnih implants on plasma follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh) levels, as well as on brain and pituitary expression of the main reproductive hormone genes and their receptors during the spermiation period (February). Treatment with sbGnih-2 increased brain gnrh2, gnih, kiss1r and gnihr transcript levels. Whereas, both Gnihs decreased lhbeta expression and plasma Lh levels, and sbGnih-1 reduced plasmatic Fsh. Finally, through behavioral recording we showed that Gnih implanted animals exhibited a significant increase in diurnal activity from late spermatogenic to early spermiogenic stages. Our results indicate that Gnih may regulate the reproductive axis of sea bass acting not only on brain and pituitary hormones but also on gonadal physiology and behavior. PMID:27788270

  7. Development of a flatfish-specific enzyme-linked immunosorbent assay for Fsh using a recombinant chimeric gonadotropin.

    PubMed

    Chauvigné, François; Verdura, Sara; Mazón, María José; Boj, Mónica; Zanuy, Silvia; Gómez, Ana; Cerdà, Joan

    2015-09-15

    In flatfishes with asynchronous and semicystic spermatogenesis, such as the Senegalese sole (Solea senegalensis), the specific roles of the pituitary gonadotropins during germ cell development, particularly of the follicle-stimulating hormone (Fsh), are still largely unknown in part due to the lack of homologous immunoassays for this hormone. In this study, an enzyme-linked immunosorbent assay (ELISA) for Senegalese sole Fsh was developed by generating a rabbit antiserum against a recombinant chimeric single-chain Fsh molecule (rFsh-C) produced by the yeast Pichia pastoris. The rFsh-C N- and C-termini were formed by the mature sole Fsh β subunit (Fshβ) and the chicken glycoprotein hormone common α subunit (CGA), respectively. Depletion of the antiserum to remove anti-CGA antibodies further enriched the sole Fshβ-specific antibodies, which were used to develop the ELISA using the rFsh-C for the standard curve. The sensitivity of the assay was 10 and 50 pg/ml for Fsh measurement in plasma and pituitary, respectively, and the cross-reactivity with a homologous recombinant single-chain luteinizing hormone was 1%. The standard curve for rFsh-C paralleled those of serially diluted plasma and pituitary extracts of other flatfishes, such as the Atlantic halibut, common sole and turbot. In Senegalese sole males, the highest plasma Fsh levels were found during early spermatogenesis but declined during enhanced spermiation, as found in teleosts with cystic spermatogenesis. In pubertal males, however, the circulating Fsh levels were as high as in adult spermiating fish, but interestingly the Fsh receptor in the developing testis containing only spermatogonia was expressed in Leydig cells but not in the primordial Sertoli cells. These results indicate that a recombinant chimeric Fsh can be used to generate specific antibodies against the Fshβ subunit and to develop a highly sensitive ELISA for Fsh measurements in diverse flatfishes.

  8. Expression of the pituitary stem/progenitor marker GFRα2 in human pituitary adenomas and normal pituitary

    PubMed Central

    Mathioudakis, Nestoras; Sundaresh, Ram; Larsen, Alexandra; Ruff, William; Schiller, Jennifer; Cázares, Hugo Guerrero; Burger, Peter; Salvatori, Roberto; Quiñones-Hinojosa, Alfredo

    2014-01-01

    Purpose Recent studies suggest that adult pituitary stem cells may play a role in pituitary tumorigenesis. We sought to explore whether the Glial cell-line derived neurotrophic factor receptor alpha 2 (GFRα2), a recently described pituitary stem/progenitor marker, might be differentially expressed in pituitary adenomas versus normal pituitary. Methods The expression of GFRα2 and other members of the GFR receptor family (GFRα1, α3, α4) were analyzed using RT-PCR, western blot, and immunohistochemistry in 39 pituitary adenomas, 14 normal pituitary glands obtained at autopsy, and cDNA from 3 normal pituitaries obtained commercially. Results GFRα2 mRNA was ~2.6 fold under-expressed in functioning adenomas (P <0.01) and ~3.5 fold over-expressed in non-functioning adenomas (NFAs) (P <0.05) compared to normal pituitary. Among NFAs, GFRα2 was significantly over-expressed (~5-fold) in the gonadotropinoma subtype only (P<0.05). GFRα2 protein expression appeared to be higher in most NFAs, although there was heterogeneity in protein expression in this group. GFRα2 protein expression appeared consistently lower in functioning adenomas by IHC and western blot. In normal pituitary, GFRα2 was localized in Rathke’s remnant, the putative pituitary stem cell niche, and in corticotropes. Conclusion Our results suggest that the pituitary stem cell marker GFRα2 is under-expressed in functioning adenomas and over-expressed in NFAs, specifically gonadotropinomas. Further studies are required to elucidate whether over-expression of GFRα2 in gonadotropinomas might play a role in pituitary tumorigenesis. PMID:24402129

  9. Treatment of gonadotropin dependent precocious puberty due to hypothalamic hamartoma with gonadotropin releasing hormone agonist depot

    PubMed Central

    de Brito, V. N; Latronico, A.; Arnhold, I.; Lo, L.; Domenice, S.; Albano, M.; Fragoso, M.; Mendonca, B.

    1999-01-01

    The gonadotropin releasing hormone (GnRH) secreting hypothalamic hamartoma (HH) is a congenital malformation consisting of a heterotopic mass of nervous tissue that contains GnRH neurosecretory neurons attached to the tuber cinereum or the floor of the third ventricle. HH is a well recognised cause of gonadotropin dependent precocious puberty (GDPP). Long term data are presented on eight children (five boys and three girls) with GDPP due to HH. Physical signs of puberty were observed before 2 years of age in all patients. At presentation with sexual precocity, the mean height standard deviation (SD) for chronological age was +1.60 (1.27) and the mean height SD for bone age was −0.92 (1.77). Neurological symptoms were absent at presentation and follow up. The hamartoma diameter ranged from 5 to 18 mm and did not change in six patients who had magnetic resonance imaging follow up. All patients were treated clinically with GnRH agonists (GnRH-a). The duration of treatment varied from 2.66 to 8.41 years. Seven of the eight children had satisfactory responses to treatment, shown by regression of pubertal signs, suppression of hormonal levels, and improvement of height SD for bone age and predicted height. One patient had a severe local reaction to GnRH-a with failure of hormonal suppression and progression of pubertal signs. It seems that HH is benign and that GnRH-a treatment provides satisfactory and safe control for most children with GDPP due to HH.

 PMID:10325702

  10. Gonadotropin-releasing hormone/human chorionic gonadotropin beta based recombinant antibodies and vaccines.

    PubMed

    Talwar, G P; Vyas, Hemant K; Purswani, Shilpi; Gupta, Jagdish C

    2009-12-01

    Gonadotropin-releasing hormone (GnRH) and human chorionic gonadotropin (hCG) are unique targets for the control of fertility. Immunological approaches to neutralizing these hormones have additional utility in cancer treatment. Vaccines have been developed against both GnRH and hCG and these have undergone Phase I/II clinical trials documenting their safety, reversibility and efficacy. The heterospecies dimer hCG vaccine prevented pregnancy in women of proven fertility without impairment of ovulation or derangement of menstrual regularity and bleeding profiles. The protective threshold of antibody titers to achieve efficacy was determined in these first-ever trials. Recently, a recombinant vaccine against the beta subunit of hCG linked to the B subunit of heat labile enterotoxin has been made and expressed as a glycosylated conjugate in Pichia pastoris. Experiments indicate its ability to generate antibodies above the protective threshold in all immunized Balb/c mice. Ectopic expression of hCG/hCGbeta is observed in many advanced stage cancers of various origins. A chimeric high affinity and specific recombinant antibody against hCGbeta linked to curcumin kills hCGbeta expressing T lymphoblastic leukemia cells without any deleterious effect. Several synthetic and recombinant vaccines have been developed against GnRH. These reduce serum testosterone to castration levels causing atrophy of the prostate. Three Phase I/II clinical trials conducted in India and Austria have shown that these vaccines elicit non-surgical reduction of testosterone, a fall in prostate specific antigen and clinical improvement of prostate carcinoma patients. A multimer recombinant vaccine against GnRH has high efficacy for sterilization of pigs and other animals.

  11. Expression patterns of gonadotropin hormones and their receptors during early sexual differentiation in Nile tilapia Oreochromis niloticus.

    PubMed

    Yan, Hongwei; Ijiri, Shigeho; Wu, Quan; Kobayashi, Tohru; Li, Shuang; Nakaseko, Taro; Adachi, Shinji; Nagahama, Yoshitaka

    2012-11-01

    In Nile tilapia, sex-specific expression of foxl2 and cyp19a1a in XX gonads and dmrt1 in XY gonads at 5-6 days after hatching (dah) is critical for differentiation of the gonads into either ovaries or testes. The factors triggering sexually dimorphic expression of these genes are unknown, and whether the gonadotropin hormones are involved in early gonadal sex differentiation of the Nile tilapia has been unclear. In the present study, we determined the precise timing of expression of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the pituitary and that of their receptors (fshra and lhcgrbb) in the undifferentiated gonad in both XX and XY tilapia fry by quantitative RT-PCR and immunohistochemical analysis. Expression of fshb mRNA and Fsh protein in the pituitary was detected from the first sampling day (3 dah) to 25 dah in both XX and XY tilapia larvae without sexual dimorphism and increased gradually after 25 dah in the pituitary. fshra mRNA was expressed beginning 5 dah and was present at significantly higher levels in XX gonads than in the XY gonads at 6-25 dah. These results indicate that the level of Fsh protein in the pituitary was not critical for differentiation of gonads into ovaries or testes, but the expression level of its receptor, fshra, in undifferentiated gonads appeared to be involved in determining gonadal sexual differentiation. Based on these observations, it is likely that in XX gonads, up-regulation of fshra may be necessary to induce cyp19a1a expression, which stimulates estradiol-17beta (E(2)) production and subsequent ovarian differentiation. On the other hand, lhb mRNA was not detected until 25 dah in the pituitaries of both sexes, and sexual dimorphism in lhcgrbb mRNA levels appeared later (10-25 dah) than that of fshra in the gonads, indicating the limited role of LH and lhcgrbb in gonadal differentiation of the Nile tilapia.

  12. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress.

    PubMed

    Tsigos, Constantine; Chrousos, George P

    2002-10-01

    The stress system coordinates the adaptive responses of the organism to stressors of any kind.(1). The main components of the stress system are the corticotropin-releasing hormone (CRH) and locus ceruleus-norepinephrine (LC/NE)-autonomic systems and their peripheral effectors, the pituitary-adrenal axis, and the limbs of the autonomic system. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. The CRH and LC/NE systems stimulate arousal and attention, as well as the mesocorticolimbic dopaminergic system, which is involved in anticipatory and reward phenomena, and the hypothalamic beta-endorphin system, which suppresses pain sensation and, hence, increases analgesia. CRH inhibits appetite and activates thermogenesis via the catecholaminergic system. Also, reciprocal interactions exist between the amygdala and the hippocampus and the stress system, which stimulates these elements and is regulated by them. CRH plays an important role in inhibiting GnRH secretion during stress, while, via somatostatin, it also inhibits GH, TRH and TSH secretion, suppressing, thus, the reproductive, growth and thyroid functions. Interestingly, all three of these functions receive and depend on positive catecholaminergic input. The end-hormones of the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoids, on the other hand, have multiple roles. They simultaneously inhibit the CRH, LC/NE and beta-endorphin systems and stimulate the mesocorticolimbic dopaminergic system and the CRH peptidergic central nucleus of the amygdala. In addition, they directly inhibit pituitary gonadotropin, GH and TSH secretion, render the target tissues of sex steroids and growth factors resistant to these substances and suppress the 5' deiodinase, which converts the relatively inactive tetraiodothyronine (T(4)) to triiodothyronine (T(3)), contributing further to the suppression of

  13. A five year prospective investigation of anterior pituitary function after traumatic brain injury: is hypopituitarism long-term after head trauma associated with autoimmunity?

