Sample records for gonadotropins pituitary

  1. Mutations of gonadotropins and gonadotropin receptors: elucidating the physiology and pathophysiology of pituitary-gonadal function

    I.T. Huhtaniemi; A.P.N. Themmen (Axel)


    textabstractThe recent unraveling of structures of genes for the gonadotropin subunits and gonadotropin receptors has provided reproductive endocrinologists with new tools to study normal and pathological functions of the hypothalamic-pituitary-gonadal axis. Rare inacti

  2. Mutations of gonadotropins and gonadotropin receptors: elucidating the physiology and pathophysiology of pituitary-gonadal function

    I.T. Huhtaniemi; A.P.N. Themmen (Axel)


    textabstractThe recent unraveling of structures of genes for the gonadotropin subunits and gonadotropin receptors has provided reproductive endocrinologists with new tools to study normal and pathological functions of the hypothalamic-pituitary-gonadal axis. Rare

  3. Gonadotropin-releasing hormone agonist-induced pituitary apoplexy

    Fergus Keane


    Full Text Available 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.

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

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


    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.

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

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


    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, 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.

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

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


    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.

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

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


    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.

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

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


    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

  9. Responsiveness of adenylate cyclase to pituitary gonadotropins and evidence of a hormone-induced desensitization in the lizard ovary.

    Borrelli, L; De Stasio, R; Bovenzi, V; Parisi, E; Filosa, S


    Gonadotropins (FSH and LH) affect several mammalian gonadal functions. In particular, FSH stimulates oogonial proliferation and oocyte growth, while LH regulates ovulation and progesterone secretion. In lacertilian reptiles, gonadal function is also regulated by pituitary gonadotropins, but which hormone controls ovarian activities and the mechanisms of action are unknown. The present study aimed to clarify mechanisms of action of pituitary gonadotropins on the ovary of Podarcis sicula (Lacertilia). The data demonstrate that mammalian gonadotropins FSH and LH produce a threefold stimulation of adenylate cyclase activity in follicular membranes, while hCG and TSH are less effective, causing a twofold increase in adenylate cyclase activity. Neurotransmitters such as dopamine, serotonin, and catecholamines have no effect on enzyme activity. The action of mammalian FSH and LH on the ovary mimics the effect of homologous hormones: in lizard ovaries incubated in vitro in the presence of isolated homologous pituitary glands, the intracellular cAMP level increased by 50% with respect to control ovaries. Mammalian gonadotropins appear homologous to lizard gonadotropin(s): Southern blot analyses show that the lizard genome contains nucleotide sequences homologous to those encoding for mammalian beta FSH and beta LH. Both homologous and heterologous desensitization of adenylate cyclase activity occurs in the lizard ovary. In fact, responsiveness of adenylate cyclase to gonadotropin stimulation is abolished in animals 2 hr after in vivo treatment with FSH. Sensitivity to gonadotropin stimulation is restored 2 weeks after the beginning of the in vivo treatment. Desensitization was also observed in ovaries incubated in vitro with mammalian FSH or with isolated pituitary glands.

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

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


    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 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.

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

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


    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.

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

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


    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.

  13. Review: Gonadotropin-inhibitory hormone action in the brain and pituitary

    Takayoshi eUbuka


    Full Text Available Gonadotropin-inhibitory hormone (GnIH was first identified in the Japanese quail as a hypothalamic neuropeptide inhibitor of gonadotropin secretion. Subsequent studies have shown that GnIH is present in the brains of birds including songbirds, and mammals including humans. The identified avian and mammalian GnIH peptides universally possess an LPXRFamide (X = L or Q motif at their C-termini. Mammalian GnIH peptides are also designated as RFamide-related peptides from their structures. The receptor for GnIH is the G protein-coupled receptor 147 (GPR147, which is thought to be coupled to Gαi protein. Cell bodies of GnIH neurons are located in the paraventricular nucleus (PVN in birds and the dorsomedial hypothalamic area (DMH in mammals. GnIH neurons in the PVN or DMH project to the median eminence to control anterior pituitary function. GPR147 is expressed in the gonadotropes and GnIH suppresses synthesis and release of gonadotropins. It was further shown in immortalized mouse gonadotrope cell line (LT2 cells that GnIH inhibits gonadotropin-releasing hormone (GnRH induced gonadotropin subunit gene transcriptions by inhibiting adenylate cyclase/cAMP/PKA dependent ERK pathway. GnIH neurons also project to GnRH neurons in the preoptic area, and GnRH neurons express GPR147 in birds and mammals. Accordingly, GnIH may inhibit gonadotropin synthesis and release by decreasing the activity of GnRH neurons as well as directly acting on the gonadotropes. GnIH also inhibits reproductive behavior possibly by acting within the brain. GnIH expression is regulated by a nocturnal hormone melatonin and stress in birds and mammals. Accordingly, GnIH may play a role in translating environmental information to inhibit reproductive physiology and behavior of birds and mammals. Finally, GnIH has therapeutic potential in the treatment of reproductive cycle and hormone-dependent diseases, such as precocious puberty, endometriosis, uterine fibroids, and prostatic and

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

    Schvartz, I.; Hazum, E.


    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.

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

    Petrino Teresa R


    Full Text Available Abstract 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.

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

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


    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

  17. 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.

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


    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

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

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


    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.

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

    Nangalama, A.W.


    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.

  20. Anterior Pituitary Leptin Expression Changes in Different Reproductive States: Stimulation, in vitro, by Gonadotropin Releasing Hormone (GnRH)

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


    This study was designed to learn more about the changes in expression of rat anterior pituitary (AP) leptin during the estrous cycle. QRT-PCR assays of cycling rat AP leptin mRNA showed 2—fold increases from metestrus to diestrus followed by an 86% decrease on the morning of proestrus. Percentages of leptin cells increased in proestrus and pregnancy to 55–60% of AP cells. Dual labeling for leptin proteins and growth hormone (GH) or gonadotropins, showed that the rise in leptin protein-bearing...

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

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


    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.

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

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


    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.

  3. Two gonadotropin-releasing hormone receptor subtypes with distinct ligand selectivity and differential distribution in brain and pituitary in the goldfish (Carassius auratus)

    Illing, Nicola; Troskie, Brigitte E.; Nahorniak, Carol S.; Janet P Hapgood; Peter, Richard E.; Millar, Robert P.


    In the goldfish (Carassius auratus) the two endogenous forms of gonadotropin-releasing hormone (GnRH), namely chicken GnRH II ([His5,Trp7,Tyr8]GnRH) and salmon GnRH ([Trp7,Leu8]GnRH), stimulate the release of both gonadotropins and growth hormone from the pituitary. This control is thought to occur by means of the stimulation of distinct GnRH receptors. These receptors can be distinguished on the basis of differential gonadotropin and growth hormone releasing activities of naturally occurring...

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

    Shimizu, Mamiko; Bédécarrats, Grégoy Y


    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.

  5. Influence of estradiol, progesterone, and nutrition on concentrations of gonadotropins and GnRH receptors, and abundance of mRNA for GnRH receptors and gonadotropin subunits in pituitary glands of beef cows.

    Looper, M L; Vizcarra, J A; Wettemann, R P; Malayer, J R; Braden, T D; Geisert, R D; Morgan, G L


    Nutritionally induced anovulatory cows (n = 28) were used to determine the effect of steroids on regulation of synthesis and secretion of gonadotropins. Anovulatory cows were ovariectomized and received intravaginal inserts containing estradiol (E2), progesterone (P4), E2 and P4 (E2P4), or a sham intravaginal insert (C) for 7 d. Concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were quantified in serum and E2 and P4 were quantified in plasma. Cows were exsanguinated within 1 to 2 h after removal of intravaginal inserts and pituitary glands were collected and stored at -80 degrees C until messenger ribonucleic acid (mRNA) for gonadotropin-releasing hormone receptor (GnRH-R) and gonadotropin subunits, pituitary content of GnRH-R, and LH and FSH were quantified. Pituitary glands from five proestrous cows were harvested to compare gonadotropin characteristics between ovariectomized, anovulatory cows and intact cows. Plasma concentrations of E2 were greater (P nutritionally induced anovulatory cows was increased (P nutritionally induced anovulatory cows with progesterone and estradiol may cause pulsatile secretion of LH.

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

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


    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.

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

    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


    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

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

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


    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.

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

    Jennes, L. (Wright State Univ. School of Medicine, Dayton, OH (USA))


    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.

  10. Effect of atrial natriuretic peptide on gonadotropin release in superfused rat pituitary cells.

    Horvath, J; Ertl, T.; Schally, A V


    Cardiac atrial muscle cells produce a polypeptide hormone that plays a role in the control of water and electrolyte balance and blood pressure. The circulating form of this hormone is the atrial natriuretic peptide (ANP), which contains 28 amino acids. Various immunohistochemical studies have shown that ANP is present in many areas of the central nervous system, including the median eminence. In our studies, we investigated the effect of ANP in a superfused rat pituitary cell system. When ANP...

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

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


    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 (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.

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

    Kile, J.P.


    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.

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

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


    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.

  14. GnRH-induced Ca2+ signaling patterns and gonadotropin secretion in pituitary gonadotrophs. Functional adaptations to both ordinary and extraordinary physiological demands

    María Luisa eDurán-Pastén


    Full Text Available 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

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

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


    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.

  16. 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.

    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


    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.

  17. Blood-brain barrier to peptides: (/sup 3/H)gonadotropin-releasing hormone accumulation by eighteen regions of the rat brain and by anterior pituitary

    Ermisch, A.; Ruehle, H.J. (Karl-Marx-Universitaet, Leipzig (German Democratic Republic). Sektion Biowissenschaften); Klauschenz, E.; Kretzschmar, R. (Akademie der Wissenschaften der DDR, Berlin. Inst. fuer Wirkstofforschung)


    After intracarotid injection of (/sup 3/H)gonadotropin-releasing hormone ((/sup 3/H)GnRH) the mean accumulation of radioactivity per unit wet weight of 18 brain samples investigated and the anterior pituitary was 0.38 +- 0.11% g/sup -1/ of the injected tracer dose. This indicates a low but measurable brain uptake of the peptide. The brain uptake of (/sup 3/H)GnRH in blood-brain barrier (BBB)-protected regions is 5% of that of separately investigated (/sup 3/H)OH. In BBB-free regions the accumulation of radioactivity was more than 25-fold higher than in BBB-protected regions. The accumulation of (/sup 3/H)GnRH among regions with BBB varies less than among regions with leaky endothelia. The data presented for (/sup 3/H)GnRH are similar to those for other peptides so far investigated.

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

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


    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.

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

    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


    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.

  20. Hypersecretion of the alpha-subunit in clinically non-functioning pituitary adenomas: Diagnostic accuracy is improved by adding alpha-subunit/gonadotropin ratio to levels of alpha-subunit

    Andersen, Marianne; Ganc-Petersen, Joanna; Jørgensen, Jens Otto Lunde;


    BACKGROUND: In vitro, the majority of clinically non-functioning pituitary adenomas (NFPAs) produce gonadotropins or their alpha-subunit; however, in vivo, measurements of alpha-subunit levels may not accurately detect the hypersecretion of the alpha-subunit. AIM: We wanted to estimate the refere......BACKGROUND: In vitro, the majority of clinically non-functioning pituitary adenomas (NFPAs) produce gonadotropins or their alpha-subunit; however, in vivo, measurements of alpha-subunit levels may not accurately detect the hypersecretion of the alpha-subunit. AIM: We wanted to estimate...... the reference intervals and decision limits for gonadotropin alpha-subunit, LH and FSH levels, and aratio (alpha-subunit/LH+FSH), especially taking into consideration patient gender and menstrual status. Furthermore, we wanted to examine if the diagnostic utility of alpha-subunit hypersecretion was improved...... patients with NFPAs. Gonadotropin alpha-subunit, LH and FSH levels were measured and alpha-ratios were calculated. RESULTS: In healthy adults, the cut-offs for alpha-subunit levels were significantly different between men and pre- and postmenopausal women: the cut-offs were 1.10, 0.48 and 3.76 IU...

  1. Involvement of Ovarian Estradiol Biosynthesis and Pituitary FSH Expression in the Mechanism of Human Chorionic Gonadotropin Stimulation of Uterine Growth in Immature Female Rats

    Sandrine Rafert


    Full Text Available In a previous work, we showed that human Chorionic Gonadotropin (hCG alone is able to stimulate uterine ponderal growth in immature female rats. In the present paper, we provide new information indicating that a single 100 ng hCG injection increased ovarian androgen availability and aromatase activity. These changes are consistent with an increase in ovarian estradiol secretion. Ovarian activin βA and activin βB subunit RNAs expression were also increased following hCG injection. Most interestingly, this treatment also led to an increase in FSHβ subunit mRNA expression in the pituitary, which might be due to hCG-stimulated ovarian activin secretion. We have not been able so far to follow the kinetics of the plasma concentrations of activin and FSH in hCG-treated animals compared to control animals. This has to be explored in the future to provide a more complete assessment of our model.

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

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


    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.

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

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


    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.

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

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


    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.

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

    Rudolf, Faidiban O; Kadokawa, Hiroya


    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.

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

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


    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 lute

  7. Klinefelter syndrome with low gonadotropin levels.

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


    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.

  8. Effects of Gonadotropin-releasing Hormone (GnRH) and Dopamine on Gonadotropin(GTH) Secretion from in vitro Pituitary Cells of Rainbow Trout%促性腺激素释放激素和多巴胺对虹鳟( Oncorhynchus mykiss )离体脑垂体细胞分泌促性腺激素的影响



    本文研究了不同性腺发育时期淡水饲养的雌雄虹鳟(Oncorhynchus mykiss)血浆促性腺激素(GTH)浓度的变化规律;以及在离体条件下,探讨了促性腺激素释放激素(GnRH)、GnRH拮抗物和多巴胺对虹鳟脑垂体细胞分泌促性腺激素(GTH-Ⅱ)的影响。结果表明:(1)在雄性,血浆中GTH-Ⅱ的水平随性腺发育而逐渐增高;在雌性,仅排卵期血浆中GTH-Ⅱ的水平明显增高。(2)未成熟期和成熟期的雌性虹鳟脑垂体细胞对sGnRH和cGnRH刺激的敏感性表现不尽相同。成熟期和排卵后的脑垂体细胞对GnRH的刺激较为敏感,GTH-Ⅱ的分泌量较多。(3)在没有sGnRH的存在下,GnRH拮抗物对GTH-Ⅱ的分泌不发生作用,而在sGnRH的存在下,GnRH拮抗物对GTH-Ⅱ的分泌表现出浓度依赖的抑制作用。(4)在没有sGnRH的存在下,多巴胺对GTH-Ⅱ的分泌不发生作用,而当多巴胺的浓度一定时,随着sGnRH浓度的增加,GTH-Ⅱ分泌的量增大。另外,不论sGnRH还是cGnRH都不影响不同时期的脑垂体细胞GTH-I的分泌这些结果可为虹鳟的人工催产提供一些理论依据。%Plasma gonadotropin (GTH) levels during immature, mature and ovulated periods and effects of gonadotropin-releasing hormone (GnRH) and dopamine on GTH secretion of in vitro pituitary cells of rainbow trout were investigated. Plasma GTH levels increased with gonadal development. The different effects of sGnRH and cGnRH on GTH- Ⅱ secretions of pituitary cells in vitro from immature, mature and ovulated periods of rainbow trout were observed. GnRH antagonist did not change GTH - Ⅱ contents under the absence of sGnRH while GnRH antagonist suppressed dose-dependently GTH- Ⅱ secretions of pituitary cells in combination with sGnRH.Dopamine also did not affect GTH- Ⅱ levels under the absence of sGnRH, while GTH- Ⅱ secretions of pituitary cells were enhanced when the dosage of sGnRH was increased with the presence of

  9. Does a nonclassical signaling mechanism underlie an increase of estradiol-mediated gonadotropin-releasing hormone receptor binding in ovine pituitary cells?

    Davis, Tracy L; Whitesell, Jennifer D; Cantlon, Jeremy D; Clay, Colin M; Nett, Terry M


    Estradiol-17beta (E2) is the major regulator of GnRH receptor (GnRHR) gene expression and number during the periovulatory period; however, the mechanisms underlying E2 regulation of the GNRHR gene remain undefined. Herein, we find that E2 conjugated to BSA (E2-BSA) mimics the stimulatory effect of E2 on GnRH binding in primary cultures of ovine pituitary cells. The time course for maximal GnRH analog binding was similar for both E2 and E2-BSA. The ability of E2 and E2-BSA to increase GnRH analog binding was blocked by the estrogen receptor (ER) antagonist ICI 182,780. Also, increased GnRH analog binding in response to E2 and the selective ESR1 agonist propylpyrazole triol was blocked by expression of a dominant-negative form of ESR1 (L540Q). Thus, membrane-associated ESR1 is the likely candidate for mediating E2 activation of the GNRHR gene. As cAMP response element binding protein (CREB) is an established target for E2 activation in gonadotrophs, we next explored a potential role for this protein as an intracellular mediator of the E2 signal. Consistent with this possibility, adenoviral-mediated expression of a dominant-negative form of CREB (A-CREB) completely abolished the ability of E2 to increase GnRH analog binding in primary cultures of ovine pituitary cells. Finally, the presence of membrane-associated E2 binding sites on ovine pituitary cells was demonstrated using a fluorescein isothiocyanate conjugate of E2-BSA. We suggest that E2 regulation of GnRHR number during the preovulatory period reflects a membrane site of action and may proceed through a nonclassical signaling mechanism, specifically a CREB-dependent pathway.

  10. 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.

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


    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.

  11. Neuroendocrine regulation of gonadotropin secretion in seasonally breeding birds

    Takayoshi eUbuka


    Full Text Available 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.

  12. Management of Nonpregnant Women with Elevated Human Chorionic Gonadotropin

    Bernd C. Schmid


    Full Text Available Human chorionic gonadotropin (hCG is useful in evaluating and monitoring early pregnancy as well as trophoblastic disease. Here we describe the management of women with elevated serum human chorionic gonadotropin in a case of a 51-year-old female who was unsuccessfully treated for ectopic pregnancy. She was subsequently diagnosed with pituitary hCG production, which should be considered as differential diagnosis before treatment is initiated.

  13. Regulation of gonadotropins by corticotropin-releasing factor and urocortin

    Kazunori eKageyama


    Full Text Available While stress activates the hypothalamic-pituitary-adrenal (HPA axis, it suppresses the hypothalamic-pituitary-gonadal (HPG axis. Corticotropin-releasing factor (CRF is a major regulatory peptide in the HPA axis during stress. Urocortin1 (Ucn1, a member of the CRF family of peptides, has a variety of physiological functions and both CRF and Ucn1 contribute to the stress response via G protein-coupled seven transmembrane receptors. Ucn2 and Ucn3, which belong to a separate paralogous lineage from CRF, are highly selective for the CRF type 2 receptor (CRF2 receptor. The HPA and HPG axes interact with each other, and gonadal function and reproduction are suppressed in response to various stressors. In this review, we focus on the regulation of gonadotropins by CRF and Ucn2 in pituitary gonadotrophs and of gonadotropin-releasing hormone (GnRH via CRF receptors in the hypothalamus. In corticotrophs, stress-induced increases in CRF stimulate Ucn2 production, which leads to the inhibition of gonadotropin secretion via the CRF2 receptor in the pituitary. GnRH in the hypothalamus is regulated by a variety of stress conditions. CRF is also involved in the suppression of the HPG axis, especially the GnRH pulse generator, via CRF receptors in the hypothalamus. Thus, complicated regulation of GnRH in the hypothalamus and gonadotropins in the pituitary via CRF receptors contributes to stress responses and adaptation of gonadal functions.

  14. Genetically modified mouse models addressing gonadotropin function.

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


    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.

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

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


    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-Phe- amide-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.

  16. Assessable Value of Nighttime Urine Gonadotropins on Function of Plypothalamic - Pituitary - Gonadal Axis in Children Treated by Gonadotropin- Releasing Hormone Analogue%夜间尿促性腺激素对判断儿童促性腺激素释放激素类似物治疗后下丘脑-垂体-性腺轴功能的价值



    Objective To monitor the adequacy of hypothalamic - pituitary - gonadal axis( HPGA) suppression after receiving gonado tropin -releasing hormone analogue(GnRHa) therapy,tracking gonadotropin (Gn) concentrations in urine by immunochemiluminometric assay (1CMA). Methods Twelve patients who were diagnosed as central precocious puberty(4 patients,all female;age 7. 3 -9. 8 years) or short predicted adult height(8 patients;3 male,5 female;age 8. 8 - 12. 3 years) ,12 h urinary Gn measured by ICMA were performed before the initiation of GnRHa therapy as well as 3 months after the beginning of therapy. Results HPGA suppression was defined as the absence of significant luteinizing hormone( LH)and follicle - stimulating hormone( FSH) responses to GnRH stimulation. LH determinations in urine was significantly lower after therapy compared to before therapy mean LH/Cr[(43.39 ±36.65) IU ? Mol-1 vs (339. 14 ±264.02) IU ? Mol-1, t=3.727,P=0.003],as well as FSH/Cr[(348.20±165.22) IU ? Mol-1 vs (1 841.59 ±1 287.46) IU ? Mol' ,t =3.968, P =0.002]. The sensitivity and specificity of urinary LH determinations ( LH/Cr> 56.44 IU ? Mol-1) to detect inadequate HPGA suppression were 91.7% and 83.3% .respectively. For urinary FSH determinations( FSH/Cr > 604. 97 IU ? Mol-1 ) , the sensitivity and specificity were 93. 8% and 85. 7% , respectively. For urinary FSH determinations (FSH/Cr > 604.97 IU ? Mol-1) and urinary LH determinations( LH/Cr > 56.44 IU ? Mol-1) ,the sensitivity and specificity were 91.7% and 100.0% .respectively. Conclusion Urine measurements of LH and FSH by ICMA, seemed suitable for monitoring HPGA suppression of GnRHa therapy in individual patients.%目的 探讨免疫化学发光法( ICMA)检测夜间12 h尿促性腺激素对判断儿童促性腺激素释放激素类似物(GnRHa)治疗后下丘脑-垂体-性腺轴(HPGA)功能状态的价值.方法 患儿12例,其中中枢性性早熟4例(女,年龄7.3 ~9.8岁),青春期预测终身高矮小8例(男3例,女5

  17. Elevation of plasma gonadotropin concentration in response to mammalian gonadotropin releasing hormone (GRH) treatment of the male brown trout as determined by radioimmunoassay

    Grim, L.W.; Cluett, D.M.


    Rapid increase of the plasma gonadotropin concentration as measured by radioimmunoassay has been demonstrated in response to GRH treatment of the sexually mature male brown trout. Peak gonadotropin values were observed within 15 minutes of GRH treatment, however, the return to baseline values was prolonged compared with the mammalian response. These data support the concept that the brain, operating via releasing hormones, plays a role in the control of pituitary hormone secretion in fish.

  18. Induction of Gonadotropins for Reproductive Control

    Elza Ibrahim Auerkari


    Full Text Available Much of the recent research on gonadotropin – related control processes of reproduction and reproductive maturation has concentrated on the neuronal and molecular biology of gonadotropin release. The reproductive development of healthy mammals requires appropriate fetal develompment and migration of the neural network controlling and including the gonadotropin releasing hormone (GnRH – producing neurons that are needed to regulate GnRH and luteinizing hormone (LH release. GnRH is also necessary for the development of the gonadotropin – producing pituitary gland. The fetal gonads respon to GnRH – induced LH production by producing the gonadal steroids required for further reproductive differentiation. Pubertal maturation is characterised by increases in LH levels, representing the corresponding pulsatile release of GnRH. This GnRH pulse generator appears to be an intrinsic property of the arcuate nucleus at the medial basal hypothalamus. The generator activity can be mediated by the neurotransmitter aspartate which activates neurons of the hypothalamus, inducing acuate releases of GnRH and hence initiates puberty. A major factor in human reproductive maturation is the decrease in the age of puberty, caused by improvement of nutritional conditions due to the socio – economic development. This implies that the pubertal activation of GnRH secretion depends on metabolic conditions. Of the substances that mediate the metabolic condition to the neuronal network regulating GnRH secretion, the role of the neuropeptide Y (NPY appears instrumental : for healthy mammals less food means more NPY, and accumulated NPY makes food to become sex. NPY does this by regulating the appropriate hypothalamic functions including the neuroendocrine control of gonadotropin release.

  19. GnRH在青年摩杂一代水牛下丘脑-垂体-卵巢轴的免疫组化定位%Distribution of Gonadotropin (GnRH) Releasing Hormone in Hypothalamus-pituitary-ovary Axis of Youth Murrah Hybrid Water Buffalo

    凌泽继; 李瑞明; 谢莹雪; 周辰瑜; 黎金秀; 秦津; 潘堂峰; 宋小白; 杨柄壮; 许典新; 韩涛; 潘琼


    [Objective] The research aimed to study the distribution of gonadotropin (GnRH) releasing hormone in hypothalamus-pituitary-ovary axis of youth murrah hybrid water buffalo.[Method] The immunohistochemistry SuperPicTureTM two step method was used to detect the distribution of GnRH in hypothalamus-pituitary-ovary axis of five femal murrah hybrid water buffalos.The association of GnRH 's distribution in hypothalamus, pituitary and ovary, and understand how the GnRH secrete releasing in hypothalamus, pituitary and ovary.[Result] The GnRH was first discovered in singulorum link of hypothalamus-pituitary-ovary axis of murrah hybrid water bufflo.The GnRH immunoreactive neurons were first discovered in every main nucleus of murrah hybrid water bufflo hypothalamus, especially distributed in supraoptic nucleus, preoptic nucleus, paraventricular nucleus most.The GnRH immunoactive productions were first discovered only in murrah hybrid water bufflo adenohypophysis for pituitary.The GnRH immunoactive productions were first discovered in the germinal epithelium cells, granulosa cells and lutein cells of murrah hybrid water bufflo.[Conclusion] The test results could provide morphological basis for the study of the GnRH's synthesis and mechanism of action, and could play reference and directions part in breeding murrah hybrid water bufflo.%[目的]研究促性腺激素释放激素(GnRH)在青年摩杂一代水牛下丘脑-垂体-卵巢轴的免疫组化定位.[方法]采用免疫组织化学SuperPicTureTM二步法检测5头青年摩杂一代水牛下丘脑、垂体和卵巢中GnRH的分布情况,研究GnRH在下丘脑、垂体及卵巢的分布上的联系,进而了解GnRH在下丘脑、垂体及卵巢三者之间分泌释放的途径.[结果]GnRH存在于青年摩杂一代水牛下丘脑-垂体-卵巢轴的各个环节.青年摩杂一代水牛下丘脑中各主要核团都有GnRH免疫阳性神经元的分布,尤其以视上核、视前核、室旁核分布较多.对于垂体,Gn

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

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


    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. Regulation of tonic gonadotropin release in prepubertal female hamsters

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


    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.

  2. Pituitary Tumors

    ... institutes of the National Institutes of Health (NIH) conduct research related to brain tumors, including pituitary tumors, in their laboratories at ... institutes of the National Institutes of Health (NIH) conduct research related to brain tumors, including pituitary tumors, in their laboratories at ...

  3. 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.

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


    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.

  4. A regulator of G Protein signaling, RGS3, inhibits gonadotropin-releasing hormone (GnRH-stimulated luteinizing hormone (LH secretion

    Musgrove Lois C


    Full Text Available Abstract Background Luteinizing hormone secreted by the anterior pituitary gland regulates gonadal function. Luteinizing hormone secretion is regulated both by alterations in gonadotrope responsiveness to hypothalamic gonadotropin releasing hormone and by alterations in gonadotropin releasing hormone secretion. The mechanisms that determine gonadotrope responsiveness are unknown but may involve regulators of G protein signaling (RGSs. These proteins act by antagonizing or abbreviating interaction of Gα proteins with effectors such as phospholipase Cβ. Previously, we reported that gonadotropin releasing hormone-stimulated second messenger inositol trisphosphate production was inhibited when RGS3 and gonadotropin releasing hormone receptor cDNAs were co-transfected into the COS cell line. Here, we present evidence for RGS3 inhibition of gonadotropin releasing hormone-induced luteinizing hormone secretion from cultured rat pituitary cells. Results A truncated version of RGS3 (RGS3T = RGS3 314–519 inhibited gonadotropin releasing hormone-stimulated inositol trisphosphate production more potently than did RSG3 in gonadotropin releasing hormone receptor-bearing COS cells. An RSG3/glutathione-S-transferase fusion protein bound more 35S-Gqα than any other member of the G protein family tested. Adenoviral-mediated RGS3 gene transfer in pituitary gonadotropes inhibited gonadotropin releasing hormone-stimulated luteinizing hormone secretion in a dose-related fashion. Adeno-RGS3 also inhibited gonadotropin releasing hormone stimulated 3H-inositol phosphate accumulation, consistent with a molecular site of action at the Gqα protein. Conclusions RGS3 inhibits gonadotropin releasing hormone-stimulated second messenger production (inositol trisphosphate as well as luteinizing hormone secretion from rat pituitary gonadotropes apparently by binding and suppressing the transduction properties of Gqα protein function. A version of RGS3 that is amino

  5. 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

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


    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.

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

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


    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.


    李远友; 林浩然


    To understand the regulatory mechanisms of gonadotropin secretion in Rana rugulosa, this study investigated the effects of dopamina (DA), estradiol (E2) and testosterone (T) on the in vitro release of luteinizing hormone (LH) and follicle-stimulation hormone (FSH) from the pituitary fragments of female Rana rugulosa using a static incubation system and radio-immunoassay (RIA). The results indicated that DA at the concentration from 0.1 μmol/L to 10μmol/L inhibited the release of LH and FSH from the pituitary fragments of sexually pre-mature or hibernation individuals, and the inhibitory effects enhanced with increasing concentrations of DA. E2at 1 μmol/L and 10μmol/L significantly stim-ulated the release of LH of sexually pre-mature individuals, but inhibited their FSH release at 0.1μmol/L to 10 μmol/L; T had no obvious effects on their FSH release, but significantly inhibited their LH release at 10 μmol/L. Neither E2 nor T, at the concentration from 0.1 μmol/L to 100 μmol/L, had obvious effects on the release of LH and FSH of hibernation individuals. The data suggest that DA and sexual steroids may have direct regulatory actions on LH and FSH release at the pituitary level in Rana rugulosa, and the action of sexual sterlids may relate to the gonadal development stages (sea-sons).%为了解虎纹蛙促性腺激素分泌的调节机理,用离体静态培育系统和放射免疫测定法,研究了多巴胺(DA)、雌二醇(E2)和睾酮(T)对雌性虎纹蛙离体脑垂体薄片促黄体激素(LH)和促卵泡激素(FSH)分泌活动的影响.结果表明:0.1~10μmol/L的DA对成熟前期和冬眠期虎纹蛙离体脑垂体薄片的LH及FSH的释放都有抑制作用,并且随着DA浓度的增加,抑制作用逐渐增强.1和10μmol/L的E2显著刺激成熟前期蛙LH的释放,而0.1~10μmol/L的E2显著抑制其FSH的释放;T对其FSH的释放无显著影响,但10μmol/L的T显著抑制其LH释放.0.1~100μmol/L的E2或T对冬眠期蛙LH和FSH的释放均

  8. [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)].

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


    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.

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

    Pekic, S; Stojanovic, M; Popovic, V


    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

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

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


    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.

  11. Pituitary tumor

    ... 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 ...

  12. Pituitary infarction

    ... during or right after childbirth, it is called Sheehan syndrome . This is a very rare condition. Risk factors ... commonly, pituitary dysfunction may appear more slowly. In Sheehan syndrome, for example, the first symptom may be a ...

  13. Pituitary apoplexy

    Salam Ranabir


    Full Text Available 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.

  14. Follicle stimulating hormone secreting pituitary adenoma: a challenging diagnosis

    Madhuri Alap Mehendale


    Full Text Available FSH secreting pituitary adenomas are relatively uncommon brain tumours and usually non-functioning. But in rare cases they produce ovarian hyperstimulation. We report a case of a 32 year old female P2L2, with amenorrhoea of 1 year, pain in abdomen and galactorrhoea since 6 months. Initially thought to be a simple prolactinoma with multicystic ovaries, but after thorough investigations to our surprise diagnosed to be a rare case of gonadotropin secreting pituitary adenoma. Patient was successfully managed by excision of the pituitary adenoma. [Int J Reprod Contracept Obstet Gynecol 2015; 4(2.000: 493-496

  15. Defective Gonadotropin-Dependent Ovarian Folliculogenesis and Granulosa Cell Gene Expression in Inhibin-Deficient Mice

    Nagaraja, Ankur K.; Middlebrook, Brooke S.; Rajanahally, Saneal; Myers, Michelle; Li, Qinglei; Matzuk, Martin M.; Pangas, Stephanie A.


    Inhibin-α knockout (Inha−/−) female mice develop sex cord-stromal ovarian cancer with complete penetrance and previous studies demonstrate that the pituitary gonadotropins (FSH and LH) are influential modifiers of granulosa cell tumor development and progression in inhibin-deficient females. Recent studies have demonstrated that Inha−/− ovarian follicles develop precociously to the early antral stage in prepubertal mice without any increase in serum FSH. These studies suggest that in the absence of inhibins, granulosa cells differentiate abnormally and thus at sexual maturity may undergo an abnormal response to gonadotropin signaling contributing to tumor development. To test this hypothesis, we stimulated immature wild-type and Inha−/− female mice with gonadotropin analogs prior to tumor formation and subsequently examined gonadotropin-induced ovarian follicle development as well as preovulatory and human chorionic gonadotropin-induced gene expression changes in granulosa cells. We find that at 3 wk of age, inhibin-deficient ovaries do not show further antral development or undergo cumulus expansion. In addition, there are widespread alterations in the transcriptome of gonadotropin-treated Inha−/− granulosa cells, with significant changes in genes involved in extracellular matrix and cell-cell communication. These data indicate the gonadotropins initiate an improper program of cell differentiation prior to tumor formation in the absence of inhibins. PMID:20739397

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

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


    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.

  17. Rheumatic manifestations of pituitary tumors.

    Stavrou, S; Kleinberg, D L


    Pituitary tumors may cause rheumatologic problems as a result of under production or overproduction of one pituitary hormone. Excessive growth hormone causes destruction of cartilage by a direct action. Facial and acral changes and arthralgias may be some of the first symptoms of acromegaly. The arthritis associated with acromegaly is often devastating. Carpal tunnel syndrome is very common in patients with acromegaly. Adrenocorticotropin (ACTH) has indirect effects via the action of glucocorticoid on bones, muscles, and the immune system. Proximal muscle weakness is a characteristic feature of Cushing's syndrome. Patients with Cushing's syndrome commonly have osteopenia and osteoporosis that lead to an increase in bone fractures. Avascular necrosis is associated with exogenous steroid administration. The effects of too much glucocorticoid or too rapid withdrawal can be severe. Gonadotropins act via the gonadal steroids and protect bone mass from loss. Prolactin is less involved in rheumatologic disease; the data for which are limited in humans. Pituitary tumors can have manifestations similar to rheumatologic disorders and should be included in the differential diagnosis of these diseases.

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

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


    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.

  19. Active immunization against gonadotropin-releasing hormone : an effective tool to block the fertility axis in mammals

    Turkstra, Jouwert Anne


    Gonadotropin releasing hormone (GnRH) plays a pivotal role in fertility and reproduction in mammals. It induces the release of luteinising hormone (LH) en follicle stimulating hormone (FSH) from the pituitary. These hormones are responsible for gonadal steroid production and indirectly for gametogen

  20. Mortality in patients with pituitary disease.

    Sherlock, Mark


    Pituitary disease is associated with increased mortality predominantly due to vascular disease. Control of cortisol secretion and GH hypersecretion (and cardiovascular risk factor reduction) is key in the reduction of mortality in patients with Cushing\\'s disease and acromegaly, retrospectively. For patients with acromegaly, the role of IGF-I is less clear-cut. Confounding pituitary hormone deficiencies such as gonadotropins and particularly ACTH deficiency (with higher doses of hydrocortisone replacement) may have a detrimental effect on outcome in patients with pituitary disease. Pituitary radiotherapy is a further factor that has been associated with increased mortality (particularly cerebrovascular). Although standardized mortality ratios in pituitary disease are falling due to improved treatment, mortality for many conditions are still elevated above that of the general population, and therefore further measures are needed. Craniopharyngioma patients have a particularly increased risk of mortality as a result of the tumor itself and treatment to control tumor growth; this is a key area for future research in order to optimize the outcome for these patients.

  1. Correlation between Urinary Gonadotropin and Onset of Hypothalamic - Pituitary - Gonadal Axis during Day time and Nighttime in Children%昼夜尿促性腺激素与儿童下丘脑-垂体-性腺轴启动的关系

    谢书艳; 徐庄剑; 马亚萍; 张婷婷; 王喜平; 王勍


    gonadotropin ( Ucn) for the documentation of hypothalamic - pituitary - go-nadal axis ( HPGA) status during daytime and nighttime in children. Methods Forty children with disorders during growth or pubertal development were hospitalized for gonadotropin - releasing hormone analogue stimulating test. Timed 12 - h diurnal and nocturnal urine were collected before the test. The serum samples collected at midnight before the test was for nocturnal serum spontaneous gonadotropin (Gn) detection , and 0 min sample collected during the test was for diurnal serum spontaneous Gn detection. Twelve normal individuals (6 prepubertal boys,6 prepubertal girls) were assigned to the control group. The determinations of luteinizing hormone ( LH) and follicle - stimulating hormone were assayed by immunochemiluminometric assay(ICMA). Results 1. In patients,the correlation coefficient between the serum peak concentrations of stimulated LH (PLH) and the quantities of diurnal urinary LH(DULH) was 0.648,0.677 for DULH concentrations/Cr.and 0.611 for diurnal serum spontaneous LH(SLH). The areas under the receiver operator characteristic ( ROC) curves of the quantities of DULH, DULH concentrations/Cr and diurnal SLH for diagnosing onset of HPGA were 0.944,0. 926 and 0. 771, respectively. The correlation coefficient between the serum PLH and die quantities of nocturnal urinary LH ( NULH) was 0. 651 ,and it was 0. 638 and 0. 656 for NULH concentrations/Cr,and for nocturnal SLH. The areas under the ROC curves of the quantities of NULH,NULH concentrations/Cr and nocturnal SLH were 0.930,0.953 and 0. 819,respectively.2. In 52 individuals (both patients and normal controls) ,the areas under the ROC curves of the quantities of DULH, DULH concentrations/Cr, the quantities of NULH and NULH concentrations/Cr were 0. 961,0. 935 ,0. 955 and 0. 959,respectively. When the quantities of DULH,DULH concentrations/Cr,the quantities of NULH,NULH concentrations/Cr were no less than 0.036 IU.20.723 0 IU ? Mol-1,0.068 IU

  2. The effect of gonadotropin-releasing hormone agonist-induced down-regulation on pituitary and ovarian function%促性腺激素释放激素激动剂降调对垂体内外的影响

    朱桂金; 徐蓓; 聂睿


    catalytic subunit.40%-60% of follicle-stimulating hormone (FSH) secretion is repressed by the immediate action of downregulation,while 90% luteinizing hormone (LH) could be repressed, so downregulation is used to prevent the premature LH surges. Regulation of paracrine secretion by downregulation requires the involvement of FSH and LH and regulatory factors of paracrine secretion have no effect on the promotion of follicular development. The negative feedback of steroid hormone is through the level of hypothalamus and pituitary, while downregulation functions at the level of the gonadotropin-releasing hormone (GnRH) receptors, so the normal positive and negative feedbacks are cancelled by downregulation.There exist GnRH receptors in granulosa cells, theca cells and luteal cells, so it could be presumed theoretically that GnRH may have direct effects on ovary. Both animal experiments and in vitro studiessuggest that GnRH may have a direct action on ovarian granulosa cells through interfering steroid synthesis and follicular development. So except for preventing the premature LH surges and decreasing the detrimental effect of high LH, the effect of GnRH agonist-induced down-regulation increasing pregnancy rate may be also through the immediate action on follicular development, oocyte maturation and endometrial receptivity, but no confirmation has been made by the existing evidence.

  3. Rapid Anti-Inflammatory Effects of Gonadotropin-Releasing Hormone Antagonism in Rheumatoid Arthritis Patients with High Gonadotropin Levels in the AGRA Trial.

    Anita Kåss

    Full Text Available Gonadotropin-releasing hormone (GnRH and pituitary gonadotropins, which appear to be proinflammatory, undergo profound secretory changes during events associated with rheumatoid arthritis (RA onset, flares, or improvement e.g. menopausal transition, postpartum, or pregnancy. Potential anti-inflammatory effects of GnRH-antagonists may be most pronounced in patients with high GnRH and gonadotropin levels. Therefore, we investigated the efficacy and safety of a GnRH-antagonist, cetrorelix, in RA patients with high gonadotropin levels.We report intention-to-treat post hoc analyses among patients with high gonadotropin levels (N = 53, i.e. gonadotropin levels>median, from our proof-of-concept, double-blind AGRA-study (N = 99. Patients with active longstanding RA, randomized to subcutaneous cetrorelix (5mg days1-2; 3mg days 3-5 or placebo, were followed through day 15. Only predefined primary and secondary endpoints were analyzed.The primary endpoint, Disease Activity Score of 28-joint counts with C-reactive protein (DAS28-CRP, improved with cetrorelix compared with placebo by day 5 (-1.0 vs. -0.4, P = 0∙010. By day 5, more patients on cetrorelix achieved at least a 20% improvement in the American College of Rheumatology scale (44% vs. 19%, P = 0.049, DAS28-CRP≤3.2 (24% vs. 0%, P = 0.012, and European League against Rheumatism 'Good-responses' (19% vs. 0%, P = 0.026. Tumor necrosis factor-α, interleukin-1β, interleukin-10, and CRP decreased with cetrorelix (P = 0.045, P = 0.034, P = 0.020 and P = 0.042 respectively compared with placebo by day 15. Adverse event rates were similar between groups.GnRH-antagonism produced rapid anti-inflammatory effects in RA patients with high gonadotropin levels. GnRH should be investigated further in NCT00667758.

  4. Presence of. beta. hCG mRNA in the human pituitary

    van Strien, A.; van Wezenbeek, P. (Organon International BV, Oss (Netherlands))


    A strong structural and biological similarity exist between human chorionic gonadotropin (hCG) and luteinizing hormone (LH). They share the same {alpha} subunit and have evolutionary related {beta} subunits. hCG is synthesized in first trimester placenta, whereas LH is synthesized in the pituitary. Substances with immunological, physical and biological properties of hCG have, however, been observed in postmenopausal urinary gonadotropin preparations as well as in pituitary extracts. Despite this finding it has not yet been proven that the hCG-like material is identical to placental hCG. This report describes the presence of a minor messenger RNA species in the human pituitary. RNA was isolated from five human pituitary glands and an amplified cDNA library was prepared.

  5. Kisspeptin regulates gonadotropin-releasing hormone secretion in gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats

    Haogang Xue; Chunying Yang; Xiaodong Ge; Weiqi Sun; Chun Li; Mingyu Qi


    Kisspeptin is essential for activation of the hypothalamo-pituitary-gonadal axis. In this study, we established gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats. Rats were injected with 1, 10, or 100 pM kisspeptin-10, a peptide derived from full-length kisspeptin, into the arcuate nucleus and medial preoptic area, and with the kisspeptin antagonist peptide 234 into the lateral cerebral ventricle. The results of immunohistochemical staining revealed that pulsatile luteinizing hormone secretion was suppressed after injection of antagonist peptide 234 into the lateral cerebral ventricle, and a significant increase in luteinizing hormone level was observed after kisspeptin-10 injection into the arcuate nucleus and medial preoptic area. The results of an enzyme-linked immunosorbent assay showed that luteinizing hormone levels during the first hour of kisspeptin-10 infusion into the arcuate nucleus were significantly greater in the 100 pM kisspeptin-10 group than in the 10 pM kisspeptin-10 group. These findings indicate that kisspeptin directly promotes gonadotropin-releasing hormone secretion and luteinizing hormone release in gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats. The arcuate nucleus is a key component of the kisspeptin-G protein-coupled receptor 54 signaling pathway underlying regulating luteinizing hormone pulse secretion.

  6. -Human Chorionic Gonadotropin Production

    Michael J. Russell


    Full Text Available Dedifferentiated liposarcomas may display a variety of “heterologous” lines of differentiation, including osseous, vascular, skeletal, and/or smooth muscular. There have been six previously reported examples of leiomyosarcomas associated with high levels of serum human chorionic gonadotropin (hCG production, comprised of cases originating from the retroperitoneum, spermatic cord, small intestine, and uterus. This report describes the first example of a dedifferentiated liposarcoma that combined both of the aforementioned features: extensive heterologous (leiomyosarcomatous differentiation and -hCG production (maximum serum levels 1046 mIU/ml, reference <5 mIU/ml. The tumor, which originated in the retroperitoneum in the region of the right kidney, was rapidly progressive and ultimately fatal within three months of its diagnosis. In addition to characteristic morphologic features, lipogenic and smooth muscle differentiation were confirmed with immunohistochemical stains for MDM2 and smooth muscle actin, respectively. The tumor also displayed diffuse immunoreactivity for -hCG in both primary and metastatic sites. This case further expands the clinicopathologic spectrum of lipogenic tumors.

  7. Pituitary stalk lesion in a 13-year-old female.

    Zilbermint, Mihail; Ramnitz, Mary S; Lodish, Maya B; Kanaka-Gantenbein, Christina; Kattamis, Antonis; Lyssikatos, Charalampos; Patronas, Nicholas J; Quezado, Martha M; Stratakis, Constantine A


    Germinomas presenting with a pituitary stalk lesion and panhypopituitarism are rare in children, and their definite diagnosis is challenging. An invasive diagnostic approach, such as a transsphenoidal biopsy, is often required prior to establishing a treatment regimen. A 13-year-old female presented with 1 year of secondary amenorrhea, fatigue, and progressive thirst with polyuria. Laboratory work-up revealed panhypopituitarism (central hypothyroidism, hypogonadotropic hypogonadism, adrenal insufficiency and central diabetes insipidus). α-Fetoprotein and β-human chorionic gonadotropin were not elevated in serum nor in cerebrospinal fluid. The magnetic resonance imaging (MRI) of the pituitary region showed an enhancing infundibular lesion, extending into the hypothalamus, and infiltrating the pituitary gland. A transsphenoidal biopsy of the infundibular lesion confirmed the diagnosis of germinoma (germ-cell tumor). After appropriate hormone replacement therapy, chemotherapy and low-dose radiation therapy, the patient achieved complete resolution of the pituitary stalk lesion on the MRI.

  8. Pituitary stalk lesion in a 13-year-old female

    Zilbermint, Mihail; Ramnitz, Mary S.; Lodish, Maya B.; Kanaka-Gantenbein, Christina; Kattamis, Antonis; Lyssikatos, Charalampos; Patronas, Nicholas J.; Quezado, Martha M.


    Germinomas presenting with a pituitary stalk lesion and panhypopituitarism are rare in children, and their definite diagnosis is challenging. An invasive diagnostic approach, such as a transsphenoidal biopsy, is often required prior to establishing a treatment regimen. A 13-year-old female presented with 1 year of secondary amenorrhea, fatigue, and progressive thirst with polyuria. Laboratory work-up revealed panhypopituitarism (central hypothyroidism, hypogonadotropic hypogonadism, adrenal insufficiency and central diabetes insipidus). α-Fetoprotein and β-human chorionic gonadotropin were not elevated in serum nor in cerebrospinal fluid. The magnetic resonance imaging (MRI) of the pituitary region showed an enhancing infundibular lesion, extending into the hypothalamus, and infiltrating the pituitary gland. A transsphenoidal biopsy of the infundibular lesion confirmed the diagnosis of germinoma (germ-cell tumor). After appropriate hormone replacement therapy, chemotherapy and low-dose radiation therapy, the patient achieved complete resolution of the pituitary stalk lesion on the MRI. PMID:24129100

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

    Masumi eNozaki


    Full Text Available 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 vertebrate 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 GTH 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.

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

    Nozaki, Masumi


    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.

  11. Acute pituitary apoplexy complicating a pituitary macroadenoma

    Febin Joseph


    Full Text Available Pituitary apoplexy is a rare but potentially life-threatening condition caused by either haemorrhage or infarction of the pituitary gland. In most cases, a pre-existing pituitary macroadenoma is present. Patients present with the clinical syndrome of headache, visual defects or ophthalmoplegia, altered state of consciousness and variable endocrine deficits.

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

    Amano, Masafumi; Ikuta, Kazumasa; Kitamura, Shoji


    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.

  13. The pituitary-gonadal axis in healthy female dogs and bitches with gynecological disorders

    Buijtels, J.J.C.W.M.|info:eu-repo/dai/nl/304830844


    The pituitary gland produces and secretes follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in a pulsatile fashion, induced by pulses of gonadotropin-releasing hormone (GnRH) from the hypothalamus. Different cells in the ovary are capable of secreting estradiol, testosterone and proges

  14. Pituitary gland height evaluated by MR in patients with {beta}-thalassemia major: a marker of pituitary gland function

    Argyropoulou, M.I.; Metafratzi, Z.; Efremidis, S.C. [Dept. of Radiology, Univ. of Ioannina (Greece); Kiortsis, D.N. [Dept. of Physiology, Univ. of Ioannina (Greece); Bitsis, S.; Tsatoulis, A. [Dept. of Internal Medicine, Univ. of Ioannina (Greece)


    In transfusion-dependent {beta}-thalassemia major, increased iron deposition in the pituitary gland has a cytotoxic effect leading mainly to hypogonadotropic hypogonadism. Our purpose was to assess in these patients the height of the pituitary gland and to evaluate whether it represents a marker of pituitary gland function. In 29 patients with {beta}-thalassemia major and 35 age- and gender-matched controls the pituitary gland height was evaluated in a midline sagittal scan using a spin echo T1-weighted (500/20 TR/TE) sequence. In all patients, an extensive endocrine evaluation was performed, including measurements of spontaneous and stimulated levels of gonadotropins, thyroid hormones, growth hormone, insulin-like growth factor, and adrenal hormones. The pituitary gland height was lower in thalassemic patients with hypogonadotropic hypogonadism (n=15) (mean 3.48; SD 0.46) than in the age- and gender-matched controls (mean 6.29; SD 0.77), (P<0.001). No statistically significant difference was found between thalassemic patients without hormone dysfunction (n=14) (mean 5.34; SD 1.52) and age- and gender-matched controls (mean 5.91; SD 1.06). We conclude that in thalassemic patients the pituitary gland height is an additional marker of pituitary gland function and might be useful in clinical management. (orig.)

  15. Pituitary tumors containing cholecystokinin

    Rehfeld, J F; Lindholm, J; Andersen, B N


    We found small amounts of cholecystokinin in the normal human adenohypophysis and therefore examined pituitary tumors from 87 patients with acromegaly, Cushing's disease, Nelson's syndrome, prolactinoma, or inactive pituitary adenomas. Five adenomas associated with Nelson's syndrome contained...

  16. Pituitary Tumors: Condition Information

    ... and metabolism. Thyroid-stimulating hormone is involved in growth, body temperature, and heart rate. Nonfunctioning pituitary tumors (also called nonsecretory tumors) do not produce hormones. They can press on or damage the pituitary ...

  17. Pituitary tumors containing cholecystokinin

    Rehfeld, J F; Lindholm, J; Andersen, B N


    We found small amounts of cholecystokinin in the normal human adenohypophysis and therefore examined pituitary tumors from 87 patients with acromegaly, Cushing's disease, Nelson's syndrome, prolactinoma, or inactive pituitary adenomas. Five adenomas associated with Nelson's syndrome contained......'s disease and 7 acromegaly with adenomas containing ACTH. The cholecystokinin peptides from the tumors were smaller and less sulfated than cholecystokinin from normal pituitary glands. We conclude that ACTH-producing pituitary cells may also produce an altered form of cholecystokinin....

  18. CT of pituitary abscess

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


    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.

  19. The apparent paradox of the negative and positive feedback control system on gonadotropin secretion.

    Yen, S S; Lein, A


    The separate and interactive effects of estradiol (E2) and luteinizing hormone-releasing factor (LRF) on the dynamics of LH storage and release were studied. Measurements were made of the serum gonadotropin responses to submaximal doses of LRF, given as brief pulses or infused over an extended period to normal women at various stages of the follicular phase of their menstrual cycles and to hypogonadal women with and without estrogen treatment. The two-pool concept of pituitary gonadotropin was verified; the dynamic responses of the two pools to the inputs of LRF and E2 were investigated and related to pituitary properties of sensitivity and reserve. Our results indicate that LRF appears to serve as a primary drive on the gonadotrophs, stimulating gonadotropin synthesis and storage (second pool), as well as release (first). E2 for the most part, amplifies the action of LRF except that it impedes LRF-induced release of gonadotropin. E2 augments the second pool activity (reserve) preferentially, and the relative activity of the first pool appears to be influenced by the E2-dependent self-priming effect of LRF. The interactions of the various elements of the system, when combined, provide a U-shaped curve to describe the over-all capacity of the gonadotrophs as a function of a broad range of E2 inputs. Negative and possitive feedback of E2 are revealed to operate by different mechanisms and to represent different segments of a single U-shaped curve rather than paradoxically disparate actions.

  20. Central and direct regulation of testicular activity by gonadotropin-inhibitory hormone and its receptor

    Takayoshi eUbuka


    Full Text Available Gonadotropin-inhibitory hormone (GnIH was first identified in Japanese quail to be an inhibitor of gonadotropin synthesis and release. GnIH peptides have since been identified in all vertebrates, and all share an LPXRFamide (X = L or Q motif at their C-termini. The receptor for GnIH is the G protein-coupled receptor 147 (GPR147, which inhibits cAMP signaling. Cell bodies of GnIH neurons are located in the paraventricular nucleus (PVN in birds and the dorsomedial hypothalamic area (DMH in most mammals. GnIH neurons in the PVN or DMH project to the median eminence to control anterior pituitary function via GPR147 expressed in gonadotropes. Further, GnIH inhibits gonadotropin-releasing hormone (GnRH -induced gonadotropin subunit gene transcription by inhibiting the adenylate cyclase/cAMP/PKA -dependent ERK pathway in an immortalized mouse gonadotrope cell line (LT2 cells. GnIH neurons also project to GnRH neurons that express GPR147 in the preoptic area (POA in birds and mammals. Accordingly, GnIH can inhibit gonadotropin synthesis and release by decreasing the activity of GnRH neurons as well as by directly inhibiting pituitary gonadotrope activity. GnIH and GPR147 can thus centrally suppress testosterone secretion and spermatogenesis by acting in the hypothalamic-pituitary-gonadal axis. GnIH and GPR147 are also expressed in the testis of birds and mammals, possibly acting in an autocrine/paracrine manner to suppress testosterone secretion and spermatogenesis. GnIH expression is also regulated by melatonin, stress and social environment in birds and mammals. Accordingly, the GnIH-GPR147 system may play a role in transducing physical and social environmental information to regulate optimal testicular activity in birds and mammals. This review discusses central and direct inhibitory effects of GnIH and GPR147 on testosterone secretion and spermatogenesis in birds and mammals.

  1. Familial pituitary tumor syndromes.

    Elston, Marianne S; McDonald, Kerrie L; Clifton-Bligh, Roderick J; Robinson, Bruce G


    The vast majority of pituitary tumors are benign and occur sporadically; however, they can still result in significant morbidity and even premature mortality through mass effects and hormone dysfunction. The etiology of sporadic tumors is still poorly understood; by contrast, advances have been made in our understanding of familial pituitary adenoma syndromes in the past decade. Currently, four genes are known to be associated with familial pituitary tumor syndromes: MEN1, CDKN1B, PRKAR1A and AIP. The first three genes are associated with a variety of extrapituitary pathologies, for example, primary hyperparathyroidism with multiple endocrine neoplasia type 1, which might aid identification of these syndromes. By contrast, AIP mutations seem to occur in the setting of isolated familial pituitary adenomas, particularly of the growth-hormone-secreting subtype. Awareness and identification of familial pituitary tumor syndromes is important because of potential associated pathologies and important implications for family members. Here, we review the current knowledge of familial pituitary tumor syndromes.

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

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


    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.

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

    Lin, Sze-Wah; Ge, Wei


    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.

  4. A FSH-Secreting Pituitary Macroadenoma Causing A Testosterone Deficiency Syndrome

    Xiong Wang


    Full Text Available FSH-secreting pituitary adenomas can affect sexual and reproductive function. In this article, we have reported the case of a 32-year-old male with secondary infertility. The patient had sexual and reproductive disturbances. The test results of the blood samples indicated obviously decreased testosterone (T and estradiol (E2 levels. Based on previous hormonal results, the patient received pituitary stimulation and human chorionic gonadotropin (hCG tests. Both follicle stimulating hormone (FSH and luteinizing hormone (LH showed low response during the pituitary stimulation test. The results of the hCG test indicated that T/E2 could recover to a normal level. In addition, this patient was diagnosed with pituitary macroadenoma, which was supported by the pituitary MRI. The man’s sexual and reproductive functions recovered following surgery. The pathological results confirmed that the tumor tissue was an FSH-secreting pituitary adenoma by immunohistochemical staining. The purpose of this report was to review the relative literature and discuss the influence of FSH-secreting pituitary adenomas on hormones through the hypothalamus-pituitary-testis axis.

  5. Progressive pituitary hormone deficiency following radiation therapy in adults; Deficiencia progressiva dos hormonios adeno-hipofisarios apos radioterapia em adultos

    Loureiro, Rafaela A.; Vaisman, Mario [Hospital Universitario Clementino Fraga Filho, Rio de Janeiro, RJ (Brazil). Servico de Endocrinologia]. E-mail:


    Hypopituitarism can be caused by radiation therapy, even when it is not directly applied on the hypothalamic-pituitary axis, and can lead to anterior pituitary deficiency mainly due to hypothalamic damage. The progressive loss of the anterior pituitary hormones usually occurs in the following order: growth hormone, gonadotropin hormones, adrenocorticotropic hormone and thyroid-stimulating hormone. Although there are several different tests available to confirm anterior pituitary deficiency, this paper will focus on the gold standard tests for patients submitted to radiation therapy. We emphasize that the decline of anterior pituitary function is time- and dose-dependent with some variability among the different axes. Therefore, awareness of the need of a joint management by endocrinologists and oncologists is essential to improve treatment and quality of life of the patients. (author)

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

    Perez-Lopez, F R


    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.

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

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


    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 (Pstimulation 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.

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

    Ganong, W F


    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

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

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


    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.

  10. The regulation and function of fibroblast growth factor 8 and its function during gonadotropin-releasing hormone neuron development

    Wilson CJ Chung


    Full Text Available 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 gonadotropin-releasing hormone (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 epigenetic modifies control mouse OP Fgf8 transcription in the context of GnRH neuronal development, and mammalian reproductive success.

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

    Kastelan, Darko; Korsic, Mirko


    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

  12. RNA interference of gonadotropin-inhibitory hormone gene induces arousal in songbirds.

    Takayoshi Ubuka

    Full Text Available Gonadotropin-inhibitory hormone (GnIH was originally identified in quail as a hypothalamic neuropeptide inhibitor of pituitary gonadotropin synthesis and release. However, GnIH neuronal fibers do not only terminate in the median eminence to control anterior pituitary function but also extend widely in the brain, suggesting it has multiple roles in the regulation of behavior. To identify the role of GnIH neurons in the regulation of behavior, we investigated the effect of RNA interference (RNAi of the GnIH gene on the behavior of white-crowned sparrows, a highly social songbird species. Administration of small interfering RNA against GnIH precursor mRNA into the third ventricle of male and female birds reduced resting time, spontaneous production of complex vocalizations, and stimulated brief agonistic vocalizations. GnIH RNAi further enhanced song production of short duration in male birds when they were challenged by playbacks of novel male songs. These behaviors resembled those of breeding birds during territorial defense. The overall results suggest that GnIH gene silencing induces arousal. In addition, the activities of male and female birds were negatively correlated with GnIH mRNA expression in the paraventricular nucleus. Density of GnIH neuronal fibers in the ventral tegmental area was decreased by GnIH RNAi treatment in female birds, and the number of gonadotropin-releasing hormone neurons that received close appositions of GnIH neuronal fiber terminals was negatively correlated with the activity of male birds. In summary, GnIH may decrease arousal level resulting in the inhibition of specific motivated behavior such as in reproductive contexts.

  13. What Are Pituitary Tumors?

    ... grow and to make steroid hormones (such as cortisol). Too much ACTH from the pituitary causes Cushing’s ... Cancer Atlas Press Room Cancer Statistics Center Volunteer Learning Center Follow Us Twitter Facebook Instagram Cancer Information, ...

  14. Pituitary Gland Disorders Overview

    ... reducing the amount of water lost in urine Oxytocin – causes milk to flow from the breasts in breastfeeding women, and may also help labor to progress Pituitary Tumors The most frequent type ...

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

    Sladjana Dukic-Stefanovic

    Full Text Available 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.

  16. Structural and Functional Divergence of Gonadotropin-Inhibitory Hormone (GnIH from Jawless Fish to Mammals

    Satoshi eOgawa


    Full Text Available 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 localised in the hypothalamic nuclei and their neural projections are widely distributed. GnIH acts on the pituitary and gonadotropin-releasing hormone (GnRH neurons to inhibit reproductive functions by decreasing gonadotropin release and synthesis. In addition, GnIH-GnIHR signalling is regulated by various factors such as environmental cues and stress. However, the function of fish GnIH-orthologs remain inconclusive because the physiological properties of fish GnIH peptides are debatable. This review summarizes the current research progress in GnIH-GnIHR signalling and their physiological functions in vertebrates with special emphasis on non-mammalian vertebrate species.

  17. Specific activity of radioiodine-labelled human chorionic gonadotropin ligand

    Crespi, M. (South African Inst. for Medical Research, Sandringham. National Inst. for Virology); Kay, G.W.; Van der Walt, L.A. (South African Inst. for Medical Research, Johannesburg. Dept. of Pathology)


    The article deals with the determination of the specific activity of radioiodine-labelled human chorionic gonadotropin ligand. The iodiation of human chorionic gonadotropin and the counting efficiency of /sup 125/I are discussed.

  18. Adrenocorticotropic hormone elicits gonadotropin secretion in premenopausal women

    J. Aleknavičiūtė (Jūratė); J.H.M. Tulen (Joke); Timmermans, M. (Mirjam); Y.B. de Rijke (Yolanda); E.F.C. van Rossum (Liesbeth); F.H. de Jong (Frank); S.A. Kushner (Steven)


    textabstractSTUDY QUESTION Does adrenocorticotropic hormone (ACTH) induce gonadotropin release in premenopausal women? SUMMARY ANSWER Administration of ACTH stimulates gonadotropin release, most likely by stimulation of the production of cortisol, in premenopausal women. WHAT IS KNOWN ALREADY In

  19. Purification of toad (Bufo japonicus) gonadotropins and development of their homologous radioimmunoassays

    Takada, Koji; Itoh, Masanori; Nishio, Hiroshi; Ishii, Susumu (Waseda Univ., Tokyo (Japan))


    We obtained three gonadotropin fractions with different electrophoretic mobilities named B1D, B3D and B5D from a glycoprotein fraction of toad (Bufo japonicus) pituitaries by cation exchange chromatography using the fast protein liquid chromatography (FPLC) system, chromatofocusing and gel filtration using the FPLC system. Gonadotropin activity was monitored by two radioreceptor assay (RRA) systems, one using bullfrog testis and bullfrog LH as the source of receptor and radioligand respectively, and the other using toad testis and bullfrog FSH respectively. Although, LH/FSH specificity was not complete in these RRAs, the fraction BID showed a higher potency in LH-RRA than in FSH-RRA, while B3D and B5D showed lower potencies in LH-RRA activity than in FSH-RRA. Furthermore, B1D had an activity to release androgen from the toad testis, while B3D and B5D had slight activities. All these fractions stimulated accumulation of cAMP in testis slices of the toad in vitro. These results suggest that B1D contains LH, and B3D and B5D contain FSH-like gonadotropin. SDS PAGE analysis in combination with immunoblot revealed that B1D was almost pure LH, but B3D seemed to be not homogeneous. Anti-B1D-serum and anti-B3D-serum were raised in rabbits, and radioimmunoassays (RIAs) for B1D and B3D were established. The cross reactivity of B3D and B5D in B1D-RIA was about 30% of B1D, while that of B1D in B3D-RIA was only 3% of B3D and B5D. These RIAs were sensitive enough to measure gonadotropins in plasma samples of Bufo japonicus. (author).

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

    Gemma Casadesus


    Full Text Available 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.

  1. MR imaging of pituitary dwarfism

    Kashimada, Akio; Machida, Kikuo; Honda, Norinari; Mamiya, Toshio; Takahashi, Taku; Kamano, Tsuyoshi; Muramatsu, Masayuki; Inoue, Yusuke (Saitama Medical School, Kawagoe (Japan). Medical Center)


    Pituitary MR imaging was performed in 32 patients with clinically diagnosed pituitary dwarfism and 12 normal controls. The patients were divided into two groups according to the severity of pituitary dwarfism based on endocrinological data. The two patients with severe dwarfism showed transection of the pituitary stalk, ectopic posterior lobe and atrophy of the anterior lobe on MR imaging, while the 27 patients with mild dwarfism showed no abnormal MR findings of the pituitary gland. The former group corresponds to typical pituitary dwarfism and the latter to partial GH deficiency, which was recently proposed as another type of pituitary dwarfism. In conclusion, pituitary MR imaging may differentiate partial GH deficiency from typical (stalk-transected) pituitary dwarfism. (author).

  2. Serum gonadotropins after gonadotropin-releasing hormone injection in bulls subjected to spacial restriction.

    Gwazdauskas, F C; Bindas, E M; Anderson, G W; McGilliard, M L


    Response patterns of luteinizing hormone, follicle-stimulating hormone, and testosterone after injection of gonadotropin-releasing hormone were investigated in bulls grouped by weight (250 to 459 kg body weight) and confined five per pen in 9.2 or 6.4 m2 space per bull in two replicates. Blood samples were collected for 1 h prior to injection of 100 micrograms gonadotropin releasing hormone and 5 h after injection at 15-min intervals. Overall mean luteinizing hormone concentrations were not affected by spacial restriction or replicate. Interaction of treatment by time revealed that luteinizing hormone response curves were not similar. Restricted bulls had a higher response of luteinizing hormone to gonadotropin-releasing hormone. Follicle-stimulating hormone increased in all groups within 15 min and peaked at 219.4 ng/ml at 45 min. Both gonadotropin responses returned to preinjection concentrations by 4 h. Testosterone was affected by treatment, replicate, and time of sampling. Testosterone was higher in restricted bulls and higher in replicate 2. Mean testosterone peak following gonadotropin-releasing hormone was 3.86 ng/ml and occurred between 105 and 120 min which was approximately 90 min after the gonadotropin peaks. It appears that hormone responses to gonadotropin-releasing hormone were not depressed by spacial restriction, and additional spacial restriction of young bulls could be used commercially.

  3. How to recognize the desensitization of pituitary-ovarian axis achieved by gonadotropin-releasing hormone analogue-induced down-regulation?%识别促性腺激素释放激素激动剂对垂体-卵巢轴降调节抑制程度及意义

    李洁; 刘倍余


    本文通过文献复习讨论促性腺激素释放激素激动剂(GnRH-a)联合促性腺激素(Gn)诱导排卵治疗方案对垂体卵巢轴的降调节作用及意义.广义的降调节作用包括:对血清促性腺激素:卵泡刺激素、黄体生成素(FSH、LH)水平、卵泡周期性发育和类固醇激素合成的影响.临床常见的垂体降调节程度包括过度抑制、部分抑制和未能达到抑制.过度抑制被认为是垂体卵巢轴完全静息状态所需要的,适用于性激素依赖性肿瘤或疾病的治疗.体外受精-胚胎移植(IVF-ET)治疗周期中仅需要达到部分垂体卵巢轴降调节,即保留进入周期募集的卵泡对促性腺激素的反应性和类固醇激素合成.未能达到抑制的垂体卵巢轴伴随着卵泡晚期早发LH峰的风险,与无降调节周期相似.GnRH-a对垂体卵巢轴的降调节作用不仅与其类型、半衰期和患者个体差异有关,并且呈现出剂量与使用时间的依赖性.大部分过度抑制效应的患者可以通过降低GnRH-a剂量逆转,恢复卵巢对外源促性腺激素的反应性.极少数妇女存在降调节的延迟反应,与LH受体变异和受体后缺陷有关.%The review is to discuss how to recognize the desensitization of the pituitary-ovarian axis after gonadotrophin-releasing hormone analogue (GnRH-a) administration, which includes hormone profile, oocytogenesis and steroidogenesis. The original down-regulation is defined as luteinizing hormone (LH) levels <5 U/L, the thickness of endometrium less than 5 mm and follicular diameter pituitary-ovarian axis could be reversed by reducing

  4. Restoration of dioxin-induced damage to fetal steroidogenesis and gonadotropin formation by maternal co-treatment with α-lipoic acid.

    Takayuki Koga

    Full Text Available 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, an endocrine disruptor, causes reproductive and developmental toxic effects in pups following maternal exposure in a number of animal models. Our previous studies have demonstrated that TCDD imprints sexual immaturity by suppressing the expression of fetal pituitary gonadotropins, the regulators of gonadal steroidogenesis. In the present study, we discovered that all TCDD-produced damage to fetal production of pituitary gonadotropins as well as testicular steroidogenesis can be repaired by co-treating pregnant rats with α-lipoic acid (LA, an obligate co-factor for intermediary metabolism including energy production. While LA also acts as an anti-oxidant, other anti-oxidants; i.e., ascorbic acid, butylated hydroxyanisole and edaravone, failed to exhibit any beneficial effects. Neither wasting syndrome nor CYP1A1 induction in the fetal brain caused through the activation of aryl hydrocarbon receptor (AhR could be attenuated by LA. These lines of evidence suggest that oxidative stress makes only a minor contribution to the TCDD-induced disorder of fetal steroidogenesis, and LA has a restorative effect by targeting on mechanism(s other than AhR activation. Following a metabolomic analysis, it was found that TCDD caused a more marked change in the hypothalamus, a pituitary regulator, than in the pituitary itself. Although the components of the tricarboxylic acid cycle and the ATP content of the fetal hypothalamus were significantly changed by TCDD, all these changes were again rectified by exogenous LA. We also provided evidence that the fetal hypothalamic content of endogenous LA is significantly reduced following maternal exposure to TCDD. Thus, the data obtained strongly suggest that TCDD reduces the expression of fetal pituitary gonadotropins to imprint sexual immaturity or disturb development by suppressing the level of LA, one of the key players serving energy production.

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

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


    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.

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

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


    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.

  7. General Information about Pituitary Tumors

    ... Tumors Treatment Pituitary Tumors Treatment (PDQ®)–Patient Version General Information About Pituitary Tumors Go to Health Professional ... by many other glands in the body. Enlarge Anatomy of the inside of the brain, showing the ...

  8. Pituitary Adenoma Segmentation

    Egger, Jan; Kuhnt, Daniela; Freisleben, Bernd; Nimsky, Christopher


    Sellar tumors are approximately 10-15% among all intracranial neoplasms. The most common sellar lesion is the pituitary adenoma. Manual segmentation is a time-consuming process that can be shortened by using adequate algorithms. In this contribution, we present a segmentation method for pituitary adenoma. The method is based on an algorithm we developed recently in previous work where the novel segmentation scheme was successfully used for segmentation of glioblastoma multiforme and provided an average Dice Similarity Coefficient (DSC) of 77%. This scheme is used for automatic adenoma segmentation. In our experimental evaluation, neurosurgeons with strong experiences in the treatment of pituitary adenoma performed manual slice-by-slice segmentation of 10 magnetic resonance imaging (MRI) cases. Afterwards, the segmentations were compared with the segmentation results of the proposed method via the DSC. The average DSC for all data sets was 77.49% +/- 4.52%. Compared with a manual segmentation that took, on the...

  9. Bone phenotypes in response to gonadotropin misexpression: the role for gonadotropins in postmenopausal osteoporosis

    Mansell, Jason


    Jason P MansellDepartment of Oral and Dental Sciences, Division of Oral Medicine, University of Bristol Dental School, Lower Maudlin Street, Bristol, BS1 2LY, UKAbstract: Scant attention has been paid to the potential role of gonadotropins in bone tissue homeostasis. The focus on estrogen and estrogen replacement therapy for osteoporosis as far back as the 1940’s may account for the paucity of gonadotropin studies in bone biology. It is conceivable that prevailing dogma may have sub...

  10. Pituitary stalk interruption syndrome in Chinese people: clinical characteristic analysis of 55 cases.

    Qinghua Guo

    Full Text Available OBJECTIVE: Pituitary stalk interruption syndrome (PSIS is characterized by the absence of pituitary stalk, pituitary hypoplasia, and ectopic posterior pituitary. Due to the rarity of PSIS, clinical data are limited, especially in Chinese people. Herein, we analyzed the clinical characteristics of patients diagnosed with PSIS from our center over 10 years. PATIENTS AND METHODS: We retrospectively analyzed the clinical manifestations and laboratory and MRI findings in 55 patients with PSIS. RESULTS: Of the 55 patients with PSIS, 48 (87.3% were male. The average age was 19.7±6.7 years and there was no familial case. A history of breech delivery was documented in 40 of 45 patients (88.9% and 19 of 55 patients (34.5% had a history of dystocia. Short stature was found in 47 of 55 patients (85.5% and bone age delayed 7.26±5.37 years. Secondary sex characteristics were poor or undeveloped in most patients. The prevalence of deficiencies in growth hormone, gonadotropins, corticotropin, and thyrotropin were 100%, 95.8%, 81.8%, 76.3%, respectively. Hyperprolactinemia was found in 36.4% of patients. Three or more pituitary hormone deficiencies were found in 92.7% of the patients. All patients had normal posterior pituitary function and absent pituitary stalk on imaging. The average height of anterior pituitary was 28 mm, documented anterior pituitary hypoplasia. Midline abnormalities were presented in 9.1% of patients. CONCLUSIONS: The clinical features of our Chinese PSIS patients seem to be different from other reported patients in regarding to the higher degree of hypopituitarism and lower prevalence of midline defects. In addition, our patients were older at the time of case detection and the bone age was markedly delayed. We also had no cases of familial PSIS.

  11. Evaluating the ovarian cancer gonadotropin hypothesis

    Lee, Alice W; Tyrer, Jonathan P; Doherty, Jennifer A


    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 o...

  12. Regulation of gonadotropin receptor gene expression

    A.P.N. Themmen (Axel); R. Kraaij (Robert); J.A. Grootegoed (Anton)


    textabstractThe receptors for the gonadotropins differ from the other G protein-coupled receptors by having a large extracellular hormone-binding domain, encoded by nine or ten exons. Alternative splicing of the large pre-mRNA of approximately 100 kb can result in mRNA species that encode truncated

  13. Review: Regulatory mechanisms of gonadotropin-inhibitory hormone (GnIH synthesis and release in photoperiodic animals

    Kazuyoshi eTsutsui


    Full Text Available Gonadotropin-inhibitory hormone (GnIH is a novel hypothalamic neuropeptide that was discovered in quail as an inhibitory factor for gonadotropin release. GnIH inhibits gonadotropin synthesis and release in birds through actions on gonadotropin-releasing hormone (GnRH neurons and gonadotropes, mediated via the GnIH receptor (GnIH-R, GPR147. Subsequently, GnIH was identified in mammals and other vertebrates. As in birds, mammalian GnIH inhibits gonadotropin secretion, indicating a conserved role for this neuropeptide in the control of the hypothalamic-pituitary-gonadal (HPG axis across species. Identification of the regulatory mechanisms governing GnIH expression and release is important in understanding the physiological role of the GnIH system. A nocturnal hormone, melatonin, appears to act directly on GnIH neurons through its receptor to induce expression and release of GnIH in quail, a photoperiodic bird. Recently, a similar, but opposite, action of melatonin on the inhibition of expression of mammalian GnIH was shown in hamsters and sheep, photoperiodic mammals. These results in photoperiodic animals demonstrate that GnIH expression is photoperiodically modulated via a melatonin-dependent process. Recent findings indicate that GnIH may be a mediator of stress-induced reproductive disruption in birds and mammals, pointing to a broad role for this neuropeptide in assessing physiological state and modifying reproductive effort accordingly. This paper summarizes the advances made in our knowledge regarding the regulation of GnIH synthesis and release in photoperiodic birds and mammals. This paper also discusses the neuroendocrine integration of environmental signals, such as photoperiods and stress, and internal signals, such as GnIH, melatonin and glucocorticoids, to control avian and mammalian reproduction.

  14. Polymorphism of gonadotropin action: clinical implications



    It has recently became apparent that the structural heterogeneity of gonadotropin molecules can contribute to variations of their action in different physiological and pathophysiological conditions. One reason for the structural variations of circulating gonadotropin molecules is the rnicroheterogeneity caused by the variability of glycosylation of individual gonadotropin molecules. The carbohydrate moieties of gonadotropins are important for their intrinsic bioactivity, as reflected by measurement of their bioactivity to immunoreactivity (B/I) ratios. We have reassessed this phenomenon by improved in vitro bioassay and immunoassay methods, and it appears that the intrinsic bioactivity of gonadotropins, in particular of LH, is more constant than previously assumed. Many of the previously documented differences, some even considered diagnostic for certain clinical conditions, have turned out to be methodological artifacts. The first part of this review summarizes our recent findings on the B/I ratios of LH, with special reference to the male. The second part of this review describes a common polymorphism that was recently discovered in the gene of the LH β-subtmit. The variant LHβ allele contains two point mutations, which introduce to LH two amino acid changes and an extra glycosylation site. The LH variant is common world-wide, with carrier frequency varying from 0 to 52% in various ethnic groups. The LH variant differs functionally from wild-type LH, and it seems to predispose its carriers,both men and women, to mild aberrations of reproductive function. It is important for the clinician to be aware of this variant LH form, not detected by all immunoassays, because it may explain some aberrant results of LH measurements in patient samples. (Asian J Androl 2000 Dec;2:241-246)

  15. Diagnosis and treatment of pituitary adenomas.

    Chanson, P; Salenave, S


    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

  16. Molecular Imaging of Pituitary Pathology.

    de Herder, Wouter W


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

  17. Pituitary adenoma: a radiotherapeutic perspective.

    Platta, Christopher S; Mackay, Christopher; Welsh, James S


    Pituitary adenomas comprise approximately 10% to 20% of all central nervous system neoplasms whereas autopsy series have suggested that the incidence of pituitary adenoma in the general population may approach 25%. Several treatment modalities are used in the treatment of pituitary adenomas, including observation, surgery, medical intervention, and radiotherapy. The treatment modality employed depends greatly on the type of pituitary adenoma and presenting symptoms. This review will discuss the biology of pituitary adenomas and the current management principles for the treatment of prolactinomas, Cushing disease, acromegaly, and nonsecretory adenomas, with an emphasis on the published radiotherapeutic literature.




    Full Text Available Pituitary apoplexy is an acute clinical condition characterized by sudden onset of headache, vomiting, visual disturbance, ophthalmoplegia and altered sensorium occurring due to infarction or haemorrhage of pituitary gland and often involving the pituita ry adenoma. Predominantly seen in non - functional adenomas and in functioning adenomas with prolactinomas having the highest risk. Patients usually present with headache, vomiting, altered sensorium, visual defect and/or endocrine dysfunction. Hemodynamic i nstability may result from adrenocorticotrophic hormone deficiency. Imaging with either CT scan or MRI is performed in suspected cases. On CT, a recent hemorrhage appears as a single or multiple hyperdense lesions with no or little contrast enhancement. MR I is useful in estimating the onset of bleeding and to show the relationship between the tumor and the surrounding structures. CT or MR Angiography is done to rule out aneurysm. Treatment is conservative and surgery is reserved for those cases with deterio rating level of consciousness or increasing visual defect. Here we present a 47 year old male who presented with history of headache and visual disturbances for 6 weeks and was evaluated with radiograph, CT and MRI. A 47 year old male patient presented to the Neurosurgical Department of Vydehi Medical College and Research Centre with history of gradual blurring of vision in the left eye for 2 months. History of diabetes or hypertension was present. The man was hemodynamically stable. Radiograph of the skull showed widening of sella with erosion of the floor. He was advised CT. CT showed widening of sella and a pituitary lesion with fluid level. MRI was advocated for further evaluation. MRI axial and coronal showed sellar and suprasellar mass with figure of e ight appearance mass suggesting pituitary mass. Hyper intense fluid level was seen suggesting bleed within the mass. Contrast MRI showed peripheral enhancement. Diagnosis of

  19. Intraovarian expression of GnRH-1 and gonadotropin mRNA and protein levels in Siberian hamsters during the estrus cycle and photoperiod induced regression/recrudescence.

    Shahed, Asha; Young, Kelly A


    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 14 weeks of LD, short days (SD;8L:16D), or 8 weeks post-transfer to LD after 14 weeks 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). 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.

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

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


    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

  1. Identification of human GnIH homologs, RFRP-1 and RFRP-3, and the cognate receptor, GPR147 in the human hypothalamic pituitary axis.

    Takayoshi Ubuka

    Full Text Available The existence of a hypothalamic gonadotropin-inhibiting system has been elusive. A neuropeptide named gonadotropin-inhibitory hormone (GnIH, SIKPSAYLPLRF-NH(2 which directly inhibits gonadotropin synthesis and release from the pituitary was recently identified in quail hypothalamus. Here we identify GnIH homologs in the human hypothalamus and characterize their distribution and biological activity. GnIH homologs were isolated from the human hypothalamus by immunoaffinity purification, and then identified as MPHSFANLPLRF-NH(2 (human RFRP-1 and VPNLPQRF-NH(2 (human RFRP-3 by mass spectrometry. Immunocytochemistry revealed GnIH-immunoreactive neuronal cell bodies in the dorsomedial region of the hypothalamus with axonal projections to GnRH neurons in the preoptic area as well as to the median eminence. RT-PCR and subsequent DNA sequencing of the PCR products identified human GnIH receptor (GPR147 mRNA expression in the hypothalamus as well as in the pituitary. In situ hybridization further identified the expression of GPR147 mRNA in luteinizing hormone producing cells (gonadotropes. Human RFRP-3 has recently been shown to be a potent inhibitor of gonadotropin secretion in cultured sheep pituitary cells by inhibiting Ca(2+ mobilization. It also directly modulates GnRH neuron firing. The identification of two forms of GnIH (RFRP-1 and RFRP-3 in the human hypothalamus which targets human GnRH neurons and gonadotropes and potently inhibit gonadotropin in sheep models provides a new paradigm for the regulation of hypothalamic-pituitary-gonadal axis in man and a novel means for manipulating reproductive functions.

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

    Mantovani, Giovanna; Spada, Anna


    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.

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

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


    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.

  4. Non-pituitary origin sellar tumours mimicking pituitary macroadenomas

    Abele, T.A., E-mail: [University of Texas Southwestern Medical Center at Dallas, Dallas, TX (United States); Yetkin, Z.F.; Raisanen, J.M.; Mickey, B.E.; Mendelsohn, D.B. [University of Texas Southwestern Medical Center at Dallas, Dallas, TX (United States)


    Although the large majority of sellar tumours are pituitary adenomas, several other pituitary and non-pituitary origin tumours arise in the sellar and parasellar regions. Given their location, non-adenomatous lesions frequently mimic pituitary macroadenomas and can pose a diagnostic challenge for the radiologist. Distinguishing rare sellar lesions from the common macroadenoma helps to direct the correct surgical approach and reduce the risk of incomplete resection and/or complications such as cerebrospinal fluid leak with the potential for meningitis. The purpose of this article is to review the imaging features of non-pituitary-origin sellar tumours, focusing on characteristics that may distinguish them from pituitary macroadenomas. Lesions include meningioma, metastatic disease, epidermoid cyst, germinoma, chondrosarcoma, giant cell tumour, and giant aneurysm.

  5. Negative feedback governs gonadotrope frequency-decoding of gonadotropin releasing hormone pulse-frequency.

    Stefan Lim

    Full Text Available The synthesis of the gonadotropin subunits is directed by pulsatile gonadotropin-releasing hormone (GnRH from the hypothalamus, with the frequency of GnRH pulses governing the differential expression of the common alpha-subunit, luteinizing hormone beta-subunit (LHbeta and follicle-stimulating hormone beta-subunit (FSHbeta. Three mitogen-activated protein kinases, (MAPKs, ERK1/2, JNK and p38, contribute uniquely and combinatorially to the expression of each of these subunit genes. In this study, using both experimental and computational methods, we found that dual specificity phosphatase regulation of the activity of the three MAPKs through negative feedback is required, and forms the basis for decoding the frequency of pulsatile GnRH. A fourth MAPK, ERK5, was shown also to be activated by GnRH. ERK5 was found to stimulate FSHbeta promoter activity and to increase FSHbeta mRNA levels, as well as enhancing its preference for low GnRH pulse frequencies. The latter is achieved through boosting the ultrasensitive behavior of FSHbeta gene expression by increasing the number of MAPK dependencies, and through modulating the feedforward effects of JNK activation on the GnRH receptor (GnRH-R. Our findings contribute to understanding the role of changing GnRH pulse-frequency in controlling transcription of the pituitary gonadotropins, which comprises a crucial aspect in regulating reproduction. Pulsatile stimuli and oscillating signals are integral to many biological processes, and elucidation of the mechanisms through which the pulsatility is decoded explains how the same stimulant can lead to various outcomes in a single cell.

  6. Negative feedback governs gonadotrope frequency-decoding of gonadotropin releasing hormone pulse-frequency.

    Lim, Stefan; Pnueli, Lilach; Tan, Jing Hui; Naor, Zvi; Rajagopal, Gunaretnam; Melamed, Philippa


    The synthesis of the gonadotropin subunits is directed by pulsatile gonadotropin-releasing hormone (GnRH) from the hypothalamus, with the frequency of GnRH pulses governing the differential expression of the common alpha-subunit, luteinizing hormone beta-subunit (LHbeta) and follicle-stimulating hormone beta-subunit (FSHbeta). Three mitogen-activated protein kinases, (MAPKs), ERK1/2, JNK and p38, contribute uniquely and combinatorially to the expression of each of these subunit genes. In this study, using both experimental and computational methods, we found that dual specificity phosphatase regulation of the activity of the three MAPKs through negative feedback is required, and forms the basis for decoding the frequency of pulsatile GnRH. A fourth MAPK, ERK5, was shown also to be activated by GnRH. ERK5 was found to stimulate FSHbeta promoter activity and to increase FSHbeta mRNA levels, as well as enhancing its preference for low GnRH pulse frequencies. The latter is achieved through boosting the ultrasensitive behavior of FSHbeta gene expression by increasing the number of MAPK dependencies, and through modulating the feedforward effects of JNK activation on the GnRH receptor (GnRH-R). Our findings contribute to understanding the role of changing GnRH pulse-frequency in controlling transcription of the pituitary gonadotropins, which comprises a crucial aspect in regulating reproduction. Pulsatile stimuli and oscillating signals are integral to many biological processes, and elucidation of the mechanisms through which the pulsatility is decoded explains how the same stimulant can lead to various outcomes in a single cell.

  7. Metastatic pituitary carcinoma: a case report and review of literature

    ZHANG Shang-fu


    Full Text Available Background As a kind of rare tumor, metastatic pituitary carcinoma is very difficult to diagnose clinically and is easy to be misdiagnosed. This article aims to discuss the clinical manifestations and histopathological features of this tumor. Methods The clinical presentations, histopathological features and immunophenotype were studied in one case of poorly differentiated lung adenocarcinoma metastatic to pituitary gland, and related literature was reviewed. Results A 47-year-old woman mainly presented with faint, headache and blurred vision. CT scan demonstrated abnormal signals in suprasellar cistern. During the resection, the tumor could be seen locating in sellar region, the size of which was about 2 cm × 1 cm × 1 cm. Histopathological examination revealed that the structure of pituitary gland was damaged and the tumor was composed of atypical round or oval cells arranged in nest or glandular patterns, in which a number of enlarged plump tumor cells contained abundant eosinophilic cytoplasm with eccentrical caryogenesis. The immunohistochemistry showed that epithelial membrane antigen (EMA, pan cytokeratin (PCK, thyroid transcription factor-1 (TTF-1 and cytokeratin 7 (CK7 were positive in tumor cells with Ki-67 labeling index being 15%, but chromogranin (CgA, cancer embryo antigen (CEA, human chorionic gonadotropin (hCG, placental alkaline phosphatase (PLAP, CD117, leukocyte common antigen (LCA, CD30, anaplastic lymphoma kinase-1 (ALK-1 were negative in tumor cells. After operation the patient received treatment with levothyroxine sodium and γ knife, but died 4 months later. Conclusion Histopathological examination and immunohistochemistry can confirm the diagnosis of metastatic pituitary carcinoma and locate the primary lesion. Postoperative comprehensive therapy is necessary.

  8. Hypothalamic-pituitary-gonadotropic function in girls with premature thelarche.

    Pasquino, A M; Piccolo, F; Scalamandre, A; Malvaso, M; Ortolani, R; Boscherini, B


    Hypothalamic-pituitary-gonadotropic activity was investigated in 9 girls with premature thelarche, and compared with that in 9 healthy girls and 6 girls with true precocious puberty. The gonadotropin stimulation test with luteinising hormone-releasing hormone was used. Girls with premature thelarche showed luteinising hormone response resembling that of normal girls, and follicle-stimulating hormone (FSH) response quite similar to that of girls with precocious puberty. This suggests that in premature thelarche there is a partial activation of the diencephalic-hypophyseal-gonadal axis, which affects FSH only. Premature thelarche therefore, should be considered as one of the disorders due to altered sensitivity of the hypothalamic receptors which regulate sex maturation. PMID:6779715

  9. Familial pituitary adenomas.

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


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

  10. Histopathologic changes of hypothalamus and pituitary in a rat model of polycystic ovary syndrome

    Jiang Yan; Meng Fan-yu; Hu Zhen-hua; Liu Fang


    Objective: To investigate the histopathologic changes of hypothalamus and pituitary in a rat model of polycystic ovary syndrome (PCOS).Methods: Rat model of PCOS was established in 6 immature female SD rats and another 6 immature rats treated with placebo were as control. The tissues of hypothalamus and pituitary were obtained and observed by light microscope and transmission electron microscope.Results: Light microscopy revealed little difference in morphology of neurons in arcuate nucleus or basophilic cells in pituitary between PCOS rats and normal rats. Electron microscopic examination showed that, compared with those in normal rats, GnRH neurons in PCOS rats were larger and fuller, with Golgi complex and mitochondria increased. The mitochondria were small, round and swelling. More high-density secretory granules and bright vesicles were observed in the cytoplasm. The Golgi complex near nucleus in pituitary gonadotropin cell in PCOS rats was fractured and expanded, and there were increased number mitochondria and different sizes of the higher electron density secretory granules in the cytoplasm. Conclusion: The morphological alterations in hypothalamus and pituitary could play a very important role in the development of PCOS.

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

    Holley, Jean L


    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.

  12. Primary hypothyroidism masquerading pituitary macroadenoma

    Agrawal Amit


    Full Text Available Diffuse and reactive pituitary gland enlargement secondary to primary hypothyroidism is an uncommon occurrence and that can masquerade many pituitary disorders. In present article, we report a case of 19 year female severe hypothyroidism presenting with diffuse enlargement of pituitary gland and hyperprolactinemia and review the clinical importance of this entity. Knowledge of this entity is very important to avoid unnecessary surgery and irreversible complications in this sub-group of patients.

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

    Silvia eLeon


    Full Text Available 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 neuro-secretion, 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 homologue, 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.

  14. Pituitary gland tumors; Hypophysentumoren

    Jesser, J.; Schlamp, K.; Bendszus, M. [Radiologische Klinik, Universitaetsklinikum Heidelberg, Abteilung fuer Neuroradiologie, Heidelberg (Germany)


    This article gives an overview of the most common tumors of the pituitary gland and the differential diagnostics with special emphasis on radiological diagnostic criteria. A selective search of the literature in PubMed was carried out. Pituitary adenomas constitute 10-15 % of all intracranial tumors and are the most common tumors of the sellar region. Tumors smaller than 1 cm in diameter are called microadenomas while those larger than 1 cm in diameter are called macroadenomas. Approximately 65 % of pituitary gland adenomas secrete hormones whereby approximately 50 % secrete prolactin, 10 % secrete growth hormone (somatotropin) and 6 % secrete corticotropin. Other tumors located in the sella turcica can also cause endocrinological symptoms, such as an oversecretion of pituitary hormone or pituitary insufficiency by impinging on the pituitary gland or its stalk. When tumors spread into the space cranial to the sella turcica, they can impinge on the optic chiasm and cause visual disorders. A common differential diagnosis of a sellar tumor is a craniopharyngeoma. In children up to 10 % of all intracranial tumors are craniopharyngeomas. Other differential diagnoses for sellar tumors are metastases, meningiomas, epidermoids and in rare cases astrocytomas, germinomas or Rathke cleft cysts As these tumors are located in an anatomically complex region of the skull base and are often very small, a highly focused imaging protocol is required. The currently favored modality is magnetic resonance imaging (MRI) with the administration of a contrast agent. The sellar region should be mapped in thin slices. In cases of suspected microadenoma the imaging protocol should also contain a sequence with dynamic contrast administration in order to assess the specific enhancement characteristics of the tumor and the pituitary gland. (orig.) [German] Diese Arbeit ist eine Uebersicht ueber die haeufigsten Hypophysentumoren und deren Differenzialdiagnosen mit Augenmerk auf die

  15. MR findings in pituitary haemosiderosis

    Ambrosetto, P. [Institute of Neurology, University of Bologna, Bologna (Italy); Zucchini, S.; Cicognani, A. [First Paediatric Clinic, University of Bologna, Bologna (Italy); Cacciari, E. [First Paediatric Clinic, University of Bologna, Bologna (Italy)]|[Clinica Pediatrica 1, Bologna (Italy)


    A girl with Diamond-Blackfan syndrome and hypopituitarism was suspected of having pituitary haemosiderosis because of the clinical picture and the long history of blood transfusions. On T1-weighted MR images the pituitary exhibited a markedly hypointense anterior lobe (mimicking the empty sella), suggesting iron deposition, while on T2W MRI the low signal of the pituitary was surrounded by the high signal of the CSF. MR may be considered the examination of choice for detecting iron overload in the pituitary. (orig.) With 2 figs., 6 refs.

  16. Is the infertility in hypothyroidism mainly due to ovarian or pituitary functional changes?

    Armada-Dias L.


    Full Text Available The objective of the present study was to examine whether hypothyroidism affects the reproductive system of adult female rats by evaluating ovarian morphology, uterus weight and the changes in serum and pituitary concentrations of prolactin and gonadotropins. Three-month-old female rats were divided into three groups: control (N = 10, hypothyroid (N = 10, treated with 0.05% 6-propyl-2-thiouracil (PTU in drinking water for 60 days, and T4-treated group (N = 10, receiving daily sc injections of L-thyroxine (0.8 µg/100 g body weight during the last 10 days of the experiment. At the end of 50 days of hypothyroidism no hypothyroid animal showed a regular cycle, while 71% of controls as well as the T4-treated rats showed regular cycles. Corpora lutea, growing follicles and mature Graafian follicles were found in all ovaries studied. The corpora lutea were smaller in both the hypothyroid and T4-replaced rats. Graafian follicles were found in 72% of controls and only in 34% of hypothyroid and 43% of T4-treated animals. Serum LH, FSH, progesterone and estradiol concentrations did not differ among the three groups. Serum prolactin concentration and the pituitary content of the three hormones studied were higher in the hypothyroid animals compared to control. T4 treatment restored serum prolactin concentration to the level found in controls, but only partially normalized the pituitary content of gonadotropins and prolactin. In conclusion, the morphological changes caused by hypothyroidism can be a consequence of higher prolactin production that can block the secretion and action of gonadotropins, being the main cause of the changes observed.

  17. Is the infertility in hypothyroidism mainly due to ovarian or pituitary functional changes?

    L. Armada-Dias


    Full Text Available The objective of the present study was to examine whether hypothyroidism affects the reproductive system of adult female rats by evaluating ovarian morphology, uterus weight and the changes in serum and pituitary concentrations of prolactin and gonadotropins. Three-month-old female rats were divided into three groups: control (N = 10, hypothyroid (N = 10, treated with 0.05% 6-propyl-2-thiouracil (PTU in drinking water for 60 days, and T4-treated group (N = 10, receiving daily sc injections of L-thyroxine (0.8 µg/100 g body weight during the last 10 days of the experiment. At the end of 50 days of hypothyroidism no hypothyroid animal showed a regular cycle, while 71% of controls as well as the T4-treated rats showed regular cycles. Corpora lutea, growing follicles and mature Graafian follicles were found in all ovaries studied. The corpora lutea were smaller in both the hypothyroid and T4-replaced rats. Graafian follicles were found in 72% of controls and only in 34% of hypothyroid and 43% of T4-treated animals. Serum LH, FSH, progesterone and estradiol concentrations did not differ among the three groups. Serum prolactin concentration and the pituitary content of the three hormones studied were higher in the hypothyroid animals compared to control. T4 treatment restored serum prolactin concentration to the level found in controls, but only partially normalized the pituitary content of gonadotropins and prolactin. In conclusion, the morphological changes caused by hypothyroidism can be a consequence of higher prolactin production that can block the secretion and action of gonadotropins, being the main cause of the changes observed.

  18. The pathophysiology of pituitary adenomas.

    Dworakowska, Dorota; Grossman, Ashley B


    The pathogenesis of tumour formation in the anterior pituitary has been intensively studied, but the causative mechanisms involved in pituitary cell transformation and tumourigenesis remain elusive. Most pituitary tumours are sporadic, but some arise as a component of genetic syndromes such as the McCune-Albright syndrome, multiple endocrine neoplasia type 1, Carney complex and, the most recently described, a MEN1-like phenotype (MEN4) and pituitary adenoma predisposition syndromes. Some specific genes have been identified that predispose to pituitary neoplasia (GNAS, MEN1, PRKAR1A, CDKN1B and AIP), but these are rarely involved in the pathogenesis of sporadic tumours. Mutations of tumour suppressor genes or oncogenes, as seen in more common cancers, do not seem to play an important role in the great majority of pituitary adenomas. The pituitary tumour transforming gene (PTTG; securin) was the first transforming gene found to be highly expressed in pituitary tumour cells, and seems to play an important role in the process of oncogenesis. Many tumour suppressor genes, especially those involved in the regulation of the cell cycle, are under-expressed, most often by epigenetic modulation - usually promoter hypermethylation - but the regulator of these co-ordinated series of methylations is also unclear. Cell signalling abnormalities have been identified in pituitary tumours, but their genetic basis is unknown. Both Raf/MEK/ERK and PI3K/Akt/mTOR pathways are over-expressed and/or over-activated in pituitary tumours: these pathways share a common root, including initial activation related to the tyrosine kinase receptor, and we speculate that a change to these receptors or their relationship to membrane matrix-related proteins may be an early event in pituitary tumourigenesis.

  19. Expression and Activation of Gonadotropin Receptors

    R. Kraaij (Robert)


    textabstractAmong the many hormones that are produced by the anterior pituitary gland, luteinizing hormone (LH, lutropin), follicle-stimulating hormone (FSH, follitropin), and thyroidstimulating hormone (TSH, thyrotropin) form the separate family of so-called glycoprotein hormones (reviewed by Ohari

  20. Intrasellar pituitary mucocele: diagnostic dilemma.

    Tang, Ing Ping; Chai, Chun Kian; Kumar, Gnana; Prepageran, Narayanan; Waran, Vicknes


    Isolated intrasellar pituitary mucocele following transsphenoidal sinus surgery is extremely rare. The clinical features resemble a pituitary tumor, therefore careful radiological interpretation is crucial to reach the correct diagnosis. We report a case of intrasellar mucocele who had transsphenoidal sinus surgery performed 15 years prior.

  1. Endometrioid Endometrial Carcinoma Indirectly Caused by Pituitary Prolactinoma:A Case Report

    Kimihiro Nishino


    Full Text Available We present the case of a 44-year-old nulliparous woman who experienced irregular menstrual cycles for about 10 years and developed both pituitary prolactinoma and endometrioid endometrial carcinoma. In premenopausal women, hyperprolactinemia causes hypogonadism by inhibiting secretion of gonadotropin-releasing hormone and thus suppressing luteinizing hormone levels, which can cause menstrual disorders ranging from amenorrhea, oligomenorrhea and chronic anovulatory cycle to short luteal phase of the menstrual cycle. A chronic anovulatory menstrual cycle is the most common cause of long-term exposure of the endometrium to endogenous estrogen without adequate opposition from progestins, which can lead to endometrioid endometrial carcinoma. In this case, pituitary prolactinoma may have caused the chronic anovulatory cycle and indirectly led to the endometrioid endometrial carcinoma. In patients for whom the cause of irregular menstruation and chronic anovulatory cycle is suspected to be hyperprolactinemia, explorations of both the hypophysis and endometrium are essential.

  2. Endometrioid endometrial carcinoma indirectly caused by pituitary prolactinoma: a case report.

    Nishino, Kimihiro; Niwa, Yuri; Mizutani, Teruyuki; Shimizu, Ken; Hayashi, Kazumasa; Chaya, Jyunya; Kato, Noriko; Yamamuro, Osamu


    We present the case of a 44-year-old nulliparous woman who experienced irregular menstrual cycles for about 10 years and developed both pituitary prolactinoma and endometrioid endometrial carcinoma. In premenopausal women, hyperprolactinemia causes hypogonadism by inhibiting secretion of gonadotropin-releasing hormone and thus suppressing luteinizing hormone levels, which can cause menstrual disorders ranging from amenorrhea, oligomenorrhea and chronic anovulatory cycle to short luteal phase of the menstrual cycle. A chronic anovulatory menstrual cycle is the most common cause of long-term exposure of the endometrium to endogenous estrogen without adequate opposition from progestins, which can lead to endometrioid endometrial carcinoma. In this case, pituitary prolactinoma may have caused the chronic anovulatory cycle and indirectly led to the endometrioid endometrial carcinoma. In patients for whom the cause of irregular menstruation and chronic anovulatory cycle is suspected to be hyperprolactinemia, explorations of both the hypophysis and endometrium are essential.

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

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


    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.

  4. Direct regulation of gonadotropin release by neurokinin B in tilapia (Oreochromis niloticus).

    Biran, Jakob; Golan, Matan; Mizrahi, Naama; Ogawa, Satoshi; Parhar, Ishwar S; Levavi-Sivan, Berta


    Neurokinin B (NKB) was recently identified as a key regulator of reproduction in mammals and fish. Fish were found to possess a specific novel neurokinin termed NKF. To study the role of NKB/NKF in the regulation of fish reproduction and to investigate the role of NKB/NKF and their receptors in the piscine pituitary, we have identified the NKB/tachikinin 3 receptor (tac3r) system in tilapia. Bioinformatics and phylogenetic analyses have demonstrated that the tilapia holds 1 putative tac3 gene and 2 NKB receptor genes (tac3ra and tac3rb) that clustered with other piscine Tac3 and NKB receptor lineages. Furthermore, we found that in African cichlids, NKB peptides differ from other vertebrate NKBs in their C-terminal sequence, possessing isoleucine instead of valine as the X in the NKB FXGLM-NH2-terminal consensus sequence. Signal transduction analysis demonstrated that tilapia NKB (tiNKB), tiNKF, and human NKB activated both CRE-luc and SRE-luc transcriptional activity of both tilapia and human NKB receptors. Two hours after ip injection of tiNKB, the plasma levels of both FSH and LH were increased, whereas tiNKF was more effective in increasing LH levels. However, tiNKB was more effective than tiNKF in increasing both FSH and LH from tilapia pituitary dispersed cells. Using in situ hybridization and fluorescent immunohistochemistry, we have shown that LH cells possess tac3, tac3ra, and tac3rb mRNAs, whereas FSH cells possess mainly tac3rb and tac3ra and tac3 to a much lesser extent. These results suggest that the members of the NKB/tac3r system may serve as paracrine/autocrine regulators of gonadotropin release in fish pituitary.

  5. Shift of the pituitary stalk in intrasellar pituitary adenomas

    Ito, Jusuke; Tokiguchi, Susumu; Nakamori, Akitoshi (Niigata Univ. (Japan). School of Medicine); Watanabe, Akira; Yokoyama, Motoharu


    Fifty-one patients from a group of 344 patients undergoing the evaluation of intrasellar or parasellar tumors were diagnosed on CT as having an intrasellar pituitary adenoma. Axial transverse sections were performed at -10/sup 0/ to Reid's basal line, using 1.5-mm-thick slices and sagittal and coronal reformation. Of these 51 patients, 17 showed a shift of the pituitary stalk. The area where a tumor was thought to be located within the sella turcica on preoperative CT became defective on CT after transsphenoidal surgery in all cases. Histological verification was obtained in all cases. Also, the shift of the pituitary stalk was normalized or markedly improved after surgery in all cases. In functioning tumors, all cases except two showed an endocrinologically normal state or a marked improvement after transsphenoidal surgery. On the basis of the above-mentioned facts, it was concluded that the shift of the pituitary stalk in intrasellar pituitary adenomas indicated the evidence of a mass and its location in the sella turcica. However, a shift of the pituitary stalk was also observed under other conditions, such as empty sella and tuberculum sellae meningioma, and so it is not a pathognomonic finding in intrasellar pituitary adenomas.

  6. Gonadotropin-releasing hormone in the ovary.

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


    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.

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

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


    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

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

    Pradip P Dalwadi


    Full Text Available 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

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

    Christina Göngrich


    Full Text Available 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.

  10. Dural enhancement in pituitary macroadenomas

    Cattin, F. [Dept. of Neuroradiology, University Hospital of Besancon (France); Dept. of Neuroradiology, Jean Minjoz Hospital, Besancon (France); Bonneville, F.; Andrea, I.; Barrali, E.; Bonneville, J.F. [Dept. of Neuroradiology, University Hospital of Besancon (France)


    We describe the normal dural enhancement patterns of the sellar region and determine whether the duramater is affected by pituitary macroadenomas. Dural enhancement appeared to be usually abnormal in 20 patients with pituitary macroadenoma compared with 20 control patients, mainly at the planum sphenoidale and carotid sulcus. However dural changes are subtle and their recognition requires knowledge of the normal enhancement patterns. Dural changes, reported in a variety of inflammatory and infectious dural diseases and after surgery, are not specific and may be also seen in pituitary macroadenomas. (orig.)

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

    Wooge, C.H.


    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.