    PubMed

    Tanriverdi, Fatih; De Bellis, Annamaria; Ulutabanca, Halil; Bizzarro, Antonio; Sinisi, Antonio A; Bellastella, Giuseppe; Amoresano Paglionico, Vanda; Dalla Mora, Liliana; Selcuklu, Ahmed; Unluhizarci, Kursad; Casanueva, Felipe F; Kelestimur, Fahrettin

    2013-08-15

    Traumatic brain injury (TBI) has been recently recognized as a common cause of pituitary dysfunction. However, there are not sufficient numbers of prospective studies to understand the natural history of TBI induced hypopituitarism. The aim was to report the results of five years' prospective follow-up of anterior pituitary function in patients with mild, moderate and severe TBI. Moreover, we have prospectively investigated the associations between TBI induced hypopituitarism and presence of anti-hypothalamus antibodies (AHA) and anti-pituitary antibodies (APA). Twenty five patients (20 men, five women) were included who were prospectively evaluated 12 months and five years after TBI, and 17 of them also had a third-year evaluation. Growth hormone (GH) deficiency is the most common pituitary hormone deficit at one, three, and five years after TBI. Although most of the pituitary hormone deficiencies improve over time, there were substantial percentages of pituitary hormone deficiencies at the fifth year (28% GH, 4% adrenocorticotropic hormone [ACTH], and 4% gonadotropin deficiencies). Pituitary dysfunction was significantly higher in strongly AHA- and APA-positive (titers ≥1/16) patients at the fifth year. In patients with mild and moderate TBI, ACTH and GH deficiencies may improve over time in a considerable number of patients but, although rarely, may also worsen over the five-year period. However in severe TBI, ACTH and GH status of the patients at the first year evaluation persisted at the fifth year. Therefore, screening pituitary function after TBI for five years is important, especially in patients with mild TBI. Moreover, close strong associations between the presence of high titers of APA and/or AHA and hypopituitarism at the fifth year were shown for the first time.

  14. Immunocytochemical and ultrastructural identification of pituitary cell types in the protogynous Thalassoma duperrey during adult sexual ontogeny

    USGS Publications Warehouse

    Parhar, I.S.; Nagahama, Y.; Grau, E.G.; Ross, R.M.

    1998-01-01

    Protogynous wrasses (Thalassoma duperrey): females (F), primary males (PM) along with a few terminal-phase males (TM) and sex-changed males (SM), were used to characterize the topographical organization of the pituitary. In general, immunocytochemical and ultrastructural features of the adenohypophyseal cell types of the saddleback wrasse pituitary resemble those of other teleosts. In the rostral pars distalis (RPD), corticotropic cells were found bordering the neurohypophysis (NH) and surrounding the centroventrally located prolactin cells. Thyrotropic cells formed a small group in the anteriodorsal part of the rostral and proximal pars distalis (PPD). The somatotropic cells were distributed in large clusters, mostly organized in cell cords around the interdigitations of the NH of the dorsal PPD. Cells containing gonadotropin I?? subunit were localized in the dorsal parts of the PPD, in close association with somatotropic cells and gonadotropin II?? subunit containing cells were seen in the centroventral parts of the PPD and along the periphery of the pars intermedia (PI). The pars intermedia was composed of melanotropic cells and somatolactin cells that lined the neurohypohysis. Distinct ultrastructural differences in corticotropic and somatotropic cells were not observed between the four groups. In all groups, prolactin cells in the ventral-most RPD could be immature cells or actively secreting prolactin. Gonadotropic II cells of PM and F had relatively higher incidence of "nuclear budding" and cell organelles compared to TM and SM. Besides gonadotropic, the active melanotropic and somatolactin cells might be associated with some aspect(s) of reproduction.

  15. Diagnostic Accuracy of Perioperative Measurement of Basal Anterior Pituitary and Target Gland Hormones in Predicting Adrenal Insufficiency After Pituitary Surgery

    PubMed Central

    Cerina, Vatroslav; Kruljac, Ivan; Radosevic, Jelena Marinkovic; Kirigin, Lora Stanka; Stipic, Darko; Pecina, Hrvoje Ivan; Vrkljan, Milan

    2016-01-01

    Abstract The insulin tolerance test (ITT) is the gold standard for diagnosing adrenal insufficiency (AI) after pituitary surgery. The ITT is unpleasant for patients, requires close medical supervision and is contraindicated in several comorbidities. The aim of this study was to analyze whether tumor size, remission rate, preoperative, and early postoperative baseline hormone concentrations could serve as predictors of AI in order to increase the diagnostic accuracy of morning serum cortisol. This prospective study enrolled 70 consecutive patients with newly diagnosed pituitary adenomas. Thirty-seven patients had nonfunctioning pituitary adenomas (NPA), 28 had prolactinomas and 5 had somatotropinomas. Thyroxin (T4), thyrotropin (TSH), prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and insulin-like growth factor 1 (IGF-I) were measured preoperatively and on the sixth postoperative day. Serum morning cortisol was measured on the third postoperative day (CORT3) as well as the sixth postoperative day (CORT6). Tumor mass was measured preoperatively and remission was assessed 3 months after surgery. An ITT was performed 3 to 6 months postoperatively. Remission was achieved in 48% of patients and AI occurred in 51%. Remission rates and tumor type were not associated with AI. CORT3 had the best predictive value for AI (area under the curve (AUC) 0.868, sensitivity 82.4%, specificity 83.3%). Tumor size, preoperative T4, postoperative T4, and TSH were also associated with AI in a multivariate regression model. A combination of all preoperative and postoperative variables (excluding serum cortisol) had a sensitivity of 75.0% and specificity of 77.8%. The predictive power of CORT3 substantially improved by adding those variables into the model (AUC 0.921, sensitivity 94.1%, specificity 78.3%, PPV 81.9%, NPV of 92.7%). In a subgroup analysis that included only female patients with NPA, LH had exactly the same predictive value as CORT3. The

  16. Diagnostic Accuracy of Perioperative Measurement of Basal Anterior Pituitary and Target Gland Hormones in Predicting Adrenal Insufficiency After Pituitary Surgery.

    PubMed

    Cerina, Vatroslav; Kruljac, Ivan; Radosevic, Jelena Marinkovic; Kirigin, Lora Stanka; Stipic, Darko; Pecina, Hrvoje Ivan; Vrkljan, Milan

    2016-03-01

    The insulin tolerance test (ITT) is the gold standard for diagnosing adrenal insufficiency (AI) after pituitary surgery. The ITT is unpleasant for patients, requires close medical supervision and is contraindicated in several comorbidities. The aim of this study was to analyze whether tumor size, remission rate, preoperative, and early postoperative baseline hormone concentrations could serve as predictors of AI in order to increase the diagnostic accuracy of morning serum cortisol. This prospective study enrolled 70 consecutive patients with newly diagnosed pituitary adenomas. Thirty-seven patients had nonfunctioning pituitary adenomas (NPA), 28 had prolactinomas and 5 had somatotropinomas. Thyroxin (T4), thyrotropin (TSH), prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and insulin-like growth factor 1 (IGF-I) were measured preoperatively and on the sixth postoperative day. Serum morning cortisol was measured on the third postoperative day (CORT3) as well as the sixth postoperative day (CORT6). Tumor mass was measured preoperatively and remission was assessed 3 months after surgery. An ITT was performed 3 to 6 months postoperatively. Remission was achieved in 48% of patients and AI occurred in 51%. Remission rates and tumor type were not associated with AI. CORT3 had the best predictive value for AI (area under the curve (AUC) 0.868, sensitivity 82.4%, specificity 83.3%). Tumor size, preoperative T4, postoperative T4, and TSH were also associated with AI in a multivariate regression model. A combination of all preoperative and postoperative variables (excluding serum cortisol) had a sensitivity of 75.0% and specificity of 77.8%. The predictive power of CORT3 substantially improved by adding those variables into the model (AUC 0.921, sensitivity 94.1%, specificity 78.3%, PPV 81.9%, NPV of 92.7%). In a subgroup analysis that included only female patients with NPA, LH had exactly the same predictive value as CORT3. The addition

  17. Impact of subclinical haemorrhage on the pituitary gland in patients with pituitary adenomas.

    PubMed

    Kinoshita, Yasuyuki; Tominaga, Atsushi; Usui, Satoshi; Arita, Kazunori; Sugiyama, Kazuhiko; Kurisu, Kaoru

    2014-05-01

    Advanced magnetic resonance imaging (MRI) and optical instruments for surgery frequently demonstrate subclinical haemorrhage in pituitary adenomas; however, the effects of subclinical haemorrhage on pituitary glands remain unclear. We sought to clarify the pituitary function in patients with subclinical pituitary adenoma haemorrhage (SPAH). Between January 2006 and December 2012, we retrospectively reviewed 328 consecutive patients who underwent surgery for pituitary adenoma. SPAH was defined as an intratumoral haemorrhage based on both 3 tesla MRI and operative findings, with no clinical symptoms of acute pituitary adenoma apoplexy. The pituitary dysfunction assessed using pre- and postoperative provocative tests was investigated in patients categorized into three groups: nonapoplectic adenoma, adenoma with SPAH and adenoma with clinical apoplexy. The main outcome measure was the incidence of pituitary dysfunction. The overall incidence of nonapoplectic adenomas, adenomas with SPAH and adenomas with clinical apoplexy was 82·3%, 14·3% and 3·4%, respectively. Clinical pituitary apoplexy frequently occurred in male patients with large nonfunctioning adenomas, causing pituitary dysfunction. Contrastingly, the incidence of SPAH was significantly higher in the patients with prolactinoma (P = 0·0260), including those with relatively small adenomas (P = 0·0007). No medications, such as dopamine agonists or somatostatin analogues, were observed to affect the occurrence of SPAH. No deterioration of the pituitary function was observed in the SPAH patients in comparison with the patients with nonapoplectic adenoma, and the size of the haematoma occupying the pituitary adenoma did not exhibit any relationships with the deterioration of the pituitary function. Furthermore, SPAH caused no deterioration of the pituitary function after a surgery based on the postoperative provocation tests. Subclinical pituitary adenoma haemorrhage does not cause any added dysfunction in

  18. Pituitary gland development: an update.

    PubMed

    Bancalari, Rodrigo E; Gregory, Louise C; McCabe, Mark J; Dattani, Mehul T

    2012-01-01

    The embryonic development of the pituitary gland involves a complex and highly spatio-temporally regulated network of integrating signalling molecules and transcription factors. Genetic mutations in any of these factors can lead to congenital hypopituitarism in association with a wide spectrum of craniofacial/midline defects ranging from incompatibility with life to holoprosencephaly (HPE) and cleft palate and septo-optic dysplasia (SOD). Increasing evidence supports a genotypic overlap with hypogonadotrophic hypogonadal disorders such as Kallmann syndrome, which is consistent with the known overlap in phenotypes between these disorders. This chapter reviews the cascade of events leading up to the successful development of the pituitary gland and to highlight key areas where genetic variations can occur thus leading to congenital hypopituitarism and associated defects. Copyright © 2012 S. Karger AG, Basel.

  19. Addison's Disease and Pituitary Enlargement.

    PubMed

    Winters, Stephen J; Vitaz, Todd; Nowacki, Michael R; Craddock, Durrett C; Silverman, Craig

    2015-06-01

    A 60-year-old man with Addison's disease, primary hypothyroidism and type 2 diabetes mellitus who was treated with stable doses of hydrocortisone and fludrocortisone developed increasing skin pigmentation and a bitemporal hemianopia. The plasma ACTH level was 14,464 pg/mL, and an invasive pituitary macroadenoma with suprasellar extension was found on magnetic resonance imaging leading to transnasal-transsphenoidal adenomectomy. The tumor demonstrated features of an eosinophilic adenoma and stained uniformly for ACTH. Residual tumor was treated with stereotactic radiotherapy. This case and the 13 cases published previously indicate that primary adrenal failure may predispose to corticotroph hyperplasia, and in some patients to the development of an invasive corticotroph adenoma. The ACTH level should be measured, and a pituitary magnetic resonance imaging is indicated when skin pigmentation increases in a patient with primary adrenal failure who is receiving customary treatment with glucocorticoids and mineralocorticoids.

  20. The neuropeptide Gonadotropin-releasing hormone modifies the spontaneous muscular contraction in the earthworm: Eisenia foetida.

    PubMed

    Luis Quintanar, J; Gutiérrez-García, Karina; Castillo-Hernández, Luis

    2011-12-01

    We investigated whether the Gonadotropin-releasing hormone affects the spontaneous muscular contraction in the earthworm Eisenia foetida. In addition, we investigated the presence of Gonadotropin-releasing hormone receptor in ventral nerve cord by immunohistochemistry and polymerase chain reaction. Gonadotropin-releasing hormone induced a significant increase on both amplitude and muscular tone and decrease in the frequency of spontaneous muscular contraction. We found the presence of immunoreactive material to Gonadotropin-releasing hormone receptor in the ventral nerve cord, likewise the Gonadotropin-releasing hormone receptor mRNA expression. In conclusion, the Gonadotropin-releasing hormone modifies the spontaneous muscular contraction in E. foetida and these effects can be due to the activation of the Gonadotropin-releasing hormone receptor.