  12. Role of estrogen receptors (ERs and G protein-coupled estrogen receptor (GPER in regulation of hypothalamic-pituitary-testis axis and spermatogenesis

    Adele eChimento


    Full Text Available Male reproductive function is under the control of both gonadotropins and androgens through a negative feedback loop that involves the hypothalamus, pituitary and testis known as hypothalamus-pituitary-gonadal axis (HPG. Indeed, also estrogens play an important role in regulating HPG axis but the relative contribution to the inhibition of gonadotropins secretion exerted by the amount of estrogens produced within the hypothalamus and/or the pituitary or by the amount of circulating estrogens are still ongoing. Moreover, it is known that maintenance of spermatogenesis is controlled by gonadotrophins and testosterone, the effects of which are modulated by a complex network of locally produced factors, including estrogens. Physiological effects of estrogens are mediated by the classical nuclear estrogen receptor alpha (ESR1 and estrogen receptor beta (ESR2, which mediate both genomic and rapid signaling events. In addition, estrogens induce rapid non-genomic responses through a membrane-associated G protein-coupled receptor (GPER. Ours and other studies reported that, in the testis, GPER is expressed in both normal germ cells and somatic cells and it is involved in mediating the estrogen action in spermatogenesis controlling proliferative and/or apoptotic events. Interestingly, GPER expression has been revealed also in hypothalamus and in pituitary. However, its role in mediating estrogen rapid actions in this context is under investigation. Recent studies indicate that GPER is involved in modulating GnRH release as well as gonadotropins secretion. In this review, we will summarize the current knowledge concerning the role of estrogen/estrogen receptors (ERs molecular pathways in regulating GnRH, FSH and LH release at hypothalamic and pituitary level in male as well as in controlling specific testicular functions such as spermatogenesis, focusing our attention mainly on estrogen signaling mediated by GPER.

  13. Optimisation of an oviposition protocol employing human chorionic and pregnant mare serum gonadotropins in the Barred Frog Mixophyes fasciolatus (Myobatrachidae

    Clulow John


    Full Text Available Abstract Background Protocols for the hormonal induction of ovulation and oviposition are essential tools for managing threatened amphibians with assisted reproduction, but responses vary greatly between species and even broad taxon groups. Consequently, it is necessary to assess effectiveness of such protocols in representative species when new taxa become targets for induction. The threatened genus Mixophyes (family Myobatrachidae has amongst the highest proportion of endangered species of all the Australian amphibians. This study developed and optimised the induction of oviposition in a non-threatened member of this taxon, the great barred frog (Mixophyes fasciolatus. Methods Gravid female M. fasciolatus were induced to oviposit on one or more occasions by administration of human chorionic gonadotropin (hCG with or without priming with pregnant mare serum gonadotropin (PMSG. Treatments involved variations in hormone doses and combinations (administered via injection into the dorsal lymph sacs, and timing of administration. Pituitary homogenates from an unrelated bufonid species (Rhinella marina were also examined with hCG. Results When injected alone, hCG (900 to 1400 IU induced oviposition. However, priming with two time dependent doses of PMSG (50 IU, 25 IU increased responses, with lower doses of hCG (200 IU. Priming increased response rates in females from around 30% (hCG alone to more than 50% (p = 0.035, and up to 67%. Increasing the interval between the first PMSG dose and first hCG dose from 3 to 6 days also produced significant improvement (p Conclusions This study found that M. fasciolatus is amongst the few amphibian species (including Xenopus (Silurana and some bufonids that respond well to the induction of ovulation utilising mammalian gonadotropins (hCG. The optimal protocol for M. fasciolatus involved two priming doses of PMSG (50 IU and 25 IU administered at 6 and 4 days respectively, prior to two doses of hCG (100 IU, 24

  14. The role of kisspeptin and gonadotropin inhibitory hormone in the seasonal regulation of reproduction in sheep.

    Smith, J T


    Sheep are seasonal breeders, experiencing an annual period of reproductive quiescence in response to increased photoperiod during the late-winter into spring and renaissance during the late summer. The nonbreeding (anestrous) season is characterized by a reduction in the pulsatile secretion of GnRH from the brain, in part because of an increase in negative feedback activity of estrogen. Neuronal populations in the hypothalamus that produce kisspeptin and gonadotropin-inhibitory hormone (GnIH) appear to be important for the seasonal shift in reproductive activity, and the former are also mandatory for puberty onset. Kisspeptin cells in the arcuate nucleus (ARC) and preoptic area appear to regulate GnRH neurons and transmit sex-steroid feedback signals to these neurons. Moreover, kisspeptin expression in the ARC is markedly up-regulated at the onset of the breeding season, as too are the number of kisspeptin fibers in close apposition to GnRH neurons. The lower levels of kisspeptin seen during the nonbreeding season can be "corrected" by infusion of kisspeptin, which causes ovulation in seasonally acyclic females. The role of GnIH is less clear, but mounting evidence supports a role for this neuropeptide in the inhibitory regulation of both GnRH secretion and gonadotropin release from the pituitary gland. Contrary to kisspeptin, GnIH expression is markedly reduced at the onset of the breeding season. In addition, the number of GnIH fibers in close apposition to GnRH neurons also decreases during this time. Importantly, exogenous GnIH treatment can block both the pulsatile release of LH and the preovulatory LH surge during the breeding season. In summary, it is most likely the integrated function of both these neuropeptide systems that modulate the annual shift in photoperiod to a physiological change in fertility.

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

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


    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.

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

    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


    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.

  17. Prospective assessment of pituitary size and shape on MR imaging after suppressive hormonal therapy in central precocious puberty

    Beek, J.T. van; Sharafuddin, M.J.A.; Kao, S.C.S. [Department of Radiology-JPP 3889, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52246 (United States); Luisiri, A. [Cardinal Glennon Children' s Hospital, St. Louis, Missouri (United States); Garibaldi, L.R. [Children' s Hospital of New Jersey, Newark Beth Israel Medical Center, Newark, New Jersey (United States); St. Barnabas Medical Center, Livingston, New Jersey (United States)


    Objective. The diagnostic significance of an enlarged pituitary gland regarding both shape and size parameters on MR imaging has previously been demonstrated in children with central precocious puberty. This study was designed to assess changes in these parameters following successful suppressive therapy of central precocious puberty with the gonadotropin-releasing hormone (GnRH) analogue. Materials and methods. Twelve girls (mean age 7.3 years) with central precocious puberty were prospectively enrolled in our study protocol. Sagittal and coronal MR images of the pituitary region were obtained in all patients before treatment and after at least 6 months of GnRH analogue therapy (mean 18.0 months). Parameters measured included pituitary gland height, length, width, sagittal cross-sectional area, and volume. Results. All patients had excellent clinical response to treatment with arrest of secondary sexual development, normalization of serum estradiol levels, and complete obliteration of the LH response to diagnostic GnRH stimulation. No significant change occurred in any pituitary size or shape parameter following GnRH analogue therapy. Conclusion. Favorable clinical response to GnRH analogue therapy in central precocious puberty is not accompanied by significant a change in pituitary gland size and shape. (orig.)

  18. Pituitary glycoprotein hormone a-subunit secretion by cirrhotic patients

    Oliveira M.C.


    Full Text Available Secretion of the a-subunit of pituitary glycoprotein hormones usually follows the secretion of intact gonadotropins and is increased in gonadal failure and decreased in isolated gonadotropin deficiency. The aim of the present study was to determine the levels of the a-subunit in the serum of patients with cirrhosis of the liver and to compare the results obtained for eugonadal cirrhotic patients with those obtained for cirrhotic patients with hypogonadotropic hypogonadism. Forty-seven of 63 patients with cirrhosis (74.6% presented hypogonadism (which was central in 45 cases and primary in 2, 7 were eugonadal, and 9 women were in normal menopause. The serum a-subunit was measured by the fluorimetric method using monoclonal antibodies. Cross-reactivity with LH, TSH, FSH and hCG was 6.5, 1.2, 4.3 and 1.1%, respectively, with an intra-assay coefficient of variation (CV of less than 5% and an interassay CV of 5%, and sensitivity limit of 4 ng/l. The serum a-subunit concentration ranged from 36 to 6253 ng/l, with a median of 273 ng/l. The median was 251 ng/l for patients with central hypogonadism and 198 ng/l for eugonadal patients. The correlation between the a-subunit and basal LH levels was significant both in the total sample (r = 0.48, P<0.01 and in the cirrhotic patients with central hypogonadism (r = 0.33, P = 0.02. Among men with central hypogonadism there was a negative correlation between a-subunit levels and total testosterone levels (r = 0.54, P<0.01 as well as free testosterone levels (r = -0.53, P<0.01. In conclusion, although the a-subunit levels are correlated with LH levels, at present they cannot be used as markers for hypogonadism in patients with cirrhosis of the liver.

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

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


    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. Purification of pituitary autoantigen by column liquid chromatography and chromatofocusing

    Gut, Paweł; Fischbach, Jakub; Ziemnicka, Katarzyna; Bączyk, Maciej; Baszko-Błaszyk, Daria; Wrotkowska, Elżbieta; Ruchała, Marek


    Introduction Pituitary autoantibodies can be determined both in patients with pituitary disease as well as patients with autoimmune endocrine diseases. The purpose of the study was to isolate and purify pituitary autoantigen using sera of patients and the microsomal fraction of the pituitary. Material and methods To isolate a pituitary autoantigen, patient sera were used, which showed a strong immune response to pituitary antigens. Pituitary microsomal fractions were prepared from pituitary t...

  1. Delayed sequelae of pituitary irradiation

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


    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.

  2. Transcranial surgery for pituitary adenomas.

    Youssef, A Samy; Agazzi, Siviero; van Loveren, Harry R


    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.

  3. Stress increases putative gonadotropin inhibitory hormone and decreases luteinizing hormone in male rats.

    Kirby, Elizabeth D; Geraghty, Anna C; Ubuka, Takayoshi; Bentley, George E; Kaufer, Daniela


    The subjective experience of stress leads to reproductive dysfunction in many species, including rodents and humans. Stress effects on reproduction result from multilevel interactions between the hormonal stress response system, i.e., the hypothalamic-pituitary-adrenal (HPA) axis, and the hormonal reproductive system, i.e., the hypothalamic-pituitary-gonadal (HPG) axis. A novel negative regulator of the HPG axis known as gonadotropin-inhibitory hormone (GnIH) was recently discovered in quail, and orthologous neuropeptides known as RFamide-related peptides (RFRPs) have also been identified in rodents and primates. It is currently unknown, however, whether GnIH/RFRPs influence HPG axis activity in response to stress. We show here that both acute and chronic immobilization stress lead to an up-regulation of RFRP expression in the dorsomedial hypothalamus (DMH) of adult male rats and that this increase in RFRP is associated with inhibition of downstream HPG activity. We also show that adrenalectomy blocks the stress-induced increase in RFRP expression. Immunohistochemistry revealed that 53% of RFRP cells express receptors for glucocorticoids (GCs), indicating that adrenal GCs can mediate the stress effect through direct action on RFRP cells. It is thought that stress effects on central control of reproduction are largely mediated by direct or indirect effects on GnRH-secreting neurons. Our data show that stress-induced increases in adrenal GCs cause an increase in RFRP that contributes to hypothalamic suppression of reproductive function. This novel insight into HPA-HPG interaction provides a paradigm shift for work on stress-related reproductive dysfunction and infertility, and indicates that future work on stress and reproductive system interactions must include investigation of the role of GnIH/RFRP.

  4. Gonadotropin releasing hormone in the primitive vertebrate family Myxinidae: reproductive neuroanatomy and evolutionary aspects.

    Sills, Eric Scott; Palermo, Gianpiero D


    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.

  5. Pituitary aspergillosis abscess in an immunocompetent black ...

    Pituitary aspergillosis abscess in an immunocompetent black woman. ... female patient showed up with amenorrhea-galactorrhea syndrome with infertility for several years. The CT Findings and hormonal studies strongly suggested pituitary ...

  6. Subarachnoid hemorrhage in pituitary tumor

    Ashis Patnaik


    Full Text Available Subarachnoid hemorrhage (SAH is the bleeding into the subarachnoid space containing cerebrospinal fluid. The most common cause of SAH is trauma. Rupture of aneurysms, vascular anomalies, tumor bleeds and hypertension are other important etiologies. SAH in the setting of pituitary tumor can result from various causes. It can be due to intrinsic tumor related pathology, injury to surrounding the vessel during the operative procedure or due to an associated aneurysm. We discuss the pathological mechanisms and review relevant literature related to this interesting phenomenon. Early and accurate diagnosis of the cause of the SAH in pituitary tumors is important, as this influences the management.

  7. Enzymatic tracer damage during the gonadotropin releasing hormone radioimmunoassay: analytical and immunological assessment

    O' Conner, J.L.; Lapp, C.A.; Clary, A.R.


    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. Pituitary gigantism: Causes and clinical characteristics.

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


    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.


    连伟; 任祖渊; 苏长保


    Thee cases of pituitary metastases were reported. They all had operations and the pathological examination confirming the diagnosis. The clinical features of diabetes insipidus and extraocular nerve palsy were presented. In two cases, the original tumors were bronchioloalveolar carcinoma; in the other one, the original tumor was unknown. All three cases had poor outcome. These cases illustrate the fact that a pituitary metastasis can closely mimic a pituitary benign tumor, such as pituitary adenoma. Especially in the presence of suggestive symptoms such as diabetes insipidus and/or cranical nerve paralysis, the possibility of metastatic disease in the differential diagnosis of a pituitary mass should always be considered.

  10. Imaging of the pituitary and sella turcica.

    Mazumdar, Avi


    The pituitary gland is housed in the sella turcica and has vital endocrinologic functions. It lies in close proximity to numerous vital structures, including the optic chiasm, sphenoid sinus, cavernous sinus and hypothalamus. An understanding of the function, anatomy and embryology of the pituitary gland and its surrounding structures is vital to understanding its normal appearance, as well as in evaluating the broad spectrum of pathology that can involve the pituitary gland. Imaging of pathology in the sellar region, including pituitary adenomas, meningiomas, craniopharyngiomas and aneurysms, plays an important role in guiding treatment decisions. Modern imaging techniques are also important in evaluating the pituitary gland after surgery.

  11. Computed tomography in pituitary abscess

    Appel, W.; Scharphuis, T.; Distelmaier, P.


    This is a report on a rare case of a recurring abscess in the pituitary gland. Diagnosis was extremely difficult to establish preoperatively. This is demonstrated via various radiological methods. Anamnesis and clinical disease pattern are important assisting factors in diagnosis.

  12. Gonadotropin releasing hormone agonists: Expanding vistas

    Navneet Magon


    Full Text Available Gonadotropin-releasing hormone (GnRH agonists are derived from native GnRH by amino acid substitution which yields the agonist resistant to degradation and increases its half-life. The hypogonadotropic hypogonadal state produced by GnRH agonists has been often dubbed as "pseudomenopause" or "medical oophorectomy," which are both misnomers. GnRH analogues (GnRH-a work by temporarily "switching off" the ovaries. Ovaries can be "switched off" for the therapy and therapeutic trial of many conditions which include but are not limited to subfertility, endometriosis, adenomyosis, uterine leiomyomas, precocious puberty, premenstrual dysphoric disorder, chronic pelvic pain, or the prevention of menstrual bleeding in special clinical situations. Rapidly expanding vistas of usage of GnRH agonists encompass use in sex reassignment of male to female transsexuals, management of final height in cases of congenital adrenal hyperplasia, and preserving ovarian function in women undergoing cytotoxic chemotherapy. Hypogonadic side effects caused by the use of GnRH agonists can be tackled with use of "add-back" therapy. Goserelin, leuprolide, and nafarelin are commonly used in clinical practice. GnRH-a have provided us a powerful therapeutic approach to the treatment of numerous conditions in reproductive medicine. Recent synthesis of GnRH antagonists with a better tolerability profile may open new avenues for both research and clinical applications. All stakeholders who are partners in women′s healthcare need to join hands to spread awareness so that these drugs can be used to realize their full potential.

  13. 21 CFR 862.1155 - Human chorionic gonadotropin (HCG) test system.


    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Human chorionic gonadotropin (HCG) test system... Test Systems § 862.1155 Human chorionic gonadotropin (HCG) test system. (a) Human chorionic gonadotropin (HCG) test system intended for the early detection of pregnancy—(1) Identification. A human...

  14. [Two autopsy cases of primary pituitary carcinoma].

    Negishi, K; Suzuki, T; Masuda, Y; Masugi, Y; Teramoto, A; Ohama, E


    We studied two autopsy cases of primary pituitary carcinoma. Case-1. A 45 year old female was admitted on Oct. 4 1978, with a complaint of right homonymous hemianopsia. And diagnosis was pituitary adenoma. Partial removal of pituitary tumor was performed on Oct. 23 1978. She died on Dec. 5 1978 due to bleeding of gastrointestinal tract. Autopsy disclosed a pituitary carcinoma invading the left hypothalamus, mamillary body, optic and V cranial nerves, and mid brain as well as sphenoid bone. No extracranial metastasis was noted. Case-2. A 44 year old female with a history of acromegaly for 6 years was admitted with a complaint of headache on May 8 1976. She was diagnosed as having pituitary adenoma. The subtotal removal of pituitary tumor was performed on May 21 1976 and followed by 4500 rad irradiation. At this time, pathological diagnosis was eosinophilic adenoma. Seven years later, she complained of progressive right hearing disturbance, dysarthria and ataxic gait 1983. The second subtotal removal of pituitary tumor was performed with a diagnosis of recurrence of pituitary adenoma on Oct. 7 1983. After the operation, she complicated sepsis and died on Jan. 14 1984. An autopsy disclosed a pituitary carcinoma from residual pituitary gland, continuously extending to the subarachnoid space of the pons, and invading right cerebello-pontine angle and cerebellum. The histological examination revealed pituitary carcinoma with high pleomorphism and glioblastoma multiform-like feature were within the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Pituitary apoplexy presenting with anorexia and hyponatraemia.

    Sasaki, Yosuke; Nakata, Kenji; Suzuki, Kenichi; Ando, Yasuyo


    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.

  16. Long-term results of stereotactic radiosurgery to the pituitary gland in Cushing's disease

    Degerblad, M.; Raehn, T.; Bergstrand, G.; Thoren, M.


    Gamma radiation from /sup 60/Co delivered with stereotactic technique was given to the pituitary gland in 35 patients, aged 18-65 years, with Cushing's disease. The doses were 70-100 Gy in each single irradiation. The size of the sella turcica was normal in the majority of the patients. The observation time was 3-9 years in 29 patiens. Out of them, 14 (48%) obtained clinical remission and normal urinary cortisol after one irradiation. Eight achieved remission after two to four irradiations. In total, 22 out of 29 patients (76%) obtained remission. In 12 of them remission was obtained in 1 year and in another 10 within 3 years. No recurrences were observed. Improvement was seen in 2 patients after one and three irradiations. Bilateral adrenalectomy was performed in 5 patients owing to unsatisfactory effect of irradiation. Pituitary insufficiency with gonadotropin, thyrotropin or cortocotropin failure was demonstrated in 12 of 22 patients in remission. This occurred 4 months to 7 years after the first irradiation. Another 6 patients were followed less than 3 years after the first irradiation. Two obtained remission after the first treatment, whereas the other 4 improved. Stereotactic pituitary irradiation is suggested as a non-invasive therapeutic alternative in Cushing's disease for example in patients with considerable surgical risk or as a supplement to pituitary microsurgery.

  17. A five year prospective investigation of anterior pituitary function after traumatic brain injury: is hypopituitarism long-term after head trauma associated with autoimmunity?

    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


    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.

  18. Long-term results of radiotherapy for pituitary adenomas. Evaluation of tumor control and hypopituitarism after radiotherapy

    Tsuchida, Emiko; Sakai, Kunio; Matsumoto, Yasuo; Sugita, Tadashi; Sasamoto, Ryuta [Niigata Univ. (Japan). School of Medicine


    To evaluate the results of conventional radiotherapy for pituitary adenomas assessed with computed tomography (CT) or magnetic resonance imaging (MRI). Endpoints include tumor control, normalization of hormone levels in functioning adenomas, and hypopituitarism after radiotherapy as an adverse effect. Forty-two patients were treated with radiotherapy from 1982 to 1995 at Niigata University Hospital. Forty patients were irradiated after surgery because of residual adenomas in 33 patients and tumor regrowth in 7 patients. One patient was treated with radiotherapy alone, and the remaining 1 patient was treated with preoperative radiotherapy. Tumor size and extension were evaluated using CT or MRI, and all tumors were macroadenomas. They consisted of 18 non-functioning and 24 functioning adenomas (growth hormone (GH)-secreting: 11, prolactinomas: 7, concomitant GH and prolactin (PRL)-secreting: 5, gonadotropin-secreting: 1). Treatment was given in 200 cGy daily fraction size and a total dose of 50 Gy was given to most patients. Sixteen patients with GH- and/or PRL-secreting adenomas received bromocriptine. Tumor progression was determined by increase in tumor size as shown by CT or MRI. Hypopituitarism after radiotherapy was evaluated using the functions of corticotropin (ACTH), thyrotropin (TSH), and gonadotropin. Median follow-up time from the end of radiotherapy was 103 months. Tumor progression occurred in 2 out of 42 patients and 10-year progression-free rate for all patients was 93.7%. Normalization of GH levels was obtained in 12 of 16 GH-secreting adenomas with a mean time of 27 months after radiotherapy, and 9 of 12 PRL-secreting adenomas achieved normalization of PRL levels with a mean time of 34 months. One gonadotropin-secreting adenoma achieved normalization of gonadotropin level at 21 months after radiotherapy. The incidence of hypopituitarism after radiotherapy increased with time, and cumulative risk of deficiencies of ACTH, TSH, and gonadotropin at 10

  19. Addison's Disease and Pituitary Enlargement.

    Winters, Stephen J; Vitaz, Todd; Nowacki, Michael R; Craddock, Durrett C; Silverman, Craig


    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. Computed tomography of pituitary microadenoma

    Lee, Kyung-Il; Katto, Keiichi; Tanaka, Teruhiko; Kosaka, Shiro; Kaimori, Mitsuhiro (Aomori Prefectural Central Hospital (Japan))


    Thirteen pituitary microadenomas detected by Delta Scan 2020 are presented, and their CT findings are analyzed in points of size, shape, limit, density and contrast enhancement. All are demonstrated as a round, well defined and homogeneous mass, and are enhanced by contrast medium. The average size is 6.2 by 7.6 mm in diameter. Two of them are prolactinoma, and are treated by Bromocriptine. The prolactinomas vanished on CT scan, 6 months after administration of Bromocriptine. Eleven of them are nonfunctioning. Five are operated and the others are followed by CT scan. In detection of pituitary microadenoma, overlapping scanning with thin-slice is necessary and coronal scanning is often helpful. The adenoma greater than 5 mm in diameter may be detectable.

  1. The effectiveness of natural and gonadotropin stimulation of young gilts

    Jan DYBAŁA


    Full Text Available The aim of the study was to compare the effectiveness of stimulation of gilts puberty by natural method and with gonadotropins. The results of reproduction parameters of gilts were also compared. Gilts were also supported by diet with easilly assimilated carbohydrates. The study was carried out on the group of 80 gilts which were divided into 2 groups (A and B according to the method of inducing puberty: by using mature boar or gonadotropins eCG and hCG. In each group were isolated two subgroups in which gilts were mated in first or second estrus (A1, A2 and B1, B2. The first estrus occured earlier in gilts induced naturally. More numerous litters were obtained from gilts mated in the second estrus independently of method of puberty stimulation. The highest effectiveness of mating was obtained in gilts induced by gonadotropins in second estrus and the lowest also in gilts stimulated by gonadotropins but mated in first estrus. More piglets for 21st day were reared by gilts mated in second estrus independently on puberty induction method.

  2. Chorionic gonadotropin induces dendritic cells to express a tolerogenic phenotype

    H. Wan (Hui); M.A. Versnel (Marjan); L.M.E. Leijten (Lonneke); C.G. van Helden-Meeuwsen; D. Fekkes (Durk); P.J. Leenen (Pieter); N.A. Khan (Nisar Ahmed); R. Benner (Robbert); R.C.M. Kiekens (Rebecca)


    textabstractThe pregnancy hormone human chorionic gonadotropin (hCG) has been suggested to play an immunoregulatory role in addition to its endocrine function, thus contributing to the prevention of fetal rejection. We hypothesized that hCG is involved in the maternal-fetal immune tolerance by the r

  3. Dopamine inhibits somatolactin gene expression in tilapia pituitary cells through the dopamine D2 receptors.

    Jiang, Quan; Lian, Anji; He, Qi


    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.

  4. Comparative studies on histological and ultra-structure of the pituitary of different ploidy level fishes

    LONG Yu; LIU Shaojun; HUANG Weiren; ZHANG Jian; SUN Yuandong; ZHANG Chun; CHEN Song; LIU Jinghui; LIU Yun


    The histological and ultra-structure of the pituitary in diploid red crucian carp (Carassius auratus red var.), triploid crucian carp and allotetraploid hybrids within and after the breeding season were comparatively studied. The result showed that there were six endocrine cell types in the pituitary of these three kinds of fishes, and there was an obvious difference in cell size among different ploidy level fishes. As for the same type of pituitary cells, the cell size was increased gradually with the increasing ploidy level. In the breeding season, the allotetraploid hybrids had higher proportion of gonadotropin cells (GTH) than triploids, and the triploids had higher proportion of GTH than diploids. The results were related to the earlier sexual maturity of allotetraploid hybrids and sterility of triploid cruclan carp. On the other hand, among the three kinds of fishes, the proportion of somatotropin (STH)cells in triploids crucian carp was the highest, whereas that in allotetraploid hybrids was the lowest.The results might be connected with the faster growth rate of triploids and slower growth rate of allotetraploid hybrids. In addition, in GTH cells of meso-adenohypophysis after the breeding season,there were many endocrine particles in triploids, while those endocrine particles were released from the cells in allotetraploids and diploids. This result showed that the sterility of triploid crucian carp might be related to the hormone which was not released from the GTH cells. In a word, the present study indicated that the differences in the structure of pituitary among different ploidy level fishes contributed to their difference in the growth rate and gonadal development.

  5. Measurement of Ki-67 antigen in 159 pituitary adenomas using the MIB-1 monoclonal antibody

    C.B. Pizarro


    Full Text Available Pituitary adenomas sometimes show rapid growth and recurrence, and about one third invade the structures surrounding the sella turcica. In an attempt to determine aggressive behavior at an early stage, we used the MIB-1 antibody to identify the Ki-67 antigen. The present study was designed to evaluate pituitary adenomatous tissue in terms of secretion and proliferation and to correlate the Ki-67 index with hormone phenotype and invasive behavior. Material from 159 patients submitted to one or more resections of pituitary adenomas was evaluated. Forty-two non-secretory adenomas and 43 adenomas immunoreactive for growth hormone, 19 for prolactin, 18 for growth hormone and prolactin, 16 for adrenocorticotropic hormone (ACTH, and 21 cases of plurihormonal/gonadotropin adenomas were detected by immunohistochemistry. The MIB-1 antibody was positive in 139 samples and the Ki-67 index ranged from 0.16 to 15.48% (mean = 1.22 ± 2.09%, with no significant difference between genders, age groups, or secretory and non-secretory status. The Ki-67 index was higher in ACTH-secreting adenomas. Invasive pituitary adenomas had a significantly higher Ki-67 index (2.01 ± 3.15% than macroadenomas with or without supra-sellar extension (1.12 ± 1.87%; P = 0.02. The index was not significantly different in the subgroup of adenomas with invasion of the cavernous sinus compared to groups with other types of invasion. We conclude that tumoral proliferative activity evaluated by the detection of the Ki-67 antigen is significantly higher in invasive than noninvasive adenomas, information which can be useful in therapeutic postoperative management since index cut-off values associated with aggressive behavior can be established.

  6. Management of nonfunctioning pituitary incidentaloma.

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


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

  7. Pituitary Apoplexy After Thyrotropin-releasing Hormone Stimulation Test in a Patient with Pituitary Macroadenoma

    Huei-Fang Wang


    Full Text Available Pituitary apoplexy is a rare complication of pituitary tumors. We report a case of a 41-year-old female with acromegaly due to a pituitary macroadenoma, who developed pituitary apoplexy after a thyrotropin-releasing hormone (TRH 200 mg intravenous injection stimulation test. Neither emergency computed tomography (CT scans nor magnetic resonance imaging (MRI, performed 6 hours and 12 hours, respectively, after the active episode, disclosed the evidence of acute hemorrhage or infarction. Two days later, the pituitary mass, removed by transsphenoidal approach, showed ischemic necrosis and acute hemorrhage. The TRH test is generally safe for evaluating pituitary function, but pituitary apoplexy may occur after the procedure. CT and MRI may miss the diagnosis of pituitary apoplexy, especially if performed immediately after the acute episode.

  8. Sellar lesion: Not always a pituitary adenoma

    Rao Shalinee


    Full Text Available Inflammatory lesions of the hypophysis account for 0.5% of all symptomatic diseases of the pituitary, which include lymphocytic hypophysitis, granulomatous hypophysitis with or without specific etiology and pituitary abscess. Sellar tuberculoma is a rare type of granulomatous hypophysitis. We document a case of a postmenopausal lady who presented with galactorrhea, headache and blurring of vision. Based on preliminary investigations, a clinical diagnosis of pituitary adenoma was made and the pituitary gland was surgically excised. Histopathological examination showed caseating granulomas, along with normal areas of preserved pituitary gland and a final diagnosis of tuberculous hypophysitis was made. This case is being documented due to the extremely rare involvement of the pituitary gland by granulomatous lesions such as tuberculosis and to emphasize the role of intraoperative consultation to obviate the need for radical surgery in such lesions.

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

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


    Selective removal of the pituitary adenoma has not been advocated in dogs with pituitary-dependent hypercortisolism because the pituitary adenoma is usually not visualized on routine computed tomography (CT).Dynamic pituitary CT scanning is aimed at the detection of the pituitary flush and, indirect

  10. A Computational Model of the Rainbow Trout Hypothalamus-Pituitary-Ovary-Liver Axis.

    Kendall Gillies


    Full Text Available 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

  11. Effect of cadmium on sexual hormone secretion from pituitary and ovary

    ZhanWC; WuZR


    The objective of this study is to provide the evidence of endocrine disruption induced by Cd.The changes of serum luteinizing hormone(LH),follicle stimulating hormone(FSH),progesterone(P) and estradiol(E2) levels were observed in female rats administrated ac with Cd.Serum FSH or LH was no significant difference between groups for 7-day and for 14-day exposure.But the serum E2 of the high dose group of 7-day exposure,the low dose and high dose group for 14d was significantly lower than that of the control group.Serum P of the low dose group of 7 day exposure was significantly lower than that of the control group.After injection of gonadotropin-release hormones (GnRH) the serum FSH and LH levels increased significantly in each group(Cd 0.5,1.0mg·kg-1,5days a week, for 6 weeks).However,the serum LH was lower significantly in the rats administrated Cd than in the control rats after the injection of GnRH.There was no difference of the number of ovum between groups(0,1.5,3.0mg·kg-1 for 5d) in the super-ovulation test(P>0.05).Cadmium has the distinct adverse effect on the ovary of female rats.But the response function of the ovary to excess gonadotropin was basically normal.Under this experimental conditions.the function of secual hormone secretion of pituitary has been damaged,but the normal level of both FSH and LH could be maintained because of the limited compensative function of pituitary.

  12. How to contribute to the progress of neuroendocrinology: New insights from discovering novel neuropeptides and neurosteroids regulating pituitary and brain functions.

    Tsutsui, Kazuyoshi


    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.

  13. Polymorphisms in gonadotropin and gonadotropin receptor genes as markers of ovarian reserve and response in in vitro fertilization.

    La Marca, Antonio; Sighinolfi, Giovanna; Argento, Cindy; Grisendi, Valentina; Casarini, Livio; Volpe, Annibale; Simoni, Manuela


    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.

  14. A novel model for development, organization and function of gonadotropes in fish pituitary

    Matan eGolan


    Full Text Available 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 GnRH 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.

  15. Adrenal and gonadal steroids and pituitary response to LHRH in girls. II. Precocious puberty.

    Pintor, C; Genazzani, A R; Ibba, P; Pecciarini-Snickars, L; Corda, R


    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.

  16. Temozolomide treatment of a pituitary carcinoma and two pituitary macroadenomas resistant to conventional therapy

    Hagen, C; Schroeder, H D; Hansen, S


    OBJECTIVE: Aggressive pituitary tumours may be difficult to treat. Temozolomide (TMZ) is an alkylating cytostaticum. In a small number of cases, TMZ therapy has been reported to reduce pituitary tumour size and hormone hypersecretion. DESIGN: We present three patients with pituitary tumours treat...

  17. A Rare Cause of Hypopituitarism: Pituitary Tuberculosis

    Şazi İmamoğlu


    Full Text Available Pituitary tuberculosis is a rare condition that can present with hypopituitarism even without any evidence of systemic tuberculosis and is easily confused with pituitary adenomas. Headache and hypopituitarism are the most common presenting symptoms. We report the case of pituitary tuberculosis in a 39-year-old male patient who presented with panhypopituitarism. Although it is rare and difficult to diagnose, pituitary tuberculosis should be considered in every nonfunctional sellar masses, especially in fairly small ones with unexpected hypopituitarism. Turk Jem 2012; 16: 26-8

  18. Light bodies in human pituitary adenomas

    Holck, S; Wewer, U M; Albrechtsen, R


    Light bodies are large cytoplasmic granules originally described in the gonadotrophic cells of the rat pituitary gland. In order to determine whether similar bodies occur in the human anterior pituitary gland, 89 pituitary adenomas and periadenomatous tissue from 20 cases were examined by transmi......Light bodies are large cytoplasmic granules originally described in the gonadotrophic cells of the rat pituitary gland. In order to determine whether similar bodies occur in the human anterior pituitary gland, 89 pituitary adenomas and periadenomatous tissue from 20 cases were examined...... by transmission electron microscopy. Double membrane bound bodies with filamentous internal structure identical to rodent light bodies were identified in 10 hormone-producing adenomas: 5 PRL, 1 PRL-GH, 2 GH, and 2 ACTH-producing tumours. No light bodies were found in the remaining 79 tumours nor in the pituitary...... cells in periadenomatous tissue from 20 cases. These results show that some human pituitary adenomas may contain light bodies identical to those seen in gonadotrophs of rat pituitary....

  19. [Old phenotype and new genotypes. Pituitary adenomas].

    Gérard, C; Jedidi, H; Petrossians, P; Krzesinski, F; Daly, A; Beckers, A


    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.

  20. Genetics Home Reference: familial isolated pituitary adenoma

    ... named? Additional Information & Resources MedlinePlus (6 links) Encyclopedia: Acromegaly Encyclopedia: Gigantism Encyclopedia: Pituitary Tumor Encyclopedia: Prolactinoma Health Topic: Endocrine ...

  1. Hormonal and morphological study of the pituitaries in reeler mice

    Lombardero, Matilde; Kovacs, Kalman; Horvath, Eva; Salazar, Ignacio


    .... Since the brain is one of the main regulator of pituitary hormone secretion and no information was reported regarding pituitary function and structure in these mutant mice, we studied pituitary...

  2. Pathobiology and oncogenesis of pituitary corticotroph adenomas in dogs

    Hanson, J.M.


    Pituitary-dependent hyperadrenocorticism (PDH) or Cushing's disease is a common endocrinopathy in the elderly dog caused by a pituitary adrenocorticotrophic hormone (ACTH) producing tumor (corticotroph adenoma) of unknown pathogenesis. Surgical removal of the pituitary tumor is applied as routine

  3. Impact of gonadotropin-releasing hormone antagonist addition on pregnancy rates in gonadotropin-stimulated intrauterine insemination cycles

    Shikha Jain


    Full Text Available OBJECTIVES: The objective of the study is to evaluate the efficacy of gonadotropin-releasing hormone (GnRH antagonist in improving clinical pregnancy rate in gonadotropin-stimulated intrauterine insemination (IUI cycles in patients of unexplained infertility. STUDY DESIGN: This was a prospective, randomized case-controlled study. SETTINGS: The study was conducted in the infertility clinic of a tertiary care center. MATERIALS AND METHODS: Four hundred twenty-seven women undergoing IUI following controlled ovarian stimulation with gonadotropins (recombinant follicle-stimulating hormone [r-FSH] 75 IU/day were randomly divided into two groups. Women in Group I received GnRH antagonist (Cetrorelix 0.25 mg/day in a multiple dose flexible protocol. Women in Group II received r-FSH alone. Ovulatory trigger was given with human chorionic gonadotropin 5000 IU when dominant follicle was ≥18 mm. IUI was performed within 44-48 h. Both groups received similar luteal phase support. Primary outcome measure was clinical pregnancy rate. The trial was powered to detect an absolute increase in clinical pregnancy rate by 13% from an assumed 20% clinical pregnancy rate in the control group, with an alpha error level of 0.05 and a beta error level of 0.20. RESULTS: Clinical pregnancy rate in Groups I and II was 27.6% (n = 56 and 26.5% (n = 54, respectively (P=0.800. Ongoing pregnancy and multiple pregnancy rates were likewise similar between the groups. CONCLUSIONS: Addition of GnRH antagonist to gonadotropin-stimulated IUI cycles results in no significant difference in clinical pregnancy rate.

  4. Effect of treatment modality on the hypothalamic-pituitary function of patients treated with radiation therapy for pituitary adenomas: Hypothalamic dose and endocrine outcomes.

    Andrew eElson


    Full Text Available 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 postoperatively 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 (SRS(n=12 were retrospectively reviewed. Dose to the hypothalamus was analyzed and postradiotherapy hormone function including growth hormone (GH, thyroid (TSH, adrenal (ACTH, prolactin (PRL, and gonadotropins (FSH/LH 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 Gy vs. 26.8 Gy p=0.02, DMax (49.8 Gy 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.

  5. Purves symposium: 2. Pituitary morphology in relationship to function. General principles.

    Purves, H D


    ," which prod uced thyrotrophin, and "gonadotrophs," which produced gonadotropin. The granules were considered to be the stored hormone product of the cells. It seemed that follicle stimulating hormone was secreted by 1 cell type and luteinizing hormone by another. Each specific hormonal function was thought to be performed by a specific cell type. In the fish pituitary gland, 5 distinctive cell types are recognizable by selective staining. In human problems, the inactivity of the thyrotrophs in pituitary glands from Graves' disease patients confirms that the source of thyroid stimulation comes from outside the pituitary gland. In Cushing's disease, that the adrenal stimulation was caused by basophilic adenomata in the adenohypophysis was confirmed.

  6. Early-life Social Isolation Impairs the Gonadotropin-Inhibitory Hormone Neuronal Activity and Serotonergic System in Male Rats

    Tomoko eSoga


    Full Text Available Social isolation in early life deregulates the serotonergic system of the brain, compromising reproductive function. Gonadotropin-inhibitory hormone (GnIH neurons in the dorsomedial hypothalamic nucleus are critical to the inhibitory regulation of gonadotropin-releasing hormone neuronal activity in the brain and release of luteinising hormone by the pituitary gland. Although GnIH responds to stress, the role of GnIH in social isolation-induced deregulation of the serotonin system and reproductive function remains unclear. We investigated the effect of social isolation in early life on the serotonergic–GnIH neuronal system using enhanced green fluorescent protein (EGFP-tagged GnIH-transgenic rats. Socially isolated rats were observed for anxious and depressive behaviours. Using immunohistochemistry, we examined c-Fos protein expression in EGFP–GnIH neurons in 9-week-old adult male rats after 6 weeks post-weaning isolation or group -housing. We also inspected serotonergic fibre juxtapositions in EGFP–GnIH neurons in control and socially isolated male rats. Socially isolated rats exhibited anxious and depressive behaviours. The total number of EGFP–GnIH neurons was the same in control and socially isolated rats, but c-Fos expression in GnIH neurons was significantly reduced in socially isolated rats. Serotonin fibre juxtapositions on EGFP–GnIH neurons was also lower in socially isolated rats. In addition, levels of tryptophan hydroxylase mRNA expression in the dorsal raphe nucleus were significantly attenuated in these rats. These results suggest that social isolation in early life results in lower serotonin levels, which reduce GnIH neuronal activity and may lead to reproductive failure.

  7. 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.

    Takeda, Tomoki; Taura, Junki; Hattori, Yukiko; Ishii, Yuji; Yamada, Hideyuki


    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.

  8. The HMG-box transcription factor Sox4b is required for pituitary expression of gata2a and specification of thyrotrope and gonadotrope cells in zebrafish.

    Quiroz, Yobhana; Lopez, Mauricio; Mavropoulos, Anastasia; Motte, Patrick; Martial, Joseph A; Hammerschmidt, Matthias; Muller, Marc


    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.

  9. Pituitary Gigantism: A Case Report

    Rana Bhattacharjee


    Full Text Available Objective: To present a rare case of gigantism. Case Report: 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 (BMI28. 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 (GHvalues 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.

  10. Radiation Therapy of Pituitary Tumors

    Park, Moon Baik; Hong, Seong Eong [Kyunghee University College of Medicine, Seoul (Korea, Republic of)


    Radiation treatment results were analyzed in a retrospective analysis of 47 patients with pituitary adenoma treated with radiation alone or combined with surgery from 1974 through 1987 at the Department of Therapeutic Radiology of Kyung Hee University. The 5-year overall survival rates for all patients was 80.4%. Radiation therapy was effective for improving visual symptoms and headache, but could not normalize amenorrhea and galactorrhoea. There was no difference of survival rate between radiation alone and combination with surgery. Prognostic factors such as age, sex, disease type, visual field, headache and surgical treatment were statistically no significant in survival rates of these patients.

  11. Pituitary gigantism causing diabetic ketoacidosis.

    Alvi, N S; Kirk, J M


    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.

  12. Estradiol and its membrane-impermeable conjugate estradiol-BSA inhibit tamoxifen-stimulated prolactin secretion in incubated rat pituitaries.

    Aguilar, R; Bellido, C; Garrido-Gracia, J C; Alonso, R; Sánchez-Criado, J E


    In the absence of estrogen (E), the selective E receptor modulator tamoxifen (TX) has two agonist effects in the rat pituitary: induction of progesterone receptor (PR)-dependent GnRH self-priming in the gonadotrope, and stimulation of prolactin (PRL) secretion in the lactotrope. TX-induced gonadotropin (GnRH) self-priming is absent when 10(-8) M estradiol-17beta (E2) is added to the incubation medium of pituitaries from TX-treated rats. The present experiments investigated whether PR-independent PRL release into the incubation medium of pituitaries from TX-treated ovariectomized (OVX) rats was affected by E2, and the effect of different ER ligands (ICI182780, TX, estradiol-17alpha, E2 -BSA) on TX-stimulated PRL secretion. Moreover, the effect of E2 on TRH-stimulated PRL secretion in pituitaries collected from estradiol benzoate- and TX-treated OVX rats was studied. It was found that: i) incubation with E2 supressed the PRL releasing effect of injected TX; ii) whereas coincubation with the pure anti-E type II ICI182780 antagonized the inhibitory effect of E2, coincubation with the anti-E type I TX did not; iii) estradiol-17alpha lacked inhibitory action, whereas a dose-dependent inhibitory effect of both E2 and E2 -BSA was noticed; and iv) TRH stimulatory effect on PRL release in pituitaries from TX-treated rats was blocked by addition of E2 to the medium. Taken together, these data argue in favor of the presence of specific membrane recognition sites for E in the lactotrope involved in steroid-specific E2 inhibition of TX-stimulated PRL secretion.

  13. Detection of Messenger RNA for Gonadotropin-Releasing Hormone (GnRH) but not for GnRH Receptors in Rat Pancreas

    王雷; 谢莉萍; 黄威权; 张荣庆


    Although gonadotropin-releasing hormone (GnRH), GnRH-like molecule, and GnRH receptor (GnRH-R) have been reported to exist in several tissues other than brain or anterior pituitary, there are no reports concerning GnRH or GnRH-R gene expression in a normal pancreatic gland. In order to define the production of GnRH as well as GnRH-R in the pancreatic gland, we examined their gene expression in various developmental stages of rat pancreas using the reverse transcriptase-polymerase chain reaction (RT-PCR).GnRH mRNA transcripts were found in pancreas of male and female rats at different ages, expressing at about the same level, whereas GnRH-R mRNA transcripts could not be detected in any rat pancreatic gland samples. These results suggest a possible biological role of GnRH in rodent pancreas.

  14. The Enigma behind Pituitary and Sella Turcica

    Umarevathi Gopalakrishnan


    Full Text Available 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.

  15. Shedding light on canine pituitary dwarfism

    Voorbij, A.M.W.Y.


    Pituitary dwarfism, associated with growth hormone deficiency, is an autosomal, recessively inherited disorder in shepherd dogs. Due to the serious nature of pituitary dwarfism and lack of efficient treatment, it is preferable to prevent dwarfs from being born by applying a correct breeding policy.

  16. Pituitary magnetic resonance imaging in Cushing's disease.

    Vitale, Giovanni; Tortora, Fabio; Baldelli, Roberto; Cocchiara, Francesco; Paragliola, Rosa Maria; Sbardella, Emilia; Simeoli, Chiara; Caranci, Ferdinando; Pivonello, Rosario; Colao, Annamaria


    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.

  17. Pituitary volume in patients with panic disorder.

    Kartalci, Sukru; Dogan, Metin; Unal, Suheyla; Ozcan, A Cemal; Ozdemir, Serdal; Atmaca, Murad


    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.

  18. Hypothalamic functions in patients with pituitary insufficiency

    Borgers, A.J.F.


    The main objective of this thesis is to increase our understanding of hypothalamic (dys)function in patients with pituitary insufficiency. This goal is driven by the clinical experience of persisting symptoms in patients adequately treated for pituitary insufficiency. We focus primarily on patients

  19. Angioscan exploration of morphology of pituitary adenoma

    Tabarin, A.; David, J.P.; Drouillard, J. and others


    Considerable progress has been made in the morphologic study of pituitary due to the availability of angioscan programs. An exceptional case is presented of a persistent intrasellar trigeminal artery associated with prolactinoma. Based on technological progress in CT scan imaging the place of angiographic explorations in the investigation of pituitary adenoma is reconsidered.

  20. Shedding light on canine pituitary dwarfism

    Voorbij, A.M.W.Y.


    Pituitary dwarfism, associated with growth hormone deficiency, is an autosomal, recessively inherited disorder in shepherd dogs. Due to the serious nature of pituitary dwarfism and lack of efficient treatment, it is preferable to prevent dwarfs from being born by applying a correct breeding policy.

  1. The Enigma behind Pituitary and Sella Turcica.

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


    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.

  2. The Enigma behind Pituitary and Sella Turcica

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


    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.

  3. Binding properties of solubilized gonadotropin-releasing hormone receptor: role of carboxylic groups

    Hazum, E.


    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.

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

    Chang, Y.S.


    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.

  5. The effects of prolactin and gonadotropin on luteal function and morphology in the cyclic golden hamster.

    Kon, Hiroe; Kishi, Hisashi; Arai, Koji Y; Shinoda, Motoo; Watanabe, Gen; Taya, Kazuyoshi


    The present study was conducted to evaluate the endocrinological effects of the pituitary on luteal maintenance and regression in the cyclic golden hamster (Mesocritus auratus). After hypophysectomy (Hypox) at 0900 h on day 1 of the estrous cycle (the day of ovulation), the animals received injection of prolactin (PRL) or PRL plus equine chorionic gonadotropin (eCG). They were decapitated at 1500 h on day 3 of the cycle, and trunk blood was collected for measurement of progesterone (P4). Corpora lutea (CLs) were dissected from one ovary for DNA ladder detection by electrophoresis, determination of DNA fragmentation ratio by fluorometric measurement method and measurement of P4. The other ovary was used for histological observation. After the Hypox, the daily injection of 1 mg ovine PRL restrained the DNA fragmentation ratio and number of apoptotic cell in the CLs. The PRL treatment maintained the luteal morphology and increased the luteal P4 concentration, but not in the plasma P4 concentration. In addition to PRL, injection of 2 IU eCG after the Hypox also restrained the DNA fragmentation ratio and number of apoptotic cells in the CLs to the level of a pregnant animal. The PRL plus eCG treatment maintained the luteal morphology in the same manner as the PRL only treatment and increased not only the luteal but also the plasma P4 concentration. These results suggest that PRL restrains luteal apoptosis and maintains luteal morphology and that the combination of PRL and eCG restrains not only structural but also functional luteal regression in the cyclic hamster.

  6. Luteinizing hormone and human chorionic gonadotropin: origins of difference.

    Choi, Janet; Smitz, Johan


    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.

  7. Posttransplantation lymphoproliferative disease involving the pituitary gland.

    Meriden, Zina; Bullock, Grant C; Bagg, Adam; Bonatti, Hugo; Cousar, John B; Lopes, M Beatriz; Robbins, Mark K; Cathro, Helen P


    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.

  8. Magnetic resonance imaging of pituitary adenomas

    Bonneville, Jean-Francois; Bonneville, Fabrice; Cattin, Francoise [University Hospital, Department of Neuroradiology, Besancon (France)


    Today, MR is the only method needed for the morphological investigation of endocrine-active pituitary adenomas. In acromegaly and Cushing's syndrome, the therapeutic attitude is directly dictated by MR data. We present the MR aspect of pituitary adenomas according to size, sex, age, endocrine activity and a few particular conditions such as hemorrhagic pituitary adenomas, pituitary adenomas during pregnancy, cavernous sinus invasion and postsurgical changes. When an intrasellar mass extending out of the sella turcica is detected, the goal of the MR examination is to indicate precisely the origin of the tumor, its extension in relation to the various surrounding structures, its structure and its enhancement in order to help in the differential diagnosis. Demonstration of very small pituitary adenomas remains a challenge. When SE T1- and Turbo SE T2-weighted sequences are non-diagnostic, enhanced imaging becomes mandatory; half-dose gadolinium injection, delayed sequence, dynamic imaging can be of some help. (orig.)

  9. Cloning of partial putative gonadotropin hormone receptor sequence from fish

    G Kumaresan; T Venugopal; A Vikas; T J Pandian; S M Athavan


    A search for the presence of mariner-like elements in the Labeo rohita genome by polymerase chain reaction led to the amplification of a partial DNA sequence coding for a putative transmembrane domain of gonadotropin hormone receptor. The amplified DNA sequence shows a high degree of homology to the available turkey and human luteinizing and follicle stimulating hormone receptor coding sequences. This is the first report on cloning such sequences of piscine origin.

  10. Chromosomal localization of the gonadotropin-releasing hormone receptor gene to human chromosome 4q13. 1-q21. 1 and mouse chromosome 5

    Kaiser, U.B.; Dushkin, H.; Beier, D.R.; Chin, W.W. (Harvard Medical School, Boston, MA (United States)); Altherr, M.R. (Los Alamos National Lab., NM (United States))


    The gonadotropin-releasing hormone receptor (GRHR) is a G-protein-coupled receptor on the cell surface of pituitary gonadotropes, where it serves to transduce signals from the extracellular ligand, the hypothalamic factor gonadotropin-releasing hormone, and to modulate the synthesis and secretion of luteinizing hormone and follicle-stimulating hormone. The authors have localized the GRHR gene to the q13.1-q21.1 region of the human chromosome 4 using mapping panels of human/rodent somatic cell hybrids containing different human chromosomes or different regions of human chromosome 4. Furthermore, using linkage analysis of single-strand conformational polymorphisms, the murine GRHR gene was localized to mouse chromosome 5, linked to the endogenous retroviral marker Pmv-11. This is consistent with the evolutionary conservation of homology between these two regions, as has been previously suggested from comparative mapping of several other loci. The localization of the GRHR gene may be useful in the study of disorders of reproduction. 22 refs., 2 figs.

  11. Involvement of gonadotropins in the induction of hypertrophy-hyperplasia in the interstitial tissues of ovaries in neonatally diethylstilbestrol-treated mice.

    Kakuta, Hanako; Tanaka, Masami; Chambon, Pierre; Watanabe, Hajime; Iguchi, Taisen; Sato, Tomomi


    Neonatally diethylstilbestrol (DES) treatment causes hypertrophy-hyperplasia in the interstitial tissue of mouse ovaries. To understand the induction mechanism of the hypertrophy, mRNA expression involved in steroidogenesis in the ovary of neonatally DES-treated mice was examined. The expression of StAR and Cyp11a1 was significantly reduced while Cyp19 and Sf-1 were stimulated in the ovary of neonatally DES-treated 3-month-old mice. Expression of those genes was not different between DES- and oil-treated mice after the gonadotropins treatment. Lhb in the pituitary of 3-month-old neonatally DES-treated mice was significantly decreased. Finally, ovaries from DES-treated mice transplanted to neonatally oil-treated hosts had developing follicles at several stages and corpora lutea, whereas grafted ovaries from neonatally oil-treated mice in 3-month-old neonatally DES-treated hosts showed lipid accumulation in the interstitial tissue. Thus, hypertrophy and accumulation of lipid droplets in interstitial cells of neonatally DES-treated mice is caused by impaired steroidogenesis due to the alterations of gonadotropins levels.

  12. Regulation of GnRH receptors by progesterone and inhibin in ovine pituitary cell culture

    Laws, S.C.