  1. Dopamine inhibits somatolactin gene expression in tilapia pituitary cells through the dopamine D2 receptors.

    PubMed

    Jiang, Quan; Lian, Anji; He, Qi

    2016-07-01

    Dopamine (DA) is an important neurotransmitter in the central nervous system of vertebrates and possesses key hypophysiotropic functions. Early studies have shown that DA has a potent inhibitory effect on somatolactin (SL) release in fish. However, the mechanisms responsible for DA inhibition of SL gene expression are largely unknown. To this end, tilapia DA type-1 (D1) and type-2 (D2) receptor transcripts were examined in the neurointermediate lobe (NIL) of the tilapia pituitary by real-time PCR. In tilapia, DA not only was effective in inhibiting SL mRNA levels in vivo and in vitro, but also could abolish pituitary adenylate cyclase-activating polypeptide (PACAP)- and salmon gonadotropin-releasing hormone (sGnRH)-stimulated SL gene expression at the pituitary level. In parallel studies, the specific D2 receptor agonists quinpirole and bromocriptine could mimic the DA-inhibited SL gene expression. Furthermore, the D2 receptor antagonists domperidone and (-)-sulpiride could abolish the SL response to DA or the D2 agonist quinpirole, whereas D1 receptor antagonists SCH23390 and SKF83566 were not effective in this respect. In primary cultures of tilapia NIL cells, D2 agonist quinpirole-inhibited cAMP production could be blocked by co-treatment with the D2 antagonist domperidone and the ability of forskolin to increase cAMP production was also inhibited by quinpirole. Using a pharmacological approach, the AC/cAMP pathway was shown to be involved in quinpirole-inhibited SL mRNA expression. These results provide evidence that DA can directly inhibit SL gene expression at the tilapia pituitary level via D2 receptor through the AC/cAMP-dependent mechanism. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Evaluation of hypothalamic-pituitary function in children following acute bacterial meningitis.

    PubMed

    Karadag-Oncel, Eda; Cakir, Meltem; Kara, Ates; Gonc, Nazli; Cengiz, Ali Bulent; Ozon, Alev; Ciftci, Ergin; Alikasifoglu, Ayfer; Ceyhan, Mehmet; Kandemir, Nurgun

    2015-02-01

    Previous studies in adults and case reports in children have shown increased frequency of hypothalamo-pituitary dysfunction after infectious diseases of the central nervous system. The aim of this study was to evaluate the function of hypothalamo-pituitary axis in children with a history of bacterial meningitis. Patients diagnosed with bacterial meningitis between April 2000 and June 2011 was included. Baseline and stimulated hormonal tests were performed as required for hormonal evaluations following a diagnosis of meningitis. Pituitary function was assessed following a period of 8-135 months (mean 53 months) after bacterial meningitis. Thirty-seven cases (27 male, 15 pubertal) with mean age of 11.1 ± 4.4 years were included. Mean height SDS was 0.01 ± 1.07 and mean BMI SDS was 0.54 ± 1.15 all patients had a SDS above -2 SD. Baseline cortisol and low dose ACTH stimulation revealed normal adrenal functions in all patients. Gonadotropin deficiency was not detected in any of the pubertal cases. Four cases (10.8%) had low IGF1 and IGFBP3 z-scores (<-2 SD) according to age, sex and Tanner stage, but peak GH response in clonidin test was >10 ng/ml in three of them suggesting neurosecretary dysfunction of GH in these cases. The fourth case has died before the test. No one had TSH deficiency and diabetes insipidus, only one case had mild hyperprolactinemia. Our findings suggest that hypothalamo-pituitary dysfunction is not as common in childhood as in adulthood. The most remarkable finding was neurosecretary dysfunction of GH in some cases.

  3. Fibrosarcoma complicating irradiated pituitary adenoma

    SciTech Connect

    Shi, T.; Farrell, M.A.; Kaufmann, J.C.

    1984-09-01

    Eight years after radiation therapy (5000 rads of 60Co) for a pituitary adenoma, a patient developed a sellar fibrosarcoma. The tumor had an aggressive growth pattern: it infiltrated the optic nerve, sphenoidal air sinus, hypothalamus, and both cavernous sinuses, where compression of the left internal carotid artery resulted in a massive hemispheric infarction. Surgery was ineffective in arresting rapid growth of the lesion; death occurring 5 months after onset of symptoms.

  4. Pituitary cretinism in two sisters.

    PubMed Central

    Kohno, H; Watanabe, N; Ootsuka, M; Kajiwara, M; Gohya, N

    1980-01-01

    Two sisters with cretinism are reported. Each showed low levels of serum triiodothyronine, thyroxine, and thyroid-stimulating hormone (TSH). In the elder sister, serum TSH did not increase after administration of thyrotropin-releasing hormone. We conclude that cretinism in these 2 sisters was due to TSH deficiency. This is the second report of 'familial' pituitary cretinism (TSH-deficient congenital hypothyroidism). PMID:7436542

  5. ACTH-producing pituitary tumors.

    PubMed

    Grua, J R; Nelson, D H

    1991-06-01

    Adrenocorticotropin (ACTH)-producing tumors of the pituitary gland usually, though not in all cases, initially show evidence of excess cortisol. The pathogenesis of these tumors--monoclonal versus polyclonal and intermediate lobe versus anterior lobe--continues to prompt debate. Important advances in the diagnostic methods (such as petrosal sinus sampling for ACTH and other hormones) are described. While the mainstay of therapy is still selective adenomectomy via the transsphenoidal approach, total hypophysectomy may occasionally be indicated.

  6. Transsphenoidal surgery for pituitary tumours

    PubMed Central

    Massoud, A; Powell, M; Williams, R; Hindmarsh, P; Brook, C

    1997-01-01

    Accepted 29 January 1997
 OBJECTIVES—Transsphenoidal surgery (TSS) is the preferred method for the excision of pituitary microadenomas in adults. This study was carried out to establish the long term efficacy and safety of TSS in children.
STUDY DESIGN—A 14 year retrospective analysis was carried out on 23 children (16 boys and seven girls), all less than 18 years of age, who had undergone TSS at our centre.
RESULTS—Twenty nine transsphenoidal surgical procedures were carried out. The most common diagnosis was an adrenocorticotrophic hormone (ACTH) secreting adenoma (14 (61%) patients). The median length of follow up was 8.0 years (range 0.3-14.0 years). Eighteen (78%) patients were cured after the first procedure. No death was related to the operation. The most common postoperative complication was diabetes insipidus, which was transient in most patients. Other complications were headaches in two patients and cerebrospinal fluid leaks in two patients. De novo endocrine deficiencies after TSS in children were as follows: three (14%) patients developed panhypopituitarism, eight (73%) developed growth hormone insufficiency, three (14%) developed secondary hypothyroidism, and four (21%) developed gonadotrophin deficiency. Permanent ACTH deficiency occurred in five (24%) patients, though all patients received postoperative glucocorticoid treatment until dynamic pituitary tests were performed three months after TSS.
CONCLUSIONS—TSS in children is a safe and effective treatment for pituitary tumours, provided it is performed by surgeons with considerable experience and expertise. Surgical complications are minimal. Postoperative endocrine deficit is considerable, but is only permanent in a small proportion of patients.

 • Transsphenoidal surgery is a safe and effective treatment for pituitary tumours in children • Transsphenoidal surgery should be performed by surgeons with considerable experience and expertise • Surgical complications of

  7. Thyrotropic activity of salmon pituitary glycoprotein hormones in the Hawaiian parrotfish thyroid in vitro.

    PubMed

    Swanson, P; Grau, E G; Helms, L M; Dickhoff, W W

    1988-02-01

    The thyrotropic activities of salmon pituitary extract, thyroid-stimulating hormone (TSH), gonadotropins (GTH), and glycoprotein fractions obtained during purification of salmon TSH and GTH were measured using the parrotfish thyroid culture system. Purified salmon TSH was approximately 1,000 times more potent than bovine TSH in stimulating thyroxine release into the culture medium. Most of the forms of salmon GTH had no thyrotropic activity. One of the forms of salmon GTH (GTH-F) and three chromatofocusing fractions (CF-B, -C, and -E) that were devoid of activity in the coho salmon in vivo had some thyrotropic activity in the parrotfish thyroid culture. Whether the activity of these fractions was due to contamination with TSH, less potent forms of TSH, or inherent thyrotropic activity of a form of GTH is discussed. These results indicate that the parrotfish thyroid culture system can be used to detect thyrotropic activity of fractions obtained during the purification of teleost TSH.

  8. 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

  9. Pituitary apoplexy: pathophysiology, diagnosis and management.

    PubMed

    Glezer, Andrea; Bronstein, Marcello D

    2015-06-01

    Pituitary apoplexy is characterized by sudden increase in pituitary gland volume secondary to ischemia and/or necrosis, usually in a pituitary adenoma. Most cases occur during the 5th decade of life, predominantly in males and in previously unknown clinically non-functioning pituitary adenomas. There are some predisposing factors as arterial hypertension, anticoagulant therapy and major surgery. Clinical picture comprises headache, visual impairment, cranial nerve palsies and hypopituitarism. Most cases improve with both surgical and expectant management and the best approach in the acute phase is still controversial. Surgery, usually by transsphenoidal route, is indicated if consciousness and/or vision are impaired, despite glucocorticoid replacement and electrolyte support. Pituitary function is impaired in most patients before apoplexy and ACTH deficiency is common, which makes glucocorticoid replacement needed in most cases. Pituitary deficiencies, once established, usually do not recover, regardless the treatment. Sellar imaging and endocrinological function must be periodic reevaluated.

  10. Invertebrate Gonadotropin-Releasing Hormone-Related Peptides and Their Receptors: An Update

    PubMed Central

    Sakai, Tsubasa; Shiraishi, Akira; Kawada, Tsuyoshi; Matsubara, Shin; Aoyama, Masato; Satake, Honoo

    2017-01-01

    Gonadotropin-releasing hormones (GnRHs) play pivotal roles in reproductive functions via the hypothalamus, pituitary, and gonad axis, namely, HPG axis in vertebrates. GnRHs and their receptors (GnRHRs) are likely to be conserved in invertebrate deuterostomes and lophotrochozoans. All vertebrate and urochordate GnRHs are composed of 10 amino acids, whereas protostome, echinoderm, and amphioxus GnRH-like peptides are 11- or 12-residue peptide containing two amino acids after an N-terminal pyro-Glu. In urochordates, Halocynthia roretzi GnRH gene encodes two GnRH peptide sequences, whereas two GnRH genes encode three different GnRH peptides in Ciona intestinalis. These findings indicate the species-specific diversification of GnRHs. Intriguingly, the major signaling pathway for GnRHRs is intracellular Ca2+ mobilization in chordates, echinoderms, and protostomes, whereas Ciona GnRHRs (Ci-GnRHRs) are endowed with multiple GnRHergic cAMP production pathways in a ligand-selective manner. Moreover, the ligand-specific modulation of signal transduction via heterodimerization among Ci-GnRHR paralogs suggests the species-specific development of fine-tuning of gonadal functions in ascidians. Echinoderm GnRH-like peptides show high sequence differences compared to those of protostome counterparts, leading to the difficulty in classification of peptides and receptors. These findings also show both the diversity and conservation of GnRH signaling systems in invertebrates. The lack of the HPG axis in invertebrates indicates that biological functions of GnRHs are not release of gonadotropins in current invertebrates and common ancestors of vertebrates and invertebrates. To date, authentic or putative GnRHRs have been characterized from various echinoderms and protostomes as well as chordates and the mRNAs have been found to be distributed not only reproductive organs but also other tissues. Collectively, these findings further support the notion that invertebrate GnRHs have

  11. Human chorionic gonadotropin: Different glycoforms and biological activity depending on its source of production.

    PubMed

    Fournier, Thierry

    2016-06-01

    Human chorionic gonadotropin (hCG) is the first hormonal message from the placenta to the mother. It is detectable in maternal blood two days after implantation and behaves like a super LH agonist stimulating progesterone secretion by the corpus luteum. In addition to maintaining the production of progesterone until the placenta itself produces it, hCG also has a role in myometrial quiescence and local immune tolerance. Specific to humans, hCG is a complex glycoprotein composed of two highly glycosylated subunits. The α-subunit is identical to the pituitary gonadotropin hormones (LH, FSH, TSH), contains two N-glycosylation sites, and is encoded by a single gene (CGA). By contrast, the β-subunits are distinct for each hormones and confer both receptor and biological specificity, although LH and hCG bind to the same receptor (LH/CG-R). The hCG ß-subunit is encoded by a cluster of genes (CGB) and contains two sites of N-glycosylation and four sites of O-glycosylation. The hCG glycosylation state varies with the stage of pregnancy, its source of production and in the pathology. It is well established that hCG is mainly secreted into maternal blood, where it peaks at 8-10weeks of gestation (WG), by the syncytiotrophoblast (ST), which represents the endocrine tissue of the human placenta. The invasive extravillous trophoblast (iEVT) also secretes hCG, and in particular hyperglycosylated forms of hCG (hCG-H) also produced by choriocarcinoma cells. In maternal blood, hCG-H is elevated during early first trimester corresponding to the trophoblastic cell invasion process and then decreases. In addition to its endocrine role, hCG has autocrine and paracrine roles. It promotes formation of the ST and angiogenesis through LH/CG-R but has no effect on trophoblast invasion in vitro. By contrast, hCG-H stimulates trophoblast invasion and angiogenesis by interacting with the TGFß receptor in a LH/CG-R independent signalling pathway. hCG is largely used in antenatal screening