    The effects of progesterone (P{sub 4}) and the gonadal protein, inhibin, on gonadotropin-releasing hormone (GnRH) receptor number and binding affinity were investigated in vitro, using ovine pituitary cells in culture. Changes in GnRH binding were correlated with GnRH-stimulated luteinizing hormone (LH) release following pretreatment with P{sub 4} and inhibin. Ovine pituitary cells in culture were preincubated with P{sub 4} or porcine inhibin (I{sub P}) for 24 or 48 hours (h). Cells were collected and analyzed for GnRH binding using a radioligand-receptor assay. des-Gly{sup 10}-(D-Ala{sup 6})-LHRH-ethyl-amide was used as the radiolabeled GnRh superagonist analog (mono-{sup 125}I-GnRH-A) and as competing ligand. Treatment with P{sub 4} progressively decreased GnRH-A binding capacity by 44.3% and 71.8% of the control following pretreatment for 24 or 48 h, respectively. When P{sub 4} was removed from the cultures, GnRH-A binding capacity partially returned to control levels within 24 h. Decreased GnRH-A binding was closely correlated with the reduction in GnRH-stimulated LH release which was observed following 24 or 48 h pretreatment with P{sub 4}.

  13. Characterization of actions of dopamine in the pituitary of the goldfish, Carassius auratus

    Omeljaniuk, R.J.


    The dopamine receptor in the goldfish (Carassius auratus) pituitary and its involvement with inhibition of gonadotropin (GtH) and {alpha}-melanocyte stimulating hormone ({alpha}-MSH) release was studied. In vitro dopamine, in a dose-related manner, inhibited spontaneous GtH and {alpha}-MSH release from superfused fragments of pars distalis (PD) and neurointermediate lob (NIL), respectively; dopamine also inhibited sGnRH-A stimulation of GtH release. Thyrotropin releasing-hormone (TRH), in a dose-related manner, stimulated {alpha}-MSH release from NIL fragments; dopamine inhibited TRH action. The stereoisomers of apomorphine were equivalent in inhibiting GtH and {alpha}-MSH release from fragments treated with releasing factors. Domperidone, in a dose-related manner, antagonized dopamine action. ({sup 3}H)-Spiperone was used to radiolabel the goldfish pituitary dopamine receptor in vitro. The binding of ({sup 3}H)-spiperone had the characteristics of a receptor: tissue specificity, dependence on tissue quantity, reversibility, saturability, displaceability, specificity of binding with various drugs and a correlation of binding with biological effects were demonstrated. This is a low-affinity, high-capacity receptor which does not show binding stereoselectivity for apomorphine; domperidone binds avidly to this receptor. The NIL contains significantly greater numbers of this receptor compared to the PD.

  14. Toxic effects of methoxychlor administered subcutaneously on the hypothalamic-pituitary-testicular axis in adult rats.

    Lafuente, A; Cabaleiro, T; Caride, A; Esquifino, A I


    This study was undertaken to evaluate the effects of methoxychlor MTX at the hypothalamic-pituitary-testicular axis in adult male rats. This global objective comprises three major aims: (1) to analyze the possible differential MTX effects in norepinephrine and serotonin concentration an in serotoninergic metabolism in anterior, mediobasal and posterior hypothalamus and median eminence; (2) to evaluate effects induced by MTX exposure on gonadotropins and testosterone; 93 to elucidate whether the regulatory interactions in the hypothalamic-pituitary-testicular axis are modified by this pesticide. Animals were administered subcutaneously 25mg/kg/day of MTX for 1 month. MTX increased norepinephrine and serotonin content in anterior hypothalamus (P < or = 0.05), but decreased serotonin concentration in posterior hypothalamus (P < or = 0.05). MTX diminished serotonin turnover in anterior hypothalamus (P < or = 0.01) and decreased plasma LH (P < or = 0.001) and testosterone (P < or = 0.05) levels but those of FSH remained unmodified. We can conclude that MTX exposure: (1) could exert differential effects in norepinephrine and serotonin concentration an in serotoninergic metabolism in anterior, mediobasal and posterior hypothalamus and median eminence, being the anterior hypothalamus the most sensitive region to the pesticide; (2) could inhibit LH and testosterone secretion without changing FSH; (3) four potential pathways might be involved in MTX effects on testosterone secretion (changing LH secretion; modifying serotonin and norepinephrine at the hypothalamic level; alterating the direct neural pathway between brain and testes; and/or by a direct effect in testes).

  15. Pattern of human chorionic gonadotropin binding in the polycystic ovary

    Brawer, J.; Richard, M.; Farookhi, R. (McGill Univ., Montreal, Quebec (Canada))


    The histologic evolution of polycystic ovaries in the estradiol valerate-treated rat coincides with the development of a unique plasma pattern of luteinizing hormone. To assess the role of luteinizing hormone in polycystic ovaries, it is necessary to evaluate the luteinizing hormone sensitivity of the specific tissues in the polycystic ovary. Therefore, we examined the pattern of luteinizing hormone binding sites in polycystic ovaries. Rats at 4 or 8 weeks after estradiol valerate treatment each received an intrajugular injection of iodine 125-labeled human chorionic gonadotropin. Some rats also received a 1000-fold excess of unlabeled human chorionic gonadotropin in the same injection. Ovaries were prepared for autoradiography. Dense accumulations of grains occurred over the theca of normal and atretic secondary follicles in all ovaries and over clusters of secondary interstitial cells. The iodine label was variable over the typically hypertrophied theca of precystic follicles. The theca of definitive cysts showed little or no label. These results indicate that cyst formation coincides with the loss of luteinizing hormone/human chorionic gonadotropin binding to the affected follicles.

  16. 77 FR 55413 - New Animal Drugs; Chorionic Gonadotropin; Naloxone; Oxymorphone; Oxytocin


    ... Gonadotropin; Naloxone; Oxymorphone; Oxytocin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule.... Painters Dr., Chadds Ford, PA 19317. 046-822 VETOCIN (oxytocin) United Vaccines, A Harlan...

  17. Defining global gene expression changes of the hypothalamic-pituitary-gonadal axis in female sGnRH-antisense transgenic common carp (Cyprinus carpio.

    Jing Xu

    Full Text Available BACKGROUND: The hypothalamic-pituitary-gonadal (HPG axis is critical in the development and regulation of reproduction in fish. The inhibition of neuropeptide gonadotropin-releasing hormone (GnRH expression may diminish or severely hamper gonadal development due to it being the key regulator of the axis, and then provide a model for the comprehensive study of the expression patterns of genes with respect to the fish reproductive system. METHODOLOGY/PRINCIPAL FINDINGS: In a previous study we injected 342 fertilized eggs from the common carp (Cyprinus carpio with a gene construct that expressed antisense sGnRH. Four years later, we found a total of 38 transgenic fish with abnormal or missing gonads. From this group we selected the 12 sterile females with abnormal ovaries in which we combined suppression subtractive hybridization (SSH and cDNA microarray analysis to define changes in gene expression of the HPG axis in the present study. As a result, nine, 28, and 212 genes were separately identified as being differentially expressed in hypothalamus, pituitary, and ovary, of which 87 genes were novel. The number of down- and up-regulated genes was five and four (hypothalamus, 16 and 12 (pituitary, 119 and 93 (ovary, respectively. Functional analyses showed that these genes involved in several biological processes, such as biosynthesis, organogenesis, metabolism pathways, immune systems, transport links, and apoptosis. Within these categories, significant genes for neuropeptides, gonadotropins, metabolic, oogenesis and inflammatory factors were identified. CONCLUSIONS/SIGNIFICANCE: This study indicated the progressive scaling-up effect of hypothalamic sGnRH antisense on the pituitary and ovary receptors of female carp and provided comprehensive data with respect to global changes in gene expression throughout the HPG signaling pathway, contributing towards improving our understanding of the molecular mechanisms and regulative pathways in the

  18. Diagnosis of pituitary microadenomas by CT scan

    Sakoda, K.; Gen, M.; Yonezawa, M.; Ohta, M.; Matsumura, S. (Hiroshima Univ. (Japan). School of Medicine)


    The presence of pituitary microadenomas can be established by the detection of minor changes on polytomograms of the sella turcica. However, as this method is a procedure for detecting secondary changes due to adenoma, it is understandable that microadenomas which fail to present secondary changes cannot be picked up. From this point of view, we investigated the possibility detecting changes in the pituitary itself by means of CT. An axial scan of pituitary microadenomas by EMI-1010 showed that some of the PRL secreting adenomas and all of the GH secreting adenomas showed areas of high density, and that some of PRL secreting adenomas and all the ACTH secreting adenomas showed areas of low density at the site of the adenomas. On a coronal scan with GE/X2, the normal pituitary is highly enhanced, and an absorption coefficient of 70 - 80 is demonstrated, but on an axial scan the coefficient becomes 25 - 35 due to the partial-volume effect. On a coronal scan pituitary microadenomas are shown as hypodense-lucent or isodense as a normal pituitary. However, the absorption coefficient of the hypodense-lucent area was 50 - 60; this is not low, but is, rather, a high density. At present, it is our belief that it is most effective to use a coronal angle with a high-resolution scanner in the diagnosis of pituitary microadenomas.

  19. The Histone Deacetylase SIRT1 Controls Male Fertility in Mice Through Regulation of Hypothalamic-Pituitary Gonadotropin Signaling

    Teerds, K.J.; Kolthur-Seerharam, U.; Rooij, de D.G.


    Sirtuins (SIRTs) are class-III NAD-dependent histone deacetylases (HDACs) that regulate various physiological processes. Inactivation of SIRT1 in the mouse leads to male sterility, but the molecular mechanisms responsible for this phenotype have not been determined. Here we show that fetal testis de

  20. The Histone Deacetylase SIRT1 Controls Male Fertility in Mice Through Regulation of Hypothalamic-Pituitary Gonadotropin Signaling

    Teerds, K.J.; Kolthur-Seerharam, U.; Rooij, de D.G.


    Sirtuins (SIRTs) are class-III NAD-dependent histone deacetylases (HDACs) that regulate various physiological processes. Inactivation of SIRT1 in the mouse leads to male sterility, but the molecular mechanisms responsible for this phenotype have not been determined. Here we show that fetal testis

  1. Serotonin, ATRX, and DAXX Expression in Pituitary Adenomas

    Casar-Borota, Olivera; Botling, Johan; Granberg, Dan


    Differential diagnosis based on morphology and immunohistochemistry between a clinically nonfunctioning pituitary neuroendocrine tumor (NET)/pituitary adenoma and a primary or secondary NET of nonpituitary origin in the sellar region may be difficult. Serotonin, a frequently expressed marker...... of the pituitary tumors expressed serotonin, suggesting that serotonin immunoreactive sellar tumors represent primary or secondary NETs of nonpituitary origin. Normal expression of ATRX and DAXX in pituitary tumors suggests that ATRX and DAXX do not play a role in the pathogenesis of pituitary endocrine tumors...... on a larger cohort of pituitary carcinomas are needed to clarify whether ATRX mutations may contribute to the metastatic potential in a subset of pituitary NETs....

  2. Hypopituitarism following pituitary irradiation for acromegaly

    Aloia, J.F.; Archambeau, J.O.


    Endocrine evaluation is reported in 8 acromegalic patients who received 5500 rad to the pituitary from a linear accelerator. There was a mean decrease in hGH levels of 72%. Plasma testosterone levels were low in 1 of the 6 male patients prior to pituitary irradiation and were below normal in all male patients on the final evaluation (3.1 +- 0.2 SD years postirradiation). Deficiency of TSH secretion developed in 2 patients following irradiation. This rather high incidence of postirradiation partial hypopituitarism was not anticipated and is thought to be related to radiation necrosis of the normal pituitary tissue which surrounds the adenoma.

  3. Management of incidental pituitary tumors

    Nicholas F. Marko


    Full Text Available Pituitary incidentalomas are common lesions for which neurosurgical referrals may become progressively more frequent, given the increasing application of neuroimaging. The initial evaluation of a patient with radiographic evidence of an incidentaloma should focus on addressing two questions: (1 is the lesion causing neurological symptoms, and (2 is the lesion hormonally active? The answers to these two questions provide a framework for subsequent clinical management. The initial patient assessment should include a detailed history and physical examination, including the bedside assessment of visual fields. High-quality MRI imaging is essential, and formal visual field testing should be obtained in patients where the lesion abuts or compresses the optic apparatus. The initial biochemical workup is intended to assess potential pituitary hypo- or hyperfunction and should include measurement of serum levels of prolactin, insulin-like growth factor type-1, free thyroxine, testosterone, and an assessment of axis hypothalamic–pituitary–adrenal axis function. Additional testing may include serum thyroid-stimulating hormone, follicle-stimulating hormone, and luteinizing hormone levels. Neurologically-asymptomatic patients without endocrine dysfunction can be managed with observation at regular intervals, including MRI imaging at 6 months and 1 year and then annually for a period of 3 years. Follow-up biochemical assessment is not necessary in the absence of clinical symptoms or radiographic enlargement of the lesion. After 3 years the follow-up interval may be prolonged, although closer follow-up may be indicated for patients with lesions C1 cm. Most patients who either present with or who subsequently develop neurologic or endocrinologic symptoms should be considered for surgery as the first-line therapy.

  4. Inflammatory Pseudotumor of the Pituitary Gland Mimicking a Pituitary Adenoma: A Case Report

    Kim, Da Mi; Yu, In Kyu [Dept. of Radiology, Eulji University Hospital, Daejeon (Korea, Republic of); Kim, Han Kyu [Dept. of Neurosurgery, Eulji University Hospital, Daejeon (Korea, Republic of); Son Hyun Jin [Dept. of Pathology, Eulji University Hospital, Daejeon (Korea, Republic of)


    A 38-year-old man was admitted to our hospital with diplopia. The patient had a relatively well-defined pituitary mass with high cellularity as well as weaker enhancement on imaging modalities including computed tomography (CT) and magnetic resonance imaging (MRI), than a typical pituitary adenoma. The distinction between a pseudotumor and an invasive neoplasm is very difficult before biopsy. In this case report, we discuss the characteristic imaging features of a fibrosing inflammatory pseudotumor of the pituitary gland

  5. Generation of immortal cell lines from the adult pituitary: role of cAMP on differentiation of SOX2-expressing progenitor cells to mature gonadotropes.

    Ginah L Kim

    Full Text Available The pituitary is a complex endocrine tissue composed of a number of unique cell types distinguished by the expression and secretion of specific hormones, which in turn control critical components of overall physiology. The basic function of these cells is understood; however, the molecular events involved in their hormonal regulation are not yet fully defined. While previously established cell lines have provided much insight into these regulatory mechanisms, the availability of representative cell lines from each cell lineage is limited, and currently none are derived from adult pituitary. We have therefore used retroviral transfer of SV40 T-antigen to mass immortalize primary pituitary cell culture from an adult mouse. We have generated 19 mixed cell cultures that contain cells from pituitary cell lineages, as determined by RT-PCR analysis and immunocytochemistry for specific hormones. Some lines expressed markers associated with multipotent adult progenitor cells or transit-amplifying cells, including SOX2, nestin, S100, and SOX9. The progenitor lines were exposed to an adenylate cyclase activator, forskolin, over 7 days and were induced to differentiate to a more mature gonadotrope cell, expressing significant levels of α-subunit, LHβ, and FSHβ mRNAs. Additionally, clonal populations of differentiated gonadotropes were exposed to 30 nM gonadotropin-releasing hormone and responded appropriately with a significant increase in α-subunit and LHβ transcription. Further, exposure of the lines to a pulse paradigm of GnRH, in combination with 17β-estradiol and dexamethasone, significantly increased GnRH receptor mRNA levels. This array of adult-derived pituitary cell models will be valuable for both studies of progenitor cell characteristics and modulation, and the molecular analysis of individual pituitary cell lineages.

  6. Computed tomographic findings in the pituitary gland and brain of horses with pituitary pars intermedia dysfunction.

    Pease, A P; Schott, H C; Howey, E B; Patterson, J S


    Pituitary pars intermedia dysfunction (PPID) is the most common endocrinologic disorder of aged horses. Pituitary glands of PPID-affected horses are larger than those of aged horses without signs of PPID, and the size difference can be detected using computed tomography (CT) imaging. Eight horses with clinical signs of PPID and supportive endocrinologic test results and 3 aged control (PPID-negative) horses. Computed tomography examination of the brain and pituitary gland was performed twice in 10 of the 11 horses, approximately 6 months apart. Six PPID-affected horses were treated with pergolide for 6 months between CT scans. The second CT scan was followed by euthanasia and pathologic examination of 6 PPID-affected horses (4 treated horses). On initial examination, pituitary glands of PPID-affected horses were larger in height (P pituitary gland length increased (P pituitary gland measurements made at the terminal CT scans and necropsy. Furthermore, pituitary gland volume calculated from the measurements was highly correlated to pituitary gland weight. Additional CT findings were bilaterally symmetrical mineralization in the thalamus and cholesterol granulomas adjacent to the lateral and fourth ventricles. CT is a useful imaging modality to determine pituitary gland size of PPID-affected horses,and CT measurements are similar to gross pathologic measurements. Copyright © 2011 by the American College of Veterinary Internal Medicine.

  7. What Happens After Treatment for Pituitary Tumors?

    ... develop pituitary hormone deficiencies after surgery or radiation therapy. These people will need hormone replacement. Thyroid hormone and adrenal steroids can be taken as pills. In men, testosterone can be given to restore sex drive and ...

  8. Pituitary adenylate cyclase activating polypeptide and migraine

    Zagami, Alessandro S; Edvinsson, Lars; Goadsby, Peter J


    Pituitary adenylate cyclase activating peptide (PACAP) is found in human trigeminocervical complex and can trigger migraine. PACAP levels were measured using a sensitive radioimmunoassay. Stimulation of the superior sagittal sinus (SSS) in cat elevated PACAP levels in cranial blood. Patients...

  9. Pituitary prolactin adenoma with Toxoplasma gondii infection

    张晓晖; 李青; 程虹; 阎庆国; 黄高昇


    Objective: To report two recent cases of pituitary adenoma associated with Toxoplasma gondii (T.Gondii) infection.Methods: Histological changes were observed in H & E and PAS staining sections microscopically.Immunohistochemistry was performed to classify the pituitary tumors and to confirm the diagnosis of T.gondii.Results: The cases were 43- and 19-year-old females, in which the latter one was a recurring case, and radiology examination showed that tumors existed in sellar region.Microscopically, the tumors consisted of small homogenous polygonal or round cells with abundant eosinophilic granular cytoplasm.Immunohistochemistry revealed they were prolactin-producing adenomas.Interestingly, we found toxoplasma infection in the tumor tissues, being confirmed by T.gondii sepicific antibody immunohistochemistry.Conclusion: The association of pituitary adenoma with toxoplasma raises the possibility that T.gondii may be involved in the development of certain cases of pituitary adenoma.

  10. Pituitary diseases : long-term clinical consequences

    Klaauw, Agatha Apolonia van der


    This thesis describes various studies during the long-term follow-up of patients after treatment for pituitary diseases. The focus of this thesis is acromegaly, growth hormone deficiency, sleep and quality of life. Various aspects are described.

  11. MicroRNAs in Human Pituitary Adenomas

    Xu-Hui Li


    Full Text Available MicroRNAs (miRNAs are a class of recently identified noncoding RNAs that regulate gene expression at posttranscriptional level. Due to the large number of genes regulated by miRNAs, miRNAs play important roles in many cellular processes. Emerging evidence indicates that miRNAs are dysregulated in pituitary adenomas, a class of intracranial neoplasms which account for 10–15% of diagnosed brain tumors. Deregulated miRNAs and their targets contribute to pituitary adenomas progression and are associated with cell cycle control, apoptosis, invasion, and pharmacological treatment of pituitary adenomas. To provide an overview of miRNAs dysregulation and functions of these miRNAs in pituitary adenoma progression, we summarize the deregulated miRNAs and their targets to shed more light on their potential as therapeutic targets and novel biomarkers.

  12. Pituitary diseases : long-term clinical consequences

    Klaauw, Agatha Apolonia van der


    This thesis describes various studies during the long-term follow-up of patients after treatment for pituitary diseases. The focus of this thesis is acromegaly, growth hormone deficiency, sleep and quality of life. Various aspects are described.

  13. Intrasellar tuberculoma presenting as pituitary apoplexy.

    Arunkumar M


    Full Text Available The combination of apoplectic symptoms and a sellar mass most often points to a diagnosis of a pituitary adenoma. Sellar tuberculomas are not considered as a cause of ′pituitary apoplexy′ and there has been no radiological documentation of haemorrhage associated with them. We report a 27 years old man who presented with 3 previous episodes of pituitary apoplexy. CT scan showed evidence of a sellar mass with haemorrhage. Transsphenoidal biopsy of the intrasellar mass was reported as ′tuberculoma′. The patient had marked reduction in the size of the lesion following antituberculous therapy with no recurrence of symptoms. Intrasellar tuberculomas must be considered as one of the differential diagnosis when patients present with a pituitary apoplexy.

  14. What Are the Symptoms of Pituitary Tumors?

    ... Clinical Trials Resources and Publications What are the symptoms of pituitary tumors? Skip sharing on social media links Share this: Page Content Symptoms of Functioning Tumors The symptoms of functioning tumors ...

  15. A study on the effects of the hydroalcholic extract of the aerial parts of Alhagi camelorum on prolactin and pituitary-gonadal activity in rats with hypercholesterolemia

    Ali Zarei


    Full Text Available Background: Although endocrine disorders are not a common cause of infertility, in some cases, testing thyroid function, and hypothalamus - pituitary - gonadal axis can determine the cause of infertility. We aimed to investigate the effect of the aerial parts of Alhagi camelorum extract on prolactin, cortisol and pituitary - gonadal axis activities in rats with hypercholesterolemia. Materials and methods: In this study, 35 male wistar rats in 5 groups (n = 7 were assigned as: control group with normal diet, the sham group with fat diet and three experimental groups of hypercholesterolaemic animals which received Alhagi camelorum extract at a minimum dose of 100 mg/kg, average dose of 200 ml/kg and maximum dose of 300 mg/kg over a period of 21 days. At the end of the period, blood samples were collected from all groups and blood factors were then measured and analyzed. Results: In the sham group compared to the control, cholesterol levels increased and FSH levels decreased, whereas cholesterol levels reduced in the experimental groups. Alhagi camelorum extract also reduced testosterone level and increased prolactin and gonadotropins. Conclusion: Alhagi camelorum extract at low and average doses reduced cortisol, testosterone and cholesterol and increased gonadotropins. So it can cause reproductive disorders in male rats. The extract at maximum dose can increase cortisol and prolactin. As these two hormones work together to produce milk, this plant can help to boost breastfeeding.

  16. Diagnostic criteria in invasive pituitary adenomas

    Moldovan Ioana-Maria


    Full Text Available Pituitary adenomas are benign pituitary primary tumors, the most frequent type of tumor in the pituitary fossa. An important part, around 1/3 of the pituitary adenomas manifests an aggressive behavior, growing faster and invading into parasellar areas (cavernous sinus, neural tissues and bones. Objectives: the first aim of this paper is to review the last findings about invasiveness diagnostic criteria, imagistic and biomarkers, which can be used in the classification of pituitary tumors and also to predict the probability of invasiveness, tumor recurrence and suspicion of malignancy. The second aim is to highlight the morphological and clinic types of invasive pituitary adenomas. Materials and methods: we performed a systematic review and analysis of the published articles, searching PubMed between January 1985 and December 2015. There were selected articles published in English, reviews and abstracts. During the advanced search type in PubMed, combinations of the following keywords were used: “pituitary adenoma”, “invasive”, “aggressive”, “biomarkers”, “classification”, “histological subtypes”, ‘”immunohistochemical markers”. Results: 215 articles were selected, regarding diagnostic, prognostic and therapeutic aspects. There were some histological subtypes of pituitary adenomas known as having an aggressive clinical behavior. Several biomarkers were identified as being associated with the invasive feature: proliferation markers (Ki-67 index, number of mitoses, p53 & p27 expression, microvascularization density, telomerase, topoisomerase 2 Alpha, matrix metalloproteinases, protein kinase C, cyclooxygenase-2, E-cadherin, transcription Factors, genetic alterations (PTTG gene, Galectin-3 protein/ LGALS3 gene, apoptosis markers. Based on their invasion and proliferation characteristics, pituitary tumors are proposed to be classified into five grades (1a, 1b, 2a, 2b, 3, the grade 2b tumor with high risk of recurrence

  17. Gonadotropin therapy in assisted reproduction: an evolutionary perspective from biologics to biotech.

    Leão, Rogério de Barros F; Esteves, Sandro C


    Gonadotropin therapy plays an integral role in ovarian stimulation for infertility treatments. Efforts have been made over the last century to improve gonadotropin preparations. Undoubtedly, current gonadotropins have better quality and safety profiles as well as clinical efficacy than earlier ones. A major achievement has been introducing recombinant technology in the manufacturing processes for follicle-stimulating hormone, luteinizing hormone, and human chorionic gonadotropin. Recombinant gonadotropins are purer than urine-derived gonadotropins, and incorporating vial filling by mass virtually eliminated batch-to-batch variations and enabled accurate dosing. Recombinant and fill-by-mass technologies have been the driving forces for launching of prefilled pen devices for more patient-friendly ovarian stimulation. The most recent developments include the fixed combination of follitropin alfa + lutropin alfa, long-acting FSH gonadotropin, and a new family of prefilled pen injector devices for administration of recombinant gonadotropins. The next step would be the production of orally bioactive molecules with selective follicle-stimulating hormone and luteinizing hormone activity.

  18. Gonadotropin therapy in assisted reproduction: an evolutionary perspective from biologics to biotech

    Rogériode Barros F. Leão


    Full Text Available Gonadotropin therapy plays an integral role in ovarian stimulation for infertility treatments. Efforts have been made over the last century to improve gonadotropin preparations. Undoubtedly, current gonadotropins have better quality and safety profiles as well as clinical efficacy than earlier ones. A major achievement has been introducing recombinant technology in the manufacturing processes for follicle-stimulating hormone, luteinizing hormone, and human chorionic gonadotropin. Recombinant gonadotropins are purer than urine-derived gonadotropins, and incorporating vial filling by mass virtually eliminated batch-to-batch variations and enabled accurate dosing. Recombinant and fill-by-mass technologies have been the driving forces for launching of prefilled pen devices for more patient-friendly ovarian stimulation. The most recent developments include the fixed combination of follitropin alfa + lutropin alfa, long-acting FSH gonadotropin, and a new family of prefilled pen injector devices for administration of recombinant gonadotropins. The next step would be the production of orally bioactive molecules with selective follicle-stimulating hormone and luteinizing hormone activity.

  19. A review of luteinising hormone and human chorionic gonadotropin when used in assisted reproductive technology

    Ezcurra, Diego; Humaidan, Peter


    Gonadotropins extracted from the urine of post-menopausal women have traditionally been used to stimulate folliculogenesis in the treatment of infertility and in assisted reproductive technology (ART). Products, such as human menopausal gonadotropin (hMG), consist not only of a mixture of the hor...

  20. Immunoregulation of mononuclear phagocytic cells by human chorionic gonadotropin

    H. Wan (Hui)


    textabstractThe pregnancy hormone hCG is secreted by trophoblasts in the placenta and peaks in the first trimester of pregnancy. hCG is a member of the pituitary glycoprotein family, and is consists of an α-subunit and a β-subunit. The primary function of hCG is to induce the production of progester

  1. Temozolomide in aggressive pituitary adenomas and carcinomas

    Leon D. Ortiz; Luis V. Syro; Scheithauer, Bernd W.; Fabio Rotondo; Humberto Uribe; Camilo E Fadul; Eva Horvath; Kalman Kovacs


    Temozolomide is an alkylating agent used in the treatment of gliomas and, more recently, aggressive pituitary adenomas and carcinomas. Temozolomide methylates DNA and, thereby, has antitumor effects. O 6-methylguanine-DNA methyltransferase, a DNA repair enzyme, removes the alkylating adducts that are induced by temozolomide, thereby counteracting its effects. A Medline search for all of the available publications regarding the use of temozolomide for the treatment of pituitary tumors was perf...

  2. Double pituitary adenomas: six surgical cases.

    Sano, T; Horiguchi, H; Xu, B; Li, C; Hino, A; Sakaki, M; Kannuki, S; Yamada, S


    While double pituitary adenomas have been found in approximately 1% of autopsy pituitaries, those in surgically resected material have been only rarely reported. We report herein 6 cases of double pituitary adenomas, which consisted of two histologically and/or immunohistochemically different areas among approximately 450 surgical specimens. Five out of 6 patients were men and the age was ranged between 18 and 61 years old. All these 6 patients presented acromegaly or acrogigantism and hyperprolactinemia was noted in 3 patients. In 2 patients (cases 1 and 2) the two adenomas belonged to different adenoma groups (GH-PRL-TSH group and FSH/LH group), while in the remaining 4 patients (cases 3-6) the two adenomas belonged to the same group (GH-PRL-TSH group). Thus, in all patients at least one of the two adenomas was GH-producing adenoma. Reasons for a high incidence of GH-producing adenomas in surgically resected double pituitary adenomas may include the presence of a variety of histologic subtypes among GH-producing adenomas and the advantage of cytokeratin immunostaining to distinguish these subtypes. In regard to pathogenesis of double pituitary adenomas, adenomas in cases 1 and 2 may be of multicentric occurrence, while those in cases 3-6 may occur through different clonal proliferation within originally one adenoma, resulting in diverse phenotypic expressions. Since there were patients with familial MEN 1 (case 2) and familial pituitary adenoma unrelated MEN 1 (case 3), genetic background should be also considered. Double pituitary adenomas in surgically resected material may not be so infrequent. Further molecular analysis will provide new insights into understanding the pathogenesis of pituitary adenomas and their mechanisms of multidirectional phenotypic diffrentiation.

  3. Pituitary Apoplexy Presented with Optic Neuritis

    Mahsa Owji


    Full Text Available The patient is a 40-years-old woman presented with visual loss in the right eye since two days ago. The patient complained of headache with gradual onset in the right parietal area since 2 years ago. The headache pattern did not alter.The left eye was normal but the vision in the right eye was 50 cm finger counting. Marcus Gunn pupil could be observed during swinging-flashlight test in the right eye. According to these findings, the first diagnosis was optic neuritis which was corroborated with visual evoked potential (the latency of P100 was 122. According to magnetic resonance imaging (MRI, there was a big cystic tumor in sella turcica extended to the suprasellar region (Figure 1-A. It had a large liquid component. Optic chiasm was under pressure and was displaced (Figure 1-B. A faint enhancement was seen after the injection (Figure 1-C.The patient was operated with the transnasal-transsphenoidal approach. Blood and fibrin were among the small monomorphic round cells andfibro-connective tissue of the pituitary gland. Considering the bleeding inside the pituitary tumor, the final diagnosis was pituitary apoplexy. After recovery from the operation the symptoms were removed.Pituitary apoplexy presents with headache, loss of vision, ophthalmoplegia, and mental alterations which is caused by infarction or sudden bleeding inside the pituitary tumor.1In our review of literature, 3 patients afflicted with pituitary apoplexy presented with optic neuritis were reported.In a study conducted by Petersen et al., all three patients referred to them suffered from unilateral visual loss and headache. They were examined with the early diagnosis of optic neuritis. After taking a Brain Computerized tomography (CT scan, pituitary adenoma together with the formation of cyst were detected in patients. After transsphenoidal adenomectomy, the patient regained full vision. Therefore, the correct diagnosis of these patients, who had been incorrectly diagnosed with

  4. A single dose of the potent gonadotropin-releasing hormone antagonist acyline suppresses gonadotropins and testosterone for 2 weeks in healthy young men.

    Herbst, Karen L; Coviello, Andrea D; Page, Stephanie; Amory, John K; Anawalt, Bradley D; Bremner, William J


    Acyline is a novel GnRH antagonist that reliably inhibits gonadotropins and testosterone (T) levels in men for 48 h after a single dose up to 75 microg/kg. In this study we examined gonadotropin and T levels in 28 healthy young men administered acyline as single doses of 150 or 300 microg/kg or serial injections of 75 microg/kg. A single 300 microg/kg dose of acyline suppressed gonadotropins and T to castrate levels for 15 d (baseline, 21.1 +/- 3.1; nadir, 1.95 +/- 0.4 nmol/liter; mean +/- sem; P gonadotropins for more than 20 d (nadir T, 1.06 +/- 0.17 nmol/liter; P hormonal male contraceptive or for treatment of hormonally dependent disease.

  5. Ovarian hyperstimulation syndrome prevention strategies: oral contraceptive pills-dual gonadotropin-releasing hormone agonist suppression with step-down gonadotropin protocols.

    Damario, Mark A


    The identification of patients at high risk for excessive responses to ovarian stimulation for in vitro fertilization and embryo transfer is essential in the tailoring of safe and effective treatment strategies. Known factors associated with increased sensitivity to gonadotropins include polycystic ovary syndrome, young age, prior ovarian hyperstimulation syndrome (OHSS), high baseline antral follicle count, and high baseline ovarian volume. Although several treatment strategies have been proposed for these patients, this report describes the experience using the dual suppression with gonadotropin step-down protocol. This protocol uses oral contraceptive pretreatment in combination with a long gonadotropin-releasing hormone agonist followed by a programmed step-down in gonadotropin dosing. Hormonal characteristics of dual suppression include an improved luteinizing hormone-to-follicle-stimulating hormone ratio and lower serum androgens, particularly dehydroepiandrosterone sulfate. Clinical characteristics of the protocol include a lower cancellation rate and favorable clinical and ongoing pregnancy rates per initiated cycle while mitigating the risk of OHSS.

  6. The various MRI patterns of pituitary apoplexy

    Piotin, M. [Department of Radiology, Montreal Neurological Hospital and Institute (Canada)]|[Department of Diagnostic and Interventional Radiology, Geneva University Hospital (Switzerland); Tampieri, D.; Garant, M.; Melanson, D. [Department of Radiology, Montreal Neurological Hospital and Institute (Canada); Ruefenacht, D.A.; Delavelle, J. [Department of Diagnostic and Interventional Radiology, Geneva University Hospital (Switzerland); Mohr, G. [Department of Neurosurgery, Sir Mortimer B. Davis Jewish General Hospital, Montreal (Canada); Del Carpio, R. [Department of Radiology, Montreal General Hospital, Montreal (Canada); Robert, F. [Department of Pathology, Sir Mortimer B. Davis Jewish General Hospital, H3T 1E2 Montreal (Canada)


    The aim of this study was to describe the various MRI features, in correlation to surgical and pathological findings, in patients who presented with pituitary apoplexy (PA). Eleven patients presenting with PA, were evaluated with various MR protocols including spin-echo (SE) T1-weighted sequences in 9 of 11 patients, post gadolinium SE T1-weighted sequences in only 8 of 11 patients, and with T2-weighted SE sequences in 2 of 11 patients. All patients had transsphenoidal pituitary surgery after MR studies. The severity of presenting symptoms ranged from headaches to coma. Ten patients had pituitary macroadenoma; one had a non-hemorrhagic metastatic lesion into a non-adenomatous pituitary gland. Of the 11 patients, one was studied at the acute stage of PA (1 day after onset), 9 at the subacute period (3-15 days after onset), and one at the late stage (5 months after onset). Images compatible with intratumoral hemorrhage were found in all macroadenomas, whereas the metastatic pituitary lesion did not show evidence of bleeding. All gadolinium-enhanced studies showed partial tumoral enhancement. The SE T2-weighted studies demonstrated areas of low and high signal intensities in keeping with the presence of blood degradation contents. Pituitary apoplexy present with different MR features, including hemorrhagic and non-hemorrhagic characteristics on T1-weighted images. Gadolinium-enhanced images do not provide complementary diagnostic information when the presence of blood is assessed on plain images. (orig.) With 4 figs., 2 tabs., 27 refs.

  7. High prevalence of chronic pituitary and target-organ hormone abnormalities after blast-related mild traumatic brain injury

    Charles W. Wilkinson


    Full Text Available Studies of traumatic brain injury from all causes have found evidence of chronic hypopituitarism, defined by deficient production of one or more pituitary hormones at least one year after injury, in 25-50% of cases. Most studies found the occurrence of posttraumatic hypopituitarism (PTHP to be unrelated to injury severity. Growth hormone deficiency (GHD and hypogonadism were reported most frequently. Hypopituitarism, and in particular adult GHD, is associated with symptoms that resemble those of PTSD, including fatigue, anxiety, depression, irritability, insomnia, sexual dysfunction, cognitive deficiencies, and decreased quality of life. However, the prevalence of PTHP after blast-related mild TBI (mTBI, an extremely common injury in modern military operations, has not been characterized. We measured concentrations of 12 pituitary and target-organ hormones in two groups of male US Veterans of combat in Iraq or Afghanistan. One group consisted of participants with blast-related mTBI whose last blast exposure was at least one year prior to the study. The other consisted of Veterans with similar military deployment histories but without blast exposure. Eleven of 26, or 42% of participants with blast concussions were found to have abnormal hormone levels in one or more pituitary axes, a prevalence similar to that found in other forms of TBI. Five members of the mTBI group were found with markedly low age-adjusted insulin-like growth factor-I (IGF-I levels indicative of probable GHD, and three had testosterone and gonadotropin concentrations consistent with hypogonadism. If symptoms characteristic of both PTHP and PTSD can be linked to pituitary dysfunction, they may be amenable to treatment with hormone replacement. Routine screening for chronic hypopituitarism after blast concussion shows promise for appropriately directing diagnostic and therapeutic decisions that otherwise may remain unconsidered and for markedly facilitating recovery and

  8. A case of pediatric virilizing adrenocortical tumor resulting in hypothalamic-pituitary activation and central precocious puberty following surgical removal.

    Miyoshi, Yoko; Oue, Takaharu; Oowari, Mitsugu; Soh, Hideki; Tachibana, Makiko; Kimura, Sadami; Kiyohara, Yuki; Yamada, Hiroyuki; Bessyo, Kazuhiko; Mushiake, Sotaro; Homma, Keiko; Hasegawa, Tomonobu; Sasano, Hironobu; Ozono, Keiichi


    We present a 6-year-old boy with a virilizing adrenocortical tumor who initially presented with peripheral precocious puberty. Development of facial acne, pubic hair and a growth spurt were noted at the age of five. A low-pitched voice as well as maturation of external genitalia was noted at the age of six. Both serum and urinary levels of adrenal androgens were elevated. Abdominal computed tomography revealed a large right suprarenal mass and he underwent surgical resection without any complications. The histological diagnosis was adrenocortical carcinoma according to the criteria of Weiss. Following surgical removal of the androgen-producing tumor, the patient subsequently developed hypothalamic-pituitary activation and demonstrated central precocious puberty. He was treated with a gonadotropin-releasing hormone agonist in order to delay further pubertal progression. Clinical follow-up of potential secondary effects of excess hormone secretion after removal is important in some pediatric patients with virilizing adrenocortical tumor.


    Tongku Nizwan Siregar


    Full Text Available The aim of this study was  to determine the effect of pituitary extracts on the reproductive threeperformance of local does. This study used 15 local female does that were divided into three treatmentgroups.  Each group consisted of five does.  All does were injected with 7.5 mg Prostaglandin F2? /PGF2?(Prostavet C, Virbac S.A intramuscularlly, twice in 10 days interval. In group 1 (K1, the does wereinseminated 36 hours after last PGF2? administration.  In group II (KII, does were injected with 500 IUpregnant mare serum gonadotropine/PMSG (Folligon ™, Intervet, Boxmeer, Holland on day 9 cycles andfollowed with injection of 7.5 mg PGF2? two days after. In group III (KIII, goats injected with pituitaryextract on days 9, 10, and 11 cycles with decreasing dose :  2, 1, and; 0.5 ml intramuscular injection locatedat some point, followed with injection of 7.5 mg PGF2? 2 days after. The does on the KII and KIII wereinseminated 36 hours after PGF2? administration. Parameters measured were oestrous percentage,pregnancy, kidding rate, twinning, total of litter size, and averages litter size.  Results showed that alldoes (100% from all groups showed estrous and kidding rate. Percentage of pregnant does group I, II, andIII were  60, 40, and 80%, respectively. Percentage of twinning group I, II, and III were 0, 50, and 25%.  Thetotal of litter size group I and II were 3 does, and group III were 5 does. The averages litter size group I, II,and III were 1; 1.5; and 1.25 respectively. In conclusion, treatment with pituitary extracts can increasereproductive performance of local does.

  10. Basic understanding of gonadotropin-releasing hormone-agonist triggering.

    Casper, Robert F


    A single bolus of human chorionic gonadotropin (hCG) at midcycle has been the gold standard for triggering final oocyte maturation and ovulation in assisted reproductive technology cycles. More recently, gonadotropin-releasing hormone (GnRH)-agonist (GnRH-a) triggering has been introduced. The GnRH-a trigger may allow a more physiologic surge of both luteinizing hormone (LH) and follicle-stimulating hormone, although whether the combined surge will result in improved oocyte and embryo quality remains to be seen. However, the short duration of the LH surge with the GnRH-a trigger (approximately 34 hours) has been shown to be beneficial for preventing ovarian hyperstimulation syndrome in GnRH antagonist in vitro fertilization (IVF) cycles when compared with the prolonged elevation of hCG (≥6 days) after exposure to an hCG bolus. This review discusses the physiologic basis for the use of a GnRH-a trigger in IVF cycles.

  11. Neuroanatomy and physiology of the avian hypothalamic/pituitary axis: clinical aspects.

    Ritchie, Midge


    This article describes the anatomy of the avian hypothalamic/pituitary axis, the hypothalamic-pituitary-thyroid axis, the hypothalamic-pituitary-adrenal axis, the hypothalamic-pituitary-gonadal axis, the somatotrophic axis, and neurohypophysis.

  12. FSH and LH Secretion from in-vitro Cultured Buffalo Anterior Pituitary Cells Following Treatment with Diethyl-Stilbestrol and Medroxy-Progesterone and Their Effects on Ovarian Activity and Hematological Variables of Female Rabbits

    Kaleem Iqbal1, Nafees Akhtar1*, Nazir Ahmad1 and Sajjad-ur-Rahman2


    Full Text Available Aims of this study were: to investigate whether FSH and LH secretion from in-vitro cultured buffalo adenohypophyseal cells can be increased by supplementing culture media with diethyl-stilbestrol and medroxy-progesterone, respectively; to monitor bioactivity of these in-vitro produced gonadotropins and to see if these gonadotropins have any adverse effects on hematology and internal body organs of female rabbits. Pituitary glands collected from 36 adult buffaloes slaughtered at a local abattoir were used. The anterior pituitary cells were cultured in-vitro using medium RPMI-1640 (code R6504-Sigma enriched with 10% fetal calf serum and GnRH and treated with 0.5 or 1.0 mg/100 ml diethyl-stilbestrol, and 2.5 or 5.0 mg/ml medroxy-progesterone, or left as untreated control. The results showed that FSH and LH concentrations from cultures treated with low or high dose of respective steroids were higher (P<0.05 than those for controls. Treatment of pre-pubertal female rabbits with in-vitro extracted FSH increased serum FSH and LH concentrations, ovarian size and number of developing follicles (GFs on the ovaries compared to controls (P<0.01. However, rabbits treated with in-vitro produced extract of LH showed increased serum FSH and LH, while there was no effect on ovarian size and number of GFs. Moreover, treatment of rabbits with both gonadotropins had no effects on body weight, hematological variables and internal body organs. In conclusion, diethyl-stilbestrol and medroxy-progesterone enhanced the secretion of FSH and LH, respectively, from cultured pituitary cells. Moreover, in-vitro produced FSH increased ovarian size, serum FSH and LH and stimulated ovarian activity, while in-vitro produced LH neither increased ovarian size nor stimulated ovarian activity.

  13. Familial idiopathic gonadotropin deficiency not linked to gene for gonadotropin-releasing hormone (GnRH) in Brazilian kindred

    Faraco, J.; Francke, U.; Toledo, S. [Stanford Univ. School of Medicine, CA (United States)


    Familial idiopathic gonadotropin deficiency (FIGD) is an autosomal recessive disorder which results in failure to develop secondary sexual characteristics. The origin is a hypothalamic defect resulting in insufficient secretion of gonadotropin-releasing hormone GnRH (also called LHRH, luteinizing hormone releasing hormone) and follicle-stimuating hormone (FSH). FIGD has been determined to be a separate entity from Kallmann syndrome which presents with hypogonadism as well as anosmia. The FIGD phenotype appears to be analogous to the phenotype of the hpg (hypogonadal) mouse. Because the hpg phenotype is the result of a structurally abnormal GnRH gene, we have studied the GnRH gene in individuals from a previously reported Brazilian FIGD family. An informative dimorphic marker in the signal peptide sequence of the GnRH gene allowed assessment of linkage between the disease gene and the GnRH locus in this pedigree. We have concluded that the GnRH locus is not linked to the disease-causing mutation in these hypogonadal individuals. Recent evidence suggests that neuropeptide Y (NPY) may play a role in the initiation of puberty. We hypothesize that mutations in NPY may result in failure to secrete GnRH. We have characterized three diallelic frequent-cutter restriction fragment length polymorphisms within the human NPY locus, and are currently using these markers to determine if the NPY gene is linked to, and possibly the site of the disease mutation in this kindred.

  14. Treatment of cryptorchidism with human chorionic gonadotropin or gonadotropin releasing hormone. A double-blind controlled study of 243 boys

    Christiansen, P; Müller, J; Buhl, S;


    We have conducted a modified double-blind study on the effect of human chorionic gonadotropin (hCG), gonadotropin releasing hormone (GnRH) and placebo on bilateral and unilateral maldescended testes. One hundred and fifty-five boys with bilateral and 88 boys with unilateral cryptorchidism fulfilled...... the inclusion criteria and completed the treatment protocol. The boys were between 1 and 13 years of age. hCG was administered as intramuscular injections twice weekly for 3 weeks. GnRH and placebo were given intranasally. hCG was superior to GnRH and placebo in the treatment of bilateral maldescended testes (p......% after placebo and GnRH, respectively (p = 0.07). The testis had moved to a more distal position in 46% of the boys treated with hCG. There was no significant difference between the treatment groups with regard to age or initial position of the testes. We conclude that a success rate of 25% justifies...

  15. Fertility Rates of Ewes Treated with Medroxyprogesterone and Injected with Equine Chorionic Gonadotropin plus Human Chorionic Gonadotropin in Anoestrous Season

    I. W. Santos


    Full Text Available The aim of the present paper was to investigate the efficiency of the equine chorionic gonadotropin (eCG plus human chorionic gonadotropin (hCG associated with medroxyprogesterone acetate (MAP to estrous ewes synchronization. Ninety Texel ewes were investigated during seasonal anoestrous. The ewes received intravaginal sponges containing MAP (60 mg for nine days. At the time of sponges' withdrawal, the ewes were divided into three groups (G: (1 receiving 2 mL of saline i.m. (n=30, (2 receiving eCG 400 IU i.m. (n=30, and (3 receiving eCG 400 IU plus hCG 200 IU i.m. (n=30. Twelve h after sponges' removal, teaser rams were used to estrus check and remained with the ewes for 96 h. The artificial insemination was made with fresh semen 10 h after estrus detection. The effect of the treatment was not significant for the estrous rates among the groups: 73%, 90%, and 86%, respectively. The main effect was observed in the pregnancy and lambing rates among the groups: 70%, 86%, 56%, and 80%, 120%, 56%, respectively. Based on these results from our study, the use of the MAP—eCG is the best choice to improve the fertility rate on ewes.

  16. New discoveries on the biology and detection of human chorionic gonadotropin

    Cole Laurence A


    Full Text Available Abstract Human chorionic gonadotropin (hCG is a glycoprotein hormone comprising 2 subunits, alpha and beta joined non covalently. While similar in structure to luteinizing hormone (LH, hCG exists in multiple hormonal and non-endocrine agents, rather than as a single molecule like LH and the other glycoprotein hormones. These are regular hCG, hyperglycosylated hCG and the free beta-subunit of hyperglycosylated hCG. For 88 years regular hCG has been known as a promoter of corpus luteal progesterone production, even though this function only explains 3 weeks of a full gestations production of regular hCG. Research in recent years has explained the full gestational production by demonstration of critical functions in trophoblast differentiation and in fetal nutrition through myometrial spiral artery angiogenesis. While regular hCG is made by fused villous syncytiotrophoblast cells, extravillous invasive cytotrophoblast cells make the variant hyperglycosylated hCG. This variant is an autocrine factor, acting on extravillous invasive cytotrophoblast cells to initiate and control invasion as occurs at implantation of pregnancy and the establishment of hemochorial placentation, and malignancy as occurs in invasive hydatidiform mole and choriocarcinoma. Hyperglycosylated hCG inhibits apoptosis in extravillous invasive cytotrophoblast cells promoting cell invasion, growth and malignancy. Other non-trophoblastic malignancies retro-differentiate and produce a hyperglycosylated free beta-subunit of hCG (hCG free beta. This has been shown to be an autocrine factor antagonizing apoptosis furthering cancer cell growth and malignancy. New applications have been demonstrated for total hCG measurements and detection of the 3 hCG variants in pregnancy detection, monitoring pregnancy outcome, determining risk for Down syndrome fetus, predicting preeclampsia, detecting pituitary hCG, detecting and managing gestational trophoblastic diseases, diagnosing quiescent

  17. Lymphocytic hypophysitis masquerading as pituitary adenoma

    Rajneesh Mittal


    Full Text Available Introduction: Pituitary hypophysitis (PH is characterized by pituitary infiltration of lymphocytes, macrophages, and plasma cells that could lead to loss of pituitary function. Hypophysitis may be autoimmune or secondary to systemic diseases or infections. Based on the histopathological findings PH is classified into lymphocytic, granulomatous, xanthomatous, mixed forms (lymphogranulomatous, xanthogranulomatous, necrotizing and Immunoglobulin- G4 (IgG4 plasmacytic types. Objective: To report a case of lymphocytic hypophysitis (LH. Case Report: A 15-year-old girl presented with history of headache, amenorrhea, and history of polyuria for past 4 months. Initial evaluation had suppressed follicular stimulating hormone (<0.01 mIU/ml, high prolactin levels (110.85 ng/ml and diabetes insipidus (DI. Magnetic resonance imaging of sella was suggestive of pituitary macroadenoma with partial compression over optic chiasma. Patient underwent surgical decompression. Yellowish firm tissue was evacuated and xanthochromic fluid was aspirated. Histopathology was suggestive of LH. She resumed her cycles postoperatively after 4 months, prolactin levels normalized, however, she continues to have DI and is on desmopressin spray. This case has been presented here for its rare presentation in an adolescent girl because it is mostly seen in young females and postpartum period and its unique presentation as an expanding pituitary mass with optic chiasma compression. Conclusion: Definitive diagnosis of LH is based on histopathological evaluation. Therapeutic approach should be based on the grade of suspicion and clinical manifestations of LH.

  18. Headache and pituitary disease: a systematic review.

    Kreitschmann-Andermahr, I; Siegel, S; Weber Carneiro, R; Maubach, J M; Harbeck, B; Brabant, G


    Headache is very common in pituitary disease and is reported to be present in more than a third of all patients with pituitary adenomas. Tumour size, cavernous sinus invasion, traction or displacement of intracranial pain-sensitive structures such as blood vessels, cranial nerves and dura mater, and hormonal hypersecretion are implicated causes. The present review attempts to systematically review the literature for any combination of headache and pituitary or hormone overproduction or deficiency. Most data available are retrospective and/or not based on the International Headache Society (IHS) classification. Whereas in pituitary apoplexy a mechanical component explains the almost universal association of the condition with headaches, this correlation is less clear in other forms of pituitary disease and a positive impact of surgery on headaches is not guaranteed. Similarly, invasion into the cavernous sinus or local inflammatory changes have been linked to headaches without convincing evidence. Some studies suggest that oversecretion of GH and prolactin may be important for the development of headaches, and treatment, particularly with somatostatin analogues, has been shown to improve symptoms in these patients. Otherwise, treatment rests on general treatment options for headaches based on an accurate clinical history and a precise classification which includes assessment of the patient's psychosocial risk factors.




    Full Text Available BACKGROUND Pituitary gland is known as the “Master Gland” of the body as it controls majority of the endocrine glands of the body. Embryologically, they are formed by two parts. There are two types of malignancies encountered namely adenomas and carcinomas. Vast majority of the neoplasms located in the sella turcica are benign pituitary adenomas derived from adenohypophyseal cells. The aim is to study the pituitary malignancies. METHODS The sample size included 100 cases of intra-cranial neoplasms that turned in the Department of Medicine in KVG Medical College, Sullia and different local private hospitals of Sullia and Mangalore. RESULTS Pituitary tumours comprised 6(6% of all the tumour studies. They occurred maximally in the age above 14 years. Tumours showed a male predominance. All the tumours were located in pituitary fossa. Principal presenting complaint was visual disturbance. Microscopically, the tumour was composed of small polyhedral to round cells with a uniform darkly staining round nucleus and scant eosinophilic cytoplasm. The cells formed papillary structures or were arranged in a trabecular pattern. CONCLUSION There is a male predominance in this study and the percentage of cases was found to be less in this region of Karnataka

  20. Growth hormone receptor expression and function in pituitary adenomas

    Clausen, Lene R; Kristiansen, Mikkel T; Rasmussen, Lars M


    OBJECTIVE AND DESIGN: Hypopituitarism, in particular GH deficiency, is prevalent in patients with clinically nonfunctioning pituitary adenomas (NFPAs) both before and after surgery. The factors regulating the growth of pituitary adenomas in general and residual tumour tissue in particular...

  1. Radiotherapy for pituitary adenomas: an endocrinologist`s perspective

    O`Halloran, D.J.; Shalet, S.M. [Christie Hospital and Holt Radium Inst., Manchester (United Kingdom)


    A brief review is given of the clinical management of patients with pituitary adenomas such as prolactinomas, adenomasin acromegoly and Leushin`s disease, and non-functioning pituitary adenomas. In particular the complications of radiotherapy are explored. (UK).

  2. A pediatric case of pituitary macroadenoma presenting with pituitary apoplexy and cranial nerve involvement: case report

    Özçetin, Mustafa; Karacı, Mehmet; Toroslu, Ertuğ; Edebali, Nurullah


    Pituitary adenomas usually arise from the anterior lobe of the pituitary gland and are manifested with hormonal disorders or mass effect. Mass effect usually occurs in nonfunctional tumors. Pituitary adenomas may be manifested with visual field defects or rarely in the form of total oculomotor palsy. Visual field defect is most frequently in the form of bitemporal hemianopsia and superior temporal defect. Sudden loss of vision, papilledema and ophthalmoplegia may be observed. Pituitary apoplexy is defined as an acute clinical syndrome characterized with headache, vomiting, loss of vision, ophthalmoplegia and clouding of consciousness. The problem leading to pituitary apoplexy may be decreased blood supply in the adenoma and hemorrhage following this decrease or hemorrhage alone. In this article, we present a patient who presented with fever, vomiting and sudden loss of vision and limited outward gaze in the left eye following trauma and who was found to have pituitary macroadenoma causing compression of the optic chiasma and optic nerve on the left side on cranial and pituitary magnetic resonance imaging.

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

    Derick Adams


    Full Text Available 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 6 weeks of oral metronidazole and intravenous vancomycin. After 6 weeks 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.

  4. A pediatric case of pituitary macroadenoma presenting with pituitary apoplexy and cranial nerve involvement: case report.

    Özçetin, Mustafa; Karacı, Mehmet; Toroslu, Ertuğ; Edebali, Nurullah


    Pituitary adenomas usually arise from the anterior lobe of the pituitary gland and are manifested with hormonal disorders or mass effect. Mass effect usually occurs in nonfunctional tumors. Pituitary adenomas may be manifested with visual field defects or rarely in the form of total oculomotor palsy. Visual field defect is most frequently in the form of bitemporal hemianopsia and superior temporal defect. Sudden loss of vision, papilledema and ophthalmoplegia may be observed. Pituitary apoplexy is defined as an acute clinical syndrome characterized with headache, vomiting, loss of vision, ophthalmoplegia and clouding of consciousness. The problem leading to pituitary apoplexy may be decreased blood supply in the adenoma and hemorrhage following this decrease or hemorrhage alone. In this article, we present a patient who presented with fever, vomiting and sudden loss of vision and limited outward gaze in the left eye following trauma and who was found to have pituitary macroadenoma causing compression of the optic chiasma and optic nerve on the left side on cranial and pituitary magnetic resonance imaging.

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

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


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

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

    Norman Beatty


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

  7. Pituitary abscess during pregnancy: Management dilemmas

    Krishna Chaitanya Joshi


    Full Text Available Pituitary abscess is a rare disorder and only one case of pituitary abscess in pregnancy has been reported in the literature. Since, its presenting manifestations are non-specific; the diagnosis is usually made per-operatively. A 35-year-old pregnant lady, with a sellar mass was managed successfully with trans-sphenoidal drainage of the abscess and antibiotic therapy. We discuss the unique set of problems faced in diagnosis and management. Choice of antibiotics, management of intra-operative cerebrospinal fluid leak and absence of any growth on cultures made the overall management challenging. Although, it can present with a dramatic course suggestive of central nervous system infection or a pituitary mass, but more often it mimics an indolent lesion, which can pose as a diagnostic and therapeutic challenge.

  8. Breast Cancer Metastasis to Pituitary Infandibulum

    Maryam Poursadegh Fard


    Full Text Available Metastasis from breast cancer to other parts of the body is very common, but the spread of the tumor to pituitary gland, especially to infandibulum, is a rare presentation. At the time of pituitary metastasis, a majority of the patients have clinical and radiological evidence of the disease. It seems that the posterior area of the gland is the most common site of metastasis, probably due to highly rich blood supply through the hypophyseal artery. The present report introduces a case of a 55-years-old woman presented with diabetes insipidus resulting from metastasis of the tumor to pituitary infandibulum, which is a rare site for metastasis, without significant complaint resulting from metastasis to other part of the body, or other primary diseases. Further evaluation revealed that in spite of previous reports, which metastasis usually happens in end stage of cancer, the patients had primary breast cancer. In subsequent evaluations of the case, hypofunction of adenohypophysis was also detected

  9. The pituitary growth hormone cell in space

    Hymer, Wesley C.; Grindeland, R.


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

  10. MRI of pituitary adenomas in acromegaly

    Marro, B. [Service de Neuroradiologie, Batiment Babinsky, Hopital Salpetriere, 47, Bd de l`Hopital, F-75013 Paris (France); Zouaoui, A. [Service de Neuroradiologie, Batiment Babinsky, Hopital Salpetriere, 47, Bd de l`Hopital, F-75013 Paris (France); Sahel, M. [Service de Neuroradiologie, Batiment Babinsky, Hopital Salpetriere, 47, Bd de l`Hopital, F-75013 Paris (France); Crozat, N. [Service de Neuroradiologie, Batiment Babinsky, Hopital Salpetriere, 47, Bd de l`Hopital, F-75013 Paris (France); Gerber, S. [Service de Neuroradiologie, Batiment Babinsky, Hopital Salpetriere, 47, Bd de l`Hopital, F-75013 Paris (France); Sourour, N. [Service de Neuroradiologie, Batiment Babinsky, Hopital Salpetriere, 47, Bd de l`Hopital, F-75013 Paris (France); Sag, K. [Service de Neuroradiologie, Batiment Babinsky, Hopital Salpetriere, 47, Bd de l`Hopital, F-75013 Paris (France); Marsault, C. [Service de Neuroradiologie, Batiment Babinsky, Hopital Salpetriere, 47, Bd de l`Hopital, F-75013 Paris (France)


    Adenomas causing acromegaly represent at least a quarter of pituitary adenomas. We studied 12 patients presenting with active acromegaly due to a pituitary adenoma with a 1.5 T superconductive MRI unit. All had T1-weighted sagittal and coronal sections before and after Gd-DTPA; six had coronal T2-weighted images. Surgical correlation was obtained in seven patients. Histologically, there were eight growth hormone (GH)-secreting and three mixed [GH and prolactin (PRL) secreting] adenomas, and one secreting GH, PRL and follicle-stimulating hormone. Macroadenomas (10) were more frequent than microadenomas (2). No correlation was found between serum GH and tumour size. There were nine adenomas in the lateral part of the pituitary gland; seven showed lateral or infrasellar invasion. Homogeneous, isointense signal on T1- and T2-weighted images was observed in six cases. Heterogeneous adenomas had cystic or necrotic components. (orig.). With 5 figs., 3 tabs.

  11. Recent advances in pituitary tumor management.

    Winder, Mark J; Mayberg, Marc R


    Advances in the neurosurgical management of pituitary tumors have included the refinement of surgical access and significant progress in navigation technology to help further reduce morbidity and improve outcome. Similarly, stereotactic radiosurgery has evolved to become an integral part in pituitary tumors not amenable to medical or surgical treatment. The evolution of minimally invasive surgery has evolved toward endoscopic versus microscopic trans-sphenoidal approaches for pituitary tumors. Debate exists regarding each approach, with advocates for both championing their cause. Stereotactic and fractional radiosurgery have been shown to be a safe and effective means of controlling tumor growth and ensuring hormonal stabilization, with longer-term data available for GammaKnife compared with CyberKnife. The advances in trans-sphenoidal surgical approaches, navigation technological improvements and the current results of stereotactic radiosurgery are discussed.

  12. [Preservation of the pituitary stalk and the gland in transsphenoidal microsurgery for pituitary adenomas].

    Li, Haoyu; Yuan, Xianrui; Liao, Yiwei; Xie, Yuanyang; Zhang, Chi; Li, Juan; Su, Jun; Wang, Xiangyu; Chen, Xiaoyu; Liu, Qing


    To improve the surgical outcome of pituitary adenomas by identifying and preserving the pituitary stalk and the gland during surgery. From October 2010 to September 2012, the author from the Department of Neurosurgery of Xiangya Hospital, Central South University operated on 51 patients with pituitary adenoma. During the operations, we carefully identified the normal adenohypophysis, pituitary stalk, neurohypophysis and the abnormal tissues either by direct observation or by medical images, aiming to excise the tumor thoroughly, protect the pituitary function and reduce the postoperative complications. Totally 37 patients (72.5%, 37/51) had total resection of the tumor, 12 (23.5%, 12/51) had subtotal tumor resection and the other 2 had major removal. The gland and the pituitary stalk were well identified and reserved. Detection of hormone content proved that the operation had little effect on the free triiodothyronine (FT3) and adrenocorticotropic hormone (ACTH), while for free tetraiodothyronine (FT4) and thyroid stimulating hormone (TSH) and postoperative followup significant alleviation was found. There was no significant fluctuation for the testosterone in the men preoperatively and postoperatively (all the above results were obtained without hormone replacement therapy). The main postoperative complications were as follows: temporary diabetes insipidus in 5 patients (9.8%, 5/51); electrolyte disorder (the appearance of hyponatremia) in 17 (33.3%, 17/51); and cerebrospinal fluid rhinorrhea and postoperative intracranial infection in 1 (2%, 1/51). No one died during the perioperation period. Microscopic transsphenoidal surgery is effective for pituitary adenomas including tumors violating the cavernous sinus. Accurate identification of the pituitary stalk, the gland and the abnormal tissue during the microscopic transsphenoidal operation plays a critical role in preserving the pituitary function and promoting postoperative rehabilitation.

  13. Pituitary autoimmunity in patients with Sheehan's syndrome.

    Goswami, Ravinder; Kochupillai, Narayana; Crock, Patricia A; Jaleel, Abdul; Gupta, Nandita


    Postpartum hemorrhage (PPH) is a frequent complication of pregnancy in India. Sheehan's description of postpartum hypopituitarism promoted the belief that PPH leads to necrosis of the enlarged pituitary gland of pregnancy and hypopituitarism. However, slow clinical progression suggests factors other than ischemia in its pathogenesis. Tissue necrosis could release sequestered antigens, triggering autoimmunity of the pituitary and delayed hypopituitarism in Sheehan's syndrome. Twenty-six consecutive patients with postpartum hypopituitarism were studied, 19 with Sheehan's syndrome based on a history of PPH and hormone profile suggesting pituitary failure [mean (SD) age 32.7 +/- 6.4 yr, duration of illness 5.5 +/- 3.1 yr], and seven patients with no history of PPH, categorized as "Other." Pituitary imaging and basal T(4), TSH, cortisol, LH, FSH, 17beta-estradiol, and autoantibodies against pituitary (PitAb) and thyroid (TMA) were evaluated. Controls included 28 healthy females without prior conception (22 +/- 5 yr) and 28 with prior conception (26 +/- 5 yr). Twelve of 19 (63.1%) patients with Sheehan's syndrome and one of seven in the Other group had PitAb against the 49-kDa autoantigen; neuron-specific enolase. Four of 28 (14.2%) controls without prior conception and 5 of 28 (17.8%) controls with prior conception had PitAb positivity (P Sheehan's syndrome, respectively). There was no significant difference in the mean serum hormone values and TMA positivity between patients with Sheehan's syndrome and the Other group as well as patients with or without PitAb positivity. Pituitary autoimmunity may play a role in the cause of hypopituitarism following PPH.

  14. Precocious puberty due to human chorionic gonadotropin secreting germinoma

    Daiane J Nascimento


    Full Text Available This study aims to report a rare case of precocious puberty (PP due to a human chorionic gonadotropin (hCG-producing germinoma located in the suprasellar region. A 10-year-old male patient presented with sexual precocity, headache, drowsiness, loss of appetite, and papilledema. Significant acceleration of bone age in relation to chronological age, high serum total testosterone levels, and hypopituitarism (unresponsiveness to stimulation test were observed. Magnetic resonance imaging (MRI of the brain showed a large suprasellar tumor and triventricular dilatation. High hCG levels were found in both blood and cerebrospinal fluid. Hormone replacement therapy and transcranial surgery associated with radiotherapy were performed, with complete regression of sexual characteristics and normal laboratory tests post-operatively. Clinical and laboratory findings, in addition to MRI scans, led to the diagnosis of an hCG-producing tumor and PP, which represents a rare report in the literature.

  15. High dose radiotherapy for pituitary tumours

    Mead, K.W. (Queensland Radium Inst., Herston (Australia))


    The results of treatment of 120 pituitary tumours are presented. Based on this experience operable chromophobe adenomas are now treated with 5,000 rads in 4 weeks and inoperable ones receive an additional central dose to 7,500 rads. Pituitary Cushing's tumours are given 10,000 rads in 5 weeks using small fields and acromegalics 5,000 rads to the whole sella and 7,500 to its lower half. The absence of complications at these dose levels is attributed to the use of small fields and the precise application of treatment.

  16. Diagnostic imaging of the pituitary gland in dogs

    Vlugt-Meijer, R.H. van der


    Pituitary-dependent hyperadrenocorticism (PDH) is a frequently encountered endocrinopathy in dogs. Transsphenoidal hypophysectomy is an effective treatment of PDH in dogs. However, for pituitary surgery to be successful information about the size of the pituitary gland and the exact location of the

  17. Follicle profile and plasma gonadotropin concentration in pubertal female ponies

    Nogueira G.P.


    Full Text Available Twelve female ponies were examined daily for 30 days and classified as ovulating (OV; N = 6; 197 ± 6 kg or prepubertal (PP; N = 6; 196 ± 9 kg. Follicles were detected by ultrasound and gonadotropins quantified by radioimmunoassay. The mean diameter of the largest follicles was significantly larger in OV (38 ± 1 mm than in PP (26 ± 2 mm but there was no difference between groups in the size of the second largest follicle. There were more small follicles (29 mm than the OV fillies. Follicle-stimulating hormone (FSH levels did not differ between groups but PP fillies had lower luteinizing hormone (LH peak (8 ± 1 ng/ml and basal (4 ± 0.5 ng/ml levels, lower peak magnitude (2 ± 0.2 ng/ml and period average (5 ± 0.6 ng/ml than OV fillies (32 ± 4.5, 8 ± 1.2, 17.1 ± 6, and 15 ± 2.3 ng/ml, respectively. The PP group, in contrast to the OV group, showed no relationship between FSH surge and follicle wave emergence. We conclude that an LH concentration higher than 8 ng/ml is needed for follicle growth to a preovulatory size. Wave emergence and FSH secretion seem to be independent events, probably due to an inhibitory neural system in these PP animals. PP fillies may provide a physiological model for the study of follicle wave emergence which apparently does not depend on gonadotropin levels.

  18. High-throughput sequencing and pathway analysis reveal alteration of the pituitary transcriptome by 17α-ethynylestradiol (EE2) in female coho salmon, Oncorhynchus kisutch

    Harding, Louisa B. [School of Aquatic and Fishery Sciences, University of Washington, Seattle, WA 98195 (United States); Schultz, Irvin R. [Battelle, Marine Sciences Laboratory – Pacific Northwest National Laboratory, 1529 West Sequim Bay Road, Sequim, WA 98382 (United States); Goetz, Giles W. [School of Aquatic and Fishery Sciences, University of Washington, Seattle, WA 98195 (United States); Luckenbach, J. Adam [Northwest Fisheries Science Center, National Marine Fisheries Service, National Oceanic and Atmospheric Administration, 2725 Montlake Blvd E, Seattle, WA 98112 (United States); Center for Reproductive Biology, Washington State University, Pullman, WA 98164 (United States); Young, Graham [School of Aquatic and Fishery Sciences, University of Washington, Seattle, WA 98195 (United States); Center for Reproductive Biology, Washington State University, Pullman, WA 98164 (United States); Goetz, Frederick W. [Northwest Fisheries Science Center, National Marine Fisheries Service, National Oceanic and Atmospheric Administration, Manchester Research Station, P.O. Box 130, Manchester, WA 98353 (United States); Swanson, Penny, E-mail: [Northwest Fisheries Science Center, National Marine Fisheries Service, National Oceanic and Atmospheric Administration, 2725 Montlake Blvd E, Seattle, WA 98112 (United States); Center for Reproductive Biology, Washington State University, Pullman, WA 98164 (United States)


    Highlights: •Studied impacts of ethynylestradiol (EE2) exposure on salmon pituitary transcriptome. •High-throughput sequencing, RNAseq, and pathway analysis were performed. •EE2 altered mRNAs for genes in circadian rhythm, GnRH, and TGFβ signaling pathways. •LH and FSH beta subunit mRNAs were most highly up- and down-regulated by EE2, respectively. •Estrogens may alter processes associated with reproductive timing in salmon. -- Abstract: Considerable research has been done on the effects of endocrine disrupting chemicals (EDCs) on reproduction and gene expression in the brain, liver and gonads of teleost fish, but information on impacts to the pituitary gland are still limited despite its central role in regulating reproduction. The aim of this study was to further our understanding of the potential effects of natural and synthetic estrogens on the brain–pituitary–gonad axis in fish by determining the effects of 17α-ethynylestradiol (EE2) on the pituitary transcriptome. We exposed sub-adult coho salmon (Oncorhynchus kisutch) to 0 or 12 ng EE2/L for up to 6 weeks and effects on the pituitary transcriptome of females were assessed using high-throughput Illumina{sup ®} sequencing, RNA-Seq and pathway analysis. After 1 or 6 weeks, 218 and 670 contiguous sequences (contigs) respectively, were differentially expressed in pituitaries of EE2-exposed fish relative to control. Two of the most highly up- and down-regulated contigs were luteinizing hormone β subunit (241-fold and 395-fold at 1 and 6 weeks, respectively) and follicle-stimulating hormone β subunit (−3.4-fold at 6 weeks). Additional contigs related to gonadotropin synthesis and release were differentially expressed in EE2-exposed fish relative to controls. These included contigs involved in gonadotropin releasing hormone (GNRH) and transforming growth factor-β signaling. There was an over-representation of significantly affected contigs in 33 and 18 canonical pathways at 1 and 6 weeks

  19. Clinical and morphological features of undifferentiated monomorphous GH/TSH-secreting pituitary adenoma.

    Skorić, T; Korsić, M; Zarković, K; Plavsić, V; Besenski, N; Breskovac, L; Giljević, Z; Paladino, J


    A 41-year-old male presented with progressive visual defects, acromegaly and hyperthyroidism. After clinical evaluation a giant GH/TSH-secreting pituitary adenoma was diagnosed. Administration of the somatostatin analog octreotide at doses of 150 microg s.c. per day inhibited the secretion of both GH and TSH. A three-week treatment with octreotide prior to surgery led to slight visual improvement and CT scan showed some new necrotic areas within the tumor mass. Transcranial surgery was performed. By immunohistochemical analyses of the adenoma tissue GH, prolactin and beta-chorionic gonadotropin were detected; TSH was negative. Electron microscopy revealed an undifferentiated, monomorphous adenoma with morphological features of an acidophil stem cell adenoma such as the presence of misplaced exocytoses, fibrous bodies and mitochondrial gigantism. However, the tumor cells contained small secretory granules (up to 250 nm) accumulated along the cell membrane characteristic of thyrotrope cells. Furthermore, some adenoma cells were fusiform with long cytoplasmic processes resembling thyrotropes. Two months after the operation CT scan revealed a large residual tumor. Serum GH and TSH levels had increased again and the TSH level was even higher than before the treatment. The patient died suddenly, most probably of lethal arrhythmia. Specimens of the adenoma tissue obtained at autopsy confirmed the previous findings with the exception of positive immunostaining for TSH which was found in less than 1% of the adenoma cells. This undifferentiated, monomorphous GH/TSH-secreting pituitary adenoma represents an entity that is unusual both in its ultrastructural features and clinical manifestations suggesting a cytogenesis from an early, undifferentiated stem cell.

  20. Hypothalamus-pituitary axis: an obligatory target for endocannabinoids to inhibit steroidogenesis in frog testis.

    Chianese, Rosanna; Ciaramella, Vincenza; Fasano, Silvia; Pierantoni, Riccardo; Meccariello, Rosaria


    Endocannabinoids - primarily anandamide (AEA) and 2-arachidonoylglycerol (2-AG) - are lipophilic molecules that bind to cannabinoid receptors (CB1 and CB2). They affect neuroendocrine activity inhibiting gonadotropin releasing hormone (GnRH) secretion and testosterone production in rodents, through a molecular mechanism supposed to be hypothalamus dependent. In order to investigate such a role, we choose the seasonal breeder, the anuran amphibian Rana esculenta, an experimental model in which components of the endocannabinoid system have been characterized. In February, at the onset of a new spermatogenetic wave, we carried out in vitro incubations of frog testis with AEA, at 10(-9)M dose. Such a treatment had no effect on the expression of cytochrome P450 17alpha hydroxylase/17,20 lyase (cyp17) nor 3-β-hydroxysteroid dehydrogenase/Δ-5-4 isomerase (3β-HSD), key enzymes of steroidogenesis. To understand whether or not the functionality of the hypothalamus-pituitary axis could be essential to support the role of endocannabinoids in steroidogenesis, frogs were injected with AEA, at 10(-8)M dose. Differently from in vitro experiment, the in vivo administration of AEA reduced the expression of cyp17 and 3β-HSD. Whereas the effect on 3β-HSD was counteracted by SR141716A (Rimonabant) - a selective antagonist of CB1, thus indicating a CB1 dependent modulation - the effect on cyp17 was not, suggesting a possible involvement of receptors other than CB1, probably the type-1 vanilloid receptor (TRPV1), since AEA works as an endocannabinoid and an endovanilloid as well. In conclusion our results indicate that endocannabinoids, via CB1, inhibit the expression of 3β-HSD in frog testis travelling along the hypothalamus-pituitary axis.

  1. Pulsatile gonadotropin secretion determined by frequent sampling from the intercavernous sinus of the mare: possible modulatory role of progesterone during luteolysis.

    Silvia, P J; Meyer, S L; Fitzgerald, B P


    Twelve horse mares were used in a repeated-measures design consisting of 3 replicates of 4 mares each. On Day 6 following ovulation, luteolysis was initiated with an i.m. injection of prostaglandin F2 alpha (PGF2 alpha; Lutalyse, 10 mg). Either 12 (-12) or 36 (-36) h before PGF2 alpha (PRE), blood samples were collected simultaneously from the intercavernous sinus (ICS) and jugular (JUG) vein at 10-min intervals for an 8-h period. Pituitary capacity to exogenous GnRH (2 micrograms/kg BW, i.v.) was evaluated at the alternate time point within this period. Frequent sampling and GnRH challenge were repeated 36 (+36) or 60 (+60) h after PGF2 alpha (POST). Progesterone reached a nadir 48 h after PGF2 alpha, while the first significant elevation in estradiol (p < 0.05) was not detected until 156 h. PRE LH and FSH pulse frequencies in ICS samples were 0.6 +/- 0.3 and 1.8 +/- 0.8 pulses/8 h, respectively. Three high-amplitude, concurrent ICS pulses of LH and FSH were observed during this period. These were associated with elevated gonadotropin levels in the corresponding JUG samples. In contrast, low-amplitude ICS pulses at this time were predominately releases of FSH alone that were not detectable in the JUG. Following luteolysis, POST gonadotropin pulse frequencies in the ICS increased (p < 0.001) to 7.4 +/- 0.4 and 6.8 +/- 0.5 pulses/8 h for LH and FSH, respectively. Concurrent LH and FSH releases of relatively low amplitude characterized 87.7% of the POST ICS pulses, none of which were measurable in corresponding JUG samples.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Adjuvant Growth Hormone for Ovulation Induction with Gonadotropins in the Treatment of a Woman with Hypopituitarism

    Ariadne Daniel


    Full Text Available Objective. To report the prestimulation use of adjuvant GH for gonadotropin ovulation induction in a woman with hypopituitarism and GH deficiency who previously failed to respond. Design, Patients, and Measurements. A 31-year-old nulliparous woman presented with hypopituitarism and GH deficiency after failing ovulation induction with high dose gonadotropins. A trial of GH was undertaken for 5 months prior to ovulation induction resulting in normalization of IGF-I levels. Results. Women with hypopituitarism are known to have lower pregnancy rates after ovulation induction with need for higher doses of gonadotropins. A small subset of these patients do not ovulate. This patient had successful ovulation induction and pregnancy with prestimulation GH. Conclusions. This case suggests that the use of adjuvant GH in a GH-deficient patient several months before the use of human menopausal gonadotropin results in ovulation and pregnancy.

  3. Hyperprolactinaemia is associated with a higher prevalence of pituitary-adrenal dysfunction in non-functioning pituitary macroadenoma

    Tjeerdsma, Geert; Sluiter, WJ; Hew, JM; Molenaar, WM; deLange, WE; Dullaart, RPF


    In non-functioning pituitary macroadenoma (NFMA), hyperprolactinaemia (hyperPRL) is considered to be a sign of hypothalamic-pituitary dysregulation, but it is unknown whether hyperPRL is associated with an increased frequency of pituitary hormone deficiencies. Forty consecutive patients with histolo

  4. [Rol of pituitary tumour-transforming gene (PTTG) in the pituitary adenomas].

    Sánchez-Ortiga, Ruth; Sánchez Tejada, Laura; Peiró Cabrera, Gloria; Moreno-Pérez, Oscar; Arias Mendoza, Nieves; Aranda López, F Ignacio; Picó Alfonso, Antonio


    The pathogenesis of pituitary tumours is far to be understood. Pituitary transforming tumour gene (PTTG), a gen that induces aneuploidy, genetic instability, cellular proliferation and to stimulate angiogenesis, has been involved in neoplasic transformation and shown overexpressed in many neoplasm as lung, breast, endometrium, thyroid and colon malignant tumours. On the other hand, PTTG has been inconsistently studied in pituitary tumours. The majority of studies have been performed in animals and there is a great variability in the methods used in its determination. The goal of this review is to resume the role of PTTG in tumourogenesis and critically to revise the studies published in humans in order to advance in the knowledge of the pathogenesis of pituitary adenomas and to find clinical useful predictors of the behavior of these tumours.


    Evi Tahapari


    Full Text Available The success of spawning is influenced by internal and external factors. One of the factors that affect the var iabi li ty of Pangasianodon hypophthalmus female reproductive is the change of seasons that cause disrupted continuity of the seed availability, especially in the dry season. In the present study, combination of PMSG (pregnant mare serum gonadotropin + HCG (hormone chorionic gonadotropin hormone injections was done to induce gonad development. The treatments in this study were without hormone injections as control (A, injection of PMSG 10 IU/kg + HCG 10 IU/kg (B, and injection of PMSG 20 IU/kg HCG + 10 IU/kg (C. Injections were conducted at intervals of two weeks as many as six times. The results showed that gonad maturation generally occurs 2-4 weeks after estradiol-17 peak. PMSG + HCG hormone injections gave a significant effect on increasing the quantity and quality of eggs production. The fecundity in the A, B, C treatments, were 233,700±220,676; 300,305±24,581 and 488,433±142,228; respectively. Number of larvae produced from the A, B, C treatments, were 156,979±170,838; 229,997±18,081 and 362,713±101,850; respectively. Combination of PMSG 20 IU/kg + HCG 10 IU/kg hormone injection gave the best result on fecundity and the number of larvae production.

  6. Antimüllerian hormone in gonadotropin releasing-hormone antagonist cycles

    Arce, Joan-Carles; La Marca, Antonio; Mirner Klein, Bjarke


    To assess the relationships between serum antimüllerian hormone (AMH) and ovarian response and treatment outcomes in good-prognosis patients undergoing controlled ovarian stimulation using a gonadotropin-releasing hormone (GnRH) antagonist protocol.......To assess the relationships between serum antimüllerian hormone (AMH) and ovarian response and treatment outcomes in good-prognosis patients undergoing controlled ovarian stimulation using a gonadotropin-releasing hormone (GnRH) antagonist protocol....

  7. Ovarian Hyper-Response to Administration of an GnRH-Agonist Without Gonadotropins

    Park, Hyun Tae; Bae, Hyo Sook; Kim, Tak; Kim, Sun Haeng


    Several case reports have indicated that a small subgroup of patients may develop ovarian hyperstimulation following the administration of gonadotropin-releasing hormone agonists (GnRHa) without gonadotropins. However, since only few such cases have been published, it is unclear what course to follow in subsequent cycles after ovarian hyperstimulation in the first cycle using only GnRHa. A 33-yr-old woman was referred to in vitro fertilization for oocyte donation. A depot preparation (3.75 mg...

  8. Negative Feedback Governs Gonadotrope Frequency-Decoding of Gonadotropin Releasing Hormone Pulse-Frequency


    The synthesis of the gonadotropin subunits is directed by pulsatile gonadotropin-releasing hormone (GnRH) from the hypothalamus, with the frequency of GnRH pulses governing the differential expression of the common alpha-subunit, luteinizing hormone beta-subunit (LHbeta) and follicle-stimulating hormone beta-subunit (FSHbeta). Three mitogen-activated protein kinases, (MAPKs), ERK1/2, JNK and p38, contribute uniquely and combinatorially to the expression of each of these subunit genes. In this...

  9. Health-related quality of life in pituitary diseases.

    Crespo, Iris; Valassi, Elena; Santos, Alicia; Webb, Susan M


    In the last 15 years, worse health-related quality of life (QoL) has been reported in patients with pituitary diseases compared with healthy individuals. Different QoL questionnaires have shown incomplete physical and psychological recovery after therapy. Residual impairments often affect QoL even long-term after successful treatment of pituitary adenomas. In this article, knowledge of factors that affect QoL in pituitary diseases is reviewed. The focus is on 5 pituitary diseases: Cushing syndrome, acromegaly, prolactinomas, nonfunctioning pituitary adenomas, and hypopituitarism.

  10. Impaired Pituitary Axes Following Traumatic Brain Injury

    Robert A. Scranton


    Full Text Available Pituitary dysfunction following traumatic brain injury (TBI is significant and rarely considered by clinicians. This topic has received much more attention in the last decade. The incidence of post TBI anterior pituitary dysfunction is around 30% acutely, and declines to around 20% by one year. Growth hormone and gonadotrophic hormones are the most common deficiencies seen after traumatic brain injury, but also the most likely to spontaneously recover. The majority of deficiencies present within the first year, but extreme delayed presentation has been reported. Information on posterior pituitary dysfunction is less reliable ranging from 3%–40% incidence but prospective data suggests a rate around 5%. The mechanism, risk factors, natural history, and long-term effect of treatment are poorly defined in the literature and limited by a lack of standardization. Post TBI pituitary dysfunction is an entity to recognize with significant clinical relevance. Secondary hypoadrenalism, hypothyroidism and central diabetes insipidus should be treated acutely while deficiencies in growth and gonadotrophic hormones should be initially observed.

  11. Pituitary and mammary growth hormone in dogs

    Bhatti, Sofie Fatima Mareyam


    Several pathological (e.g. obesity and chronic hypercortisolism) and non-pathological (e.g. ageing) states in humans are characterized by a reduction in pituitary growth hormone (GH) secretion. Chronic hypercortisolism in humans is also associated with an impaired GH response to various stimuli. Pit


    陶蔚; 任祖渊; 苏长保; 王任直; 杨义; 马文斌


    Objective. To clarify the frequency, presentation, associated factors, treatment and outcome of hy-ponatremia after transsphenoidal surgery of pituitary adenomas.Methods. Retrospectively reviewed the database of 183 patients who underwent transsphenoidal surgeryof pituitary adenomas between January 1999 and June 2000 in our department.Result.s. 38.8% (71/183) had postoperative hyponatremia. Among them, 59.2% (42/71) appeared onthe 4th to 7th day postoperatively. 59.2% (42/71) presented with nausea, vomiting, headache, dizzi-ness, confusion and weakness. Hyponatremia was related to age, tumor size and adenoma type, but notrelated to sex and degree of resection. Treatment consisted of salt replacement and mild fluid restrictionin 4 patients and salt and fluid replacement in 67 patients. Hyponatremia resolved within 16 days in allthe patients.Conclusions. Hyponatremia often appeared about 7 days after transsphenoidal surgery of pituitary ade-nomas, especially in elderly and patients with macroadenomas and huge pituitary adenomas. The principleof treatment was salt and fluid replacement.

  13. MRI of pituitary adenomas following treatment

    Gouliamos, A. [Dept. of Radiology, CT and MRI Section, Areteion Hospital, Univ. of Athens (Greece); Athanassopoulou, A. [Dept. of Radiology, CT and MRI Section, Areteion Hospital, Univ. of Athens (Greece); Rologis, D. [Neurosurgical Clinic, Athens General Hospital (Greece); Kalovidouris, A. [Dept. of Radiology, CT and MRI Section, Areteion Hospital, Univ. of Athens (Greece); Kotoulas, G. [Dept. of Radiology, CT and MRI Section, Areteion Hospital, Univ. of Athens (Greece); Vlahos, L. [Dept. of Radiology, CT and MRI Section, Areteion Hospital, Univ. of Athens (Greece); Papavassiliou, C. [Dept. of Radiology, CT and MRI Section, Areteion Hospital, Univ. of Athens (Greece)


    The purpose of this study was to assess pituitary adenomas following surgical and/or medical treatment in 28 patients. All patients were evaluated with both computed tomography (CT) and magnetic resonance imaging (MRI). The results were correlated with the clinical findings. Apart from the visualization of the adenoma itself (either residual or recurrent) other findings and in particular, morphological changes of the optic chiasm, the pituitary stalk and the sellar floor were evaluated with both imaging modalities. By comparing the two imaging modalities it was found that MRI was superior to CT in demonstrating residual/recurrent adenoma as well as evaluating the morphological changes of the optic chiasm and optic nerves. CT was superior or equal to MR in demonstrating the sellar floor changes. The intra-operatively implanted fat was equally seen by CT and MR. In conclusion, the anatomical variations of the optic chiasm and pituitary stalk are better visualized by MRI and allow a more precise evaluation of changes attributed to surgical or medical treatment of pituitary adenomas. (orig.)

  14. Chorioretinopathy and pituitary dysfunction. The CPD syndrome.

    Judisch, G F; Lowry, R B; Hanson, J W; McGillivary, B C


    Four reports of a rare syndrome characterized by severe, early-onset chorioretinopathy, trichosis, and evidence of pituitary dysfunction are reviewed. Recently obtained follow-up information about these four patients is presented. A new example of this disease, the fifth case to be reported, to our knowledge, is described.

  15. Pituitary diseases : long-term psychological consequences

    Tiemensma, Jitske


    Nowadays, pituitary adenomas can be appropriately treated, but patients continue to report impaired quality of life (QoL) despite long-term remission or cure. In patients with Cushing’s disease, Cushing’s syndrome or acromegaly, doctors should be aware of subtle cognitive impairments and the

  16. [Pituitary tumors manifesting with amenorrhea-galactorrhea].

    Bartal, A; Razon, N


    The amenorrhea-galactorrhea syndrome which occurs at a time other than the post-partum period is most often seen in association with a tumor of the pituitary gland; the symptoms are caused by a hypersecretion of prolactin. Among a series of 19 patients in Tel Aviv who underwent surgery for treatment of pituitary tumors, 2 presented with the amenorrhea-galactorrhea syndrome. The first patient, a 16 year old, presented with headaches, nausea, and diplopia; she underwent a series of 3 surgical procedures and died of a respiratory arrest in the third post-operative period. The second patient was a 39 year old woman who had borne 5 children; she presented with loss of vision, underwent surgery, and did well post-operatively. The authors point out that whereas either amenorrhea or galactorrhea alone may be associated with a number of disorders, the combination of the two symptoms is characteristic of pituitary tumors. Both patients who were presented in this article had chromophobe adenomas of the pituitary. The authors also discuss the various biologic actions of prolactin and its interrelationships with other hormones.

  17. Pituitary tuberculoma--a case report.

    Manghani D


    Full Text Available Pituitary tuberculomas, mimicking adenomas are very unusual. We describe a rare case of a patient with an exclusively intrasellar mass, and who presented with severe headaches and loss of libido. The lesion was approached trans-sphenoidally and pathological examination revealed a tuberculoma. Complete removal was achieved and the patient followed on anti-tuberculous therapy.

  18. Expression of orexin receptors in the pituitary.

    Kaminski, Tadeusz; Smolinska, Nina


    Orexin receptors type 1 (OX1R) and type 2 (OX2R) are G protein-coupled receptors whose structure is highly conserved in mammals. OX1R is selective for orexin A, and OX2R binds orexin A and orexin B with similar affinity. Orexin receptor expression was observed in human, rat, porcine, sheep as well as Xenopus laevis pituitaries, both in the adenohypophysis and in the neurohypophysis. The expression level is regulated by gonadal steroid hormones and GnRH. The majority of orexins reaching the pituitary originate from the lateral hypothalamus, but due to the presence of the receptors and the local production of orexins in the pituitary, orexins could deliver an auto/paracrine effect within the gland. Cumulative data indicate that orexins are involved in the regulation of LH, GH, PRL, ACTH, and TSH secretion by pituitary cells, pointing to orexins' effect on the functioning of the endocrine axes. Those hormones may also serve as a signal linking metabolic status with endocrine control of sleep, arousal, and reproduction processes.

  19. How effective is external pituitary irradiation for growth hormone-secreting pituitary tumours

    Feek, C.M.; McLelland, J.; Seth, J.; Toft, A.D.; Irvine, W.J.; Padfield, P.L.; Edwards, C.R.W. (Western General Hospital, Edinburgh (UK); Royal Infirmary, Edinburgh (UK))


    Forty-six patients with GH-secreting pituitary tumours were treated with external pituitary irradiation through two opposed fields to a total dose of 3750 cGy over 15 fractions. Thirty-patients received external radiotherapy as primary treatment; 16 received radiotherapy combined with pituitary surgery. The mean (+- SD) serum GH in the former group was 74.3 +- 74.8 mU/l before treatment, falling by 28% per year over 0-5 years and by 16% per year over 0-20 years. The mean (+- SD) serum GH in the latter group was 265.4 +- 209.3 mU/l before treatment, falling by 76% in the first year-a direct result of surgery-then by 30% per year over 1-5 years and 16% per year over 1-20 years. Progressive failure of normal anterior pituitary function developed by 10 years, with variable loss of gonadotrophin, corticotrophin and thyrotrophin function. The respective figures for patients treated with radiotherapy alone were 47.4, 29.6 and 16.0% and for the combined group 70.2, 53.9 and 38.1%. Whilst external pituitary irradiation appears to reduce serum GH concentrations in patients with GH-secreting pituitary tumours the major disadvantages are the time taken to achieve a cure and the high incidence of hypopituitarism.

  20. Pituitary and placental hormone levels in pseudocyesis.

    Osotimehin, B O; Ladipo, O A; Adejuwon, C A; Otolorin, E O


    Twelve patients with clinical features of pseudocyesis were divided into two groups according to the presence or absence of galactorrhea. The mean serum prolactin level of patients with galactorrhea was significantly higher than the normal values of the patients without galactorrhea. The mean serum levels of luteinizing hormone and follicle-stimulating hormone were markedly elevated in patients without galactorrhea. This was especially true of luteinizing hormone. Serum levels of human chorionic gonadotropin were undetectable in all patients. The significance of these observations is discussed.

  1. Maternal behavior in transgenic mice with reduced fibroblast growth factor receptor function in gonadotropin-releasing hormone neurons

    Brooks Leah R


    Full Text Available Abstract Background Fibroblast growth factors (FGFs and their receptors (FGFRs are necessary for the proper development of gonadotropin-releasing hormone (GnRH neurons, which are key activators of the hypothalamo-pituitary-gonadal axis. Transgenic mice that have the targeted expression of a dominant negative FGFR (dnFGFR in GnRH neurons (dnFGFR mice have a 30% decrease of GnRH neurons. Additionally, only 30–40% of the pups born to the transgenic dams survive to weaning age. These data raised the possibility that FGFR defects in GnRH neurons could adversely affect maternal behavior via novel mechanisms. Methods We first determined if defective maternal behavior in dnFGFR mothers may contribute to poor pup survival by measuring pup retrieval and a battery of maternal behaviors in primiparous control (n = 10–12 and dnFGFR (n = 13–14 mothers. Other endocrine correlates of maternal behaviors, including plasma estradiol levels and hypothalamic pro-oxyphysin and GnRH transcript levels were also determined using enzyme-linked immunoassay and quantitative reverse transcription polymerase chain reaction, respectively. Results Maternal behaviors (% time crouching with pups, time off pups but not feeding, time feeding, and total number of nesting bouts were not significantly different in dnFGFR mice. However, dnFGFR dams were more likely to leave their pups scattered and took significantly longer to retrieve each pup compared to control dams. Further, dnFGFR mothers had significantly lower GnRH transcripts and circulating E2, but normal pro-oxyphysin transcript levels. Conclusions Overall, this study suggests a complex scenario in which a GnRH system compromised by reduced FGF signaling leads to not only suboptimal reproductive physiology, but also suboptimal maternal behavior.

  2. Histone deacetylases regulate gonadotropin-releasing hormone I gene expression via modulating Otx2-driven transcriptional activity.

    Lu Gan

    Full Text Available BACKGROUND: Precise coordination of the hypothalamic-pituitary-gonadal axis orchestrates the normal reproductive function. As a central regulator, the appropriate synthesis and secretion of gonadotropin-releasing hormone I (GnRH-I from the hypothalamus is essential for the coordination. Recently, emerging evidence indicates that histone deacetylases (HDACs play an important role in maintaining normal reproductive function. In this study, we identify the potential effects of HDACs on Gnrh1 gene transcription. METHODOLOGY/PRINCIPAL FINDINGS: Inhibition of HDACs activities by trichostatin A (TSA and valproic acid (VPA promptly and dramatically repressed transcription of Gnrh1 gene in the mouse immortalized mature GnRH neuronal cells GT1-7. The suppression was connected with a specific region of Gnrh1 gene promoter, which contains two consensus Otx2 binding sites. Otx2 has been known to activate the basal and also enhancer-driven transcription of Gnrh1 gene. The transcriptional activity of Otx2 is negatively modulated by Grg4, a member of the Groucho-related-gene (Grg family. In the present study, the expression of Otx2 was downregulated by TSA and VPA in GT1-7 cells, accompanied with the opposite changes of Grg4 expression. Chromatin immunoprecipitation and electrophoretic mobility shift assays demonstrated that the DNA-binding activity of Otx2 to Gnrh1 gene was suppressed by TSA and VPA. Overexpression of Otx2 partly abolished the TSA- and VPA-induced downregulation of Gnrh1 gene expression. CONCLUSIONS/SIGNIFICANCE: Our data indicate that HDAC inhibitors downregulate Gnrh1 gene expression via repressing Otx2-driven transcriptional activity. This study should provide an insight for our understanding on the effects of HDACs in the reproductive system and suggests that HDACs could be potential novel targets for the therapy of GnRH-related diseases.

  3. Influence of multiple injections of human chorionic gonadotropin (hCG) on urine and serum endogenous steroids concentrations.

    Strahm, Emmanuel; Marques-Vidal, Pedro; Pralong, François; Dvorak, Jiri; Saugy, Martial; Baume, Norbert


    Since it is established that human chorionic gonadotropin (hCG) affects testosterone production and release in the human body, the use of this hormone as a performance enhancing drug has been prohibited by the World Anti-Doping Agency. Nowadays, the only validated biomarker of a hCG doping is its direct quantification in urine. However, this specific parameter is subjected to large inter-individual variability and its determination is directly dependent on the reliability of hCG immunoassays used. In order to counteract these weaknesses, new biomarkers need to be evidenced. To address this issue, a pilot clinical study was performed on 10 volunteers submitted to 3 subsequent hCG injections. Blood and urine samples were collected during two weeks in order to follow the physiological effects on related compounds such as the steroid profile or hormones involved in the hypothalamo-pituitary axis. The hCG pharmacokinetic observed in all subjects was, as expected, prone to important inter-individual variations. Using ROC plots, level of testosterone and testosterone on luteinizing hormone ratio in both blood and urine were found to be the most relevant biomarker of a hCG abuse, regardless of inter-individual variations. In conclusion, this study showed the crucial importance of reliable quantification methods to assess low differences in hormonal patterns. In regard to these results and to anti-doping requirements and constraints, blood together with urine matrix should be included in the anti-doping testing program. Together with a longitudinal follow-up approach it could constitute a new strategy to detect a hCG abuse, applicable to further forms of steroid or other forbidden drug manipulation.

  4. The estrogen myth: potential use of gonadotropin-releasing hormone agonists for the treatment of Alzheimer's disease.

    Casadesus, Gemma; Garrett, Matthew R; Webber, Kate M; Hartzler, Anthony W; Atwood, Craig S; Perry, George; Bowen, Richard L; Smith, Mark A


    Estrogen and other sex hormones have received a great deal of attention for their speculative role in Alzheimer's disease (AD), but at present a direct connection between estrogen and the pathogenesis of AD remains elusive and somewhat contradictory. For example, on one hand there is a large body of evidence suggesting that estrogen is neuroprotective and improves cognition, and that hormone replacement therapy (HRT) at the onset of menopause reduces the risk of developing AD decades later. However, on the other hand, studies such as the Women's Health Initiative demonstrate that HRT initiated in elderly women increases the risk of dementia. While estrogen continues to be investigated, the disparity of findings involving HRT has led many researchers to examine other hormones of the hypothalamic-pituitary-gonadal axis such as luteinising hormone (LH) and follicle-stimulating hormone. In this review, we propose that LH, rather than estrogen, is the paramount player in the pathogenesis of AD. Notably, both men and women experience a 3- to 4-fold increase in LH with aging, and LH receptors are found throughout the brain following a regional pattern remarkably similar to those neuron populations affected in AD. With respect to disease, serum LH level is increased in women with AD relative to non-diseased controls, and levels of LH in the brain are also elevated in AD. Mechanistically, we propose that elevated levels of LH may be a fundamental instigator responsible for the aberrant reactivation of the cell cycle that is seen in AD. Based on these aforementioned aspects, clinical trials underway with leuprolide acetate, a gonadotropin-releasing hormone agonist that ablates serum LH levels, hold great promise as a ready means of treatment in individuals afflicted with AD.

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

    Apostolos K A Karagiannis


    Full Text Available Pituitary abscess is a rare life-threating entity that is usually misdiagnosed as a pituitary tumor with a definite diagnosis only made postoperatively. Over the last several decades, advances in healthcare have led to a significant decrease in morbidity and mortality due to pituitary abscess. We report a case of a 34-year-old woman who was admitted to our department for investigation of a pituitary mass and with symptoms of pituitary dysfunction, headaches and impaired vision. During her admission, she developed meningitis-like symptoms and was treated with antibiotics. She eventually underwent transsphenoidal surgery for excision of the pituitary mass. A significant amount of pus was evident intraoperatively; however, no pathogen was isolated. Six months later, the patient was well and had full recovery of the anterior pituitary function. Her menses returned, and she was only on treatment with desmopressin for diabetes insipidus that developed postoperatively.

  6. Regulation of pituitary cell function by adiponectin.

    Rodriguez-Pacheco, Francisca; Martinez-Fuentes, Antonio J; Tovar, Sulay; Pinilla, Leonor; Tena-Sempere, Manuel; Dieguez, Carlos; Castaño, Justo P; Malagon, María M


    Adiponectin is a member of the family of adipose tissue-related hormones known as adipokines, which exerts antidiabetic, antiatherogenic, antiinflammatory, and antiangiogenic properties. Adiponectin actions are primarily mediated through binding to two receptors expressed in several tissues, AdipoR1 and AdipoR2. Likewise, adiponectin expression has been detected in adipocytes as well as in a variety of extra-adipose tissues, including the chicken pituitary. Interestingly, adiponectin secretion and adiponectin receptor expression in adipocytes have been shown to be regulated by pituitary hormones. These observations led us to investigate whether adiponectin, like the adipokine leptin, regulates pituitary hormone production. Specifically, we focused our analysis on somatotrophs and gonadotrophs because of the relationship between the control of energy metabolism, growth and reproduction. To this end, the effects of adiponectin on both GH and LH secretion as well as its interaction with major stimulatory regulators of somatotrophs (ghrelin and GHRH) and gonadotrophs (GnRH) and with their corresponding receptors (GHS-R, GHRH-R, and GnRH-R), were evaluated in rat pituitary cell cultures. Results show that adiponectin inhibits GH and LH release as well as both ghrelin-induced GH release and GnRH-stimulated LH secretion in short-term (4 h) treated cell cultures, wherein the adipokine also increases GHRH-R and GHS-R mRNA content while decreasing that of GnRH-R. Additionally, we demonstrate that the pituitary expresses both adiponectin and adiponectin receptors under the regulation of the adipokine. In sum, our data indicate that adiponectin, either locally produced or from other sources, may play a neuroendocrine role in the control of both somatotrophs and gonadotrophs.

  7. Estrus behavior and fecal steroid profiles in the Asiatic lion (Panthera leo persica) during natural and gonadotropin-induced estrus.

    Umapathy, Govindhaswamy; Sontakke, Sadanand D; Srinivasu, K; Kiran, Thomas; Kholkute, S D; Shivaji, S


    In this paper the behavior of the Asiatic lion was studied during natural and gonadotropin-induced estrus in relation to fecal estradiol and progesterone concentration. The average length of estrus was 5.4 days and no significant difference was observed between natural and gonadotropin-induced estrus. Vocalization and rolling were the major estrus behavioral activities of Asiatic lions and the frequency of these activities were similar in both natural and gonadotropin-induced estrus and treatment with exogenous gonadotropin did not alter estrus behavioral activities. A significant positive correlation was observed between fecal estradiol and frequency of estrus behavior during natural and gonadotropin-induced estrus. Following gonadotropin treatment estrus could be induced in 69% of animals and these induced animals ovulated following hCG treatment. This study reports for the first time the successful use of the non-invasive fecal steroid assay for monitoring the induction of estrus and ovulation in the Asiatic lion.

  8. Thin-section CT scan of the pituitary gland

    Fukuda, T.; Inoue, Y.; Taniguchi, S. (Osaka City Univ. (Japan). Faculty of Medicine)


    Topographic anatomy of the pituitary fossa was studied by 2 mm thin-section CT scan (Somatom II). Nineteen with normal pituitary (control group) and 20 with suspected pituitary abnormality were selected. Plain and contrast CT were performed in all cases. Contrast CT was carried out immediately after the rapid infusion of 220 ml of 30% iodinated contrast medium. In all of control group but two, pituitary gland was detected as homogeneous density and its density was the same as the density of normal brain tissues, and was enhanced in degree of about 25 CT number. In 2 cases, small low density was visualized in the pituitary gland. Pituitary gland was differentiated from cavernous sinus was usually higher than the pituitary gland. In the abnormal group, microadenoma of the pituitary gland was diagnosed in 5 cases and 3 out of 5 cases was proved by surgery. All 3 microadenomas proved slightly dense by plain CT and enhanced higher than normal pituitary gland by contrast CT. Polytomograms showed no abnormality of the sella turcica in one of these 3 cases. Although 3 microadenomas were detected by the abnormal enhancement, we are not sure whether all microadenoma can be detected by CT alone. Arachnoid herniation into the pituitary fossa was diagnosed in 7 of the control group and 2 of the abnormal group. Four out of these 9 cases were verified by using Metrizamide CT. By plain thin-section CT, the diagnosis of arachnoid herniation seems to be possible without Metrizamide CT.

  9. 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

    Takeda, Tomoki; Taura, Junki; Hattori, Yukiko; Ishii, Yuji; Yamada, Hideyuki, E-mail:


    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. - Highlights: • The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on mouse growth was studied. • TCDD reduced the levels of luteinizing hormone and growth hormone in perinatal pups. • Maternal exposure to TCDD also attenuated testicular steroidogenesis in pups. • The above effects of TCDD were more pronounced in C57BL/6J than in DBA/2J

  10. Colorectal cancer manifesting with metastasis to prolactinoma: report of a case involving symptoms mimicking pituitary apoplexy.

    Thewjitcharoen, Yotsapon; Shuangshoti, Shanop; Lerdlum, Sukalaya; Siwanuwatn, Rungsak; Sunthornyothin, Sarat


    Pituitary metastasis is an uncommon first presentation of systemic malignancy. The most common presenting symptom of pituitary metastasis is diabetes insipidus reflecting involvement of the stalk and/or posterior pituitary. We herein present a unique case of the coexistence of both a functioning pituitary adenoma (prolactinoma) and pituitary metastasis of advanced colorectal cancer with pituitary apoplexy as the first manifestation of underlying malignancy. The present case emphasizes the need to consider pituitary metastasis as a differential diagnosis in patients presenting with pituitary lesions and be aware that tumor-to-tumor metastasis can occur unexpectedly in those with pituitary metastases.

  11. Chorionic gonadotropin and uterine dialogue in the primate

    Strakova Zuzana


    Full Text Available Abstract Implantation is a complex spatio-temporal interaction between the growing embryo and the mother, where both players need to be highly synchronized to be able to establish an effective communication to ensure a successful pregnancy. Using our in vivo baboon model we have shown that Chorionic Gonadotropin (CG, as the major trophoblast derived signal, not only rescues the corpus luteum but also modulates the uterine environment in preparation for implantation. This response is characterized by an alteration in both the morphological and biochemical activity in the three major cell types: luminal and glandular epithelium and stromal fibroblasts. Furthermore, CG and factors from the ovary have a synergistic effect on the receptive endometrium. Novel local effects of CG which influence the immune system to permit the survival of the fetal allograft and prevent endometrial cell death are also discussed in this review. An alternate extracellular signal-regulated kinase (ERK activation pathway observed in epithelial endometrial cells and the possibility of differential expression of the CG/LH-R isoforms during gestation, open many questions regarding the mechanism of action of CG and its signal transduction pathway within the primate endometrium.