  12. Novel Genetic Causes of Pituitary Adenomas.

    PubMed

    Caimari, Francisca; Korbonits, Márta

    2016-10-15

    Recently, a number of novel genetic alterations have been identified that predispose individuals to pituitary adenomas. Clinically relevant pituitary adenomas are relatively common, present in 0.1% of the general population. They are mostly benign monoclonal neoplasms that arise from any of the five hormone-secreting cell types of the anterior lobe of the pituitary gland, and cause disease due to hormonal alterations and local space-occupying effects. The pathomechanism of pituitary adenomas includes alterations in cell-cycle regulation and growth factor signaling, which are mostly due to epigenetic changes; somatic and especially germline mutations occur more rarely. A significant proportion of growth hormone- and adrenocorticotrophin-secreting adenomas have activating somatic mutations in the GNAS and USP8 genes, respectively. Rarely, germline mutations predispose to pituitary tumorigenesis, often in a familial setting. Classical tumor predisposition syndromes include multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4) syndromes, Carney complex, and McCune-Albright syndrome. Pituitary tumors have also been described in association with neurofibromatosis type 1, DICER1 syndrome, and SDHx mutations. Pituitary adenomas with no other associated tumors have been described as familial isolated pituitary adenomas. Patients with AIP or GPR101 mutations often present with pituitary gigantism either in a familial or simplex setting. GNAS and GPR101 mutations that arise in early embryonic age can lead to somatic mosaicism involving the pituitary gland and resulting in growth hormone excess. Senescence has been suggested as the key mechanism protecting pituitary adenomas turning malignant in the overwhelming majority of cases. Here we briefly summarize the genetic background of pituitary adenomas, with an emphasis on the recent developments in this field. Clin Cancer Res; 22(20); 5030-42. ©2016 AACR SEE ALL ARTICLES IN THIS CCR FOCUS SECTION, "ENDOCRINE CANCERS

  13. Cushing's disease presenting with pituitary apoplexy.

    PubMed

    Chan, Daniel; Rong, Teo Cheng; Dalan, Rinkoo

    2012-11-01

    Pituitary tumour apoplexy is a rare but life threatening condition. Cushing's disease usually presents with clinical features of Cushing's syndrome. We report a 30-year-old male patient with Cushing's disease who presented with severe headache and right third nerve palsy. MRI of the pituitary gland revealed a pituitary adenoma with infarction suggestive of apoplexy. After a transsphenoidal surgery he developed pan-hypopituitarism with diabetes insipidus. We also review the relevant literature. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Pathology of the human pituitary adenomas

    PubMed Central

    Kajiya, Hanako; Takei, Mao; Egashira, Noboru; Tobita, Maya; Takekoshi, Susumu; Teramoto, Akira

    2008-01-01

    This article describes pertinent aspects of histochemical and molecular changes of the human pituitary adenomas. The article outlines individual tumor groups with general, specific and molecular findings. The discussion further extends to the unusual adenomas or carcinomas. The description in this article are pertinent not only for the practicing pathologists who are in the position of making proper diagnosis, but also for the pituitary research scientists who engage in solving basic problems in pituitary neoplasms by histochemistry and molecular biology. PMID:18688636

  15. A Computational Model of the Rainbow Trout Hypothalamus-Pituitary-Ovary-Liver Axis

    PubMed Central

    Gillies, Kendall; Krone, Stephen M.; Nagler, James J.; Schultz, Irvin R.

    2016-01-01

    Reproduction in fishes and other vertebrates represents the timely coordination of many endocrine factors that culminate in the production of mature, viable gametes. In recent years there has been rapid growth in understanding fish reproductive biology, which has been motivated in part by recognition of the potential effects that climate change, habitat destruction and contaminant exposure can have on natural and cultured fish populations. New approaches to understanding the impacts of these stressors are being developed that require a systems biology approach with more biologically accurate and detailed mathematical models. We have developed a multi-scale mathematical model of the female rainbow trout hypothalamus-pituitary-ovary-liver axis to use as a tool to help understand the functioning of the system and for extrapolation of laboratory findings of stressor impacts on specific components of the axis. The model describes the essential endocrine components of the female rainbow trout reproductive axis. The model also describes the stage specific growth of maturing oocytes within the ovary and permits the presence of sub-populations of oocytes at different stages of development. Model formulation and parametrization was largely based on previously published in vivo and in vitro data in rainbow trout and new data on the synthesis of gonadotropins in the pituitary. Model predictions were validated against several previously published data sets for annual changes in gonadotropins and estradiol in rainbow trout. Estimates of select model parameters can be obtained from in vitro assays using either quantitative (direct estimation of rate constants) or qualitative (relative change from control values) approaches. This is an important aspect of mathematical models as in vitro, cell-based assays are expected to provide the bulk of experimental data for future risk assessments and will require quantitative physiological models to extrapolate across biological scales. PMID

  16. How to contribute to the progress of neuroendocrinology: New insights from discovering novel neuropeptides and neurosteroids regulating pituitary and brain functions.

    PubMed

    Tsutsui, Kazuyoshi

    2016-02-01

    Obtaining new insights by discovering novel neuropeptides and neurosteroids regulating pituitary and brain functions is essential for the progress of neuroendocrinology. At the beginning of 1970s, gonadotropin-releasing hormone (GnRH) was discovered in mammals. Since then, it was generally accepted that GnRH is the only hypothalamic neuropeptide regulating gonadotropin release in vertebrates. In 2000, however, gonadotropin-inhibitory hormone (GnIH), a novel hypothalamic neuropeptide that actively inhibits gonadotropin release, was discovered in quail. The follow-up studies demonstrated that GnIH acts as a new key player for regulation of reproduction across vertebrates. It now appears that GnIH acts on the pituitary and the brain to serve a number of behavioral and physiological functions. On the other hand, a new concept has been established that the brain synthesizes steroids, called neurosteroids. The formation of neurosteroids in the brain was originally demonstrated in mammals and subsequently in other vertebrates. Recently, 7α-hydroxypregnenolone was discovered as a novel bioactive neurosteroid inducing locomotor behavior of vertebrates, indicating that neurosteroidogenesis in the brain is still incompletely elucidated in vertebrates. At the beginning of 2010s, it was further found that the pineal gland actively produces neurosteroids. Pineal neurosteroids act on the brain to regulate locomotor rhythms and neuronal survival. Furthermore, the interaction of neuropeptides and neurosteroids is becoming clear. GnIH decreases aggressive behavior by regulating neuroestrogen synthesis in the brain. This review summarizes these new insights by discovering novel neuropeptides and neurosteroids in the field of neuroendocrinology.

  17. Polymorphisms in gonadotropin and gonadotropin receptor genes as markers of ovarian reserve and response in in vitro fertilization.

    PubMed

    La Marca, Antonio; Sighinolfi, Giovanna; Argento, Cindy; Grisendi, Valentina; Casarini, Livio; Volpe, Annibale; Simoni, Manuela

    2013-03-15

    Since gonadotropins are the fundamental hormones that control ovarian activity, genetic polymorphisms may alter gonadal responsiveness to glycoproteins; hence they are important regulators of hormone activity at the target level. The establishment of the pool of primordial follicles takes place during fetal life and is mainly under genetic control. Consequently, single nucleotide polymorphisms (SNPs) in gonadotropins and their receptors do not seem to be associated with any significant modification in the endowment of nongrowing follicles in the ovary. Indeed, the age at menopause, a biological characteristic strongly related to ovarian reserve, as well as markers of functional ovarian reserve such as anti-Müllerian hormone and antral follicle count, are not different in women with different genetic variants. Conversely, some polymorphisms in FSH receptor (FSHR) seem to be associated with modifications in ovarian activity. In particular, studies suggest that the Ser680 genotype for FSHR is a factor of relative resistance to FSH stimulation resulting in slightly higher FSH serum levels, thus leading to a prolonged duration of the menstrual cycle. Moreover, some FSHR gene polymorphisms show a positive association with ovarian response to exogenous gonadotropin administration, hence exhibiting some potential for a pharmacogenetic estimation of the FSH dosage in controlled ovarian stimulation. The study of SNPs of the FSHR gene is an interesting field of research that could provide us with new information about the way each woman responds to exogenous gonadotropin administration during ovulation induction.

  18. From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): an International Pituitary Pathology Club proposal.

    PubMed

    Asa, S L; Casar-Borota, O; Chanson, P; Delgrange, E; Earls, P; Ezzat, S; Grossman, A; Ikeda, H; Inoshita, N; Karavitaki, N; Korbonits, M; Laws, E R; Lopes, M B; Maartens, N; McCutcheon, I E; Mete, O; Nishioka, H; Raverot, G; Roncaroli, F; Saeger, W; Syro, L V; Vasiljevic, A; Villa, C; Wierinckx, A; Trouillas, J

    2017-04-01

    The classification of neoplasms of adenohypophysial cells is misleading because of the simplistic distinction between adenoma and carcinoma, based solely on metastatic spread and the poor reproducibility and predictive value of the definition of atypical adenomas based on the detection of mitoses or expression of Ki-67 or p53. In addition, the current classification of neoplasms of the anterior pituitary does not accurately reflect the clinical spectrum of behavior. Invasion and regrowth of proliferative lesions and persistence of hormone hypersecretion cause significant morbidity and mortality. We propose a new terminology, pituitary neuroendocrine tumor (PitNET), which is consistent with that used for other neuroendocrine neoplasms and which recognizes the highly variable impact of these tumors on patients.

  19. Adrenal and gonadal steroids and pituitary response to LHRH in girls. II. Precocious puberty.

    PubMed

    Pintor, C; Genazzani, A R; Ibba, P; Pecciarini-Snickars, L; Corda, R

    1978-04-01

    Three baby girls between 22 and 30 months of age, presenting with isosexual idiopathic precocious puberty apparently not due to any organic cause, were studied. Basal levels of plasma steroids of adrenal and gonadal origin, circadian rhythm of plasma cortisol, and pituitary response to 25 microgram of LHRH were evaluated. All cases were characterized by high levels of plasma gonadotropins and by a marked response to exogenous LHRH. Normal cortisol circadia rhythm was found in all cases, one of which characterized by slightly raised plasma values. The other adrenal steroids were all higher than those expected for the chronological age, corresponding to those of 5-6 years old girls. On the other hand, steroids of both adrenal and ovarian (A, T) or mainly ovarian origin (E2) and DHT were all found to be higher than those normally reported in girls at stage 2 of sexual development. These data indicate a hypersecretion of gonadotropins in idiopathic isosexual precocious puberty, with a marked gonadal steroidogenetic response. The secretion of adrenal androgens does not appear to have an important role in the etiology of this condition.

  20. Pituitary abscess after autologous bone marrow transplantation.

    PubMed

    Leff, R S; Martino, R L; Pollock, W J; Knight, W A

    1989-05-01

    The first case of pituitary abscess arising in a patient during recovery from autologous bone marrow transplantation is reported. A 31-year-old man with a 9 month history of T-cell lymphoma died suddenly more than 60 days after successful treatment with high-dose cyclophosphamide, total body irradiation, and autologous bone marrow infusion. Autopsy revealed a pituitary abscess associated with clinically silent sphenoid sinusitis. Unique aspects of this case are presented and clinical and pathologic features of pituitary abscess are reviewed. Although rare, pituitary abscess may complicate recovery from bone marrow transplantation.

  1. Hereditary pituitary hyperplasia with infantile gigantism.

    PubMed

    Gläsker, Sven; Vortmeyer, Alexander O; Lafferty, Antony R A; Hofman, Paul L; Li, Jie; Weil, Robert J; Zhuang, Zhengping; Oldfield, Edward H

    2011-12-01

    We report hereditary pituitary hyperplasia. The objective of the study was to describe the results of the clinical and laboratory analysis of this rare instance of hereditary pituitary hyperplasia. The study is a retrospective analysis of three cases from one family. The study was conducted at the National Institutes of Health, a tertiary referral center. A mother and both her sons had very early-onset gigantism associated with high levels of serum GH and prolactin. The condition was treated by total hypophysectomy. We performed clinical, pathological, and molecular evaluations, including evaluation basal and provocative endocrine testing, neuroradiological assessment, and assessment of the pituitary tissue by microscopic evaluation, immunohistochemistry, and electron microscopy. All three family members had very early onset of gigantism associated with abnormally high serum levels of GH and prolactin. Serum GHRH levels were not elevated in either of the boys. The clinical, radiographic, surgical, and histological findings indicated mammosomatotroph hyperplasia. The pituitary gland of both boys revealed diffuse mammosomatotroph hyperplasia of the entire pituitary gland without evidence of adenoma. Prolactin and GH were secreted by the same cells within the same secretory granules. Western blot and immunohistochemistry demonstrated expression of GHRH in clusters of cells distributed throughout the hyperplastic pituitary of both boys. This hereditary condition seems to be a result of embryonic pituitary maldevelopment with retention and expansion of the mammosomatotrophs. The findings suggest that it is caused by paracrine or autocrine pituitary GHRH secretion during pituitary development.

  2. [Old phenotype and new genotypes. Pituitary adenomas].

    PubMed

    Gérard, C; Jedidi, H; Petrossians, P; Krzesinski, F; Daly, A; Beckers, A

    2015-11-01

    Gigantism and acromegaly, usually caused by a pituitary adenoma linked inappropriate secretion of growth hormone (GH), are generally considered as very rare diseases, even if, according to some authors, their cumulative prevalence is about 1/5000. Starting from the historical case of a giant from Liège we shall describe the different types of GH pituitary adenomas and their pathophysiology. We shall particularly discuss rare forms of inherited GH secreting pituitary adenomas like the FIPA (familial inherited isolated pituitary adenomas) and the X-LAG (X linked acrogigantism), both described for the first time in Liège, in 2000 and 2014, respectively.

  3. Effect of Treatment Modality on the Hypothalamic–Pituitary Function of Patients Treated with Radiation Therapy for Pituitary Adenomas: Hypothalamic Dose and Endocrine Outcomes

    PubMed Central

    Elson, Andrew; Bovi, Joseph; Kaur, Kawaljeet; Maas, Diana; Sinson, Grant; Schultz, Chris

    2014-01-01

    Background: Both fractionated external beam radiotherapy and single fraction radiosurgery for pituitary adenomas are associated with the risk of hypothalamic–pituitary (HP) axis dysfunction. Objective: To analyze the effect of treatment modality (Linac, TomoTherapy, or gamma knife) on hypothalamic dose and correlate these with HP-axis deficits after radiotherapy. Methods: Radiation plans of patients treated post-operatively for pituitary adenomas using Linac-based 3D-conformal radiotherapy (CRT) (n = 11), TomoTherapy-based intensity modulated radiation therapy (IMRT) (n = 10), or gamma knife stereotactic radiosurgery (n = 12) were retrospectively reviewed. Dose to the hypothalamus was analyzed and post-radiotherapy hormone function including growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, prolactin, and gonadotropins (follicle stimulating hormone/luteinizing hormone) were assessed. Results: Post-radiation, 13 of 27 (48%) patients eligible for analysis developed at least one new hormone deficit, of which 8 of 11 (72%) occurred in the Linac group, 4 of 8 (50%) occurred in the TomoTherapy group, and 1 of 8 (12.5%) occurred in the gamma knife group. Compared with fractionated techniques, gamma knife showed improved hypothalamic sparing for DMax Hypo and V12Gy. For fractionated modalities, TomoTherapy showed improved dosimetric characteristics over Linac-based treatment with hypothalamic DMean (44.8 vs. 26.8 Gy p = 0.02), DMax (49.8 vs. 39.1 Gy p = 0.04), and V12Gy (100 vs. 76% p = 0.004). Conclusion: Maximal dosimetric avoidance of the hypothalamus was achieved using gamma knife-based radiosurgery followed by TomoTherapy-based IMRT, and Linac-based 3D conformal radiation therapy, respectively. PMID:24782984

  4. The origins of the vertebrate hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-thyroid (HPT) endocrine systems: new insights from lampreys.

    PubMed

    Sower, Stacia A; Freamat, Mihael; Kavanaugh, Scott I

    2009-03-01

    The acquisition of a hypothalamic-pituitary axis was a seminal event in vertebrate evolution leading to the neuroendocrine control of many complex functions including growth, reproduction, osmoregulation, stress and metabolism. Lampreys as basal vertebrates are the earliest evolved vertebrates for which there are demonstrated functional roles for two gonadotropin-releasing hormones (GnRHs) that act via the hypothalamic-pituitary-gonadal axis controlling reproductive processes. With the availability of the lamprey genome, we have identified a novel GnRH form (lamprey GnRH-II) and a novel glycoprotein hormone receptor, lGpH-R II (thyroid-stimulating hormone-like receptor). Based on functional studies, in situ hybridization and phylogenetic analysis, we hypothesize that the newly identified lamprey GnRH-II is an ancestral GnRH to the vertebrate GnRHs. This finding opens a new understanding of the GnRH family and can help to delineate the evolution of the complex neuro/endocrine axis of reproduction. A second glycoprotein hormone receptor (lGpH-R II) was also identified in the sea lamprey. The existing data suggest the existence of a primitive, overlapping yet functional HPG and HPT endocrine systems in this organism, involving one possibly two pituitary glycoprotein hormones and two glycoprotein hormone receptors as opposed to three or four glycoprotein hormones interacting specifically with three receptors in gnathostomes. We hypothesize that the glycoprotein hormone/glycoprotein hormone receptor systems emerged as a link between the neuro-hormonal and peripheral control levels during the early stages of gnathostome divergence. The significance of the results obtained by analysis of the HPG/T axes in sea lamprey may transcend the limited scope of the corresponding physiological compartments by providing important clues in respect to the interplay between genome-wide events (duplications), coding sequence (mutation) and expression control level evolutionary mechanisms

  5. Detection of Pituitary Antibodies by Immunofluorescence: Approach and Results in Patients With Pituitary Diseases

    PubMed Central

    Ricciuti, Adriana; De Remigis, Alessandra; Landek-Salgado, Melissa A.; De Vincentiis, Ludovica; Guaraldi, Federica; Lupi, Isabella; Iwama, Shintaro; Wand, Gary S.; Salvatori, Roberto

    2014-01-01

    Context: Pituitary antibodies have been measured mainly to identify patients whose disease is caused or sustained by pituitary-specific autoimmunity. Although reported in over 100 publications, they have yielded variable results and are thus considered of limited clinical utility. Objectives: Our objectives were to analyze all publications reporting pituitary antibodies by immunofluorescence for detecting the major sources of variability, to experimentally test these sources and devise an optimized immunofluorescence protocol, and to assess prevalence and significance of pituitary antibodies in patients with pituitary diseases. Study Design and Outcome Measures: We first evaluated the effect of pituitary gland species, section fixation, autofluorescence quenching, blockade of unwanted antibody binding, and use of purified IgG on the performance of this antibody assay. We then measured cross-sectionally the prevalence of pituitary antibodies in 390 pituitary cases and 60 healthy controls, expressing results as present or absent and according to the (granular, diffuse, perinuclear, or mixed) staining pattern. Results: Human pituitary was the best substrate to detect pituitary antibodies and yielded an optimal signal-to-noise ratio when treated with Sudan black B to reduce autofluorescence. Pituitary antibodies were more common in cases (95 of 390, 24%) than controls (3 of 60, 5%, P = .001) but did not discriminate among pituitary diseases when reported dichotomously. However, when expressed according to their cytosolic staining, a granular pattern was highly predictive of pituitary autoimmunity (P < .0001). Conclusion: We report a comprehensive study of pituitary antibodies by immunofluorescence and provide a method and an interpretation scheme that should be useful for identifying and monitoring patients with pituitary autoimmunity. PMID:24606106

  6. Free β-human chorionic gonadotropin, total human chorionic gonadotropin and maternal risk of breast cancer

    PubMed Central

    Toriola, Adetunji T; Tolockiene, Egle; Schock, Helena; Surcel, Helja-Marja; Zeleniuch-Jacquotte, Anne; Wadell, Goran; Toniolo, Paolo; Lundin, Eva; Grankvist, Kjell; Lukanova, Annekatrin

    2014-01-01

    Background We investigated whether the free β-human chorionic gonadotropin (free β-hCG) would provide additional information to that provided by total hCG alone and thus be useful in future epidemiological studies relating hCG to maternal breast cancer risk. Materials & methods Cases (n = 159) and controls (n = 286) were a subset of our previous study within the Northern Sweden Maternity Cohort on total hCG during primiparous pregnancy and breast cancer risk. Results The associations between total hCG (hazard ratio: 0.79; 95% CI: 0.49–1.27), free β-hCG (hazard ratio: 0.85; 95% CI: 0.33–2.18) and maternal risk of breast cancer were very similar in all analyses and mutual adjustment for either one had minor effects on the risk estimates. Conclusion In the absence of a reliable assay on intact hCG, total hCG alone can be used in epidemiological studies investigating hCG and breast cancer risk, as free β-hCG does not appear to provide any additional information. PMID:24559445

  7. Distinct sequence of gonadotropin-releasing hormone (GnRH) in dogfish brain provides insight into GnRH evolution.

    PubMed Central

    Lovejoy, D A; Fischer, W H; Ngamvongchon, S; Craig, A G; Nahorniak, C S; Peter, R E; Rivier, J E; Sherwood, N M

    1992-01-01

    In vertebrates, gonadotropin-releasing hormone (GnRH) belongs to a family of decapeptides characterized by the conservation of residues 1, 2, 4, 9, and 10. In the jawed vertebrates only positions 5, 7, and 8 in the GnRH molecules vary. We have now purified two forms of GnRH from the brains of spiny dogfish (Squalus acanthias) by using reverse-phase high-performance liquid chromatography. The primary structures were established by automated Edman degradation and mass spectral analysis. The distinct structure of the first form (dogfish GnRH) is pGlu-His-Trp-Ser-His-Gly-Trp-Leu-Pro-Gly-NH2 (pGlu represents pyroglutamyl). The second peptide is identical to a form of GnRH originally isolated from chicken brains (chicken GnRH-II; pGlu-His-Trp-Ser-His-Gly-Trp-Tyr- Pro-Gly-NH2) and is widespread throughout the vertebrates. We are aware of no other species of cartilaginous fish in which the primary structures of two forms of GnRH have been determined. The presence of chicken GnRH-II in dogfish supports the idea that chicken GnRH-II is the oldest GnRH to evolve in jawed vertebrates. With the addition of the dogfish GnRH structure to the family, two main structural branches of GnRH can be delineated. The physiological effects of dogfish GnRH included the release of not only gonadotropin but also growth hormone from goldfish pituitary fragments. PMID:1631133

  8. Receptor specificity and functional comparison of recombinant sea bass (Dicentrarchus labrax) gonadotropins (FSH and LH) produced in different host systems.

    PubMed

    Molés, Gregorio; Zanuy, Silvia; Muñoz, Iciar; Crespo, Berta; Martínez, Iago; Mañanós, Evaristo; Gómez, Ana

    2011-06-01

    Different yields, biopotency, and in vivo pharmacokinetics are obtained for recombinant sea bass gonadoltropins depending on the production system and DNA construct, but they show specific activation of their corresponding receptors. Gonadotropins (GTHs) are glycoprotein hormones that play a major role in the regulation of gonadal functions. Recently, we succeeded in isolating the native sea bass Fsh from sea bass pituitaries, but to ensure the availability of bioactive GTHs and no cross-contamination with other related glycoproteins, recombinant sea bass GTHs were produced using two expression systems-insect and mammalian cells-and different constructs that yielded tethered or noncovalently bound dimers. Their production levels, binding specificity to their homologous cognate receptors, and bioactivity were investigated and compared. Both expression systems were successful in the generation of bioactive recombinant GTHs, but insect Sf9 cells yielded higher amounts of recombinant proteins than mammalian Chinese Hamster Ovary (CHO) stable clones. All recombinant GTHs activated their cognate receptors without cross-ligand binding and were able to stimulate sea bass gonadal steroidogenesis in vitro, although with different biopotencies. To assess their use for in vivo applications, their half-life in sea bass plasma was evaluated. Sf9-GTHs had a lower in vivo stability compared with CHO-GTHs due to their rapid clearance from the blood circulation. Cell-dependent glycosylation could be contributing to the final in vivo stability and biopotency of these recombinant glycoproteins. In conclusion, both insect and mammalian expression systems produced bioactive sea bass recombinant gonadotropins, although with particular features useful for different proposes (e.g., antibody production or in vivo studies, respectively).