  12. Temozolomide treatment in aggressive pituitary tumors and pituitary carcinomas: a French multicenter experience.

    Raverot, Gérald; Sturm, Nathalie; de Fraipont, Florence; Muller, Marie; Salenave, Sylvie; Caron, Philippe; Chabre, Olivier; Chanson, Philippe; Cortet-Rudelli, Christine; Assaker, Richard; Dufour, Henry; Gaillard, Stephan; François, Patrick; Jouanneau, Emmanuel; Passagia, Jean-Guy; Bernier, Michèle; Cornélius, Aurélie; Figarella-Branger, Dominique; Trouillas, Jacqueline; Borson-Chazot, Françoise; Brue, Thierry


    To date only 18 patients with aggressive pituitary tumors or carcinomas treated with temozolomide have been reported. Increased expression of O6-methylguanine-DNA-methyltranferase (MGMT) has been suggested to predict resistance to temozolomide. The objective of the study was to describe the antitumoral efficacy and toxicity of temozolomide in patients with aggressive pituitary tumors or carcinomas and evaluate the possible prognostic value of MGMT promoter methylation and protein expression. Eight patients, five with pituitary carcinomas (three prolactin (PRL) and two ACTH) and three with aggressive pituitary tumors (one PRL and two ACTH), all treated with temozolomide administered orally for four to 24 cycles, were included in our French multicenter study. MGMT expression was assessed by immunohistochemistry and MGMT promoter methylation by pyrosequencing. Three of the eight patients (two ACTH adenomas and one PRL carcinoma) responded to temozolomide as demonstrated by significant tumor shrinkage and reduced hormone secretion. Three cycles of temozolomide were sufficient to identify treatment-responsive patients. Additional cycles did not improve treatment efficacy in those not responding, even when associated with carboplatin and vepeside. MGMT expression did not predict tumoral response to temozolomide because it was positive in one responder and negative in two nonresponders. Similarly, MGMT promoter methylation (three of seven tumors) did not predict clinical response. Toxicity remained mild in all patients. Temozolomide treatment may be an effective option for some aggressive pituitary tumors or carcinomas. Response to a trial of three cycles of treatment seems sufficient to identify responders and more reliable than patient MGMT status.

  13. Progression of an Invasive ACTH Pituitary Macroadenoma with Cushing’s Disease to Pituitary Carcinoma

    Clarissa Groberio Borba


    Full Text Available Pituitary carcinomas are very rare tumors that in most cases produce prolactin and adrenocorticotropic hormone (ACTH. It is a challenge to diagnosis of a pituitary carcinoma before disclosed symptomatic metastasis. We report the case of a female patient with Cushing’s disease who underwent three transsphenoidal surgeries, with pathological findings of common ACTH pituitary adenoma including Ki-67 expression <3%. She achieved hypocortisolism after the 3rd surgery although ACTH levels remained slightly elevated. The patient returned some time later with fast worsening of hypercortisolism. Magnetic resonance imaging showed clivus invasion, which led to a fourth surgery and radiation. This time, immunohistochemistry revealed strong Ki-67 (10% to 15% and p53 expression. Liver and lumbar spine metastases were found on workup. The patient died after few months due to lung infection. Pituitary carcinomas are rare, and the transformation of an ACTH-secreting pituitary adenoma into a carcinoma is exceptional. The difficulty of defining markers for the diagnosis of carcinoma, before metastasis diagnosis, in order to change the management of the disease, is a challenge.

  14. Oxytocin and hypothalamo-pituitary- adrenal axis

    Berrak Ç. Yeğen


    Full Text Available BSTRACT: Upon exposure to different types of stressors, neuroendocrine and behavioral responses that include the activation of the hypothalamus-pituitary-adrenal (HPA axis are given to allow the individuals to cope with stress conditions. It was proven that oxytocin, anonapeptide released from the posterior pituitary, has behavioral and stress-attenuating effects by dampening HPA activity. On the other hand, the neuropeptide was also shown to exert anti-inflammatory effects through the modulation of immune and inflammatory processes in several experimental models of tissue injury. The findings of recent studies suggest that the anti-inflammatory effect of oxytocin depends on its role on HPA axis activity and subsequent release of cortisol. Thus, oxytocin seems to restrain the activity within the HPA-axis, which becomes overactive during many inflammatory processes

  15. Pituitary apoplexy presenting as myocardial infarction

    Vishal Gupta


    Full Text Available We describe a male patient who presented with sudden onset severe headache and right sided ptosis that was diagnosed to be secondary to pituitary apoplexy on the background of diabetes mellitus. This was complicated by left ventricular failure and acute coronary syndrome. The case highlights the importance of considering hypocortisolism/hypopituitarism as an important and rare precipitant of an acute coronary event as occurred in the case.

  16. Pituitary gland volumes in bipolar disorder.

    Clark, Ian A; Mackay, Clare E; Goodwin, Guy M


    Bipolar disorder has been associated with increased Hypothalamic-Pituitary-Adrenal axis function. The mechanism is not well understood, but there may be associated increases in pituitary gland volume (PGV) and these small increases may be functionally significant. However, research investigating PGV in bipolar disorder reports mixed results. The aim of the current study was twofold. First, to assess PGV in two novel samples of patients with bipolar disorder and matched healthy controls. Second, to perform a meta-analysis comparing PGV across a larger sample of patients and matched controls. Sample 1 consisted of 23 established patients and 32 matched controls. Sample 2 consisted of 39 medication-naïve patients and 42 matched controls. PGV was measured on structural MRI scans. Seven further studies were identified comparing PGV between patients and matched controls (total n; 244 patients, 308 controls). Both novel samples showed a small (approximately 20mm(3) or 4%), but non-significant, increase in PGV in patients. Combining the two novel samples showed a significant association of age and PGV. Meta-analysis showed a trend towards a larger pituitary gland in patients (effect size: .23, CI: -.14, .59). While results suggest a possible small difference in pituitary gland volume between patients and matched controls, larger mega-analyses with sample sizes greater even than those used in the current meta-analysis are still required. There is a small but potentially functionally significant increase in PGV in patients with bipolar disorder compared to controls. Results demonstrate the difficulty of finding potentially important but small effects in functional brain disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Hypothalamic-pituitary dysfunction in respiratory hypoxia.

    Semple, P D; Beastall, G H; Watson, W S; Hume, R


    Eight hypoxic male patients with stable chronic obstructive airways disease were submitted for combined anterior pituitary function testing. All subjects showed normal growth hormone and essentially normal cortisol responses to adequate hypoglycaemia, two subjects showed delayed responses of thyroid stimulating hormone to administered thyrotrophin releasing hormone and all had basal prolactin levels within normal limits. Basal levels of luteinising hormone were significantly lower than in the...

  18. Population pharmacokinetic/pharmacodynamic (PK/PD) modelling of the hypothalamic-pituitary-gonadal axis following treatment with GnRH analogues

    Tornøe, Christoffer Wenzel; Agersø, Henrik; Senderovitz, Thomas;


    Aims To develop a population pharmacokinetic/pharmacodynamic (PK/PD) model of the hypothalamic-pituitary-gonadal (HPG) axis describing the changes in luteinizing hormone (LH) and testosterone concentrations following treatment with the gonadotropin-releasing hormone (GnRH) agonist triptorelin...... and the GnRH receptor blocker degarelix. Methods Fifty-eight healthy subjects received single subcutaneous or intramuscular injections of 3.75 mg of triptorelin and 170 prostate cancer patients received multiple subcutaneous doses of degarelix of between 120 and 320 mg. All subjects were pooled...... for the different dynamic responses observed after administration of both GnRH agonists and GnRH receptor blockers, suggesting that the model adequately characterizes the underlying physiology of the endocrine system....

  19. Population pharmacokinetic/pharmacodynamic (PK/PD) modelling of the hypothalamic-pituitary-gonadal axis following treatment with GnRH analogues

    Tornøe, Christoffer Wenzel; Agersø, Henrik; Senderovitz, Thomas


    for the population PK/PD data analysis. A systematic population PK/PD model-building framework using stochastic differential equations was applied to the data to identify nonlinear dynamic dependencies and to deconvolve the functional feedback interactions of the HPG axis. Results In our final PK/PD model of the HPG......Aims To develop a population pharmacokinetic/pharmacodynamic (PK/PD) model of the hypothalamic-pituitary-gonadal (HPG) axis describing the changes in luteinizing hormone (LH) and testosterone concentrations following treatment with the gonadotropin-releasing hormone (GnRH) agonist triptorelin...... for the different dynamic responses observed after administration of both GnRH agonists and GnRH receptor blockers, suggesting that the model adequately characterizes the underlying physiology of the endocrine system....

  20. Temozolomide in aggressive pituitary adenomas and carcinomas

    Leon D. Ortiz


    Full Text Available Temozolomide is an alkylating agent used in the treatment of gliomas and, more recently, aggressive pituitary adenomas and carcinomas. Temozolomide methylates DNA and, thereby, has antitumor effects. O6-methylguanine-DNA methyltransferase, a DNA repair enzyme, removes the alkylating adducts that are induced by temozolomide, thereby counteracting its effects. A Medline search for all of the available publications regarding the use of temozolomide for the treatment of pituitary tumors was performed. To date, 46 cases of adenohypophysial tumors that were treated with temozolomide, including 30 adenomas and 16 carcinomas, have been reported. Eighteen of the 30 (60% adenomas and 11 of the 16 (69% carcinomas responded favorably to treatment. One patient with multiple endocrine neoplasia type 1 and an aggressive prolactin-producing adenoma was also treated and demonstrated a good response. No significant complications have been attributed to temozolomide therapy. Thus, temozolomide is an effective treatment for the majority of aggressive adenomas and carcinomas. Evidence indicates that there is an inverse correlation between levels of O6-methylguanine-DNA methyltransferase immunoexpression and therapeutic response. Alternatively, high-level O6-methylguanine-DNA methyltransferase immunoexpression correlates with an unfavorable response. Here, we review the use of temozolomide for treating pituitary neoplasms.

  1. Advances in trans-sphenoidal pituitary surgery.

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


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

  2. Autocrine IL-6 mediates pituitary tumor senescence

    Fuertes, Mariana; Ajler, Pablo; Carrizo, Guillermo; Cervio, Andrés; Sevlever, Gustavo; Stalla, Günter K.; Arzt, Eduardo


    Cellular senescence is a stable proliferative arrest state. Pituitary adenomas are frequent and mostly benign, but the mechanism for this remains unknown. IL-6 is involved in pituitary tumor progression and is produced by the tumoral cells. In a cell autonomous fashion, IL-6 participates in oncogene-induced senescence in transduced human melanocytes. Here we prove that autocrine IL-6 participates in pituitary tumor senescence. Endogenous IL-6 inhibition in somatotroph MtT/S shRNA stable clones results in decreased SA-β-gal activity and p16INK4a but increased pRb, proliferation and invasion. Nude mice injected with IL-6 silenced clones develop tumors contrary to MtT/S wild type that do not, demonstrating that clones that escape senescence are capable of becoming tumorigenic. When endogenous IL-6 is silenced, cell cultures derived from positive SA-β-gal human tumor samples decrease the expression of the senescence marker. Our results establish that IL-6 contributes to maintain senescence by its autocrine action, providing a natural model of IL-6 mediated benign adenoma senescence. PMID:27902467

  3. Final Oocyte Maturation in Assisted Reproduction with Human Chorionic Gonadotropin and Gonadotropin-releasing Hormone agonist (Dual Trigger).

    Oliveira, Sofia Andrade de; Calsavara, Vinícius Fernando; Cortés, Gemma Castillón


    Final oocyte maturation with Human Chorionic Gonadotropin (hCG) and ovarian stimulation with Follicle Stimulation Hormone (FSH) combined with Gonadotrophin-releasing Hormone (GnRH) antagonist to block Luteinizing hormone (LH) surge is a standard procedure of in vitro Fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI). However, GnRH agonist has been replacing the use of hCG in certain situations, especially in patients at risk of Ovarian Hyperstimulation Syndrome (OHSS). Some studies have also shown advantages in the combined use of GnRH agonist concurrently with hCG in inducing final oocyte maturation, a treatment known as "Dual Trigger". In theory, this method combines the advantages of both induction regimens, and it has brought promising results. The objective of this study is to compare Dual Trigger with the use of hCG alone or the use of GnRH agonist alone. A systematic review of articles on Dual Trigger and a retrospective cohort study comparing the three methods of induction of final oocyte maturation have been conducted. It has been found that Dual Triggering for poor responder patients had a statistically significant increase in the number of retrieved oocytes, mature oocytes, and fertilized embryos in the positive beta hCG rate, implantation rate, and newborn/transferred embryo (TE) rate.

  4. Pituitary transplantation: Part 1. Successful reconstitution of pituitary-dependent hormone levels.

    Tulipan, N B; Zacur, H A; Allen, G S


    Neonatal or adult pituitary glands were transplanted to the median eminence of adult rats of the same or a histoincompatible inbred strain. The hormonal status of 39 transplanted rats and of control animals was evaluated by serial determination of serum prolactin and thyroxine. Grafts of neonatal tissue to adults of the same strain resulted in normal postoperative hormone levels. This indicates not only that pituitary grafts had survived, but also that the transplants were under hypothalamic control. Grafts of adult tissue were less successful. The prolactin value was lower, but still within the normal range, whereas the thyroxine value was lower than normal, suggesting that viable pituitary tissue had survived but was not under hypothalamic control. Transplantation across a histocompatibility barrier was uniformly unsuccessful. Postoperative prolactin levels were low and thyroxine levels were not significantly different from those in hypophysectomized controls.

  5. Pituitary oncocytoma presenting as Cushing′s disease

    M K Garg


    Full Text Available A 19-year-old girl presented with classical features of Cushing′s syndrome. Endocrinal evaluation was consistent with pituitary source of ACTH; but imaging showed normal pituitary. Bilateral inferior petrosal sinus sampling confirmed the diagnosis. A successful remission was achieved after adenomectomy by transphenoidal route. Histopathological examination was consistent with pituitary oncocytoma and immunohistochemistry was positive for synaptophysin, chromogranin, neuron specific enolase, S-100, ACTH, prolactin, and GH.

  6. A gonadotropin-releasing hormone-like molecule modulates the activity of diverse central neurons in a gastropod mollusk, Aplysia californica

    Biao eSun


    Full Text Available In vertebrates, gonadotropin-releasing hormone (GnRH is a crucial decapeptide that activates the hypothalamic-pituitary-gonadal (HPG axis to ensure successful reproduction. Recently, a GnRH-like molecule has been isolated from a gastropod mollusk, Aplysia californica. This GnRH (ap-GnRH is deduced to be an undecapeptide, and its function remains to be explored. Our previous study demonstrated that ap-GnRH did not stimulate a range of reproductive parameters. Instead, it affected acute behavioral and locomotive changes unrelated to reproduction. In this study, we used electrophysiology and retrograde tracing to further explore the central role of ap-GnRH. Sharp electrode intracellular recordings revealed that ap-GnRH had diverse effects on central neurons that ranged from excitatory, inhibitory, to the alteration of membrane potential. Unexpectedly, extracellular recordings revealed that ap-GnRH suppressed the onset of electrical afterdischarge (AD in bag cell neurons, suggesting an inhibitory effect on female reproduction. Lastly, using immunocytochemistry (ICC coupled with nickel-backfill, we demonstrated that some ap-GnRH neurons projected to efferent nerves known to innervate the foot and parapodia, suggesting ap-GnRH may directly modulate the motor output of these peripheral tissues. Overall, our results suggested that in A. californica, ap-GnRH more likely functioned as a central modulator of complex behavior and motor regulation rather than as a conventional reproductive stimulator.

  7. Effects of MboII and BspMI polymorphisms in the gonadotropin releasing hormone receptor (GnRHR) gene on sperm quality in Holstein bulls.

    Yang, Wu-Cai; Tang, Ke-Qiong; Yu, Jun-Na; Zhang, Chun-Yan; Zhang, Xiao-Xia; Yang, Li-Guo


    The hypothalamic gonadotropin-releasing hormone receptor (GnRHR) plays an essential physiological role in reproductive function, which triggers the synthesis and release of luteinizing hormone and follicle stimulating hormone in the pituitary. The objective of this study was to investigate the effects of polymorphisms of GnRHR gene on the quality of fresh and frozen semen in Holstein bulls. The PCR-RFLP method was applied to detect G286A and T340C transitions determining MboII and BspMI polymorphisms, respectively, in the exon I of bovine GnRHR gene and evaluated its associations with sperm quality traits in 131 Holstein bulls. In polymorphic locus 286, bulls with the GA genotype had significantly higher sperm motility in frozen semen (FMOT) than GG genotype (P bulls with heterozygote CT genotype had significantly higher sperm motility (MOT), semen volume per ejaculate (VOL), and lower abnormal spermatozoa rate (ASR) than homozygote TT genotype (P Bulls contained one A allele or C allele had a favorable, positive effect on sperm quality traits. These results indicate that GnRHR gene can be a potential marker for improving sperm quality traits, and imply that bulls with GA or CT genotype should be selected in breeding program.

  8. β-human chorionic gonadotropin-secreting intracranial germ-cell tumor associated with high testosterone in an adult man: A case report.

    Yang, Wen-Ping; Chien, Hung-Yu; Lin, Yi-Chun


    A 38-year-old male patient presented with general weakness, polydipsia and a body weight loss of 10 kg in two years. Hypopituitarism with central hypothyroidism and central adrenal insufficiency were noted at Taipei City Hospital (Taipei, Taiwan). However, hypogonadotropic hypergonadism was also observed. The patient was diagnosed with an intracranial β-human chorionic gonadotropin (β-hCG) secreting germ-cell tumor, and brain magnetic resonance imaging revealed that the tumor involved the pineal gland, stalk, posterior pituitary gland, right basal ganglion, hypothalamus, corpus callosum and posterior hippocampus. The cerebrospinal fluid (CSF) β-hCG level was 1936 IU/l, while the α-fetoprotein (AFP) level was 2:1. The patient was successfully treated with chemotherapy and radiotherapy, as demonstrated by a marked decrease in size of the tumor and in the serum β-hCG levels. Intracranial β-hCG secreting germ-cell tumors are rare in adults and manifest differently compared with patients of early pubertal age. In contrast with the precocious puberty frequently observed in young patients, the diagnosis of adult patients is often delayed and the symptoms are associated with tumor size and location. The present case report described an adult male with an intracranial β-hCG secreting GCT, demonstrating hypopituitarism and asymptomatic hyperandrogenemia, and reviews and discusses the literature relevant to the case.

  9. [Impact of pregnancy on pituitary disorders].

    Marek, J


    In pregnancy, the volume of pituitary increases by multiplication of lactotopic and gonadotropic cells and developing placenta is the source of numerous hormones and enzymes that significantly affect and alter the function of the endocrine system. This naturally has an impact on the course of pituitary disorders and their treatment. The most common disorders of pituitary gland, which we can meet in pregnancy, are adenomas, particularly prolactinomas, and functionless adenomas. During pregnancy we avoid the treatment of microprolactinomas, but in macroprolactinomas where there is the risk of their enlargement by stimulation of placental estrogens, we administer preventively the dopaminergic agonists. Patients with acromegaly usually do not need the treatment during pregnancy, unless there is a danger to damage the visual pathway or heavy headaches occur. ACTH secreting adenomas (Cushings disease) in pregnancy are rare, they are difficult to diagnose but existing hypercortisolism is very dangerous to fetus and may damage even mother. Large functionless adenomas, unless treated before pregnancy, may damage the visual pathway. The volume of the enlarged pituitary gland in pregnancy and sometimes even of the functionless adenoma adenoma, may be reduced by cabergoline, so that the urgent neurosurgery in pregnancy is very rare. A typical disease that occurs primarily in pregnant women is autoimmune lymphocytic hypophysitis. Diagnosis is established on the basis of headaches and symptoms and signs of the deficits of adrenocorticotropic and thyreotropic function usually in the last third of pregnancy or in the first six months after birth, using a specific image in magnetic resonance. Treatment is limited to hormone replacement. It is also possible to meet pregnant women with deficient pituitary functions. In hypocortical women with exception of strains like as pregnancy vomiting, doses of hydrocortisone replacement usually do not change until birth. Childbirth, however

  10. The molecular pathogenesis of pituitary tumors: implications for clinical management.

    Dworakowska, D; Grossman, A B


    Pituitary adenomas are unique in several ways, and while they are rarely malignant they may be invasive and/or recurrent. Several attempts have been made to determine the growth potential of pituitary adenomas. Pituitary tumors predominantly arise in a sporadic setting or more rarely as part of hereditary genetic syndromes. Molecular analysis of these familial pituitary adenomas has provided significant insight into pituitary tumorigenesis. Some specific genes have been identified that predispose to pituitary neoplasia, but these are rarely involved in the pathogenesis of sporadic tumors. The number of genes or molecular alterations involved in pituitary tumorigenesis is progressively increasing, providing a hope for development of new predictive and prognostic markers. The aim of this review is to focus on the molecular pathology of pituitary adenomas in the context of their implications on management and targeted therapy. We have summarized our current knowledge on the molecular biology in familial and sporadic pituitary adenomas, and we subsequently focus on prognostic factors as well as specific predictive markers for new promising targeted therapies.

  11. MRI of the hypothalamic-pituitary axis in children

    Argyropoulou, Maria I. [University of Ioannina, Department of Radiology, Medical School, Ioannina (Greece); Kiortsis, Dimitrios Nikiforos [University of Ioannina, Department of Physiology, Medical School, Ioannina (Greece)


    In childhood, the MR characteristics of the normal pituitary gland are well established. During the first 2 months of life the adenohypophysis demonstrates high signal. Pituitary gland height (PGH) decreases during the 1st year of life and then increases, reaching a plateau after puberty. The magnetization transfer ratio (MTR) increases in both sexes up to the age of 20 years. On dynamic contrast-enhanced studies, the posterior pituitary lobe enhances simultaneously with the straight sinus, and the adenohypophysis later, but within 30 s. In genetically determined dysfunctional states, the adenohypophysis may be normal, hypoplastic, or enlarged. Pituitary enlargement, observed in Prop 1 gene mutations, is characterized by a mass interposed between the anterior and posterior lobes. An ectopic posterior lobe (EPP), associated with a hypoplastic or absent pituitary stalk, may be observed in patients with hypopituitarism. Tumors of the hypothalamic-pituitary (HP) axis may be the origin of adenohypophyseal deficiencies. A small hypointense adenohypophysis is found in iron overload states and is often associated with hypogonadotrophic hypogonadism. Absence of the posterior lobe bright signal, with or without a thick pituitary stalk or a mass at any site from the median eminence to the posterior pituitary lobe, may be found in diabetes insipidus. Hydrocephalus, suprasellar arachnoid cysts, hypothalamic hamartomas and craniopharyngiomas may result in central precocious puberty (CPP). Increased PGH in girls with idiopathic CPP is useful for its differential diagnosis from premature thelarche (PT). Pituitary adenomas, observed mainly in adolescents, present the same MR characteristics as those in adults. (orig.)

  12. Aspergillosis of the sphenoid sinus simulating a pituitary tumor

    Larranaga, J.; Fandino, J.; Gomez-Bueno, J.; Botana, C.; Rodriguez, D.; Gonzalez-Carrero, J.


    Sphenoidal aspergillosis is an unusual cause of sella turcica enlargement. Pituitary abscess secondary to Aspergillus had been reported. In the present case, a woman with sphenoid sinus aspergillosis mimiced a pituitary tumor. This patient survived her infection with intact pituitary function following a transsphenoidal approach. No postoperative amphotericine-B and 5-fluorocytosine were necessary. CT scan revealed a mass occupying the sphenoid sinus extending to the sella turcica. Factors that should alert the clinican to the presence of a sphenoidal and pituitary abscess in a patient with sella turcica enlargement are prior episodes of sinusitis, meningitis and immunosuppression and, as in the present case, hyperglycemia. (orig.).

  13. Consensus statement on the use of gonadotropin-releasing hormone analogs in children

    Carel, Jean-Claude; Eugster, Erica A; Rogol, Alan;


    OBJECTIVE: Gonadotropin-releasing hormone analogs revolutionized the treatment of central precocious puberty. However, questions remain regarding their optimal use in central precocious puberty and other conditions. The Lawson Wilkins Pediatric Endocrine Society and the European Society...... for Pediatric Endocrinology convened a consensus conference to review the clinical use of gonadotropin-releasing hormone analogs in children and adolescents. PARTICIPANTS: When selecting the 30 participants, consideration was given to equal representation from North America (United States and Canada) and Europe...... assembly for final review. If consensus could not be reached, conclusions were based on majority vote. All participants approved the final statement. CONCLUSIONS: The efficacy of gonadotropin-releasing hormone analogs in increasing adult height is undisputed only in early-onset (girls

  14. Molecular Mechanisms of Gonadotropin-Releasing Hormone Signaling: Integrating Cyclic Nucleotides into the Network

    Craig Alexander McArdle


    Full Text Available Gonadotropin-releasing hormone (GnRH is the primary regulator of mammalian reproductive function in both males and females. It acts via G-protein coupled receptors on gonadotropes to stimulate synthesis and secretion of the gonadotropin hormones luteinizing hormone and follicle-stimulating hormone. These receptors couple primarily via G-proteins of the Gq/11 family, driving activation of phospholipase C and mediating GnRH effects on gonadotropin synthesis and secretion. There is also good evidence that GnRH causes activation of other heterotrimeric G-proteins (Gs and Gi with consequent effects on cyclic AMP production, as well as for effects on the soluble and particulate guanylyl cyclases that generate cGMP. Here we provide an overview of these pathways. We emphasise mechanisms underpinning pulsatile hormone signaling and the possible interplay of GnRH and autocrine or paracrine regulatory mechanisms in control of cyclic nucleotide signaling.

  15. Relationship between stem cell factor and gonadotropin in ovarian follicles development during superovulation cycles

    WANG Gui-hong; ZHAO Hai-bo; XIN Xiao-yan; LIN Guo-cheng


    Objective: To study whether stem cell factor (SCF) and gonadotropin work synergisticly in superovulation stimulation of an in-vitro fertilization and embryo transfer (IVF-ET) program. Methods: Total cycles of 30 IVF-ET patients with regular menstrual period were studied. The same superovulation regimen was employed. Enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA) were used to determine the levels of SCF, follicular-stimulating hormone (FSH) and luteinizing hormone (LH) in follicular fluid (FF) during ooeyte pick-up (OPU) and in serum before and after superovulation. Results: FF-SCF of follicles with diameter over 20 mm were different in three groups [(2. 6±0. 4), (4. 7±0. 5), and (5.3±0. 9), respectively, P<0. 01], whereas the total numbers of developing follicles (diametre≥5 mm) were similar. Conclusion: SCF and gonadotropin may have synergistic effects on the development of follicles during gonadotropin stimulation in IVF-ET program.

  16. MR imaging in children with ectopic pituitary gland and anterior hypopituitarism.

    Patkar D


    Full Text Available Posterior pituitary ectopia refers to an absent normal posterior pituitary bright spot within the sella with ectopic bright signal at another site (such as the median eminence on a weighted magnetic resonance. We describe two children with idiopathic anterior hypopituitarism who showed an ectopic posterior pituitary and absent pituitary stalk on imaging. We emphasize the association of the absent pituitary stalk in ectopic pituitary gland and low growth hormone levels.

  17. Hypopituitarism as the presenting feature of bronchogenic carcinoma with metastases to the pituitary gland

    Philip C Johnston


    Full Text Available Tumours metastasizing to the pituitary gland are uncommon. Symptomatic patients with pituitary metastases can present with diabetes insipidus, headache, visual field defects and/or anterior pituitary hormonal dysfunction. Treatment options for pituitary metastases include, surgical resection, cranial or parasellar irradiation and/or chemotherapy, and hormonal replacement if indicated. The overall prognosis of pituitary metastases is poor. We present a case of hypopituitarism as the presenting feature of bronchogenic carcinoma with metastases to the pituitary gland.

  18. Quantitative evaluation of indium-111 (In-111) octreotide pituitary activity: Comparison in patient with and without pituitary tumors

    Gupta, P.; Waxman, A.; Nguyen, K. [Cedars-Sinai Medical Center, Los Angeles, CA (United States)] [and others


    Indium 111 Octreotide is known to detect pituitary tumors. Variable low level pituitary activity has been reported in pts. with no demonstrable pituitary tumors. To our knowledge, there have been no studies which quantitatively categorize pituitary activity with respect to distinguishing normal subject from pts. with pituitary tumors. 13 pts. with proven, treated acromegaly were included, as well as 15 pts. with no history of pituitary disorder. Both groups underwent SPECT In-111 scintigraphy 24 hours post-injection Average count per pixel ratios were obtained for the pituitary/calvarium (P/C) and pituitary/brain (P/B) regions. 10 pts. with acromegaly underwent growth hormone (GH) measurements 2 hours post-glucose load. Statistical correlation between growth hormone levels using P/C and P/B ratios were obtained. P/C ratios, as well as P/B ratios demonstrated high correlation with serum GH levels correlation coefficient(r)= .717 for P/C p<0.05, and correlation coefficient(r) = 0.828 for P/B ratios p<0.005. P/C ratios and P/B ratios for controls correlated closely with the upper level of normal predicted by P/C or P/B ratios as a function of serum growth hormone found in patients with acromegaly. Somatostatin receptor SPECT scintigraphy of the pituitary and appropriate quantitation can predict patients with growth hormone secreting tumors.

  19. Gonadotrofina coriônica humana e hormônio liberador de gonadotrofina como indutores da reprodução do jundiá = Human chorionic gonadotropin and gonadotropin-releasing hormone as breeding inducers of jundiá

    Paulo César Falanghe Carneiro


    Full Text Available Este trabalho foi realizado com o objetivo de avaliar parâmetros reprodutivos de machos e fêmeas de jundiá adultos após a aplicação do HCG (gonadotrofina coriônica humana e do GnRHa (hormônio liberador do hormônio gonadotrópico e compará-los àqueles obtidos quando usado o extrato hipofisário da carpa comum. Etapa 1 (Machos - quatro grupos, com oito machos cada, receberam os seguintes tratamentos: M1: sem hormônio; M2: extrato hipofisário 0,5 mg kg-1; M3: HCG 200 UI kg-1; M4: GnRHa+inibidor dopaminergético 0,1 glóbulo(Ovopel® kg-1. Etapa 2 (fêmeas – 36 fêmeas foram divididas em cinco grupos: F1: extrato hipofisário em duas aplicações, 0,5 e 5,0 mg kg-1; F2: HCG em duas aplicações, 200 e 400 UI kg-1; F3: HCG 400 UI kg-1 em doseúnica; F4: HCG 1000 UI kg-1 em dose única; F5: GnRHa+inibidor dopaminergético 1 glóbulo(Ovopel® kg-1. O uso do extrato hipofisário da carpa comum aumentou significativamente o volume de sêmen liberado e estimulou maior quantidade de fêmeas à liberar óvulos. O HCG e o GnRHa não apresentaram resultados positivos no tocante à reprodução induzida do jundiá, nas doses utilizadas neste estudo.In this study we analyzed reproductive parameters of males and females of jundiá induced by HCG (human chorionic gonadotropin and GnRHa (gonadotropin-releasing hormone, and compared the results tothose using carp pituitary extract. Stage 1 (Males - four groups with eight males each received one of the following treatments: M1: without hormone; M2: pituitary extract 0.5 mg kg-1; M3: HCG 200 UI kg-1; M4: GnRHa+dopamine receptor antagonist 0.1 pellet (Ovopel® kg-1. Stage 2 (Females – thirty-six females were separated in 5 groups: F1: pituitary extract in two applications, 0.5 and 5.0 mg kg-1; F2: HCG in two applications, 200 and 400 UI kg-1; F3: HCG 400 UI kg-1 in a single dose; F4: HCG 1000 UI kg-1 in a singledose; F5: GnRHa+dopamine receptor antagonist 1 pellet (Ovopel® kg-1. The pituitary extract

  20. Gonadotropin promotion of adventitious root production on cuttings of Begonia semperflorens and Vitis vinifera.

    Leshem, Y; Lunenfeld, B


    Adventitious rooting of Begonia semperflorens cv. Indian Maid and Vitis vinifera cv. Semillon stem cuttings was significantly promoted by human chorionic gonadotropin (HCG). Basal sections of HCG treated cuttings upon which promoted rooting took place had markedly less endogenous gibberellin (GA) activity than non-treated controls or apical sections of treated ones, while changes in auxin levels were not found. HCG also inhibited GA(3)-induced reducing sugar release from embryoless barley endosperm halves. These findings are discussed in the light of a possible analogy to gonadotropin action in animal systems.

  1. Gonadotropin Promotion of Adventitious Root Production on Cuttings of Begonia semperflorens and Vitis vinifera 1

    Leshem, Y.; Lunenfeld, B.


    Adventitious rooting of Begonia semperflorens cv. Indian Maid and Vitis vinifera cv. Semillon stem cuttings was significantly promoted by human chorionic gonadotropin (HCG). Basal sections of HCG treated cuttings upon which promoted rooting took place had markedly less endogenous gibberellin (GA) activity than non-treated controls or apical sections of treated ones, while changes in auxin levels were not found. HCG also inhibited GA3-induced reducing sugar release from embryoless barley endosperm halves. These findings are discussed in the light of a possible analogy to gonadotropin action in animal systems. PMID:5641189

  2. [Activity of clobazam on plasma prolactin and gonadotropins after administration of sulpiride in the male rat].

    Valli, M; Courtiere, A; Tamalet, C; Jadot, G


    The acute administration of the 1,5 benzodiazepine clobazam (20 and 100 mg/kg orally) reduces the sulpiride-induced release of prolactin in the male rat. The decrease in prolactin plasma level is respectively of 66 and 75% for the two doses, whereas it has minimal effects on the gonadotropins (FSH and LH). The clobazam induced prolactin lowering effect is compared to the one observed after diazepam administration. Finally, we have shown that the two benzodiazepines have no effect either on prolactin or on gonadotropins, when administered alone.

  3. Purification of pituitary autoantigen by column liquid chromatography and chromatofocusing.

    Gut, Paweł; Fischbach, Jakub; Ziemnicka, Katarzyna; Bączyk, Maciej; Baszko-Błaszyk, Daria; Wrotkowska, Elżbieta; Ruchała, Marek


    Pituitary autoantibodies can be determined both in patients with pituitary disease as well as patients with autoimmune endocrine diseases. The purpose of the study was to isolate and purify pituitary autoantigen using sera of patients and the microsomal fraction of the pituitary. To isolate a pituitary autoantigen, patient sera were used, which showed a strong immune response to pituitary antigens. Pituitary microsomal fractions were prepared from pituitary tissue homogenates. In the study, sera of patients with pituitary disease, Addison and Graves' disease were used. The initial stages were carried out by affinity chromatography on CN -Br sepharose column whereas purification was continued by column liquid chromatography on AcA54 Ultrogel. Chromatofocusing was performed by Polybuffer exchanger PBE 94. (125)I-labeled pituitary antigens after isolation appeared in column chromatography in three peaks. The first peak contained 50-70 kDa proteins, the second peak - 17 to 22 kDa proteins and the third peak contains (125)-iodides. Three fractions obtained from filtration on Ultrogel were separated in a polyacrylamide gel. In the first peak two bands 67 and 55 kDa appeared. The second peak contained low molecular weight substances, and the third peak contained (125)I. The first peak from Ultrogel was isolated by chromatofocusing - the first peak with pH 5.9 and the second one with pH 4.9. Isolation and purification of pituitary autoantigen with the use of column liquid chromatography and chromatofocusing resulted in obtainment of two antigenic proteins of specific gravity of 67 and 55 kDa.

  4. Pituitary imaging findings in male patients with hypogonadotrophic hypogonadism.

    Hirsch, Dania; Benbassat, Carlos; Toledano, Yoel; S'chigol, Irena; Tsvetov, Gloria; Shraga-Slutzky, Ilana; Eizenberg, Yoav; Shimon, Ilan


    Data on pituitary imaging in adult male patients presenting with hypogonadotrophic hypogonadism (HH) and no known pituitary disease are scarce. To assess the usefulness of pituitary imaging in the evaluation of men presenting with HH after excluding known pituitary disorders and hyperprolactinemia. A historical prospective cohort of males with HH. Men who presented for endocrine evaluation from 2011 to 2014 with testosterone levels pituitary disease. Seventy-five men were included in the analysis. Their mean age and BMI were 53.4 ± 14.8 years and 30.7 ± 5.2 kg/m2, respectively. Mean total testosterone, LH, and FSH were 6.2 ± 1.7 nmol/L, 3.4 ± 2 and 4.7 ± 3.1 mIU/L, respectively. Prolactin level within the normal range was obtained in all men (mean 161 ± 61, range 41-347 mIU/L). Sixty-two men had pituitary MRI and 13 performed CT. In 61 (81.3%) men pituitary imaging was normal. Microadenoma was found in 8 (10.7%), empty sella and thickened pituitary stalk in one patient (1.3%) each. In other four patients (5.3%) a small or mildly asymmetric pituitary gland was noted. No correlation was found between testosterone level and the presence of pituitary anomalies. This study suggests that the use of routine hypothalamic-pituitary imaging in the evaluation of IHH, in the absence of clinical characteristics of other hormonal loss or sellar compression symptoms, will not increase the diagnostic yield of sellar structural abnormalities over that reported in the general population.

  5. Role of Gonadotropin-releasing Hormone Stimulation Test in Diagnosing Gonadotropin Deficiency in Both Males and Females with Delayed Puberty

    Qi-Hong Sun; Yu Zheng; Xiao-Lin Zhang; Yi-Ming Mu


    Background:Delayed puberty can result either from constitutional delay of growth and puberty (CDP) or idiopathic hypogonadotropic hypogonadism (IHH).Gonadotropin-releasing hormone (GnRH) stimulation test has been generally accepted as a current method for diagnosing delayed puberty.The objective of this research was to assess the cut-off values and the efficacy of GnRH stimulation test in the diagnosis of delayed puberty in both males and females.Methods:A study of 91 IHH,27 CDP patients,6 prepubertal children,and 20 pubertal adults was undertaken.Blood samples were obtained at 0,30,60,and 120 min after GnRH administration and the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured.For each parameter,the sensitivities and specificities were estimated,and the receiver operating characteristic (ROC) curves were constructed.Results:The ROC curves indicated that a serum basal LH <0.6 IU/L or peak LH <9.74 IU/L resulted in moderate sensitivity (73.8% or 80.0%) and specificity (90.9% or 86.4%) in the diagnosis of HH in males.Serum basal LH <0.85 IU/L or basal FSH <2.43 IU/L resulted in moderate sensitivity (80.0% or 100.0%) and specificity (75.0% or 50.0%) in the diagnosis of HH in females.Conclusions:Our data suggest that isolated use of the gonadorelin stimulation test is almost sufficient to discriminate between HH and CDP in males,but unnecessary in females.The most useful predictor is serum basal or peak LH to differentiate these two disorders in males,but serum basal LH or FSH in females.

  6. Non-functioning pituitary tumors: 2012 update.

    Cámara Gómez, Rosa


    Non-functioning pituitary adenomas are the most common pituitary macroadenomas in adults, accounting for approximately 14%-28% of all clinically relevant pituitary tumors. They are a heterogeneous group of tumors that cause symptoms by compression and/or hormone deficiencies. The possibility of tumor growth is increased in macroadenomas and solid tumors as compared to microadenomas and cystic tumors. Diagnosis is based on imaging procedures (magnetic resonance imaging), but there are studies reporting promising potential biomarkers. Transsphenoidal surgery remains the first therapeutic option for large tumors with compressive symptoms. There is no evidence that endoscopic procedures improve outcomes, but they decrease morbidity. There is no unanimity in finding prognostic predictors of recurrence. Radiosurgery achieves tumor control and, sometimes, adenoma size reduction. Its adverse effects increase with higher doses and tumor sizes>4cm(3). Drug treatment is of little value. In aggressive non-functioning tumors, temozolomide (TMZ) may be used with caution because no controlled studies are available. TMZ achieves tumor control in 38%-40% of aggressive non-functioning tumors. The optimal treatment regimen and duration have not been defined yet. Lack of response to TMZ after 3 cycles predicts for treatment resistance, but initial response does not ensure optimal mid or long-term results. O6-methylguanine-DNA methyltransferase expression has a limited predictive value of response to treatment with TMZ in aggressive non-functioning tumors. It should therefore not be a determinant factor in selection of patients to be treated with TMZ. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  7. Hemorrhagic chondroid chordoma mimicking pituitary apoplexy

    Lee, H.J.; Kalnin, A.J.; Holodny, A.I. [Dept. of Radiology, University Hospital, Newark, NJ (United States); Schulder, M.; Grigorian, A. [Dept. of Neurosurgery, University Hospital, Newark, NJ (United States); Sharer, L.R. [Dept. of Pathology, University Hospital, Newark, NJ (United States)


    We describe a hemorrhagic chondroid chordoma involving the sella turcica with suprasellar extension. The CT and MRI appearances mimiked a hemorrhagic pituitary adenoma. Chondroid chordoma is a variant composed of elements of both chordoma and cartilaginous tissue. An uncommon bone neoplasm, located almost exclusively in the spheno-occipital region, it is usually not considered in the differential diagnosis of a tumor with acute hemorrhage in the sellar region. We discuss the clinical and radiological characteristics which may allow one to differentiate chondroid chordoma from other tumors of this area. (orig.) With 3 figs., 9 refs.

  8. The Localization of Ghrelin and Its mRNA in the Rat Hypothalamus and Pituitary%Ghrelin及其mRNA在大鼠下丘脑和垂体上的定位

    王琳; 方富贵; 章孝荣; 张运海; 王索路; 蒲勇; 李运生


    To investigate the regulation of Ghrelin on the hypothalamus and pituitary of rat. The localization of Ghrelin and its mRNA in hypothalamus and pituitary tissues were detected by immunohistochemical PV-9000 2-step and in situ hybridization, respectively. Results showed that Ghrelin and its mRNA was mainly distributed in the arcuate nuclei, ventromedial nucleus, median eminence, periventricular nucleus of hypothalamus and anterior pituitary, the colour of cells in nuclei were different. A large number of positive cells were found in anterior pituitary, no positive cells were distributed in neurohypophysis. Ghrelin and its mRNA were both presented in the hypothalamus and pituitary tissues of rat, which suggested that the Ghrelin may play a role in the secretion of gonadotropinreleasing hormone and gonadotropin.%为了阐明Ghrelin对大鼠下丘脑与垂体的调控规律,拟采用PV-9000两步法免疫组化和原位杂交方法分别确定Ghrelin及其mRNA在大鼠下丘脑和垂体组织中的定位.结果表明Ghrelin及其mRNA主要分布在下丘腩的弓状核、腹内侧核、正中隆起、室旁核等处的核团,各部分核团细胞着色程度深浅不一,腺垂体细胞中也有大量阳性细胞分布,但神经垂体则无阳性细胞分布.结果提示,Ghrelin及其mRNA在大鼠下丘脑、垂体中均有分布,揭示Ghrelin可能对大鼠促性腺激素释放激素和促性腺激素分泌有一定的调控作用.

  9. Correlation between plasma neuropeptide Y and growth hormone in patients with pituitary adenoma%垂体腺瘤患者血浆神经肽Y与生长激素水平相关性研究

    甄自刚; 陈胜利; 马景鑑


    目的 探讨垂体腺瘤患者血浆神经肽Y与生长激素之间的相关关系.方法 收集82例垂体腺瘤患者空腹静脉血3ml,进行血浆神经肽Y放射免疫测定分析,并与生长激素水平进行相关分析.初步探讨神经肽Y与生长激素之间的相关性.结果 促性腺激素细胞腺瘤患者中血浆神经肽Y与生长激素呈负相关.而在其他组别中神经肽Y与生长激素均无相关.结论神经肽Y参与了垂体腺瘤病理生理状态中下丘脑.垂体轴生长激素的调节,可能与垂体腺瘤的发生有关.%Objective To investigate the correlation between plasma neuropeptide Y (NPY) and growth hormone (GH) in patients with pituitary adenoma. Methods Fasting venous blood (3 ml per patient) was collected from 82 patients with pituitary adenoma. The level of plasma NPY was measured using radioimmunoassay, and the correlation with GH was analyzed. Results The level of plasma GH was negatively correlated with NPY in patients with go-nadotropin cell adenoma but not in those with pituitary adenoma of other cell-types. Conclusion NPY is involved in the regulation of growth hormone production from the hypothalamus-pituitary axis in pathological conditions, and is possibly associated with development of pituitary adenoma.

  10. Peroxisome proliferator-activated receptor gamma in the human pituitary gland: expression and splicing pattern in adenomas versus normal pituitary.

    Occhi, G; Albiger, N; Berlucchi, S; Gardiman, M; Scanarini, M; Scienza, R; Fassina, A; Mantero, F; Scaroni, C


    Pituitary adenomas are slow-growing tumours arising within the pituitary gland. If secreting, they give rise to well-known syndromes such as Cushing's disease or acromegaly; when hormonally inactive, they come to clinical attention often with local mass effects or pituitary deficiency. Peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear hormone receptor with a key role in fat and glucose metabolism, but also involved in several neoplasia, has recently been detected in pituitary adenomas. In the present study, we evaluated the occurrence and splicing profile of PPARgamma in 43 cases of pituitary adenoma of different subtypes and compared it to 12 normal pituitary glands. By real-time polymerase chain reaction, PPARgamma was expressed as much in adrenocorticotrophic hormone (ACTH)-secreting and ACTH-silent adenomas as in controls, with a moderate underexpression in somatotrophinomas and prolactinomas and overexpression in 54% of nonfunctioning pituitary adenomas (NFPA). There was no apparent qualitative change in the splicing profile of pathological pituitary glands, nor was the presence of specific isoforms with dominant negative effects against PPARgamma detected. Western blotting revealed similar expression levels in the different subgroups of pituitary adenomas and normal glands. Immunohistochemistry confirmed PPARgamma expression in approximately one-half of analysed samples. The intra- and intergroup differences observed in pituitary adenomas may represent new elements in the process of understanding the different clinical responses of Cushing's and Nelson patients to PPARgamma-ligand treatment. Moreover, the higher level of PPARgamma expression detected in the NFPA subgroup may suggest its possible role as a molecular target in these pituitary adenomas, paving the way for investigations on the effectiveness of treatment with thiazolidinediones in such patients.

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

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


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

  12. Dynamic pituitary hormones change after traumatic brain injury

    Ping Zheng


    Full Text Available Objective: To study the dynamic changes of pituitary hormones in traumatic brain injury (TBI and to correlate the severity and neurological outcome. Patients and Methods: Dynamic changes in the pituitary hormones were evaluated in 164 patients with TBI on day-1, day-7, day-14, day-21, and day-28 post injury. Admission TBI severity and long-term outcome were assessed with Glasgow Coma Scale (GCS score and Glasgow Outcome Scale (GOS score. The pituitary hormonal changes were correlated with TBI severity and outcome. Results: Of the 164 patients included in the study, pituitary dysfunction was found in 84 patients and in the remaining 80 patients pituitary function was normal. Most of the pituitary hormone deficiencies observed resolved over time; however, a significant proportion of patients had pituitary dysfunction at one month post injury. The hormones associated with poor outcome included growth hormone, thyrotropic hormone, and gonadotropic hormone. Conclusion: Dynamic changes of pituitary hormones in patients with TBI may reflect the severity of injury and also determine the outcome. Deficiency of growth hormone, gonadotropic hormone, and thyrotropic hormone can adversely affect neurological outcome.

  13. Volume of the adrenal and pituitary glands in depression

    Kessing, Lars Vedel; Willer, Inge Stoel; Knorr, Ulla


    Numerous studies have shown that the hypothalamic-pituitary-adrenal (HPA) axis is hyperactive in some depressed patients. It is unclear whether such hyperactivity results in changed volumes of the adrenal glands, pituitary gland and hypothalamus. We systematically reviewed all controlled studies ...

  14. Pituitary Volume Prospectively Predicts Internalizing Symptoms in Adolescence

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


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

  15. Pituitary Volume Prospectively Predicts Internalizing Symptoms in Adolescence

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


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

  16. Hyperprolactinemia associated to calcification of the pituitary stalk: case report



    Full Text Available In this work, the authors report the case of a female patient with 24 years of age with hyperprolactinemia, who presented a pituitary stalk calcification as seen by CT scan. Once other possible etiologies were excluded, we concluded that the calcification was probably related to hyperprolactinemia caused by interruption of the input of dopamine to the pituitary gland.

  17. Mechanism of neuroadenolysis of the pituitary for cancer pain control

    Trouwborst, A.; Yanagida, H.; Erdmann, W.; Kok, A.


    Studied whether neuronal activity of the pituitary gland, as related to the primary somatosensory cortex, may be involved in the pain perception pathway influenced by neuroadenolysis of the pituitary. EEG and tooth-pulp EPs (TPEPs) were examined in 3 rhesus monkeys (Macaca mulatta). Findings

  18. Mechanism of neuroadenolysis of the pituitary for cancer pain control

    Trouwborst, A.; Yanagida, H.; Erdmann, W.; Kok, A.


    Studied whether neuronal activity of the pituitary gland, as related to the primary somatosensory cortex, may be involved in the pain perception pathway influenced by neuroadenolysis of the pituitary. EEG and tooth-pulp EPs (TPEPs) were examined in 3 rhesus monkeys (Macaca mulatta). Findings indicat

  19. Xanthomatosis, pituitary gland, Magnetic Resonance Imaging, Sella turcica

    Jang, Seok Jin; Kim, Eui Jong; Choi, Woo Seok [Dept. of Radiology, Kyunghee Medical Center, Kyunghee University College of Medicine, Seoul (Korea, Republic of); Park, Bong Jin [Dept. of Neurosurgery, Kyunghee Medical Center, Kyunghee University College of Medicine, Seoul (Korea, Republic of)


    Xanthomatous hypophysitis is a rare inflammatory disorder of the pituitary gland of unknown prevalence that causes pituitary dysfunction and a mass-like lesion. The authors report a case of 40-year-old man with a visual disturbance and a confirmed diagnosis of xanthomatous hypophysitis.

  20. Expression of growth hormone (GH)-releasing factor gene in GH-producing pituitary adenoma.

    Wakabayashi, I; Inokuchi, K; Hasegawa, O; Sugihara, H; Minami, S


    Pituitary cells synthesize various neuropeptides that influence pituitary hormone secretion. GH-releasing factor (GRF) may also be produced by normal or pituitary tumor cells. We examined GRF gene expression in pituitary tumors. Standard techniques for the analysis of GRF gene expression did not appear to be suitable. Highly sensitive reverse transcription coupled to polymerase chain reaction was used. Specimens of pituitary adenoma were obtained by transsphenoidal adenomectomy from six patients with acromegaly and three patients with no clinical evidence of pituitary hormone overproduction; non-functioning adenoma. Pituitary glands were collected at autopsy from three patients who died from nonendocrine disorders. A specific GRF gene transcript was detected in five out of six GH-producing pituitary adenomas, whereas this was not found in three separate specimens of nonfunctioning pituitary adenoma or anterior and posterior pituitary tissue. The data suggest that GRF is synthesized as an intrinsic product in human GH-producing pituitary adenoma.

  1. Sudden and unexpected death from pituitary tumor apoplexy.

    Shields, Lisa B E; Balko, M Gregory; Hunsaker, John C


    Pituitary tumor apoplexy refers to a clinical syndrome precipitated by the expansion of a pituitary adenoma by hemorrhage or infarction. Individuals may present with myriad signs, including sudden onset of severe headache, visual changes, altered mental status, cranial nerve palsies, and hormonal dysfunction. This disorder constitutes a medical emergency and warrants an expedited evaluation, diagnosis, and treatment to prevent the potential sequelae of permanent visual loss, endocrine abnormalities, or death. We report a case of sudden death from undiagnosed pituitary tumor apoplexy. The decedent was evaluated by medical personnel on three occasions in the week prior to her death for severe headache, nausea, vomiting, and photophobia. Postmortem examination demonstrated a hemorrhagic infarction of a pituitary adenoma with necrosis and expansion out of the sella turcica. The recognition of and treatment for a patient with pituitary tumor apoplexy requires a rapid multidisciplinary effort. Failure of prompt diagnosis may be fatal and require a medico-legal death investigation for sudden and unexpected death.