  9. Adipokinetic hormone signaling through the gonadotropin-releasing hormone receptor modulates egg-laying in Caenorhabditis elegans

    PubMed Central

    Lindemans, Marleen; Liu, Feng; Janssen, Tom; Husson, Steven J.; Mertens, Inge; Gäde, Gerd; Schoofs, Liliane

    2009-01-01

    In mammals, hypothalamic gonadotropin-releasing hormone (GnRH) is a neuropeptide that stimulates the release of gonadotropins from the anterior pituitary. The existence of a putative functional equivalent of this reproduction axis in protostomian invertebrates has been a matter of debate. In this study, the ligand for the GnRH receptor in the nematode Caenorhabditis elegans (Ce-GnRHR) was found using a bioinformatics approach. The peptide and its precursor are reminiscent of both insect adipokinetic hormones and GnRH-preprohormone precursors from tunicates and higher vertebrates. We cloned the AKH-GnRH-like preprohormone and the Ce-GnRHR and expressed the GPCR in HEK293T cells. The GnRHR was activated by the C. elegans AKH-GnRH-like peptide (EC50 = 150 nM) and by Drosophila AKH and other nematode AKH-GnRHs that we found in EST databases. Analogous to both insect AKH receptor and vertebrate GnRH receptor signaling, Ce-AKH-GnRH activated its receptor through a Gαq protein with Ca2+ as a second messenger. Gene silencing of Ce-GnRHR, Ce-AKH-GnRH, or both resulted in a delay in the egg-laying process, comparable to a delay in puberty in mammals lacking a normal dose of GnRH peptide or with a mutated GnRH precursor or receptor gene. The present data support the view that the AKH-GnRH signaling system probably arose very early in metazoan evolution and that its role in reproduction might have been developed before the divergence of protostomians and deuterostomians. PMID:19164555

  10. Dioxin-induced retardation of development through a reduction in the expression of pituitary hormones and possible involvement of an aryl hydrocarbon receptor in this defect: a comparative study using two strains of mice with different sensitivities to dioxin.

    PubMed

    Takeda, Tomoki; Taura, Junki; Hattori, Yukiko; Ishii, Yuji; Yamada, Hideyuki

    2014-08-01

    We have previously revealed that treating pregnant rats with 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD) reduces the expression of gonadotropins and growth hormone (GH) in the fetal and neonatal pituitary. A change in gonadotropin expression impairs the testicular expression of steroidogenic proteins in perinatal pups, and imprint defects in sexual behavior after reaching maturity. In this study, we examined whether TCDD also affects the expression of gonadotropin and GH in mice using C57BL/6J and DBA/2J strains which express the aryl hydrocarbon receptor (Ahr) exhibiting a different affinity for TCDD. When pregnant C57BL/6J mice at gestational day (GD) 12 were given oral TCDD (0.2-20 μg/kg), all doses significantly attenuated the pituitary expression of gonadotropin mRNAs in fetuses at GD18. On the other hand, in DBA/2J mice, a much higher dose of TCDD (20 μg/kg) was needed to produce a significant attenuation. Such reduction in the C57BL/6J strain continued until at least postnatal day (PND) 4. In agreement with this, TCDD reduced the testicular expression of steroidogenic proteins in C57BL/6J neonates at PND2 and 4, although the same did not occur in the fetal testis and ovary. Furthermore, TCDD reduced the perinatal expression of GH, litter size and the body weight of newborn pups only in the C57BL/6J strain. These results suggest that 1) also in mice, maternal exposure to TCDD attenuates gonadotropin-regulated steroidogenesis and GH expression leading to the impairment of pup development and sexual immaturity; and 2) Ahr activation during the late fetal and early postnatal stages is required for these defects.

  11. Successful Pregnancies and Deliveries in a Patient With Evolving Hypopituitarism due to Pituitary Stalk Transection Syndrome: Role of Growth Hormone Replacement.

    PubMed

    Yoshizawa, Miyako; Ieki, Yasuhiko; Takazakura, Eisuke; Fukuta, Kaori; Hidaka, Takao; Wakasugi, Takanobu; Shimatsu, Akira

    2017-01-01

    We herein report a 31-year-old Japanese woman with evolving hypopituitarism due to pituitary stalk transection syndrome. She had a history of short stature treated with growth hormone (GH) in childhood and had hypothyroidism and primary amenorrhea at 20 years old. Levothyroxine replacement and recombinant follicle stimulating hormone-human chorionic gonadotropin (FSH-hCG) therapy for ovulation induction were started. GH replacement therapy (GHRT) was resumed when she was 26 years old. She developed mild adrenocortical insufficiency at 31 years old. She succeeded in becoming pregnant and delivered twice. GHRT was partially continued during pregnancy and stopped at the end of the second trimester without any complications.

  12. 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.

  13. The HMG-Box Transcription Factor Sox4b Is Required for Pituitary Expression of gata2a and Specification of Thyrotrope and Gonadotrope Cells in Zebrafish

    PubMed Central

    Quiroz, Yobhana; Lopez, Mauricio; Mavropoulos, Anastasia; Motte, Patrick; Martial, Joseph A.; Hammerschmidt, Matthias

    2012-01-01

    The pituitary is a complex gland comprising different cell types each secreting specific hormones. The extensive network of signaling molecules and transcription factors required for determination and terminal differentiation of specific cell types is still not fully understood. The SRY-like HMG-box (SOX) transcription factor Sox4 plays important roles in many developmental processes and has two homologs in zebrafish, Sox4a and Sox4b. We show that the sox4b gene is expressed in the pituitary anlagen starting at 24 h after fertilization (hpf) and later in the entire head region including the pituitary. At 48 hpf, sox4b mRNA colocalizes with that for TSH (tshβ), glycoprotein subunit α (gsuα), and the Zn finger transcription factor Gata2a. Loss of Sox4b function, using morpholino knockdown or expression of a dominant-negative Sox4 mutant, leads to a drastic decrease in tshβ and gsuα expression and reduced levels of gh, whereas other anterior pituitary gland markers including prl, slβ, pomc, and lim3 are not affected. Sox4b is also required for expression of gata2a in the pituitary. Knockdown of gata2a leads to decreased tshβ and gsuα expression at 48 hpf, similar to sox4b morphants. Injection of gata2a mRNA into sox4b morphants rescued tshβ and gsuα expression in thyrotrope cells. Finally, sox4b or gata2a knockdown causes a significant decrease of gonadotropin expression (lhβ and fshβ) at 4 d after fertilization. In summary, our results indicate that Sox4b is expressed in zebrafish during pituitary development and plays a crucial role in the differentiation of thyrotrope and gonadotrope cells through induction of gata2a expression in the developing pituitary. PMID:22543271

  14. The HMG-box transcription factor Sox4b is required for pituitary expression of gata2a and specification of thyrotrope and gonadotrope cells in zebrafish.

    PubMed

    Quiroz, Yobhana; Lopez, Mauricio; Mavropoulos, Anastasia; Motte, Patrick; Martial, Joseph A; Hammerschmidt, Matthias; Muller, Marc

    2012-06-01

    The pituitary is a complex gland comprising different cell types each secreting specific hormones. The extensive network of signaling molecules and transcription factors required for determination and terminal differentiation of specific cell types is still not fully understood. The SRY-like HMG-box (SOX) transcription factor Sox4 plays important roles in many developmental processes and has two homologs in zebrafish, Sox4a and Sox4b. We show that the sox4b gene is expressed in the pituitary anlagen starting at 24 h after fertilization (hpf) and later in the entire head region including the pituitary. At 48 hpf, sox4b mRNA colocalizes with that for TSH (tshβ), glycoprotein subunit α (gsuα), and the Zn finger transcription factor Gata2a. Loss of Sox4b function, using morpholino knockdown or expression of a dominant-negative Sox4 mutant, leads to a drastic decrease in tshβ and gsuα expression and reduced levels of gh, whereas other anterior pituitary gland markers including prl, slβ, pomc, and lim3 are not affected. Sox4b is also required for expression of gata2a in the pituitary. Knockdown of gata2a leads to decreased tshβ and gsuα expression at 48 hpf, similar to sox4b morphants. Injection of gata2a mRNA into sox4b morphants rescued tshβ and gsuα expression in thyrotrope cells. Finally, sox4b or gata2a knockdown causes a significant decrease of gonadotropin expression (lhβ and fshβ) at 4 d after fertilization. In summary, our results indicate that Sox4b is expressed in zebrafish during pituitary development and plays a crucial role in the differentiation of thyrotrope and gonadotrope cells through induction of gata2a expression in the developing pituitary.

  15. Pituitary gigantism: a case report.

    PubMed

    Bhattacharjee, Rana; Roy, Ajitesh; Goswami, Soumik; Selvan, Chitra; Chakraborty, Partha P; Ghosh, Sujoy; Biswas, Dibakar; Dasgupta, Ranen; Mukhopadhyay, Satinath; Chowdhury, Subhankar

    2012-12-01

    To present a rare case of gigantism. A 25-year-old lady presented with increased statural growth and enlarged body parts noticed since the age of 14 years, primary amenorrhea, and frontal headache for the last 2 years. She has also been suffering from non-inflammatory low back pain with progressive kyphosis and pain in the knees, ankles, and elbows for the last 5 years. There was no history of visual disturbance, vomiting, galactorrhoea, cold intolerance. She had no siblings. Family history was non-contributory. Blood pressure was normal. Height 221 cm, weight 138 kg, body mass index (BMI)28. There was coarsening of facial features along with frontal bossing and prognathism, large hands and feet, and small goitre. Patient had severe kyphosis and osteoarthritis of knees. Confrontation perimetry suggested bitemporal hemianopia. Breast and pubic hair were of Tanner stage 1. Serum insulin like growth factor-1 (IGF1) was 703 ng/ml with all glucose suppressedgrowth hormone (GH)values of >40 ng/ml. Prolactin was 174 ng/ml. Basal serum Lutenising Hormone (LH), follicle stimulating Hormone (FSH) was low. Oral glucose tolerance test (OGTT), liver and renal function tests, basal cortisol and thyroid profile, Calcium, phosphorus and Intact Parathyroid hormone (iPTH) were normal. Computed tomographyscan of brain showed large pituitary macroadenoma. Automated perimetry confirmed bitemporal hemianopia. A diagnosis of gigantism due to GH secreting pituitary macroadenoma with hypogonadotrophichypogonadism was made. Debulking pituitary surgery followed by somatostatin analogue therapy with gonadal steroid replacement had been planned, but the patient refused further treatment.

  16. Apoptosis: its role in pituitary development and neoplastic pituitary tissue.

    PubMed

    Guzzo, M F; Carvalho, L R S; Bronstein, M D

    2014-04-01

    Apoptosis, also known as programmed cell death, is a phenomenon in which different stimuli trigger cellular mechanisms that culminate in death, in the absence of inflammatory cell response. Two different activation pathways are known, the intrinsic pathway (or mitochondrial) and extrinsic (or death-receptor pathway), both pathways trigger enzymatic reactions that lead cells to break up and be phagocytized by neighboring cells. This process is a common occurrence in physiological and pathological states, participating in the control of cell proliferation, differentiation and remodeling of organs. In the early steps of pituitary gland formation, numerous apoptotic cells are detected in the separation of Rathke's pouch from the roof of oral ectoderm. In the distal part of the gland, which will form the adenohypophysis, the ratio of apoptosis was significantly lower. However, there is evidence that neoplastic pituitary cells undergo unbalance in genes that control apoptosis leading to uncontrolled cell growth. No direct evidence of apoptosis was found in the drugs used for tumors producing prolactin and growth hormone. In conclusion, an unbalancing in the apoptosis process is the boundary between development and tumor growth.

  17. The progestin levonorgestrel disrupts gonadotropin expression and sex steroid levels in pubertal roach (Rutilus rutilus).

    PubMed

    Kroupova, H K; Trubiroha, A; Lorenz, C; Contardo-Jara, V; Lutz, I; Grabic, R; Kocour, M; Kloas, W

    2014-09-01

    The aim of the present study was to investigate the effects of the synthetic progestin levonorgestrel (LNG) on the reproductive endocrine system of a teleost fish, the roach (Rutilus rutilus). Pubertal roach were exposed for 28 days in a flow-through system to four concentrations of LNG (3, 31, 312, and 3124 ng/l). Both males and females treated with 3124 ng/l LNG exhibited the upregulated levels of vitellogenin and oestrogen receptor 1 mRNA in the liver. At the same concentration, LNG caused a significant upregulation of the mRNA expression of the gene encoding luteinising hormone β-subunit (lhβ) and the suppression of the mRNA expression of the gene encoding follicle-stimulating hormone β-subunit (fshβ) in the pituitary of both male and female roach. A lower LNG concentration (312 ng/l) suppressed mRNA expression of fshβ in males only. Females treated with 3124 ng/l LNG exhibited significantly lower plasma 11-ketotestosterone (11-KT) and oestradiol (E2) concentrations, whereas their testosterone (T) level was higher compared with the control. Females exposed to 312 ng/l LNG presented significantly lower plasma E2 concentrations. Males exposed to ≥31 ng/l LNG exhibited significantly reduced 11-KT levels. As determined through a histological analysis, the ovaries of females were not affected by LNG exposure, whereas the testes of males exposed to 31 and 312 ng/l LNG exhibited a significantly higher percentage of spermatogonia B compared with the control. The results of the present study demonstrate that LNG disrupts the reproductive system of pubertal roach by affecting the pituitary gonadotropin expression and the sex steroid levels. This disruption was determined to occur in males after exposure to an environmentally relevant concentration (31 ng/l). Moreover, the highest tested concentration of LNG (3124 ng/l) exerted an oestrogenic effect on fish of both sexes. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Pituitary gigantism causing diabetic ketoacidosis.

    PubMed

    Alvi, N S; Kirk, J M

    1999-01-01

    Although growth hormone excess (acromegaly) in association with glucose intolerance and diabetes mellitus is well documented in adult medicine, it is much less common in the paediatric age group. We report the case of a 13 year-old boy who presented with tall stature secondary to a large growth hormone secreting adenoma of the pituitary gland. Random growth hormone was 630 mIU/l and did not suppress during an oral glucose tolerance test. Following debulking of the tumour, he developed diabetic ketoacidosis requiring insulin treatment, but after further surgery glucose handling returned to normal. He has been started on testosterone to arrest further increase in height.

  19. Effects of zinc deficiency on pituitary somatotrophs

    SciTech Connect

    Focht, S.; Fosmire, G.; Hymer, W.C. )

    1991-03-15

    To test whether the growth retardation that accompanies zinc deficiency may involve a direct effect of zinc on pituitary, rats were divided into three groups and fed a Zn deficient diet for 10 days. On day 10 rats were anesthetized and blood, femurs, and pituitaries were collected. Pituitaries from each group were either enzymatically dissociated into individual cells or homogenized and centrifuged into three fractions. Growth retardation was evidenced by decreased body weights and narrower epiphyseal widths in PF and ZD rats. Pituitary weights were also lower in PF and ZD rats. Pituitary zinc per unit tended to be highest in PF and lowest in ZD rats, although this trend was significant only for the 250g pellet fraction. Total cell counts from dissociated pituitaries tended to be highest for AL and lowest for ZD rats. Total growth hormone (HGH) per pituitary also followed this trend, although the amount of GH per somatotroph did not buffer between groups. Interestingly, GH released from dissociated pituitary cells cultured in defined media for 3 days was twice as great from ZD vs PF, AL being intermediate. Serum GH levels did not differ between groups although the trend was ZD > PF >AL.

  20. Pituitary magnetic resonance imaging in Cushing's disease.

    PubMed

    Vitale, Giovanni; Tortora, Fabio; Baldelli, Roberto; Cocchiara, Francesco; Paragliola, Rosa Maria; Sbardella, Emilia; Simeoli, Chiara; Caranci, Ferdinando; Pivonello, Rosario; Colao, Annamaria

    2017-03-01

    Adrenocorticotropin-secreting pituitary tumor represents about 10 % of pituitary adenomas and at the time of diagnosis most of them are microadenomas. Transsphenoidal surgery is the first-line treatment of Cushing's disease and accurate localization of the tumor within the gland is essential for selectively removing the lesion and preserving normal pituitary function. Magnetic resonance imaging is the best imaging modality for the detection of pituitary tumors, but adrenocorticotropin-secreting pituitary microadenomas are not correctly identified in 30-50 % of cases, because of their size, location, and enhancing characteristics. Several recent studies were performed with the purpose of better localizing the adrenocorticotropin-secreting microadenomas through the use in magnetic resonance imaging of specific sequences, reduced contrast medium dose and high-field technology. Therefore, an improved imaging technique for pituitary disease is mandatory in the suspect of Cushing's disease. The aims of this paper are to present an overview of pituitary magnetic resonance imaging in the diagnosis of Cushing's disease and to provide a magnetic resonance imaging protocol to be followed in case of suspicion adrenocorticotropin-secreting pituitary adenoma.

  1. Retroclival subdural haematoma secondary to pituitary apoplexy.

    PubMed

    Mohamed, Amr Hazem; Rodrigues, Jonathan C L; Bradley, Marcus D; Nelson, Richard J

    2013-12-01

    Retroclival haematomas are rare entity and they are mostly caused by trauma. There has been only one case published to have a retroclival haematoma following pituitary apoplexy. We present a patient diagnosed with pituitary apoplexy who was found to have acute subdural retroclival haematoma on the MRI.

  2. 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

  3. [Pituitary disease: which treatment in the future?].

    PubMed

    Briet, C; Chanson, P

    2011-10-01

    Even if major progress has been made in the medical treatment for pituitary adenomas in the last decades, currently available drugs do not always control hormonal secretion of these tumors. New molecules or new formulations of old drugs are under development. Pituitary stem cells research is currently also very active. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  4. Pituitary volume in first-episode schizophrenia.

    PubMed

    Gruner, Patricia; Christian, Christopher; Robinson, Delbert G; Sevy, Serge; Gunduz-Bruce, Handan; Napolitano, Barbara; Bilder, Robert M; Szeszko, Philip R

    2012-07-30

    Pituitary volumes were measured in 55 first-episode schizophrenia patients at a baseline timepoint with 38 receiving a followup scan after antipsychotic treatment. Fifty-nine healthy volunteers had baseline scans with 34 receiving a followup scan. There were no baseline group differences in pituitary volumes or changes in volume following antipsychotic treatment.

  5. Pituitary volume in first-episode schizophrenia

    PubMed Central

    Gruner, Patricia; Christian, Christopher; Robinson, Delbert G.; Sevy, Serge; Gunduz-Bruce, Handan; Napolitano, Barbara; Bilder, Robert M.; Szeszko, Philip R.

    2011-01-01

    Pituitary volumes were measured in 55 first-episode schizophrenia patients at a baseline timepoint with 38 receiving a followup scan after antipsychotic treatment. Fifty-nine healthy volunteers had baseline scans with 34 receiving a followup scan. There were no baseline group differences in pituitary volumes or changes in volume following antipsychotic treatment. PMID:22858406

  6. Pituitary volume in patients with panic disorder.

    PubMed

    Kartalci, Sukru; Dogan, Metin; Unal, Suheyla; Ozcan, A Cemal; Ozdemir, Serdal; Atmaca, Murad

    2011-01-15

    Panic patients have many functional deficiencies in the hypothalamic-pituitary-adrenal (HPA) axis. Previous studies have shown changed pituitary gland volume in some psychiatric disorders that have functional deficiencies in the HPA axis. However, to date no study has evaluated the pituitary gland volume in patients with panic disorder (PD). We investigated the pituitary gland volume in patients with PD (n=27) and age- and sex-matched healthy controls (n=27), using 1.5-T magnetic resonance imaging in this study. Analysis showed that patients with PD had significantly smaller pituitary volume compared to healthy subjects. Patients with agoraphobia especially had a significantly smaller pituitary volume than patients without agoraphobia. There was a significant relationship between the pituitary volume and both the severity of symptoms and the illness duration in the patient group. The results show that patients with PD have reduced pituitary volume, which may reflect the functional abnormalities seen in this disorder. These findings may help us better understand the pathology of PD. Copyright © 2010 Elsevier Inc. All rights reserved.

  7. 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.

  8. 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

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

    SciTech Connect

    Chang, Y.S.

    1985-01-01

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

  10. Binding properties of solubilized gonadotropin-releasing hormone receptor: role of carboxylic groups

    SciTech Connect

    Hazum, E.

    1987-11-03

    The interaction of /sup 125/I-buserelin, a superactive agonist of gonadotropin-releasing hormone (GnRH), with solubilized GnRH receptor was studied. The highest specific binding of /sup 125/I-buserelin to solubilized GnRH receptor is evident at 4/sup 0/C, and equilibrium is reached after 2 h of incubation. The soluble receptor retained 100% of the original binding activity when kept at 4 or 22/sup 0/C for 60 min. Mono- and divalent cations inhibited, in a concentration-dependent manner, the binding of /sup 125/I-buserelin to solubilized GnRH receptor. Monovalent cations require higher concentrations than divalent cations to inhibit the binding. Since the order of potency with the divalent cations was identical with that of their association constants to dicarboxylic compounds, it is suggested that there are at least two carboxylic groups of the receptor that participate in the binding of the hormone. The carboxyl groups of sialic acid residues are not absolutely required for GnRH binding since the binding of /sup 125/I-buserelin to solubilized GnRH receptor was only slightly affected by pretreatment with neuraminidase and wheat germ agglutinin. The finding that polylysines stimulate luteinizing hormone (LH) release from pituitary cell cultures with the same efficacy as GnRH suggest that simple charge interactions can induce LH release. According to these results, the authors propose that the driving force for the formation of the hormone-receptor complex is an ionic interaction between the positively charged amino acid arginine in position 8 and the carboxyl groups in the binding site.

  11. Mollusc gonadotropin-releasing hormone directly regulates gonadal functions: a primitive endocrine system controlling reproduction.

    PubMed

    Treen, Nicholas; Itoh, Naoki; Miura, Hanae; Kikuchi, Ippei; Ueda, Takenori; Takahashi, Keisuke G; Ubuka, Takayoshi; Yamamoto, Kazutoshi; Sharp, Peter J; Tsutsui, Kazuyoshi; Osada, Makoto

    2012-04-01

    Gonadotropin-releasing hormone (GnRH) is central to the control of vertebrate reproductive cycles and since GnRH orthologs are also present in invertebrates, it is likely that the common ancestor of bilateral animals possessed a GnRH-like peptide. In order to understand the evolutionary and comparative biology of GnRH peptides we cloned the cDNA transcripts of prepro GnRH-like peptides from two species of bivalve molluscs, the Yesso scallop Patinopecten yessoensis and the Pacific oyster Crassostrea gigas. We compared their deduced uncleaved and mature amino acid sequences with those from other invertebrates and vertebrates, and determined their sites of expression and biological activity. The two molluscan GnRH sequences increased the number of known protostome GnRHs to six different forms, indicating the current classification of protostome GnRHs requires further revision. In both molluscs, RT-PCR analysis showed that the genes were highly expressed in nervous tissue with lower levels present in peripheral tissues including the gonads, while immunocytochemistry, using anti-octopus GnRH-like peptide, demonstrated the presence of GnRH-like peptide in neural tissue. Putative scallop GnRH-like peptide stimulated spermatogonial cell division in cultured scallop testis, but the scallop GnRH-like peptide did not stimulate LH release from cultured quail pituitary cells. This is the first report of the cloning of bivalve GnRH-like peptide genes and of molluscan GnRH-like peptides that are biologically active in molluscs, but not in a vertebrate.

  12. Gonadotropin-releasing hormone neurones innervate kisspeptin neurones in the female mouse brain.

    PubMed

    Kalló, Imre; Vida, Barbara; Bardóczi, Zsuzsanna; Szilvásy-Szabó, Anett; Rabi, Fruzsina; Molnár, Tamás; Farkas, Imre; Caraty, Alain; Mikkelsen, Jens; Coen, Clive W; Hrabovszky, Erik; Liposits, Zsolt

    2013-01-01

    Kisspeptin (KP) neurones in the rostral periventricular area of the third ventricle (RP3V) and arcuate nucleus (Arc) are important elements in the neuronal circuitry regulating gonadotropin-releasing hormone (GnRH) secretion. KP and co-synthesised neuropeptides/neurotransmitters act directly on GnRH perikarya and processes. GnRH neurones not only form the final output pathway regulating the reproductive functions of the anterior pituitary gland, but also provide neuronal input to sites within the hypothalamus. The current double-label immunohistochemical studies investigated whether GnRH-immunoreactive (IR) projections to the RP3V and/or Arc establish morphological connections with KP-IR neurones at these sites. To optimise visualisation of KP immunoreactivity in, respectively, the RP3V and Arc, ovariectomised (OVX) oestrogen-treated and OVX oil-treated female mice were studied. Confocal laser microscopic analysis of immunofluorescent specimens revealed GnRH-IR axon varicosities in apposition to approximately 25% of the KP-IR neurones in the RP3V and 50% of the KP-IR neurones in the Arc. At the ultrastructural level, GnRH-IR neurones were seen to establish asymmetric synaptic contacts, which usually reflect excitatory neurotransmission, with KP-IR neurones in both the RP3V and Arc. Together with previous data, these findings indicate reciprocal connectivity between both of the KP cell populations and the GnRH neuronal system. The functional significance of the GnRH-IR input to the two separate KP cell populations requires electrophysiological investigation. © 2013 S. Karger AG, Basel.