  2. Unusual Complication of Pituitary Macroadenoma: A Case Report and Review

    Abbas, Mohamed Said; AlBerawi, Mohamad Najm; Bozom, Issam Al; Shaikh, Nissar F.; Salem, Khalid Yacout


    Patient: Male, 48 Final Diagnosis: Pituitary apoplexy complicated by cerebral infarction Symptoms: Disturbed conscious level • loss of vision Medication: — Clinical Procedure: — Specialty: Radiology Objective: Unusual clinical course Background: Pituitary macroadenoma is a common benign tumor that usually presents with visual field defects or hormonal abnormalities. Cerebral infarction can be a complication of a large pituitary adenoma. We report a rare case of bilateral anterior cerebral arteries infarcts by a large pituitary macroadenoma with apoplexy. Case Report: A 48-year-old male patient presented with altered conscious level and sudden loss of vision for one-day duration. Magnetic resonance imaging of the brain showed a large seller and suprasellar hemorrhagic mass of pituitary origin, with associated bilateral areas of diffusion restriction in the frontal parasagittal regions, consistent with infarctions. Magnetic resonance angiography showed elevation and compression of A1 segment of both anterior cerebral arteries by the hemorrhagic pituitary macroadenoma. The patient underwent trans-sphenoidal resection of the pituitary adenoma, but unfortunately, ischemia was irreversible. Computed tomography (CT) done post-operatively showed hypodensity in the frontal and parietal parasagittal areas, which was also persistent in the follow up CT scans. The patient’s neurological function remained poor, with GCS of 8/15, in vegetative state. Conclusions: Vascular complications of the pituitary apoplexy, although uncommon, can be very severe and life threatening. Early detection of vascular compromise caused by hemorrhagic pituitary macroadenoma can prevent delay in intervention. Clinicians should also consider pituitary adenoma as a possible cause of stroke. PMID:27708253

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

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


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

  4. Pituitary infiltration by non-Hodgkin's lymphoma: a case report

    Aral Ferihan


    Full Text Available Abstract Introduction Pituitary adenomas represent the most frequently observed type of sellar masses; however, the presence of a rapidly growing sellar tumor, diabetes insipidus, ophthalmoplegia and headaches in an older patient strongly suggests metastasis to the pituitary. Since the anterior pituitary has a great reserve capacity, metastasis to the pituitary and pituitary involvement in lymphoma are usually asymptomatic. Whereas diabetes insipidus is the most frequent symptom, patients can present with headaches, ophthalmoplegia and bilateral hemianopsia. Case presentation A 70-year-old woman with no previous history of malignancy presented with headaches, right oculomotor nerve palsy and diabetes insipidus. As magnetic resonance imaging revealed a sellar mass involving the pituitary gland and infundibular stalk, which also extended into the right cavernous sinus and sphenoid sinus, the patient underwent an immediate transsphenoidal decompression surgery. Her prolactin was 102.4 ng/ml, whereas her gonadotropic hormone levels were low. A low level of urine osmolality after overnight water deprivation, along with normal plasma osmolality suggested diabetes insipidus. Histological examination revealed that the mass had been the infiltration of a high grade B-cell non-Hodgkin's lymphoma involving respiratory system epithelial cells. Paranasal sinus computed tomography scanning and magnetic resonance imaging of the thorax and abdomen were performed. Since magnetic resonance imaging did not reveal any abnormality, after paranasal sinus computed tomography was performed, we concluded that the primary lymphoma originated from the sphenoid sinus and infiltrated the pituitary. Chemotherapy and radiotherapy to the sellar area were planned, but the patient died and her family did not permit an autopsy. Conclusion Lymphoma infiltration to the pituitary is difficult to differentiate from pituitary adenoma, meningioma and other sellar lesions. To plan the

  5. Preoperative preparation of patients with pituitary gland disorders.

    Malenković, Vesna; Gvozdenović, Ljiljana; Milaković, Branko; Sabljak, Vera; Ladjević, Nebojsa; Zivaljević, Vladan


    This paper presents the most common disorders of pituitary function: acromegaly, hypopituitarism, diabetes insipidus and syndrome similar to diabetes insipidus, in terms of their importance in preoperative preparation of patients. Pituitary function manages almost the entire endocrine system using the negative feedback mechanism that is impaired by these diseases. The cause of acromegaly is a pituitary adenoma, which produces growth hormone in adults. Primary therapy of acromegaly is surgical, with or without associated radiotherapy. If a patient with acromegaly as comorbidity prepares for non-elective neurosurgical operation, then it requires consultation with brain surgeons for possible delays of that operation and primary surgical treatment of pituitary gland. If operative treatment of pituitary gland is carried out, the preoperative preparation (for other surgical interventions) should consider the need for perioperative glucocorticoid supplementation. Panhypopituitarism consequences are different in children and adults and the first step in diagnosis is to assess the function of target organs. Change of electrolytes and water occurs in the case of pituitary lesions in the form of central or nephrogenic diabetes insipidus as a syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Preoperative preparation of patients with pituitary dysfunction should be multidisciplinary, whether it is a neurosurgical or some other surgical intervention. The aim is to evaluate the result of insufficient production of pituitary hormones (hypopituitarism), excessive production of adenohypophysis hormones (acromegaly, Cushing's disease and hyperprolactinemia) and the influence of pituitary tumours in surrounding structures (compression syndrome) and to determine the level of perioperative risk. Pharmacological suppressive therapy of the hyperfunctional pituitary disorders can have significant interactions with drugs used in the perioperative period.

  6. Lymphocitic infundibuloneurohypophysitis mimicking a pituitary adenoma

    Hubertus Maximilian Mehdorn


    Full Text Available A rare case of infundibulo-neurohypophysitis mimicking a pituitary adenoma is presented. A 69-years-old female patient developed polyuria and polydipsia. Laboratory analysis revealed central diabetes insipidus. No hormonal abnormalities. Cranial-magnetic resonance imaging (MRI showed a left sided mass in the adenohypophysis presuming a pituitary adenoma. The mass had contact to both internal carotids. Admission to our department for neurosurgical treatment followed. Ophthalmo - logic examination and neurological examination yielded normal findings. A second MRI focussing on the sellar-region showed a leftsided (T2-MRI.hyperintense, distended adenohypophysis, without contrast enhancement in T1. The stalk appeared thickened. T1- weighted sequences of the neurohypophysis showed loss of signal intensity. We diagnosed an infundibulo-neurohypophysitis and abstai - ned from surgical removal. The patient was discharged under treatment with corticosteroids and desmopressin. Hypophysitis is rare and shows special clinical characteristics. Despite defined radiological features to differentiate between hypophysitis and adenoma the possibility of misdiagnosis, and unnecessary surgical procedures, should always kept in mind.

  7. Respiration rate in human pituitary tumor explants.

    Anniko, M; Bagger-Sjöbäck, D; Hultborn, R


    Studies on the respiration rate of human pituitary tumor tissue have so far been lacking in the literature. This study presents the results from four adenomas causing acromegaly, all with different clinical degrees of the disease. Determination of oxygen uptake was performed in vitro with a spectrophotorespirometric system. Pieces of the tumors were explanted to an organ culture system with a high degree of stability. The secretion rate of growth hormone (GH) and prolactin (PRL) was determined. After 4-8 days in vitro, specimens were analyzed for respiration rate. This was approximately 1-1.5 microliters O2/h/micrograms dry weight. The activity of the pituitary tumor tissue was characterized by both the hormone secretion rate and the respiration rate. Particularly active foci were found to occur in the adenoma tissue. Depending on the individual tumor, the GH secretion rate was approximately 0.1-100 pmol/micrograms dry weight/h and PRL secretion rate approximately 0.4-18 micrograms/micrograms dry weight/h. The respiration rate--as is also the hormone secretion rate--is dependent on the time in vitro prior to analysis. The respiration rate in individual tumors is a parameter which does not reflect GH or PRL serum levels or clinical activity of the disease.

  8. Endoscopic transnasal approach for removing pituitary tumors

    Mirian Cabral Moreira de Castro


    Full Text Available To describe a series of 129 consecutive patients submitted to the resection of pituitary tumors using the endoscopic transsphenoidal approach in a public medical center. Method: Retrospective analysis based on the records of patients submitted to the resection of a pituitary tumor through the endoscopic transsphenoidal approach between 2004 and 2009. Results: One hundred and twenty-nine records were analyzed. The tumor was non-secreting in 96 (74.42% and secreting in 33 patients (22.58%. Out of the secretory tumors, the most prevalent was the growth hormone producer (7.65%, followed by the prolactinoma, (6.98%. Eleven patients developed cerebral spinal fluid (CSF fistulas, and four of them developed meningitis. One patient died due to intracerebral hemorrhage in the postoperative period. Conclusion: The endoscopic transsphenoidal approach to sellar tumors proved to be safe when the majority of the tumors were non-secreting. The most frequent complication was CSF. This technique can be done even in a public hospital with financial limits, since the health professionals are integrated.




    A patient with acromegaly and hyperthyroidism due to a growth hormone-, thyrotrophin- and alpha-subunit-secreting pituitary adenoma is described. His deceased father had suffered from a pituitary tumour, and was likely to have had acromegaly as well. Plasma growth hormone and insulin-like growth fac

  10. Effects of aqueous extract from Asparagus officinalis L. roots on hypothalamic-pituitary-gonadal axis hormone levels and the number of ovarian follicles in adult rats

    Hojatollah Karimi Jashni


    Full Text Available Background: Asparagus is a plant with high nutritional, pharmaceutical, and industrial values. Objective: The present study aimed to evaluate the effect of aqueous extract of asparagus roots on the hypothalamic-pituitary-gonadal axis hormones and oogenesis in female rats. Materials and Methods: In this experimental study, 40 adult female Wistar rats were divided into five groups, which consist 8 rats. Groups included control, sham and three experimental groups receiving different doses (100, 200, 400 mg/kg/bw of aqueous extract of asparagus roots. All dosages were administered orally for 28 days. Blood samples were taken from rats to evaluate serum levels of Gonadotropin releasing hormone (GnRH, follicular stimulating hormone (FSH, Luteinal hormone (LH, estrogen, and progesterone hormones. The ovaries were removed, weighted, sectioned, and studied by light microscope. Results: Dose-dependent aqueous extract of asparagus roots significantly increased serum levels of GnRH, FSH, LH, estrogen, and progestin hormones compared to control and sham groups. Increase in number of ovarian follicles and corpus luteum in groups treated with asparagus root extract was also observed (p<0.05. Conclusion: Asparagus roots extract stimulates secretion of hypothalamic- pituitary- gonadal axis hormones. This also positively affects oogenesis in female rats.

  11. Sexually dimorphic effects of NMDA receptor antagonism on brain-pituitary-gonad axis development in the platyfish

    Flynn, Katherine M.; Miller, Shelly A.; Sower, Stacia A.; Schreibman, Martin P.


    The N-methyl-D-aspartate glutamate receptor (NMDAR) is found in hypothalamic nuclei involved in the regulation of reproduction in several species of mammals and fishes. NMDAR is believed to affect reproductive development and function by regulating gonadotropin releasing hormone (GnRH)-producing cells. These pathways are likely to be sexually dimorphic, as are several other neurotransmitter systems involved in reproductive function. In this report, male and female platyfish received intraperitoneal injections of 0, 5, 10, 20, 40 or 60 microg/g body wt. of the non-competitive NMDAR antagonist MK-801. Injections began at 6 weeks of age and continued thrice weekly until control animals reached puberty, as evidenced by anal fin maturation. The percent of pubescent animals was significantly affected by sex and treatment, with fewer MK-801-injected females in puberty than control females at each dose (PHistological analyses revealed typical immature gonads and pituitary glands in treated females, and typical mature morphology in control females and all males. Immunocytochemical distribution of the R1 subunit of the NMDAR within the brain-pituitary-gonad (BPG) axis was limited to GnRH-containing brain cells in all animals; however, NMDAR1 distribution was in an immature pattern in treated females and a mature pattern in all others. Neural concentrations of GnRH were unaffected by MK-801 treatment in both sexes. These data suggest that in the platyfish, NMDAR influence on reproductive development is sexually dimorphic and occurs at, or above, the level of GnRH-containing cells of the BPG axis.

  12. IVF-ET中促性腺激素释放激素激动剂的超促排卵应用与剂量研究%Gonadotropin-releasing Hormone Agonist for Controlled Ovarian Hyperstimulation and Dose-finding Study in In Vitro Fertilization-Embryo Transfer

    郜虹媛; 匡延平


    Gonadotropin-releasing hormone agonist(GnRH-a) is one of the most effective drugs used for controlled ovarian hyperstimulation (COH) in in vitro fertilization-embryo transfer (IVF-ET). The early "flare up" of GnRH-a can stimulate the sharp release of endogenous gonadotropins. Continuous administration of GnRH-a caused reversibly block of pituitary function and low level of endogenous gonadotropin, which is the so-called down-regulation. Therefore, GnRH agonist protocol with exogenous gonadotropins can prevent a luteinizing nor-mone surge, premature oocyte maturation and luteinization. In addition, GnRH-a triggering which can take the place of hCG triggering leads to a significant reduction of OHSS rate. To explore the effective low dose of GnRH-a which can prevent a LH surge without excessive pituitary desensitization has a critical role for COH.%促性腺激素释放激素激动剂(GnRH-a)是体外受精-胚胎移植(IVF-ET)技术中重要用药.GnRH-a与GnRH受体结合后,早期"突发"作用可刺激垂体促性腺激素急剧释放,持续应用后使垂体受抑制,内源性促性腺激素(Gn)水平下降,即所谓的降调节作用.利用这种生物学特性,GnRH-a联合Gn超促排卵可预防早发黄体生成素(LH)峰,避免卵泡过早黄素化.另外,GnRH-a代替人绒毛膜促性腺激素诱发排卵可降低卵巢过度刺激综合征(OHSS)发生率.探索既能有效抑制LH峰,又不使垂体过度抑制的GnRH-a有效低剂量对于超促排卵有重要意义.

  13. A review of luteinising hormone and human chorionic gonadotropin when used in assisted reproductive technology.

    Ezcurra, Diego; Humaidan, Peter


    Gonadotropins extracted from the urine of post-menopausal women have traditionally been used to stimulate folliculogenesis in the treatment of infertility and in assisted reproductive technology (ART). Products, such as human menopausal gonadotropin (hMG), consist not only of a mixture of the hormones, follicle-stimulating hormone (FSH), luteinising hormone (LH) and human chorionic gonadotropin (hCG), but also other biologically active contaminants, such as growth factors, binding proteins and prion proteins. The actual amount of molecular LH in hMG preparations varies considerably due to the purification process, thus hCG, mimicking LH action, is added to standardise the product. However, unlike LH, hCG plays a different role during the natural human menstrual cycle. It is secreted by the embryo and placenta, and its main role is to support implantation and pregnancy. More recently, recombinant gonadotropins (r-hFSH and r-hLH) have become available for ART therapies. Recombinant LH contains only LH molecules. In the field of reproduction there has been controversy in recent years over whether r-hLH or hCG should be used for ART. This review examines the existing evidence for molecular and functional differences between LH and hCG and assesses the clinical implications of hCG-supplemented urinary therapy compared with recombinant therapies used for ART.

  14. Structure and Function Relationship of Gonadotropin Releasing Hormone(GnRH) and its Potential Clinical Application



    The structures of porcine, and ovine hypothalmic gonadotropin releasinghormone(GnRH) have been found to be identical It is a linear decapetide withdistinctive structural features and blocked N-and C-termini. Variants of GnRHare present in lower vertebrates (Table).

  15. Linear regression of postevacuation serum human chorionic gonadotropin concentrations predicts postmolar gestational trophoblastic neoplasia

    Lybol, C.; Sweep, F.C.; Ottevanger, P.B.; Massuger, L.F.A.G.; Thomas, C.M.G.


    OBJECTIVE: Currently, human chorionic gonadotropin (hCG) follow-up after evacuation of hydatidiform moles is essential to identify patients requiring chemotherapeutic treatment for gestational trophoblastic neoplasia (GTN). We propose a model based on linear regression of postevacuation serum hCG co

  16. Random mutagenesis and screening of complex glycoproteins : expression of human gonadotropins in Dictyostelium discoideum

    Linskens, Maarten H.K.; Grootenhuis, Peter D.J.; Blaauw, Mieke; Huisman-de Winkel, Bianca; Ravestein, Arno van; Haastert, Peter J.M. van; Heikoop, Judith C.


    The soil amoeba Dictyostelium discoideum is a host cell that provides simple genetics in combination with complex protein synthesis. We show that the complex human heterodimeric gonadotropins can be produced and secreted by this organism, Furthermore, both follicle stimulation hormone and choriogona

  17. Myth vs. Fact: The Human Chorionic Gonadotropin (hCG) Diet

    ... exactly is hCG? Human chorionic gonadotropin is a hormone produced during pregnancy to help nourish the growing fetus. The U.S. Food and Drug Administration (FDA) approved hCG for a number of medical uses. ... understand that hormones are powerful and must be prescribed with caution. ...

  18. 76 FR 27888 - Implantation or Injectable Dosage Form New Animal Drugs; Gonadotropin Releasing Factor-Diphtheria...


    ... drug regulations to reflect approval of a new animal drug application (NADA) filed by Pfizer, Inc. The NADA provides for the veterinary prescription use of gonadotropin releasing factor-diphtheria toxoid...-5755, filed NADA 141-322 that provides for the veterinary prescription use of IMPROVEST...

  19. 77 FR 4227 - Implantation or Injectable Dosage Form New Animal Drugs; Gonadotropin Releasing Factor Analog...


    ... drug regulations to reflect approval of a supplemental new animal drug application (NADA) filed by Pfizer, Inc. The supplemental NADA extends the slaughter interval for intact male swine injected with..., filed a supplement to NADA 141-322 for IMPROVEST (gonadotropin releasing factor analog-diphtheria...

  20. Differential regulation of two forms of gonadotropin-releasing hormone messenger ribonucleic acid by gonadotropins in human immortalized ovarian surface epithelium and ovarian cancer cells.

    Choi, Jung-Hye; Choi, Kyung-Chul; Auersperg, Nelly; Leung, Peter C K


    Although gonadotropin-releasing hormone (GnRH) has been shown to play a role as an autocrine/ paracrine regulator of cell growth in ovarian surface epithelium and ovarian cancer, the factors which regulate the expression of GnRH and its receptor in these cells are not well characterized. In the present study, we employed real-time PCR to determine the potential regulatory effect of gonadotropins on the expression levels of GnRH I (the mammalian GnRH), GnRH II (a second form of GnRH) and their common receptor (GnRHR) in immortalized ovarian surface epithelial (IOSE-80 and IOSE-80PC) cells and ovarian cancer cell lines (A2780, BG-1, CaOV-3, OVCAR-3 and SKOV-3). The cells were treated with increasing concentrations (100 and 1000 ng/ml) of recombinant follicle-stimulating hormone (FSH) or luteinizing hormone (LH) for 24 h. Treatment with FSH or LH reduced GnRH II mRNA levels in both IOSE cell lines and in three out of five ovarian cancer cell lines (A2780, BG-1 and OVCAR-3). A significant decrease in GnRHR mRNA levels was observed in IOSE and ovarian cancer cells, except CaOV-3 cells, following treatment with FSH or LH. In contrast, treatment with either FSH or LH had no effect on GnRH I mRNA levels in these cells, suggesting that gonadotropins regulate the two forms of GnRH and its receptor differentially. In separate experiments, the effect of gonadotropins on the anti-proliferative action of GnRH I and GnRH II agonists in IOSE-80, OVCAR-3 and SKOV-3 cells was investigated. The cells were pretreated with FSH or LH (100 ng/ml) for 24 h after which they were treated with either GnRH I or GnRH II (100 ng/ml) for 2 days, and cell growth was assessed by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] assay. Pretreatment of the cells with FSH or LH significantly reversed the growth inhibitory effect of GnRH I and GnRH II agonists in these cell types. These results provide the first demonstration of a potential interaction between gonadotropins and the

  1. Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy.

    Hsieh, Tung-Chin; Pastuszak, Alexander W; Hwang, Kathleen; Lipshultz, Larry I


    Testosterone replacement therapy results in decreased serum gonadotropins and intratesticular testosterone, and impairs spermatogenesis, leading to azoospermia in 40% of patients. However, intratesticular testosterone can be maintained during testosterone replacement therapy with co-administration of low dose human chorionic gonadotropin, which may support continued spermatogenesis in patients on testosterone replacement therapy. We retrospectively reviewed the records of hypogonadal men treated with testosterone replacement therapy and concomitant low dose human chorionic gonadotropin. Testosterone replacement consisted of daily topical gel or weekly intramuscular injection with intramuscular human chorionic gonadotropin (500 IU) every other day. Serum and free testosterone, estradiol, semen parameters and pregnancy rates were evaluated before and during therapy. A total of 26 men with a mean age of 35.9 years were included in the study. Mean followup was 6.2 months. Of the men 19 were treated with injectable testosterone and 7 were treated with transdermal gel. Mean serum hormone levels before vs during treatment were testosterone 207.2 vs 1,055.5 ng/dl (p testosterone 8.1 vs 20.4 pg/ml (p = 0.02) and estradiol 2.2 vs 3.7 pg/ml (p = 0.11). Pretreatment semen parameters were volume 2.9 ml, density 35.2 million per ml, motility 49.0% and forward progression 2.3. No differences in semen parameters were observed during greater than 1 year of followup. No impact on semen parameters was observed as a function of testosterone formulation. No patient became azoospermic during concomitant testosterone replacement and human chorionic gonadotropin therapy. Nine of 26 men contributed to pregnancy with the partner during followup. Low dose human chorionic gonadotropin appears to maintain semen parameters in hypogonadal men on testosterone replacement therapy. Concurrent testosterone replacement and human chorionic gonadotropin use may preserve fertility in hypogonadal males

  2. Glyphosate impairs male offspring reproductive development by disrupting gonadotropin expression.

    Romano, Marco Aurelio; Romano, Renata Marino; Santos, Luciana Dalazen; Wisniewski, Patricia; Campos, Daniele Antonelo; de Souza, Paula Bargi; Viau, Priscila; Bernardi, Maria Martha; Nunes, Maria Tereza; de Oliveira, Claudio Alvarenga


    Sexual differentiation in the brain takes place from late gestation to the early postnatal days. This is dependent on the conversion of circulating testosterone into estradiol by the enzyme aromatase. The glyphosate was shown to alter aromatase activity and decrease serum testosterone concentrations. Thus, the aim of this study was to investigate the effect of gestational maternal glyphosate exposure (50 mg/kg, NOAEL for reproductive toxicity) on the reproductive development of male offspring. Sixty-day-old male rat offspring were evaluated for sexual behavior and partner preference; serum testosterone concentrations, estradiol, FSH and LH; the mRNA and protein content of LH and FSH; sperm production and the morphology of the seminiferous epithelium; and the weight of the testes, epididymis and seminal vesicles. The growth, the weight and age at puberty of the animals were also recorded to evaluate the effect of the treatment. The most important findings were increases in sexual partner preference scores and the latency time to the first mount; testosterone and estradiol serum concentrations; the mRNA expression and protein content in the pituitary gland and the serum concentration of LH; sperm production and reserves; and the height of the germinal epithelium of seminiferous tubules. We also observed an early onset of puberty but no effect on the body growth in these animals. These results suggest that maternal exposure to glyphosate disturbed the masculinization process and promoted behavioral changes and histological and endocrine problems in reproductive parameters. These changes associated with the hypersecretion of androgens increased gonadal activity and sperm production.

  3. Expression of Neuropeptide Y in Human Pituitary Adenoma

    Laizhao Chen; Jingjian Ma; Anchao Zheng; Honggang Zheng


    OBJECTIVE Neuropeptid e Y (NPY) acts as a neuroendocrine modulator in the anterior pituitary, and NPY mRNA and NPY-immunoreactivity have been detected in normal human anterior pituitaries. However, only a few studies of NPY expression in human pituitary adenomas have been published. Our study was conducted to determine whether or not adenomatous cells express NPY, to investigate the relationship between NPY expression and the subtypes of pituitary adenoma and to explore the clinical significance of NPY.METHODS The study included tissues from 58 patients with pituitary adenomas who underwent surgery because of their clinical diagnosis.Using a highly specific anti-NPY polyclonal antibody, immunohistochemical analysis was performed on the surgically removed pituitary adenomas. Six fresh specimens also were examined using immuno-electron microscopy. NPY was labeled with colloidal gold in order to study the distribution of NPY at the subcellular level.RESULTS The NPY expression level was significantly different among subgroups of pituitary adenomas (P<0.05). NPY was immuno-detected in 58.6% of all adenomas, in 91.7% of gonadotrophic adenomas and in 14.3% of prolactinomas. NPY expression was slightly lower in invasive pituitary adenomas compared to noninvasive adenomas, but the difference was not significant (t=1.81, P>0.05). Of particular interest was the finding that vascular endothelial cells showed positive NPY expression in some pituitary adenomas. Parts of strongly positive tumor cells were seen in channels formed without endothelial cells, but which contained some red blood cells in a formation similar to so-called vasculogenic mimicry. Immuno-electron microscopy demonstrated that 4 of the 6 fresh specimens displayed positive NPY staining with a high density of gold particles located mainly in the secretory granulas. In addition, gold particles were sparsely detected in the rough endoplasmic reticulum and cell matrix.CONCLUSION NPY exists in pituitary adenomas

  4. Maternal programming of sexual behavior and hypothalamic-pituitary-gonadal function in the female rat.

    Nicole Cameron

    Full Text Available Variations in parental care predict the age of puberty, sexual activity in adolescence and the age at first pregnancy in humans. These findings parallel descriptions of maternal effects on phenotypic variation in reproductive function in other species. Despite the prevalence of such reports, little is known about potential biological mechanisms and this especially true for effects on female reproductive development. We examined the hypothesis that parental care might alter hypothalamic-pituitary-ovarian function and thus reproductive function in the female offspring of rat mothers that vary pup licking/grooming (LG over the first week postpartum. As adults, the female offspring of Low LG mothers showed 1 increased sexual receptivity; 2 increased plasma levels of luteinizing hormone (LH and progesterone at proestrus; 3 an increased positive-feedback effect of estradiol on both plasma LH levels and gonadotropin releasing-hormone (GnRH expression in the medial preoptic region; and 4 increased estrogen receptor alpha (ERalpha expression in the anterioventral paraventricular nucleus, a system that regulates GnRH. The results of a cross-fostering study provide evidence for a direct effect of postnatal maternal care as well as a possible prenatal influence. Indeed, we found evidence for increased fetal testosterone levels at embryonic day 20 in the female fetuses of High compared to Low LG mothers. Finally, the female offspring of Low LG mothers showed accelerated puberty compared to those of High LG mothers. These data suggest maternal effects in the rat on the development of neuroendocrine systems that regulate female sexual behaviour. Together with studies revealing a maternal effect on the maternal behavior of the female offspring, these findings suggest that maternal care can program alternative reproductive phenotypes in the rat through regionally-specific effects on ERalpha expression.

  5. Institution of combined treatment with testosterone and charcoal-extracted porcine follicular fluid immediately after orchidectomy prevents the postcastration hypersecretion of follicle-stimulating hormone in the hypothalamus-lesioned rhesus monkey (Macaca mulatta) receiving an invariant intravenous gonadotropin-releasing hormone infusion.

    Abeyawardene, S A; Plant, T M


    In the male rhesus monkey, the negative feedback regulation of gonadotropin secretion by the gonad involves a specific inhibitory action of a testicular hormone on FSH release at the level of the anterior pituitary gland. Neither circulating testosterone (T) nor estradiol appears to be able to account for the testicular inhibition of FSH in this species. The purpose of the present study was to begin to examine the role of gonadal peptides in this regard. To this end, an episodic pattern of activity in the pituitary-Leydig cell axis was restored in seven hypothalamus-lesioned male rhesus monkeys with a chronic and unchanging intermittent iv infusion of GnRH (0.1 microgram/min for 3 min every 3 h). This preparation, known as the hypophysiotropic clamp, has been described in detail previously. Charcoal-extracted porcine follicular fluid (pFF) was used as the source of gonadal peptides. In five animals, initiation of combined T replacement and pFF treatment (10-15 ml, sc, every 12 h for 8 days) maintained circulating FSH at concentrations similar to those observed before gonadectomy. Withdrawal of pFF treatment for 8 days while maintaining T replacement resulted in a progressive and dramatic rise in plasma FSH concentrations. Reinitiation of pFF treatment resulted in a return of circulating FSH concentrations toward precastration control values. Changes in LH secretion throughout the experiment were unremarkable. In an attempt to assess any nonspecific effects of porcine protein on gonadotropin secretion, the remaining two animals received charcoal-extracted pig serum instead of pFF. In these animals circulating FSH concentrations rose 7- to 8-fold during the 8 days of combined T replacement and pig serum treatment. These findings provide evidence to support the view that a testicular peptide, most probably inhibin, plays a major role in the negative feedback regulation of gonadotropin secretion in the monkey by exerting an inhibitory action on FSH secretion directly

  6. Photoperiod-independent changes in immunoreactive brain gonadotropin-releasing hormone (GnRH) in a free-living, tropical bird.

    Moore, Ignacio T; Bentley, George E; Wotus, Cheryl; Wingfield, John C


    Timing of seasonal reproduction in high latitude vertebrates is generally regulated by photoperiodic cues. Increasing day length in the spring is associated with changes in the brain that are responsible for mediating reproductive activities. A primary example of this is the increased content of gonadotropin-releasing hormone (GnRH) in the preoptic area of the hypothalamus in birds as they enter the spring breeding season. Increased GnRH activity stimulates the release of luteinizing hormone and follicle-stimulating hormone from the anterior pituitary. These gonadotropins induce growth of the gonads and release of sex steroids which act on the brain to mediate reproductive behaviors. By contrast, seasonal breeding in the tropics can occur in the absence of significant changes in photoperiod. To our knowledge, no studies have investigated whether seasonal breeding in free-living tropical vertebrates is associated with seasonal changes in the GnRH system. We studied two populations of rufous-collared sparrows (Zonotrichia capensis) at the equator, separated by only 25 km, but with asynchronous reproductive phenologies associated with local climate and independent of photoperiodic cues. We collected brains and measured GnRH immunoreactivity (GnRH-ir) during each population's breeding and non-breeding periods. Breeding males had larger, but not more, GnRH-ir cells than non-breeding birds. The plasticity of the GnRH system was associated with local climate, such that the two populations exhibited asynchronous changes in GnRH-ir despite experiencing identical photoperiod conditions. Our results demonstrate that tropical birds can exhibit neural changes similar to those exhibited in higher latitude birds. However, these tropical populations appear to be using supplementary cues (e.g., rainfall, temperature, food availability) in a similar way to higher latitude species using an initial predictive cue (photoperiod). These results raise questions about the evolution of

  7. Etiology and therapeutic outcomes of children with gonadotropin-independent precocious puberty

    Kang, Eungu; Cho, Ja Hyang; Choi, Jin-Ho


    Purpose This study was performed to investigate the etiology, clinical features, and outcomes of patients with gonadotropin-independent precocious puberty (GIPP). Methods The study included 16 patients (14 female and 2 male patients) who manifested secondary sexual characteristics, elevated sex hormones, or adrenal androgens with prepubertal luteinizing hormone levels after gonadotropin releasing hormone stimulation diagnosed between May 1994 and December 2015. Patients with congenital adrenal hyperplasia were excluded. Clinical features, laboratory findings, treatment modalities, and outcomes were retrospectively reviewed. Results The median age at diagnosis was 2.6 years (range, 0.7–7.9 years) and median follow-up duration was 4.6 years (range, 1 month–9.8 years). Patients with McCune-Albright syndrome (n=5) and functional ovarian cysts (n=4) presented with vaginal bleeding and elevated estradiol levels (23.3±17.5 pg/mL); adrenocortical tumors (n=4) with premature pubarche and elevated dehydroepiandrosterone sulfate levels (87.2–6,530 µg/dL); and human chorionic gonadotropin (hCG)-producing tumor (n=1) with premature pubarche and elevated β-human chorionic gonadotropin levels (47.4 mIU/mL). Two patients were idiopathic. Six patients transited to gonadotropin-dependent precocious puberty median 3.3 years (range, 0.3–5.1 years) after the onset of GIPP. Initial and follow-up height standard deviation scores (0.99±0.84 vs. 1.10±1.10, P=0.44) and bone age advancement (1.49±1.77 years vs. 2.02±1.95 years, P=0.06) were not significantly different. Conclusion The etiologies of GIPP are heterogeneous, and treatment and prognosis is quite different according to the etiology. Efficacy of treatment with aromatase inhibitors needs to be evaluated after long-term follow-up. PMID:27777905

  8. Primary hypothyroidism mimicking a pituitary macroadenoma: regression after thyroid hormone replacement therapy

    Eom, Ki Seong; Kim, Jong Moon; Kim, Tae Young [Wonkwang University School of Medicine, Department of Neurosurgery, Iksan (Korea); See-Sung, Choi [Wonkwang University School of Medicine, Department of Radiology, Iksan (Korea); Kim, Jong Duck [Wonkwang University School of Medicine, Department of Pediatrics, Iksan (Korea)


    We report a 9-year-old girl with pituitary hyperplasia due to primary hypothyroidism. She presented with growth arrest, abnormal thyroid function studies, and a pituitary mass on MRI. With thyroxine therapy, the pituitary mass regressed and her symptoms resolved. Primary hypothyroidism should be considered in the differential diagnosis of solid mass lesions of the pituitary gland. (orig.)

  9. Sequential pituitary MR imaging in Sheehan syndrome: report of 2 cases.

    Kaplun, J; Fratila, C; Ferenczi, A; Yang, W C; Lantos, G; Fleckman, A M; Schubart, U K


    We present the evolution of pituitary changes in the cases of 2 patients with Sheehan syndrome as assessed by MR imaging. Both patients had severe postpartum hemorrhage, symptoms of pituitary gland apoplexy, and hypopituitarism. Sequential MR imaging demonstrated evidence of ischemic infarct in the pituitary gland with enlargement followed by gradual shrinkage during several months, to pituitary atrophy.

  10. The pathology of pituitary adenomas from a clinical perspective.

    Dworakowska, Dorota; Korbonits, Marta; Aylwin, Simon; McGregor, Alan; Grossman, Ashley B


    Pituitary adenomas present with a variety of clinical endocrine manifestations and arise in a sporadic setting or rarely as part of hereditary genetic syndromes. Molecular analysis of familial pituitary adenomas has provided significant insight into pituitary tumorigenesis. Some specific genes have been identified that predispose to pituitary neoplasia, but these are rarely involved in the pathogenesis of sporadic tumors. The number of identified genes involved in pituitary tumorigenesis is progressively increasing. The possible resulting mechanisms of action involve abnormalities in signal transduction pathways, cell cycle regulators, growth factors, chromosome stability and others. Further studies are needed to evaluate the clinical significance of genetic alterations and their implications for patient prognosis, as well as to identify targets for existing and new therapeutic options. The aim of this review is to focus on the molecular pathology of pituitary adenomas from a practical perspective and discuss the possible clinical implications which may relate to particular molecular alterations. We have summarised familial syndromes related to pituitary adenomas and considered the prognostic value of selected molecular alterations in these tumors.

  11. HMGA1-pseudogene expression is induced in human pituitary tumors

    Esposito, Francesco; De Martino, Marco; D'Angelo, Daniela; Mussnich, Paula; Raverot, Gerald; Jaffrain-Rea, Marie-Lise; Fraggetta, Filippo; Trouillas, Jacqueline; Fusco, Alfredo


    Numerous studies have established that High Mobility Group A (HMGA) proteins play a pivotal role on the onset of human pituitary tumors. They are overexpressed in pituitary tumors, and, consistently, transgenic mice overexpressing either the Hmga1 or the Hmga2 gene develop pituitary tumors. In contrast with HMGA2, HMGA1 overexpression is not related to any rearrangement or amplification of the HMGA1 locus in these tumors. We have recently identified 2 HMGA1 pseudogenes, HMGA1P6 and HMGA1P7, acting as competitive endogenous RNA decoys for HMGA1 and other cancer related genes. Here, we show that HMGA1 pseudogene expression significantly correlates with HMGA1 mRNA levels in growth hormone and nonfunctioning pituitary adenomas likely inhibiting the repression of HMGA1 through microRNAs action. According to our functional studies, these HMGA1 pseudogenes enhance the proliferation and migration of the mouse pituitary tumor cell line, at least in part, through their upregulation. Our results point out that the overexpression of HMGA1P6 and HMGA1P7 could contribute to increase HMGA1 levels in human pituitary tumors, and then to pituitary tumorigenesis. PMID:25894544

  12. Pituitary null cell adenoma in a domestic llama (Lama glama).

    Chalkley, M D; Kiupel, M; Draper, A C E


    Pituitary gland neoplasia has been reported rarely in camelids. A 12-year-old neutered male llama (Lama glama) presented with lethargy, inappetence and neurological signs. On physical examination, the llama was mentally dull and exhibited compulsive pacing and circling to the left. Complete blood count and serum biochemistry revealed haemoconcentration, mild hypophosphataemia, hyperglycaemia, hypercreatininaemia and hyperalbuminaemia. Humane destruction was elected due to rapid clinical deterioration and poor prognosis. Post-mortem examination revealed a pituitary macroadenoma and bilateral internal hydrocephalus. Microscopically, the pituitary tumour was composed of neoplastic chromophobic pituitary cells. Ultrastructural studies revealed similar neoplastic cells to those previously described in human null cell adenomas. Immunohistochemically, the neoplastic cells were strongly immunoreactive for neuroendocrine markers (synaptophysin and chromogranin A), but did not exhibit immunoreactivity for epithelial, mesenchymal, neuronal and all major pituitary hormone markers (adrenocorticotropic hormone, follicle stimulating hormone, growth hormone, luteinizing hormone, melanocyte-stimulating hormone, prolactin and thyroid stimulating hormone), consistent with the diagnosis of a pituitary null cell adenoma. This is the first report of pituitary neoplasia in a llama.

  13. Development and sexual dimorphism of the pituitary gland

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


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

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

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


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

  15. Relationship Between Histopathology and Clinical Prognosis of Invasive Pituitary Adenoma

    LIYong; SHUKai; DONGFangyong; WANFeng; LEITing; LILing


    Objective: To study the relationship between histopathology and clinical prognosis of invasive pituitary adenoma subjected to transsphenoidal surgery. Methods: The enrolled were 82 patients with invasive pituitary adenomas undergoing transsphenoidal surgery during Jan. 2000 May 2003 in our department with full MR imaging findings, pathology data and follow-up information. The follow-up duration was 5-30 months. Results: MR imaging findings of invasive pituitary adenoma included: depression of the sellar floor, involvement of sphenoid sinus and cavernous sinus, breakthrough of diaphragma sellae,encasement of internal carotid artery, etc. Pathological examination revealed that the invasion rate of dura in sella turcica was the highest among the structures around tumor. Pituitary adenoma apoplexy was found in 20 cases (24.4%). The total removal rate for PRL-secreting adenomas was significantly lower than that for non-secreting adenomas (P<0.01), but non-, GH-, ACTH-secreting adenomas had no significant differences. The recurrence rate of PRL-secreting adenornas was higher than that of non- and GH-secreting adenomas (P<0.05). Conclusion: Among invasive pituitary adenomas, the therapeutic effects of nonand GH-secreting pituitary adenomas are better than that of PRL-secreting adenomas. Invasive biological behaviors of invasive pituitary adenomas result in radical operation failure and postoperative recurrence.

  16. Cushing-type ectopic pituitary adenoma with unusual pathologic features

    Kristopher T. Kimmell, MD


    Full Text Available Ectopic pituitary adenomas comprise, by varying reports, approximately 1-2% of all pituitary adenomas. They are often located in the nasopharyngeal region associated with the pharyngeal pituitary. The location and pathologic features of these masses make them atypical when compared with intrasellar pituitary adenomas. A 54-year-old man presented with vertebral compression fracture and physical stigmata of Cushing’s disease. Biochemical testing confirmed hypercortisolemia responsive to high dose dexamethasone suppression. MRI of the head demonstrated an enhancing mass in the posterior aspect of the sphenoid sinus not involving the sella turcica. Endoscopic biopsy followed by resection confirmed this mass to be a pituitary adenoma with unusual pathologic features. Most notably, the tumor cells demonstrated large, eosinophilic, vacuolated cytoplasm. Immunohistochemical profile of the tumor was typical of an ACTH secreting tumor, notably with positivity for ACTH. The patient did well from his surgery. Post-operatively his serum cortisol level normalized and he remains in chemical remission one year after surgery. Ectopic pituitary adenomas are an unusual manifestation of hormonally active pituitary neoplastic disease. Their atypical clinical presentations, location, and pathologic features can make them a diagnostic challenge. Clinicians should be aware of these entities, especially when considering differential diagnosis for a mass in the sphenoid sinus and nasopharyngeal region.

  17. Does lower dose of long-acting triptorelin maintain pituitary suppression and produce good live birth rate in long down-regulation protocol for in-vitro fertilization?

    Chen, Xin; Feng, Shu-xian; Guo, Ping-ping; He, Yu-xia; Liu, Yu-dong; Ye, De-sheng; Chen, Shi-ling


    The effects of pituitary suppression with one-third depot of long-acting gonadotropin-releasing hormone (GnRH) agonist in GnRH agonist long protocol for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) were investigated. A retrospective cohort study was performed on 3186 cycles undergoing IVF/ICSI with GnRH agonist long protocol in a university-affiliated infertility center. The pituitary was suppressed with depot triptorelin of 1.25 mg or 1.875 mg. There was no significant difference in live birth rate between 1.25 mg triptorelin group and 1.875 mg triptorelin group (41.2% vs. 43.7%). The mean luteinizing hormone (LH) level on follicle-stimulating hormone (FSH) starting day was significantly higher in 1.25 mg triptorelin group. The mean LH level on the day of human chorionic gonadotrophin (hCG) administration was slightly but statistically higher in 1.25 mg triptorelin group. There was no significant difference in the total FSH dose between the two groups. The number of retrieved oocytes was slightly but statistically less in 1.25 mg triptorelin group than in 1.875 mg triptorelin group (12.90±5.82 vs. 13.52±6.97). There was no significant difference in clinical pregnancy rate between the two groups (50.5% vs. 54.5%). It was suggested that one-third depot triptorelin can achieve satisfactory pituitary suppression and produce good live birth rates in a long protocol for IVF/ICSI.

  18. The Effect of Chelidonium majus Extract on the Lipid Profile and Activity of Pituitary-Gonadal Axis in Hypercholesterolemic Rats

    Saeed Changizi-Ashtiyani


    Full Text Available Background: Over the past centuries, global population has increased at different rates and so has been the case with cardiovascular diseases. Therefore, given the importance of population and cholesterol control, the purpose of this study is to investigate the effect of Chelidonium majus (C. majus aerial parts extract on the lipid profile and prolactin levels and the activity of pituitary-gonadal axis in hypercholesterolemic rats. Materials and Methods: In this experimental study, 35 Wistar rats were selected and categorized into 5 groups. The control group had ordinary diet, the model group had high-fat diet, and experimental groups consisted of hypercholesterolemic rats that respectively received minimal dosages of 100, 200 and 300 mg/kg of C. majus extract. After 21 days, blood samples were taken and the factors of interest were measured. Then, the gathered data were analyzed using SPSS-11.5. Results: The amount of triglyceride and cholesterol were increased in the model group compared to the control group whereas the same items were decreased in the experimental group. C. majus extract also decreased testosterone and increased prolactin and gonadotropins. Conclusion: In this study, C. majus extract resulted in decreased fat and testosterone levels as well as increased prolactin level; however, since many sources have informed of the toxicity of this plant, cautious use of the plant is advised.

  19. Chronic Administration of High Doses of Nandrolone Decanoate on the Pituitary-Gonadal Axis in Male Rats



    Full Text Available Background Anabolic-androgenic steroids (AAS are abused by athletes. Objectives The present study was designed to evaluate chronic administration of high doses of nandrolone decanoate (ND on the pituitary-gonadal axis and hematological parameters in normal male rats. Materials and Methods Thirty Wistar-Albino male rats were divided assigned to control (C, placebo (P and test (T groups (n = 10. Group T received 15 mg/kg intramuscular (IM ND for eight weeks. Group P received the same volume of peanut oil, but group C did not receive any agent during the trial period. At the end, animals were anesthetized, killed and blood samples collected from cervical vessels. Serum follicle stimulating hormone (FSH and luteinizing hormone (LH levels were determined by sensitive rat gonadotropins kit, using ELISA methods. Serum testosterone and hematological parameters were measured by ordinary laboratory methods. Obtained data was analyzed using SPSS 17 by ANOVA and Tukey statistical tests. Results were expressed as Mean ± SD. Statistical difference considered significantly by P < 0.05. Results Serum testosterone, LH, FSH, weight gain, food and water intake in group T were significantly decreased compared to other groups (P < 0.05. In addition erythrocyte, leucocytes, hemoglobin and hematocrit in group T were significantly increased compared to those of other groups (P < 0.05. Conclusions Chronic administration of high doses of ND can alter serum FSH, LH and testosterone and hematological parameters in male rats.

  20. Dual trigger with combination of gonadotropin-releasing hormone agonist and human chorionic gonadotropin significantly improves the live-birth rate for normal responders in GnRH-antagonist cycles

    Lin, Ming-Huei; Wu, Frank Shao-Ying; Lee, Robert Kuo-Kuang; Li, Sheng-Hsiang; Lin, Shyr-Yeu; Hwu, Yuh-Ming


    ...) agonist and human chorionic gonadotropin (hCG) can improve the live-birth rate for normal responders in GnRH-antagonist in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) cycles...

  1. Pregnancy in patients with pituitary tumors.

    Husami, N; Jewelewicz, R; Vande Wiele, R L


    Thirteen patients with pituitary tumors had a total of seventeen pregnancies. Nine of these patients were treated prior to conception (four by radiation therapy, four by hypophysectomy, and one with lergotrile); four patients received no treatment. The untreated group had a total of six pregnancies, two of which were complicated by visual symptoms which regressed spontaneously after delivery. One of the hypophysectomized patients developed diabetes insipidus at 34 weeks' gestation which resolved spontaneously after delivery. Of the four irradiated patients, one had a child with Down's syndrome and another had a child with multiple congenital anomalies who died. The clinical course and various modes of treatment of these patients are discussed and the pertinent literature is reviewed.

  2. Painful vertical diplopia as a presentation of a pituitary mass

    Mandal Kaveri


    Full Text Available Abstract Background Pituitary tumours may present with a variety of neurological and endocrinological signs and symptoms. It is very rare however for them to present with sudden onset painful diplopia. The current literature and possible mechanisms for this are discussed. Case presentation We describe a case of a pituitary mass which presented with sudden onset painful diplopia with an associated restricted pattern on Lees Chart testing. This led to an initial working diagnosis of orbital myositis. Conclusion Awareness of different modes of presentation of pituitary lesions is important so that appropriate imaging may be requested and delay in diagnosis prevented.

  3. Addison's disease and ACTH-producing pituitary microadenoma

    S.S. Ortega


    Full Text Available A 28-year-old man diagnosed with primary adrenal insufficiency (Addison's disease in 2002. Following diagnosis, replacement therapy with hydrocortisone and fludrocortisone was indicated. Hydrocortisone replacement therapy was unsuccessful, and increased ACTH levels as high as 996 pg/dl were observed on outpatient follow-up. A pituitary MRI revealed a pituitary microadenoma. These findings raised three possibilities: (1 treatment is insufficient; (2 there is no relationship between Addison's disease and pituitary microadenoma; and (3 the microadenoma is similar to Nelson's syndrome. This latter is the most satisfactory explanation of this patient's clinical picture.

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

    Hymer, W. C.


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

  5. Early hyponatraemia after pituitary surgery: cerebral salt-wasting syndrome.

    Guerrero, R; Pumar, A; Soto, A; Pomares, M A; Palma, S; Mangas, M A; Leal, A; Villamil, F


    Hyponatraemia is a common complication in patients undergoing neurosurgery. It can be caused either by the syndrome of inappropriate secretion of antidiuretic hormone or by the cerebral salt-wasting syndrome (CSWS). CSWS frequently occurs in patients suffering from subarachnoid haemorrhage and brain injury, but it is rare after pituitary tumour surgery. However, this diagnostic possibility should be considered as these disorders require specific treatment and have different prognoses. In this article, we present a case of acute and early hyponatraemia caused by CSWS after pituitary tumour surgery. We also revise the aetiology, mechanisms, differential diagnosis and treatment of hyponatraemia after pituitary surgery.

  6. Ectopic Neurohypophysis in Patient with Pituitary Dwarfism: A Case Report

    İlhan Kılınç


    Full Text Available Ectopic neurohypophysis is an anomaly of the Pituitary gland whichmay be associated with short stature due to Growth hormone deficiency.MRI is the modality of choice in diagnosing this condition. We present acase of pituitary dwarfism and ectopic neurohypophysis with clinical andradiological findings. 21 year-old male admitted with short stature. Allhormones, except prolactin, of anterior hypophysis were low. Bright spotwas ectopically located at level of median eminence on enhanced MRI ofhypophysis and stalk of hypophysis was not observed. Ectopicneurohypophysis may be present with pituitary dwarfism. Cranial MRI maybe useful to investigate related pathologies in such cases.

  7. Nonadenomatous tumors of the pituitary and sella turcica.

    Huang, Benjamin Y; Castillo, Mauricio


    While pituitary adenomas make up over 90% of all sellar masses, there are a number of less known tumors, both malignant and benign, which may arise within the sella turcica. These include relatively common tumors such as meningiomas and craniopharyngiomas, as well as extremely rare tumors such as pituitary astrocytomas and granular cell tumors. Unfortunately, many of these tumors lack characteristic imaging features, often making it extremely difficult to distinguish them by imaging alone from the more common pituitary adenoma. In this article, we review several nonadenomatous tumors of the sella, with a focus on their clinical features and typical MR imaging characteristics.

  8. Persistent expression of activated notch in the developing hypothalamus affects survival of pituitary progenitors and alters pituitary structure.

    Aujla, Paven K; Bogdanovic, Vedran; Naratadam, George T; Raetzman, Lori T


    As the pituitary gland develops, signals from the hypothalamus are necessary for pituitary induction and expansion. Little is known about the control of cues that regulate early signaling between the two structures. Ligands and receptors of the Notch signaling pathway are found in both the hypothalamus and Rathke's pouch. The downstream Notch effector gene Hes1 is required for proper pituitary formation; however, these effects could be due to the action of Hes1 in the hypothalamus, Rathke's pouch, or both. To determine the contribution of hypothalamic Notch signaling to pituitary organogenesis, we used mice with loss and gain of Notch function within the developing hypothalamus. We demonstrate that loss of Notch signaling by conditional deletion of Rbpj in the hypothalamus does not affect expression of Hes1 within the posterior hypothalamus or expression of Hes5. In contrast, expression of activated Notch within the hypothalamus results in ectopic Hes5 expression and increased Hes1 expression, which is sufficient to disrupt pituitary development and postnatal expansion. Taken together, our results indicate that Rbpj-dependent Notch signaling within the developing hypothalamus is not necessary for pituitary development, but persistent Notch signaling and ectopic Hes5 expression in hypothalamic progenitors affects pituitary induction and expansion. © 2015 Wiley Periodicals, Inc.

  9. Reversible pituitary hyperplasia at birth in a macrosomic full-term baby boy

    Osipoff, Jennifer; Wilson, Thomas A. [State University of New York, Division of Pediatric Endocrinology, Department of Pediatrics, Stony Brook, NY (United States); Peyster, Robert [Stony Brook University Medical Center, Department of Radiology, Stony Brook, NY (United States)


    Pituitary hyperplasia is generally associated with end-organ failure such as primary hypothyroidism, physiological changes such as puberty and pregnancy, or neoplasms secreting releasing factors. We present a full-term infant with an enlarged pituitary height of 8 mm at age 3 days despite a normal endocrinological evaluation. Repeat imaging at 5 months of age revealed a normal-size pituitary gland. To our knowledge, pituitary hyperplasia has not been described in a neonate with normal pituitary function. (orig.)

  10. A new pathway mediating social effects on the endocrine system: female presence acting via norepinephrine release stimulates gonadotropin-inhibitory hormone in the paraventricular nucleus and suppresses luteinizing hormone in quail.

    Tobari, Yasuko; Son, You Lee; Ubuka, Takayoshi; Hasegawa, Yoshihisa; Tsutsui, Kazuyoshi


    Rapid effects of social interactions on transient changes in hormonal levels are known in a wide variety of vertebrate taxa, ranging from fish to humans. Although these responses are mediated by the brain, neurochemical pathways that translate social signals into reproductive physiological changes are unclear. In this study, we analyzed how a female presence modifies synthesis and/or release of various neurochemicals, such as monoamines and neuropeptides, in the brain and downstream reproductive hormones in sexually active male Japanese quail. By viewing a female bird, sexually active males rapidly increased norepinephrine (NE) release in the paraventricular nucleus (PVN) of the hypothalamus, in which gonadotropin-inhibitory hormone (GnIH) neuronal cell bodies exist, increased GnIH precursor mRNA expression in the PVN, and decreased luteinizing hormone (LH) concentration in the plasma. GnIH is a hypothalamic neuropeptide that inhibits gonadotropin secretion from the pituitary. It was further shown that GnIH can rapidly suppress LH release after intravenous administration in this study. Centrally administered NE decreased plasma LH concentration in vivo. It was also shown that NE stimulated the release of GnIH from diencephalic tissue blocks in vitro. Fluorescence double-label immunohistochemistry indicated that GnIH neurons received noradrenergic innervations, and immunohistochemistry combined with in situ hybridization have further shown that GnIH neurons expressed α2A-adrenergic receptor mRNA. These results indicate that a female presence increases NE release in the PVN and stimulates GnIH release, resulting in the suppression of LH release in sexually active male quail.

  11. Long-Term Outcome and MGMT as a Predictive Marker in 24 Patients With Atypical Pituitary Adenomas and Pituitary Carcinomas Given Treatment With Temozolomide

    Bengtsson, Daniel; Schrøder, Henrik Daa; Andersen, Marianne


    CONTEXT/OBJECTIVE: Locally aggressive pituitary tumors (LAPT) and pituitary carcinomas respond poorly to conventional therapy and cytotoxic drugs. Temozolomide (TMZ) is an oral alkylating drug with good tolerability, approved for treatment of malignant gliomas. The experience of its use...