  13. Gonadotropin characterization, localization and expression in the European hake (Merluccius merluccius).

    PubMed

    Candelma, Michela; Fontaine, Romain; Colella, Sabrina; Santojanni, Alberto; Weltzien, Finn-Arne; Carnevali, Oliana

    2017-02-01

    In vertebrates, the regulation of gametogenesis is under the control of gonadotropins (Gth), follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh). In fish, the physiological role of Gths is not fully understood, especially in species with asynchronous ovarian development. To elucidate the role of Gths in species with asynchronous ovary, we studied European hake (Merluccius merluccius) during the reproductive season. For this aim, we first cloned and sequenced both hormones. Then, we characterized their amino acid sequence and performed phylogenetic analyses to verify the relationship to their orthologues in other species. In addition, the quantification of gene expression during their natural reproductive season was analyzed in wild-caught female hake. Our results revealed that fshb peaked during the vitellogenic phase, remaining high until spawning. This is in contrast to the situation in species with synchronous ovary. lhb, on the other hand, peaked during maturation as it is also common in species with synchronous ovarian development. Finally, combining double-labeling fluorescent in situ hybridization (FISH) for Gth mRNAs with immunofluorescence for Lh protein, we evidenced the specific expression of fshb and lhb in different cells within the proximal pars distalis (PPD) of the pituitary. In addition to gonadotrope cells specific to expression of either fshb or lhb, some cells showed co-expression of both genes. This suggests either that gonadotropes with co-expression are not yet specified or they could have a plasticity that permits changes from one cell phenotype to another during certain life stages and in turn during different physiological states.

  14. 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

  15. Isolated gonadotropin deficiency secondary to glioma in septum pellucidum.

    PubMed

    Kitamura, M; Namiki, M; Okuyama, A; Arita, N; Mizutani, S; Sonoda, T

    1988-01-01

    A 21-year-old man, who had had normal sexuality beforehand, noticed a decrease in libido and potency, as well as loss of ejaculation. Endocrine evaluation showed normal serum levels of gonadotropins but a low testosterone level. The response to clomiphene citrate was poor while those to luteinizing hormone-releasing hormone and human chorionic gonadotropin were within normal limits. A tumor found in the septum pellucidum through brain-computerized tomography was resected. Histologically it proved to be a mixed tumor composed of astrocytoma and oligodendroglioma. Three months after the operation the patient had recovered normal sexual functions and endocrine evaluations, including the responsiveness to clomiphene citrate, had been restored. This case suggests the existence of some stimulatory fiber for the secretion of luteinizing hormone in the septum pellucidum.

  16. Luteinizing hormone and human chorionic gonadotropin: origins of difference.

    PubMed

    Choi, Janet; Smitz, Johan

    2014-03-05

    Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are widely recognized for their roles in ovulation and the support of early pregnancy. Aside from the timing of expression, however, the differences between LH and hCG have largely been overlooked in the clinical realm because of their similar molecular structures and shared receptor. With technologic advancements, including the development of highly purified and recombinant gonadotropins, researchers now appreciate that these hormones are not as interchangeable as once believed. Although they bind to a common receptor, emerging evidence suggests that LH and hCG have disparate effects on downstream signaling cascades. Increased understanding of the inherent differences between LH and hCG will foster more effective diagnostic and prognostic assays for use in a variety of clinical contexts and support the individualization of treatment strategies for conditions such as infertility.

  17. Posttransplantation lymphoproliferative disease involving the pituitary gland.

    PubMed

    Meriden, Zina; Bullock, Grant C; Bagg, Adam; Bonatti, Hugo; Cousar, John B; Lopes, M Beatriz; Robbins, Mark K; Cathro, Helen P

    2010-11-01

    Posttransplantation lymphoproliferative disorders (PTLD) are heterogeneous lesions with variable morphology, immunophenotype, and molecular characteristics. Multiple distinct primary lesions can occur in PTLD, rarely with both B-cell and T-cell characteristics. Lesions can involve both grafted organs and other sites; however, PTLD involving the pituitary gland has not been previously reported. We describe a patient who developed Epstein-Barr virus-negative PTLD 13 years posttransplantation involving the terminal ileum and pituitary, which was simultaneously involved by a pituitary adenoma. Immunohistochemistry of the pituitary lesion showed expression of CD79a, CD3, and CD7 with clonal rearrangements of both T-cell receptor gamma chain (TRG@) and immunoglobulin heavy chain (IGH@) genes. The terminal ileal lesion was immunophenotypically and molecularly distinct. This is the first report of pituitary PTLD and illustrates the potentially complex nature of PTLD. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. 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.

  19. Developmental changes and day-night expression of the gonadotropin-inhibitory hormone system in the European sea bass: Effects of rearing temperature.

    PubMed

    Paullada-Salmerón, José A; Loentgen, Guillaume Henri; Cowan, Mairi; Aliaga-Guerrero, María; Rendón-Unceta, María Del Carmen; Muñoz-Cueto, José A

    2017-04-01

    The role of rearing temperature on fish development, sex differentiation and puberty has been largely addressed, but the impact of water temperature on the ontogeny of the main neuroendocrine systems controlling reproduction has received little attention. Gonadotropin-inhibitory hormone (GnIH) has been shown to act on gonadotropin-releasing hormone (GnRH) neurons and on the pituitary to inhibit gonadotropin release and synthesis in vertebrates, including sea bass, Dicentrarchus labrax. In the present study we investigated the effects of rearing temperature during the thermosensitive period (5-60days post-fertilization, dpf) on the expression of the GnIH gene (gnih) and its receptor (gnihr). Animals were maintained under two different conditions, low temperature (LT, 15°C) or high temperature (HT, 21°C), throughout the thermosensitive period and sampled from 5 to 360dpf at mid-light (ML) and mid-dark (MD). Our results showed significant effects of temperature on gnih and gnihr expression during the thermosensitive period, with higher transcript levels under LT condition. Some differences were also evident after the completion of the sex differentiation process. Moreover, we revealed daily variations in the developmental expression of gnih and gnihr, with higher diurnal mRNA levels at early stages (until 25dpf), and a shift to higher nocturnal expression levels at 300-360dpf, which corresponded with the beginning of the winter (reproductive season). To the best of our knowledge, this work represents the first study reporting the effects of rearing temperature on the transcription of gnih system genes, as well as its daily variations during the development of a fish species.

  20. Evaluating the ovarian cancer gonadotropin hypothesis: A candidate gene study

    PubMed Central

    Lee, Alice W.; Tyrer, Jonathan P.; Doherty, Jennifer A.; Stram, Douglas A.; Kupryjanczyk, Jolanta; Dansonka-Mieszkowska, Agnieszka; Plisiecka-Halasa, Joanna; Spiewankiewicz, Beata; Myers, Emily J.; Chenevix-Trench, Georgia; Fasching, Peter A.; Beckmann, Matthias W.; Ekici, Arif B.; Hein, Alexander; Vergote, Ignace; Van Nieuwenhuysen, Els; Lambrechts, Diether; Wicklund, Kristine G.; Eilber, Ursula; Wang-Gohrke, Shan; Chang-Claude, Jenny; Rudolph, Anja; Sucheston-Campbell, Lara; Odunsi, Kunle; Moysich, Kirsten B.; Shvetsov, Yurii B.; Thompson, Pamela J.; Goodman, Marc T.; Wilkens, Lynne R.; Dörk, Thilo; Hillemanns, Peter; Dürst, Matthias; Runnebaum, Ingo B.; Bogdanova, Natalia; Pelttari, Liisa M.; Nevanlinna, Heli; Leminen, Arto; Edwards, Robert P.; Kelley, Joseph L.; Harter, Philipp; Schwaab, Ira; Heitz, Florian; du Bois, Andreas; Orsulic, Sandra; Lester, Jenny; Walsh, Christine; Karlan, Beth Y.; Hogdall, Estrid; Kjaer, Susanne K.; Jensen, Allan; Vierkant, Robert A.; Cunningham, Julie M.; Goode, Ellen L.; Fridley, Brooke L.; Southey, Melissa C.; Giles, Graham G.; Bruinsma, Fiona; Wu, Xifeng; Hildebrandt, Michelle A.T.; Lu, Karen; Liang, Dong; Bisogna, Maria; Levine, Douglas A.; Weber, Rachel Palmieri; Schildkraut, Joellen M.; Iversen, Edwin S.; Berchuck, Andrew; Terry, Kathryn L.; Cramer, Daniel W.; Tworoger, Shelley S.; Poole, Elizabeth M.; Olson, Sara H.; Orlow, Irene; Bandera, Elisa V.; Bjorge, Line; Tangen, Ingvild L.; Salvesen, Helga B.; Krakstad, Camilla; Massuger, Leon F.A.G.; Kiemeney, Lambertus A.; Aben, Katja K.H.; van Altena, Anne M.; Bean, Yukie; Pejovic, Tanja; Kellar, Melissa; Le, Nhu D.; Cook, Linda S.; Kelemen, Linda E.; Brooks-Wilson, Angela; Lubinski, Jan; Gronwald, Jacek; Cybulski, Cezary; Jakubowska, Anna; Wentzensen, Nicolas; Brinton, Louise A.; Lissowska, Jolanta; Yang, Hannah; Nedergaard, Lotte; Lundvall, Lene; Hogdall, Claus; Song, Honglin; Campbell, Ian G.; Eccles, Diana; Glasspool, Rosalind; Siddiqui, Nadeem; Carty, Karen; Paul, James; McNeish, Iain A.; Sieh, Weiva; McGuire, Valerie; Rothstein, Joseph H.; Whittemore, Alice S.; McLaughlin, John R.; Risch, Harvey A.; Phelan, Catherine M.; Anton-Culver, Hoda; Ziogas, Argyrios; Menon, Usha; Ramus, Susan J.; Gentry-Maharaj, Aleksandra; Harrington, Patricia; Pike, Malcolm C.; Modugno, Francesmary; Rossing, Mary Anne; Ness, Roberta B.; Pharoah, Paul D.P.; Stram, Daniel O.; Wu, Anna H.; Pearce, Celeste Leigh

    2016-01-01

    Objective Ovarian cancer is a hormone-related disease with a strong genetic basis. However, none of its high-penetrance susceptibility genes and GWAS-identified variants to date are known to be involved in hormonal pathways. Given the hypothesized etiologic role of gonadotropins, an assessment of how variability in genes involved in the gonadotropin signaling pathway impacts disease risk is warranted. Methods Genetic data from 41 ovarian cancer study sites were pooled and unconditional logistic regression was used to evaluate whether any of the 2185 SNPs from 11 gonadotropin signaling pathway genes was associated with ovarian cancer risk. A burden test using the admixture likelihood (AML) method was also used to evaluate gene-level associations. Results We did not find any genome-wide significant associations between individual SNPs and ovarian cancer risk. However, there was some suggestion of gene-level associations for four gonadotropin signaling pathway genes: INHBB (p = 0.045, mucinous), LHCGR (p = 0.046, high-grade serous), GNRH (p = 0.041, high-grade serous), and FSHB (p = 0.036, overall invasive). There was also suggestive evidence for INHA (p = 0.060, overall invasive). Conclusions Ovarian cancer studies have limited sample numbers, thus fewer genome-wide susceptibility alleles, with only modest associations, have been identified relative to breast and prostate cancers. We have evaluated the majority of ovarian cancer studies with biological samples, to our knowledge, leaving no opportunity for replication. Using both our understanding of biology and powerful gene-level tests, we have identified four putative ovarian cancer loci near INHBB, LHCGR, GNRH, and FSHB that warrant a second look if larger sample sizes and denser genotype chips become available. PMID:25528498

  1. Human chorionic gonadotropin and CA 15-3 producing adenocarcinoma.

    PubMed

    Uçkaya, G; Ozet, A; Arpaci, A; Kömürcü, S

    1998-01-01

    50 years old man suffering from primary lung adenocarcinoma presented with high levels of both beta subunit human chorionic gonadotropin (beta HCG) and cancer antigen 15-3 (CA 15-3) in the absence of elevated carcinoembrionic antigen (CEA), alfa fetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9). Although beta HCG or CA 15-3 high levels were reported in adenocarcinoma of lung, this is the first report of a patient with high levels of both markers.

  2. Evaluating the ovarian cancer gonadotropin hypothesis: a candidate gene study.

    PubMed

    Lee, Alice W; Tyrer, Jonathan P; Doherty, Jennifer A; Stram, Douglas A; Kupryjanczyk, Jolanta; Dansonka-Mieszkowska, Agnieszka; Plisiecka-Halasa, Joanna; Spiewankiewicz, Beata; Myers, Emily J; Chenevix-Trench, Georgia; Fasching, Peter A; Beckmann, Matthias W; Ekici, Arif B; Hein, Alexander; Vergote, Ignace; Van Nieuwenhuysen, Els; Lambrechts, Diether; Wicklund, Kristine G; Eilber, Ursula; Wang-Gohrke, Shan; Chang-Claude, Jenny; Rudolph, Anja; Sucheston-Campbell, Lara; Odunsi, Kunle; Moysich, Kirsten B; Shvetsov, Yurii B; Thompson, Pamela J; Goodman, Marc T; Wilkens, Lynne R; Dörk, Thilo; Hillemanns, Peter; Dürs