  12. Elevated serum progesterone/ MII oocyte ratio on the day of human chorionic gonadotropin administration can predict impaired endometrial receptivity


    Background: Increased serum progesterone on the day of human chorionic gonadotropin administration may affect in vitro fertilization (IVF) outcome. Objective: The aim of this study was to evaluate whether progesterone elevation on the day of human chorionic gonadotropin administration is associated with poor IVF outcome. Materials and Methods: To determine the relationship between serum progesterone on the day of HCG and the outcome of IVF-embryo transfer treatment, 378 infertile patients und...

  13. Pareidolia in Neuroendocrinology: A Pituitary Macroadenoma Resembling "Big Bird".

    de Herder, Wouter W


    The MRI picture of a pituitary macroadenoma with supra- and perisellar expansion resembled a famous character from a children's television series demonstrating that pareidolia is also observed in neuro-endocrinology and -radiology.

  14. Volume of the adrenal and pituitary glands in depression

    Kessing, Lars Vedel; Willer, Inge Stoel; Knorr, Ulla


    Numerous studies have shown that the hypothalamic-pituitary-adrenal (HPA) axis is hyperactive in some depressed patients. It is unclear whether such hyperactivity results in changed volumes of the adrenal glands, pituitary gland and hypothalamus. We systematically reviewed all controlled studies...... on the adrenal or pituitary glands or hypothalamus volume in unipolar depressive disorder published in PubMed 1966 to December 2009. We identified three studies that investigated the volume of the adrenal glands and eight studies that examined the volume of the pituitary gland, but no studies on hypothalamus...... identified such as small population samples, different subtypes of depression and insufficient matching of patients and controls. Due to large heterogeneity of study designs and data, it was futile to make a meta-analysis. It is concluded that it remains unclear whether hyperactivity of the HPA axis results...

  15. Ectopic pituitary adenoma presenting as midline nasopharyngeal mass.

    Ali, R


    INTRODUCTION: Ectopic pituitary adenomas are extremely rare. We report a case of ectopic pituitary adenoma in the midline of the nasopharynx. This adenoma probably arose from the pharyngeal remnant of Rathke\\'s pouch. METHODS: We discuss a case of a lady who presented to our unit with 2 months history of dryness and sensation of lump in her throat and a long standing history of hypothyroidism. Examination of nasopharynx revealed a smooth and fluctuant midline mass. CT scan of nose and paranasal sinuses confirmed the midline mass with small defect communicating with the sphenoid sinus. An initial diagnosis of Thornwaldt\\'s cyst was made and she underwent upper aerodigestive tract endoscopy and marsupialization of the mass. Histopathological examination revealed ectopic pituitary adenoma. CONCLUSION: Ectopic pituitary adenoma is an important differential diagnosis for a midline nasopharyngeal mass. It is recommended that prior to surgical resection of midline nasopharyngeal mass biopsy is taken and MRI is performed.

  16. Preoperative preparation of patients with pituitary gland disorders

    Malenković, Vesna; Gvozdenović, Ljiljana; Milaković, Branko; Sabljak, Vera; Ladjević, Nebojsa; Zivaljević, Vladan


    This paper presents the most common disorders of pituitary function: acromegaly, hypopituitarism, diabetes insipidus and syndrome similar to diabetes insipidus, in terms of their importance in preoperative preparation of patients...

  17. Immediate postoperative complications in transsphenoidal pituitary surgery: A prospective study

    Tumul Chowdhury


    Full Text Available Background: Considering the important role of pituitary gland in regulating various endocrine axes and its unique anatomical location, various postoperative complications can be anticipated resulting from surgery on pituitary tumors. We examined and categorized the immediate postoperative complications according to various tumor pathologies. Materials and Methods: We carried out a prospective study in 152 consecutive patients and noted various postoperative complications during neurosurgical intensive care unit stay (within 48 hrs of hospital stay in patients undergoing transsphenoidal removal of pituitary tumors. Results: In our series, various groups showed different postoperative complications out of which, cerebrospinal fluid leak was the commonest followed by diabetes insipidus, postoperative nausea and vomiting, and hematoma at operation site. Conclusion: Various immediate postoperative complications can be anticipated in transsphenoidal pituitary surgery even though, it is considered to be relatively safe.

  18. Pregnancy and pituitary disorders: Challenges in diagnosis and management

    Bashir A Laway


    Full Text Available Pregnancy is associated with normal physiological changes in endocrine system that assists fetal survival as well as preparation of labor. The pituitary gland is one of the most affected organs in which major changes in anatomy and physiology take place. Due to overlapping clinical and biochemical features of pregnancy, sometimes the diagnosis of pituitary disorders may be challenging. It is important to know what normal parameters of changes occur in endocrine system in order to diagnose and manage complex endocrine problems in pregnancy. In our present review, we will focus on pituitary disorders that occur exclusively during pregnancy like Sheehan′s syndrome and lymphocytic hypophysitis and pre-existing pituitary disorders (like prolactinoma, Cushing′s disease and acromegaly, which poses significant challenge to endocrinologists.

  19. Coexisting intracranial tumors with pituitary adenomas: Genetic association or coincidence?

    Furtado Sunil


    Full Text Available The co-occurrence of two or more brain tumors with different histological features is rare. The authors report three rare cases of intracranial tumors associated with pituitary adenomas. Two of the pituitary tumors were functioning adenomas: a prolactinoma and a thyrotropin secreting adenoma. Two of the associated intracranial neoplasms were gliomas and one was a meningioma. Radiological and clinical examination for syndromal association was negative in all cases. We briefly discuss the presentation and treatment options of these cases and review the 19 previous publications in the literature of pituitary tumors occurring in association with other neoplasms and explore the possible links underlying these co-occurring neoplasms. Our three cases represent 0.86% of all pituitary tumors operated at our institute over a 9-year period.

  20. Pregnancy and pituitary disorders: Challenges in diagnosis and management

    Laway, Bashir A.; Mir, Shahnaz A.


    Pregnancy is associated with normal physiological changes in endocrine system that assists fetal survival as well as preparation of labor. The pituitary gland is one of the most affected organs in which major changes in anatomy and physiology take place. Due to overlapping clinical and biochemical features of pregnancy, sometimes the diagnosis of pituitary disorders may be challenging. It is important to know what normal parameters of changes occur in endocrine system in order to diagnose and manage complex endocrine problems in pregnancy. In our present review, we will focus on pituitary disorders that occur exclusively during pregnancy like Sheehan's syndrome and lymphocytic hypophysitis and pre-existing pituitary disorders (like prolactinoma, Cushing's disease and acromegaly), which poses significant challenge to endocrinologists. PMID:24381874

  1. Flattened sella turcica and CT appearence of normal pituitary gland

    Matsui, T.; Ueno, I.; Miki, Y.; Fuchinoue, T.; Kobayashi, N.


    A flattened sella turcica, not previously reported, was found incidentally in a 21-year-old male. Various neuroradiological and hormonal examinations have proved it to be a normal varient. Subsequently a normal pituitary gland was shown by CT.

  2. Deletion of Vax1 from Gonadotropin-Releasing Hormone (GnRH) Neurons Abolishes GnRH Expression and Leads to Hypogonadism and Infertility.

    Hoffmann, Hanne M; Trang, Crystal; Gong, Ping; Kimura, Ikuo; Pandolfi, Erica C; Mellon, Pamela L


    Hypothalamic gonadotropin-releasing hormone (GnRH) neurons are at the apex of the hypothalamic-pituitary-gonadal axis that regulates mammalian fertility. Herein we demonstrate a critical role for the homeodomain transcription factor ventral anterior homeobox 1 (VAX1) in GnRH neuron maturation and show that Vax1 deletion from GnRH neurons leads to complete infertility in males and females. Specifically, global Vax1 knock-out embryos had normal numbers of GnRH neurons at 13 d of gestation, but no GnRH staining was detected by embryonic day 17. To identify the role of VAX1 specifically in GnRH neuron development,Vax1(flox)mice were generated and lineage tracing performed in Vax1(flox/flox):GnRH(cre):RosaLacZ mice. This identified VAX1 as essential for maintaining expression of Gnrh1 The absence of GnRH staining in adult Vax1(flox/flox):GnRH(cre)mice led to delayed puberty, hypogonadism, and infertility. To address the mechanism by which VAX1 maintains Gnrh1 transcription, the capacity of VAX1 to regulate Gnrh1 transcription was evaluated in the GnRH cell lines GN11 and GT1-7. As determined by luciferase and electrophoretic mobility shift assays, we found VAX1 to be a direct activator of the GnRH promoter through binding to four ATTA sites in the GnRH enhancer (E1) and proximal promoter (P), and able to compete with the homeoprotein SIX6 for occupation of the identified ATTA sites in the GnRH promoter. We conclude that VAX1 is expressed in GnRH neurons where it is required for GnRH neuron expression of GnRH and maintenance of fertility in mice. Infertility classified as idiopathic hypogonadotropic hypogonadism (IHH) is characterized by delayed or absent sexual maturation and low sex steroid levels due to alterations in neuroendocrine control of the hypothalamic-pituitary-gonadal axis. The incidence of IHH is 1-10 cases per 100,000 births. Although extensive efforts have been invested in identifying genes giving rise to IHH, >50% of cases have unknown genetic origins

  3. Effects of kisspeptin1 on electrical activity of an extrahypothalamic population of gonadotropin-releasing hormone neurons in medaka (Oryzias latipes).

    Zhao, Yali; Wayne, Nancy L


    Kisspeptin (product of the kiss1 gene) is the most potent known activator of the hypothalamo-pituitary-gonadal axis. Both kiss1 and the kisspeptin receptor are highly expressed in the hypothalamus of vertebrates, and low doses of kisspeptin have a robust and long-lasting stimulatory effect on the rate of action potential firing of hypophysiotropic gonadotropin releasing hormone-1 (GnRH1) neurons in mice. Fish have multiple populations of GnRH neurons distinguished by their location in the brain and the GnRH gene that they express. GnRH3 neurons located in the terminal nerve (TN) associated with the olfactory bulb are neuromodulatory and do not play a direct role in regulating pituitary-gonadal function. In medaka fish, the electrical activity of TN-GnRH3 neurons is modulated by visual cues from conspecifics, and is thought to act as a transmitter of information from the external environment to the central nervous system. TN-GnRH3 neurons also play a role in sexual motivation and arousal states, making them an important population of neurons to study for understanding coordination of complex behaviors. We investigated the role of kisspeptin in regulating electrical activity of TN-GnRH3 neurons in adult medaka. Using electrophysiology in an intact brain preparation, we show that a relatively brief treatment with 100 nM of kisspeptin had a long-lasting stimulatory effect on the electrical activity of an extrahypothalamic population of GnRH neurons. Dose-response analysis suggests a relatively narrow activational range of this neuropeptide. Further, blocking action potential firing with tetrodotoxin and blocking synaptic transmission with a low Ca(2+)/high Mg(2+) solution inhibited the stimulatory action of kisspeptin on electrical activity, indicating that kisspeptin is acting indirectly through synaptic regulation to excite TN-GnRH3 neurons. Our findings provide a new perspective on kisspeptin's broader functions within the central nervous system, through its

  4. Gigantism caused by growth hormone secreting pituitary adenoma.

    Rhee, Noorisaem; Jeong, Kumi; Yang, Eun Mi; Kim, Chan Jong


    Gigantism indicates excessive secretion of growth hormones (GH) during childhood when open epiphyseal growth plates allow for excessive linear growth. Case one involved a 14.7-year-old boy presented with extreme tall stature. His random serum GH level was 38.4 ng/mL, and failure of GH suppression was noted during an oral glucose tolerance test (OGTT; nadir serum GH, 22.7 ng/mL). Magnetic resonance imaging (MRI) of the brain revealed a 12-mm-sized pituitary adenoma. Transsphenoidal surgery was performed and a pituitary adenoma displaying positive immunohistochemical staining for GH was reported. Pituitary MRI scan was performed 4 months after surgery and showed recurrence/residual tumor. Medical treatment with a long-acting somatostatin analogue for six months was unsuccessful. As a result, secondary surgery was performed. Three months after reoperation, the GH level was 0.2 ng/mL and insulin-like growth factor 1 was 205 ng/mL. Case two involved a 14.9-year-old boy, who was referred to our department for his tall stature. His basal GH level was 9.3 ng/mL, and failure of GH suppression was reported during OGTT (nadir GH, 9.0 ng/mL). Pituitary MRI showed a 6-mm-sized pituitary adenoma. Surgery was done and histopathological examination demonstrated a pituitary adenoma with positive staining for GH. Three months after surgery, the GH level was 0.2 ng/mL and nadir GH during OGTT was less than 0.1 ng/mL. Pituitary MRI scans showed no residual tumor. We present two cases of gigantism caused by a GH-secreting pituitary adenoma with clinical and microscopic findings.

  5. Thyroxine 5'-deiodinase in human anterior pituitary tumors.

    Itagaki, Y; Yoshida, K; Ikeda, H; Kaise, K; Kaise, N; Yamamoto, M; Sakurada, T; Yoshinaga, K


    The activity of T4 5'-monodeiodinase (5'D) in the pituitary was measured in 12 patients with pituitary adenoma (3 patients with acromegaly, 2 with prolactinoma, 1 with Cushing's disease, 1 with TSH-producing tumor, and 5 with nonfunctioning tumor) and, as a control, in a patient who died of parotid cancer. The pituitaries, obtained at operation or autopsy, were homogenized in 0.1 mol/L potassium phosphate buffer, pH 7.0, and centrifuged at 800 x g. Supernatants were incubated with [125I]T4 and 20 mmol/L dithiothreitol (DTT) at 37C for 90 min. T4 5'-D was measured by the release of 125I- with the ion exchange method. The activity of T4 5'-D in the pituitaries from patients with prolactinoma and parotid cancer was dependent on protein concentration, incubation time, incubation temperature, and T4 concentration, and was labile to prior heating at 70 C for 30 min. T4 5'-D was not inhibited by 1 mmol/L propylthiouracil, but was inhibited 95% by 0.1 mmol/L iopanoic acid. The apparent Km and maximum velocity for T4 5'-D in homogenates of prolactinoma at 20 mmol/L DTT were 11 nmol/L and 1.54 pmol/mg protein.h, respectively. This reaction followed sequential-type reaction kinetics when the DTT concentration was varied. All other homogenates of pituitary tumors, except two nonfunctioning tumors, also demonstrated T4 5'-D activity. These results indicate that 1) the human pituitary express a low Km and PTU-insensitive T4 5'-D activity which is very similar to the type II enzyme activity in the rat pituitary; and 2) various types of pituitary tumor cells contain T4 5'-D activity.

  6. Endoscopic endonasal trans-sphenoid surgery of pituitary adenoma

    Yadav, Y. R.; Sachdev, S.; Parihar, V.; H Namdev; P R Bhatele


    Endoscopic endonasal trans-sphenoid surgery (EETS) is increasingly used for pituitary lesions. Pre-operative CT and MRI scans and peroperative endoscopic visualization can provide useful anatomical information. EETS is indicated in sellar, suprasellar, intraventricular, retro-infundibular, and invasive tumors. Recurrent and residual lesions, pituitary apoplexy and empty sella syndrome can be managed by EETS. Modern neuronavigation techniques, ultrasonic aspirators, ultrasonic bone curette can...

  7. Acromegaly with sleep disturbances relieved by yttrium-90 pituitary implantation

    Rosenstock, J.; Doyle, F.H.; Joplin, G.F.; Jung, R.T.; Mashiter, K. (Hammersmith Hospital, London (UK). Postgraduate Medical School)


    A brief case history is presented of a patient, who, after yttrium-90 implantation, showed a complete clinical and hormonal remission of her acromegaly, maintaining normal pituitary function. The remarkable feature was the rapid disappearance of her attacks of somnolence within 96 hours of pituitary implantation, despite persistence of nocturnal snoring and well before any remodelling of soft tissues could have occurred. This response suggests that her daytime somnolence had a narcoleptic component.

  8. Zinc influences on brain development, pituitary an thyroidfunction iniodine-deficient pregnant and neonatal rats

    Xiaoxia Yang; Jianchao Bian; Xin Wang; Haiming Wang; Yongping Liu; Shuzhen Wang; Zhichun Mu; Xinluan Li


    BACKGROUND: Zinc (Zn) has been shown to greatly influence brain development. Zn supplements may reduce injury to cell membranes of the thyroid gland due to iodine deficiency. OBJECTIVE: To establish an iodine deficiency rat model using low-iodine food, which was supplemented with compound Zn and Zn gluconate, to observe the effects of Zn on brain development, as well as pituitary gland and thyroid gland function in iodine-deficient rats. DESIGN, TIME AND SETTING: Randomized grouping study of neural development was performed in the central laboratory of Shandong Institute for Prevention and Treatment of Endemic Disease from 1998 to 1999. MATERIALS: A total of 270 Wistar, female rats, one month after weaning, were used in this study, including 150 pregnant and 120 neonatal rats. Rats were randomly divided into six groups: normal control, model, iodine, compound Zn, iodine and compound Zn, and zinc gluconate. Each group contained 25 pregnant rats and 20 nenoatal rats. METHODS: The pregnant rats and 20 neonatal rats, and well as the normal group, were fed standard chow and allowed free access to tap water (containing 5 μ g/L iodine and 1 mg/L Zn). The remaining five groups were fed low-iodine chow. However, the model group received distilled water, the iodine group received potassium-iodide distilled water (containing 300 μ g/L iodine), the compound Zn group received distilled water and intragastrically administrated 10 mL/kg compound Zn solution, once per day, the iodine and compound Zn group received distilled water with 300 p g/L iodine and intragastrically administrated 10 mL/kg compound Zn solution, once per day. All treatments lasted 90 days. MAIN OUTCOME MEASURES: All pregnant rats were sacrificed on the day 21 of pregnancy. Body mass, number and rate of fetal absorption, as well as fetal death and malformation, were determined. Thyroid and pituitary gland weights were measured, as well as serum levels of thyroid hormone, gonadotropin, and sex hormones. In the

  9. Gonadotropin-releasing hormone (GnRH) receptors of cattle aggregate on the surface of gonadotrophs and are increased by elevated GnRH concentrations.

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


    The presence of gonadotropin-releasing hormone (GnRH) receptors (GnRHRs) on gonadotrophs in the anterior pituitary (AP) is an important factor for reproduction control. However, little is known regarding GnRHR gene expression in gonadotrophs of cattle owing to the lack of an appropriate anti-GnRHR antibody. Therefore, an anti-GnRHR antibody for immunohistochemistry, flow cytometry, and immunocytochemistry assays was developed to characterize GnRHR gene expression in gonadotrophs. The anti-GnRHR antibody could suppress GnRH-induced LH secretion from cultured AP cells of cattle. The GnRHR, luteinizing hormone (LH), and follicle stimulating hormone (FSH) in the AP tissue was analyzed by fluorescence immunohistochemistry. The GnRHRs were aggregated on a limited area of the cell surface of gonadotrophs, possibly localized to lipid rafts. The LH secretion was stimulated with increasing amounts of GnRH; however, excessive concentrations (> 1 nM) resulted in a decrease in LH secretion. A novel method to purify gonadotrophs was developed using the anti-GnRHR antibody and fluorescence-activated cell sorting. Flow cytometric analysis using the anti-GnRHR antibody for cultured bovine AP cells, however, failed to support the hypothesis that GnRH induces GnRHR internalization and decreases GnRHR on the surface of GnRHR-positive AP cells. In contrast, immunocytochemistry using primary antibodies for cultured bovine AP cells showed that 10 nM (P < 0.05) and 100 nM (P < 0.01) GnRH, but not 0.01-1 nM GnRH, increased GnRHR in the cytoplasm of LH-positive cells. In conclusion, these data suggested that GnRHRs were aggregated on the surface of gonadotrophs and GnRHR inside gonadotrophs increased with elevated concentrations of GnRH.

  10. Polymorphisms in luteinizing hormone receptor and hypothalamic gonadotropin-releasing hormone genes and their effects on sperm quality traits in Chinese Holstein bulls.

    Sun, Li-Ping; Du, Qing-Zhi; Song, Ya-Pan; Yu, Jun-Na; Wang, Shu-Juan; Sang, Lei; Song, Luo-Wen; Yue, Yao-Min; Lian, Yu-Ze; Zhang, Sheng-Li; Hua, Guo-Hua; Zhang, Shu-Jun; Yang, Li-Guo


    Genes of hypothalamic-pituitary-gonadal axis play a key role in male reproductive performance. This study evaluated the polymorphisms of luteinizing hormone receptor (LHR) and hypothalamic gonadotropin-releasing hormone (GnRH) genes and their effects on sperm quality traits including semen volume per ejaculate (VOL), sperm density (SD), fresh sperm motility (FSM), thawed sperm motility (TSM), acrosome integrity rate (AIR), and abnormal sperm rate (ASR) collected from 205 Chinese Hostein bulls. The study bulls consisted of 205 mature Chinese Holstein, 27 Simmental, 28 Charolais, and 14 German yellow cattle. One single nucleotide polymorphism (SNP) (A883G) in exon 2 of GnRH and two SNPs (A51703G and G51656T) in intron 9 of LHR were identified in 274 bulls. Analysis of variance in 205 Chinese Holstein bulls showed that age had significant effect on both SD and FSM (P bulls with AG genotype had higher FSM than bulls with AA and GG genotype in LHR at 51,703 locus (P bulls with GG genotype had higher SD than bulls with TT genotype in LHR at G51656T locus (P < 0.10). Phenotypic correlation among the traits revealed that significant negative correlations were observed between ASR and AIR (r = -0.736, P < 0.01), ASR and AIR (r = -0.500, P < 0.01). There were moderate positive correlations between VOL and SD (r = 0.422, P < 0.01), as well as FSM (r = 0.411, P < 0.01). In conclusion, LHR may be a potential marker for sperm quality of SD and FSM.

  11. Development of quantitative real-time PCR assays for fathead minnow (Pimephales promelas) gonadotropin ß subunit mRNAs to support endocrine disruptor research.

    Villeneuve, Daniel L.; Miracle, Ann L.; Jensen, Kathleen M.; Degitz, Sigmund J.; Kahl, Michael D.; Korte, Joseph J.; Greene, Katie J.; Blake, Lindsey S.; Linnum, Ann; Ankley, Gerald T.


    Fathead minnows (Pimephales promelas) are one of the most widely-used small fish models for regulatory ecotoxicology testing and research related to endocrine disrupting chemicals (EDCs). In this study, we isolated and sequenced cDNAs for fathead minnow follicle-stimulating hormone-like and luteinizing hormone-like β (FSHβ and LHβ) and glycoprotein α (GPα) subunits. Quantitative real-time PCR assays for measuring gonadotropin (GtH) β subunit transcripts were developed and used to examine “baseline” transcript levels over a range of age classes and reproductive states encompassed in EDC testing. In females, FSHβ and LHβ transcripts were greater in 4-5 month old than in younger fish and were significantly correlated with one another across all age classes examined. In males, FSHβ transcripts were greatest in 2-3 month old fish and were inversely correlated with various measures of testis development including, gonadal-somatic index (GSI), and histological stage. Overall, the pattern of GtHβ expression over age classes associated with gonad development was similar to that reported for other asynchronous-spawning fish. Despite significant changes in female GSI, gonad stage, and plasma vitellogenin within 24 h of spawning, GtHβ transcript levels in fish that had spawned within the preceding 24 h were not significantly different from those in fish that were 2-3 days post-spawn and expected to spawn within the next 24 h based on spawning history. Results of this study provide insights related to the role of GtHs in fathead minnow reproductive development and function. Additionally they provide useful “baseline” data needed to design and interpret effective experiments for studying direct and indirect effects of EDCs on GtH subunit mRNA expression, which will facilitate a greater understanding of integrated system-wide responses of the fathead minnow brain-pituitary-gonadal axis to stressors including EDCs.

  12. Molecular cloning of cDNAs and structural model analysis of two gonadotropin beta-subunits of snakehead fish (Channa maculata).

    Chatterjee, Abhijit; Shen, San-Tai; Yu, John Yuh-Lin


    The cDNAs encoding beta-subunits of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) have been cloned from the pituitary of snakehead fish, Channa maculata, and the three-dimensional structural models of the encoded FSH and LH were investigated. The cloned cDNAs, including 5'-untranslated region (UTR), open-reading frame, and 3'-UTR followed by a poly(A) tail, were obtained by reverse transcription-polymerase chain reaction and rapid amplification of cDNA end methods. The open-reading frames of FSH-beta cDNA encodes a 120-amino acid protein with a signal peptide of 18 amino acids and a mature protein of 102 amino acids; while LH-beta cDNA encodes a 140-amino acid protein with a signal peptide of 33 amino acids and a mature protein of 115 amino acids. The amino acid sequence identities of snakehead fish FSH-beta and LH-beta in comparison with other fish are 27.8-81.9% and 45.2-88.8%, respectively; while in comparison with tetrapods are 26.2-28.9% and 37.5-51.2%, respectively. Both FSH-beta and LH-beta of snakehead fish resemble most to those of Perciformes, implying their closer phylogenetic relationship. All 12 cysteine residues are conserved in snakehead fish LH-beta; while 11 cysteine residues are conserved in its FSH-beta. The third cysteine is absent in snakehead fish FSH-beta; instead, a positionally shifted cysteine residue is present at the N-terminus, as found in some phylogenetic related fish. The structure models of snakehead fish FSH and LH, constructed by using the crystal structures of human FSH and human chorionic gonadotropin as respective template, showed that the positionally shifted N-terminal cysteine residue of snakehead fish FSH-beta likely can substitute the third cysteine to form a disulfide bond with the 12th cysteine.

  13. Melanin-concentrating hormone (MCH) and gonadotropin-releasing hormones (GnRH) in Atlantic cod, Gadus morhua: tissue distributions, early ontogeny and effects of fasting.

    Tuziak, Sarah M; Volkoff, Hélène


    Melanin-concentrating hormone (MCH) is classically known for its role in regulating teleost fish skin color change for environmental adaptation. Recent evidence suggests that MCH also has appetite-stimulating properties. The gonadotropin-releasing hormone (GnRH) peptide family has dual roles in endocrine control of reproduction and energy status in fish. Atlantic cod (Gadus morhua) are a commercially important aquaculture species inhabiting the shores of Atlantic Canada. In this study, we examine MCH and GnRH transcript expression profiles during early development as well as in central and peripheral tissues and quantify juvenile Atlantic cod MCH and GnRH hypothalamic mRNA expressions following food deprivation. MCH and GnRH3 cDNAs are maternally deposited into cod eggs, while MCH has variable expression throughout early development. GnRH2 and GnRH3 mRNAs "turn-on" during mid-segmentation once the brain is fully developed. For both MCH and GnRH, highest expression appears during the exogenous feeding stages, perhaps supporting their functions as appetite regulators during early development. MCH and GnRH transcripts are found in brain regions related to appetite regulation (telencephalon/preoptic area, optic tectum/thalamus, hypothalamus), as well as the pituitary gland and the stomach, suggesting a peripheral function in food intake regulation. Atlantic cod MCH mRNA is upregulated during fasting, while GnRH2 and GnRH3 transcripts do not appear to be influenced by food deprivation. In conclusion, MCH might be involved in stimulating food intake in juvenile Atlantic cod, while GnRHs may play a more significant role in appetite regulation during early development.

  14. Effects of inorganic and organic manganese supplementation on gonadotropin-releasing hormone-I and follicle-stimulating hormone expression and reproductive performance of broiler breeder hens.

    Xie, Jingjing; Tian, Chuanhuan; Zhu, Yongwen; Zhang, Liyang; Lu, Lin; Luo, Xugang


    Manganese is an essential microelement. Manganese deficiency affects reproduction performance and reproductive hormones in layers. However, little is known about its effects and the possible mechanism in regulating reproduction in broiler breeder hens. In the current study, broiler breeder hens at peak production were fed with diets supplemented with 0, 120, or 240 mg of Mn/kg as MnSO4 or Mn proteinate for 13 wk. Manganese supplementation did not alter egg laying rate, egg weight, fertility, hatchability, or hatchling weight over a 13-wk trial period. However, 240 mg of Mn/kg supplementation significantly increased serum Mn (P Manganese supplements increased the eggshell breaking strength (P < 0.05) without affecting the eggshell thickness. There was no difference in serum cholesterol and estradiol. Expression of follicle-stimulating hormone) and gonadotropin-releasing hormone-I (GnRH-I) genes was significantly elevated by 240 mg of Mn/kg (P < 0.05). Furthermore, inorganic Mn supplementation doubled GnRH-I expression compared with supplementation with the organic form (P < 0.05), although serum Mn was comparable between these 2 supplements. No obvious difference was shown in gene expression of luteinizing hormone, prolactin, GnRH-I receptor, inducible NO synthase, and dopamine receptor D1 in the pituitary as well as tyrosine hydroxylase and inducible NO synthase in the hypothalamus. This suggests that dietary Mn supplementation could improve eggshell quality in the long term. The central mechanism of nontoxic high doses of Mn suggested the transcriptional activation of GnRH-I and follicle-stimulating hormone genes. The central effect of inorganic Mn activating GnRH-I genes compared with the reduced effect by organic Mn could possibly be due to a decreased capacity of the latter passing through the blood-brain barrier.

  15. The Influence of Pituitary Size on Outcome After Transsphenoidal Hypophysectomy in a Large Cohort of Dogs with Pituitary-Dependent Hypercortisolism

    van Rijn, Sarah; Galac, S.; Tryfonidou, M. A.; Hesselink, J. W.; Penning, L. C.; Kooistra, H. S.; Meij, B. P.


    BACKGROUND Transsphenoidal hypophysectomy is one of the treatment strategies in the comprehensive management of dogs with pituitary-dependent hypercortisolism (PDH). OBJECTIVES To describe the influence of pituitary size at time of pituitary gland surgery on long-term outcome. ANIMALS Three-hundred-

  16. Primary pulmonary choriocarcinoma after human chorionic gonadotropin normalization following hydatidiform mole

    Maestá, Izildinha; Leite, Fábio Vicente; Michelin, Odair Carlito


    BACKGROUND: Primary pulmonary choriocarcinoma (PPC) is rare and frequently leads to death. CASES: Two young patients presented with previous molar pregnancy and spontaneous serum human chorionic gonadotropin (hCG) normalization. Patient 1 was referred to our center after partial response to chemo......BACKGROUND: Primary pulmonary choriocarcinoma (PPC) is rare and frequently leads to death. CASES: Two young patients presented with previous molar pregnancy and spontaneous serum human chorionic gonadotropin (hCG) normalization. Patient 1 was referred to our center after partial response...... 3 years after diagnosis. Patient 2 presented with persistently high hCG, though the affected organ was not identified. Chemotherapy was unsuccessful. Patient reevaluation showed an isolated pulmonary mass. Pulmonary lobectomy was performed; 2 weeks later, hCG was normal and consolidation with 2...

  17. [Diagnosis of ovum viability: comparative analysis between ultrasound and chorionic gonadotropin hormone].

    Romero Gutiérrez, G; Farías Gómez, E; Castelazo Guemez, J M


    In a retrospective study carried out in the Hospital de Gineco-Obstetricia del Centro Médico León, Gto., Instituto Mexicano del Seguro Social, 61 patients were studied in order to compare the sensitivity and specificity values and the correlation coefficient between the hormonal assays (Human Chorionic Gonadotropin, HCG) and the ultrasound scanning. The qualitative concentrations of HCG had a sensitivity of 37.5% and a specificity of 100%. The levels of subunit beta of HCG had sensitivity of 25% and specificity of 100%. The whole correlation coefficient of the hormonal method (HCG) was R = 0.51 (P less than 0.01). The ultrasound monitoring had a sensitivity of 855 and specificity of 100%, with a correlation coefficient R = 0.88 (P less than 0.01). It was concluded that ultrasound scanning has a better sensitivity and higher correlation than human chorionic gonadotropin assays in the diagnosis of ovum vitality.

  18. Effects of dexamethasone and gonadotropins on the testis of the adrenalectomized lizard Mabuya carinata (Schn.)

    Yajurvedi, H N; Chandramohan, K


    The effects of gonadotropins (LH + FSH) and dexamethasone on the spermatogenic and steroidogenic activity in the adrenalectomized Mabuya carinata have been studied. Secondary spermatocytes, spermatids, and spermatozoa were absent, and there was a significant decrease in the activity levels of delta 5-3 beta-hydroxysteroid dehydrogenase (delta 5-3 beta-HSDH) and glucose-6-phosphate dehydrogenase in the adrenalectomized lizards compared with those of controls. Administration of either dexamethasone or LH + FSH to adrenalectomized lizards resulted in restoration of testicular activity as revealed by the appearance of secondary spermatocytes, spermatids, and spermatozoa and a significant increase in the activity level of delta 5-3 beta-HSDH compared to that of adrenalectomized lizards. The results indicate that impairment in gonadotropin secretion might be a major factor in inducing testicular regression following adrenalectomy in M. carinata.

  19. Beta-Human Chorionic Gonadotropin Producing Osteosarcoma of the Sacrum in a 26-Year-Old Woman: A Case Report and Review of the Literature

    Ryan Glass


    Full Text Available Ectopic secretion of beta-human chorionic gonadotropin is considered a poor prognostic marker in epithelial tumors. However, very few cases have been reported in sarcomas. We present the case of a 26-year-old female who presented with a metastatic osteosarcoma. She underwent usual testing prior to starting treatment and was found to have elevated levels of beta-human chorionic gonadotropin. As the patient was not pregnant, another source of beta-human chorionic gonadotropin secretion had to be considered. The tumor cells demonstrated positive staining for beta-human chorionic gonadotropin by immunohistochemistry, and serum levels of beta-human chorionic gonadotropin were used to monitor tumor progression and response to chemotherapy. We review the literature and discuss a potential role of beta-human chorionic gonadotropin in the treatment of such patients.

  20. Impact of gene polymorphisms of gonadotropins and their receptors on human reproductive success.

    Casarini, Livio; Santi, Daniele; Marino, Marco


    Gonadotropins and their receptors' genes carry several single-nucleotide polymorphisms resulting in endocrine genotypes modulating reproductive parameters, diseases, and lifespan leading to important implications for reproductive success and potential relevance during human evolution. Here we illustrate common genotypes of the gonadotropins and gonadotropin receptors' genes and their clinical implications in phenotypes relevant for reproduction such as ovarian cycle length, age of menopause, testosterone levels, polycystic ovary syndrome, and cancer. We then discuss their possible role in human reproduction and adaptation to the environment. Gonadotropins and their receptors' variants are differently distributed among human populations. Some hints suggest that they may be the result of natural selection that occurred in ancient times, increasing the individual chance of successful mating, pregnancy, and effective post-natal parental cares. The gender-related differences in the regulation of the reproductive endocrine systems imply that many of these genotypes may lead to sex-dependent effects, increasing the chance of mating and reproductive success in one sex at the expenses of the other sex. Also, we suggest that sexual conflicts within the FSH and LH-choriogonadotropin receptor genes contributed to maintain genotypes linked to subfertility among humans. Because the distribution of polymorphic markers results in a defined geographical pattern due to human migrations rather than natural selection, these polymorphisms may have had only a weak impact on reproductive success. On the contrary, such genotypes could acquire relevant consequences in the modern, developed societies in which parenthood attempts often occur at a later age, during a short, suboptimal reproductive window, making clinical fertility treatments necessary.

  1. Does Postevacuation β -Human Chorionic Gonadotropin Level Predict the Persistent Gestational Trophoblastic Neoplasia?


    β -human chorionic gonadotropin (HCG) level is not a reliable marker for early identification of persistent gestational trophoblastic neoplasia (GTN) after evacuation of hydatidiform mole. Thus, this study was conducted to evaluate β -HCG regression after evacuation as a predictive factor of malignant GTN in complete molar pregnancy. Methods. In this cross-sectional study, we evaluated a total of 260 patients with complete molar pregnancy. Sixteen of the 260 patients were excluded. Serum leve...

  2. Inhibitory effect of submaximal doses of ghrelin on gonadotropin secretion in women.

    Messini, C I; Dafopoulos, K; Malandri, M; Georgoulias, P; Anifandis, G; Messinis, I E


    The effect of ghrelin on gonadotropin secretion has been equivocal. Recent data have shown an inhibitory effect of repeated injections of ghrelin on nocturnal LH and FSH secretion in women. The aim of this study was to investigate the effect of submaximal doses of ghrelin on the diurnal secretion of gonadotropins. Ten normally cycling women received 2 consecutive dosages of ghrelin (0.15 μg/kg and 0.30 μg/kg) intravenously in the early and late follicular phases of the cycle. Saline was injected in the preceding cycle. Blood samples in relation to ghrelin or saline administration (time 0 and 90 min) were taken at -15, 0, 30, 90, 120, 150, and 180 min. Serum estradiol concentrations were significantly higher in the late than in the early follicular phase. Following ghrelin administration, serum LH and FSH levels decreased significantly, in relation to the saline injection, in the late (pghrelin on diurnal gonadotropin secretion throughout the follicular phase of the cycle.

  3. Effect of Withania somnifera (L.) Dunal on Sex Hormone and Gonadotropin Levels in Addicted Male Rats

    Rahmati, Batool; Ghosian Moghaddam, Mohammad Hassan; Khalili, Mohsen; Enayati, Ehsan; Maleki, Maryam; Rezaeei, Saeedeh


    Background Opioid consumption has been widely increasing across the globe; how- ever, it can cause adverse effects on the body. Morphine, an opioid, can reduce sex hor- mones and fertility. Withania somnifera (WS) is a traditional herb used to improve sexual activities. This study strives to investigate the effect of WS on sex hormones and gonado- tropins in addicted male rats. Materials and Methods In this experimental study, forty-eight male National Maritime Research Institute (NMRI) rats were randomly divided into four groups: i. Control group, ii. WS-treated control group, iii. Addicted group, and iv. WS-treated addicted group. Wa- ter-soluble morphine was given to rats for 21 days to induce addiction, concurrently the treated groups (2 and 4) also received WS plant-mixed pelleted food (6.25%). At the end of the treatment, the sex hormone and gonadotropin levels of the rats’ sera were deter- mined in all the groups. Results Except for follicle-stimulating hormone (FSH), morphine reduced most of the gonadotropin and sex hormone levels. Whereas WS caused a considerable increase in the hormones in the treated addicted group, there was only a slight increase in the treated control group. Conclusion WS increased sex hormones and gonadotropins-especially testosterone, es- trogen, and luteinizing hormone-in the addicted male rats and even increased the proges- terone level, a stimulant of most sex hormones in addicted male rats. PMID:27441058

  4. Success of frozen embryo transfer: Does the type of gonadotropin influence the outcome?

    Hesham Al-Inany


    Full Text Available Hesham Al-Inany1, Pieter van Gelder21Egyptian IVF-ET Center, Maadi, Egypt; 2PSCT BV, Den Haag, The NetherlandsObjectives: To determine whether there is a difference in outcome between different ovulationinduced cycles after frozen-thawed embryo transfer (FET.Methods: We searched the Cochrane Menstrual Disorders and Subfertility Group’s trials register in May 2009, the Cochrane Central Register of Controlled Trials (Cochrane Library, Issue 1, 2008, ISI Web of Knowledge (1985 to August 2009, and reference lists of articles. Relevant conference proceedings were hand-searched and researchers in the field were contacted. Randomized controlled trials and retrospective studies were included, comparing the various cycle regimens and different methods during FET in assisted reproductive technology, ie, in vitro fertilization and intracytoplasmic sperm injection.Results: Using the agonist long protocol for downregulation, five trials provided extractable data for live-birth rates, ongoing pregnancy, and clinical pregnancy rates following FET. One trial provided extractable data for clinical pregnancy rate. There was no evidence of a significant difference in any outcome between the users of urinary gonadotropins versus recombinant follicle-stimulating hormone. Data on implantation and miscarriage rates following FET were not available for analysis.Conclusions: It seems that clinical pregnancy rate after FET is not influenced by the type of gonadotropins used. Research should be directed towards improving freezing and thawing techniques.Keywords: infertility, assisted reproductive technology, frozen embryo transfer, gonadotropins

  5. Studies of pituitary function in lactating ewes.

    Restall, B J; Kearins, R D; Starr, B G


    The release of LH from the pituitary of lactating ewes was studied. In Exp. 1, ewes were injected with 50 microng oestradiol benzoate (OB), 2-0 mg testosterone propionate (TP) or oil only (control) on days 5, 10, or 20 after lambing. LH was measured in peripheral plasma samples obtained 20-38 h after treatment, and the ovulations were recorded. The number of ewes in which an LH release was detected, and the amount released, declined between Day 5 and 20 after OB treatment but increased after TP treatment. The releases of LH were not always accompanied by ovulation and the incidence of ovulation was higher in ewes treated with TP. In Exp. 2, lactating ewes were injected with 1 or 5 (at 2-h intervals) doses of 50 microng Gn-RH, on Days 12 or 25 after lambing. LH was measured in peripheral plasma samples collected every 2 h for 10 h and every 3 h for a further 70 h. Release of LH occurred in all ewes, the amount being greater in ewes receiving multiple injections and in ewes treated on Day 25. The incidence of ovulation was higher after treatment on Day 25. Multiple injections of Gn-RH appeared to reduce the incidence of abnormal corpora lutea.

  6. Gamma knife radiosurgery for secreting pituitary tumors

    Noren, G. [Brown Univ., Providence, RI (United States). Rhode Island Hospital; Jackson, I.M.D.; Chougule, P.; Zheng, Z.; Epstein, M.H.


    Transsphenoidal surgery usually represents first line treatment for pituitary adenomas with the aim of removing the tumor, decompressing the optic apparatus and, in secreting tumors, eliminating the hypersecretion. Gamma Knife radiosurgery is indicated for tumor remnants or recurrences in or above the sella including those invading the cavernous sinus and also as initial treatment in patients who are unable to tolerate an open surgical procedure and where medication has failed. In this study, the target definition was retrospectively studied and when necessary corrected in 10 acromegalic patients, 8 with Cushing`s disease, and 12 with prolactinomas undergoing Gamma Knife radiosurgery. The dose plan was analyzed and the volume of the target covered by a minimum of 15, 20, 25, 30 and 35 Gy was estimated. A dose/volume profile for each treatment was created and correlated to the endocrinological and clinical outcome. Cure, according to strict endocrinological criteria, was seen in 6 of the acromegalic patients, in 2 of the patients with ACTH hypersecretion, and in 2 of the patients with prolactinomas. Analysis of these profiles, also for the patients with partial effect, show that a minimum radiation dose of 20 Gy may be adequate to eliminate the hypersecretion in acromegalic patients whereas a dose of at least 25 Gy may be required in patients with Cushing`s disease and prolactinoma. (author)

  7. MR imaging of pituitary hyperplasia in a child with growth arrest and primary hypothyroidism

    Papakonstantinou, O.; Bakantaki, A.; Papadaki, E.; Gourtsoyiannis, N. [Dept. of Radiology, Medical School, University of Crete, Heraklion (Greece); Bitsori, M.; Mamoulakis, D. [Dept. of Pediatrics, Medical School, University of Crete, Heraklion (Greece)


    Magnetic resonance imaging of pituitary hyperplasia has been rarely described in children with primary hypothyroidism. We report a case of pituitary hyperplasia in a child presented with significant growth arrest and laboratory evidence of hypothyroidism. Magnetic resonance imaging revealed symmetrical pituitary enlargement simulating macroadenoma. After thyroid hormone replacement therapy, the child's height increased and pituitary enlargement regressed to normal. Awareness of MRI appearance of pituitary hyperplasia in children with laboratory evidence of hypothyroidism might avoid misdiagnosis for pituitary tumor, which may also manifest as growth disorder, obviating unnecessary surgery. (orig.)

  8. Regulation of P450 oxidoreductase by gonadotropins in rat ovary and its effect on estrogen production

    Uesaka Miki


    Full Text Available Abstract Background P450 oxidoreductase (POR catalyzes electron transfer to microsomal P450 enzymes. Its deficiency causes Antley-Bixler syndrome (ABS, and about half the patients with ABS have ambiguous genitalia and/or impaired steroidogenesis. POR mRNA expression is up-regulated when mesenchymal stem cells (MSCs differentiate into steroidogenic cells, suggesting that the regulation of POR gene expression is important for steroidogenesis. In this context we examined the regulation of POR expression in ovarian granulosa cells by gonadotropins, and its possible role in steroidogenesis. Methods Changes in gene expression in MSCs during differentiation into steroidogenic cells were examined by DNA microarray analysis. Changes in mRNA and protein expression of POR in the rat ovary or in granulosa cells induced by gonadotropin treatment were examined by reverse transcription-polymerase chain reaction and western blotting. Effects of transient expression of wild-type or mutant (R457H or V492E POR proteins on the production of estrone in COS-7 cells were examined in vitro. Effects of POR knockdown were also examined in estrogen producing cell-line, KGN cells. Results POR mRNA was induced in MSCs following transduction with the SF-1 retrovirus, and was further increased by cAMP treatment. Expression of POR mRNA, as well as Cyp19 mRNA, in the rat ovary were induced by equine chorionic gonadotropin and human chorionic gonadotropin. POR mRNA and protein were also induced by follicle stimulating hormone in primary cultured rat granulosa cells, and the induction pattern was similar to that for aromatase. Transient expression of POR in COS-7 cells, which expressed a constant amount of aromatase protein, greatly increased the rate of conversion of androstenedione to estrone, in a dose-dependent manner. The expression of mutant POR proteins (R457H or V492E, such as those found in ABS patients, had much less effect on aromatase activity than expression of wild

  9. Hindbrain lactate regulates preoptic gonadotropin-releasing hormone (GnRH) neuron GnRH-I protein but not AMPK responses to hypoglycemia in the steroid-primed ovariectomized female rat.

    Shrestha, P K; Briski, K P


    Steroid positive-feedback activation of the gonadotropin-releasing hormone (GnRH)-pituitary luteinizing hormone (LH) neuroendocrine axis propagates the pre ovulatory LH surge, a crucial component of female reproduction. Our work shows that this key event is restrained by inhibitory metabolic input from hindbrain A2 noradrenergic neurons. GnRH neurons express the ultra-sensitive energy sensor adenosine 5'-monophosphate-activated protein kinase (AMPK); here, we investigated the hypothesis that GnRH nerve cell AMPK and peptide neurotransmitter responses to insulin-induced hypoglycemia are controlled by hindbrain lack of the oxidizable glycolytic end-product L-lactate. Data show that hypoglycemic inhibition of LH release in steroid-primed ovariectomized female rats was reversed by coincident caudal hindbrain lactate infusion. Western blot analyses of laser-microdissected A2 neurons demonstrate hypoglycemic augmentation [Fos, estrogen receptor-beta (ER-β), phosphoAMPK (pAMPK)] and inhibition (dopamine-beta-hydroxylase, GLUT3, MCT2) of protein expression in these cells, responses that were normalized by insulin plus lactate treatment. Hypoglycemia diminished rostral preoptic GnRH nerve cell GnRH-I protein and pAMPK content; the former, but not the latter response was reversed by lactate. Results implicate caudal hindbrain lactoprivic signaling in hypoglycemia-induced suppression of the LH surge, demonstrating that lactate repletion of that site reverses decrements in A2 catecholamine biosynthetic enzyme and GnRH neuropeptide precursor protein expression. Lack of effect of lactate on hypoglycemic patterns of GnRH AMPK activity suggests that this sensor is uninvolved in metabolic-inhibition of positive-feedback-stimulated hypophysiotropic signaling to pituitary gonadotropes.

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

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


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

  11. Changes of pituitary gland volume in Kennedy disease.

    Pieper, C C; Teismann, I K; Konrad, C; Heindel, W L; Schiffbauer, H


    Kennedy disease is a rare X-linked neurodegenerative disorder caused by a CAG repeat expansion in the first exon of the androgen-receptor gene. Apart from neurologic signs, this mutation can cause a partial androgen insensitivity syndrome with typical alterations of gonadotropic hormones produced by the pituitary gland. The aim of the present study was therefore to evaluate the impact of Kennedy disease on pituitary gland volume under the hypothesis that endocrinologic changes caused by partial androgen insensitivity may lead to morphologic changes (ie, hypertrophy) of the pituitary gland. Pituitary gland volume was measured in sagittal sections of 3D T1-weighted 3T-MR imaging data of 8 patients with genetically proven Kennedy disease and compared with 16 healthy age-matched control subjects by use of Multitracer by a blinded, experienced radiologist. The results were analyzed by a univariant ANOVA with total brain volume as a covariant. Furthermore, correlation and linear regression analyses were performed for pituitary volume, patient age, disease duration, and CAG repeat expansion length. Intraobserver reliability was evaluated by means of the Pearson correlation coefficient. Pituitary volume was significantly larger in patients with Kennedy disease (636 [±90] mm(3)) than in healthy control subjects (534 [±91] mm(3)) (P = .041). There was no significant difference in total brain volume (P = .379). Control subjects showed a significant decrease in volume with age (r = -0.712, P = .002), whereas there was a trend to increasing gland volume in patients with Kennedy disease (r = 0.443, P = .272). Gland volume correlated with CAG repeat expansion length in patients (r = 0.630, P = .047). The correlation coefficient for intraobserver reliability was 0.94 (P pituitary volume that correlated with the CAG repeat expansion length. This could reflect hypertrophy as the result of elevated gonadotropic hormone secretion caused by the androgen receptor mutation with partial

  12. Longitudinal evaluation of the hypothalamic-pituitary-testicular function in 8 boys with adrenal hypoplasia congenita (AHC due to NR0B1 mutations.

    Caroline Galeotti

    Full Text Available BACKGROUND: Boys carrying mutations in the NR0B1 gene develop adrenal hypoplasia congenita (AHC and impaired sexual development due to the combination of hypogonadotropic hypogonadism (HH and primary defects in spermatogenesis. METHODS: We analysed the evolution of hypothalamic-pituitary-testicular function of 8 boys with AHC due to NR0B1 mutations. Our objective was to characterize and monitor the progressive deterioration of this function. RESULTS: The first symptoms appeared in the neonatal period (n = 5 or between 6 months and 8.7 years (n = 3. Basal plasma adrenocorticotrophic hormone (ACTH concentrations increased in all boys, whilst cortisol levels decreased in one case. The natremia was equal or below 134 mmol/L and kaliemia was over 5 mmol/L. All had increased plasma renin. In 3 of 4 patients diagnosed in the neonatal period and evaluated during the first year, the basal plasma gonadotropins concentrations, and their response to gonadotropin releasing hormone (GnRH test (n = 2, and those of testosterone were normal. The plasma inhibin B levels were normal in the first year of life. With the exception of two cases these concentrations decreased to below the normal for age. Anti-Müllerian hormone concentrations were normal for age in all except one case, which had low concentrations before the initiation of testosterone treatment. In 3 of the 8 cases the gene was deleted and the remaining 5 cases carried frameshift mutations that are predicted to introduce a downstream nonsense mutation resulting in a truncated protein. CONCLUSIONS: The decreases in testosterone and inhibin B levels indicated a progressive loss of testicular function in boys carrying NR0B1 mutations. These non-invasive examinations can help to estimate the age of the testicular degradation and cryopreservation of semen may be considered in these cases as investigational procedure with the aim of restoring fertility.

  13. Effects of repeated ether stress on the hypothalamic-pituitary-testes axis in adult rats with special reference to inhibin secretion.

    Tohei, A; Tomabechi, T; Mamada, M; Akai, M; Watanabe, G; Taya, K


    Effects of ether stress on the hypothalamo-hypophysial-gonadal axis in adult male rats were examined. To clarify the role of adrenal glucocorticoids in gonadal function, the effects of adrenalectomy and Dexamethasone treatment were also investigated. Ether stress increased the plasma concentrations of ACTH and corticosterone, but decreased the plasma concentrations of LH, FSH, inhibin and testosterone. The pituitary responsiveness to LH-RH for LH release and testicular responsiveness to the endogenous LH for testosterone release were maintained in stressed rats. Adrenalectomy caused an increase in the plasma concentrations of ACTH, but decreased the plasma concentrations of LH, FSH and testosterone. Dexamethasone treatment in adrenalectomized rats recovered the levels of plasma gonadotropins to control levels. The concentration of plasma inhibin did not change in adrenalectomized rats, but it was decreased compared to control rats by Dexamethasone treatment. Treatments of Dexamethasone in intact male rats resulted in a decline in plasma levels of testosterone and inhibin without a decrease in the levels of LH and FSH, indicating the direct effect of Dexamethasone on the testes. These results indicate that increased ACTH secretion in stressed rats is probably due to hypersecretion of CRH from the hypothalamus, which suppresses gonadotropin secretion via the inhibition of LH-RH. The decreased levels of testosterone may be caused by a stress-induced decrease in plasma LH concentrations and increased secretion of corticosterone in the ether stressed rats. The low levels of plasma inhibin in stressed rats was also probably due to the direct effect of corticosterone on the Sertoli cells.

  14. MRI of the liver and the pituitary gland in patients with {beta}-thalassemia major: Does hepatic siderosis predict pituitary iron deposition?

    Argyropoulou, Maria I.; Efremidis, Stavros C. [Department of Radiology, Medical School, University of Ioannina, 45110 Ioannina (Greece); Kiortsis, Dimitrios N. [Laboratory of Physiology, Medical School, University of Ioannina, 45110 Ioannina (Greece)


    Our objective was to study, in thalassemic patients, if hepatic siderosis evaluated by MRI could predict the pituitary iron overload. In 36 thalassemic patients (age range 6-44 years, mean age 21.7 years) the liver/fat ratio (L/F), the pituitary/fat ratio (P/F), the liver and pituitary T2 relaxation times were evaluated, by using a multiecho spin-echo sequence. Serum ferritin levels were measured and an extensive endocrine evaluation was performed. The L/F, the P/F and pituitary T2 showed a good correlation with serum ferritin (r=-0.55, r=-0.55 and r=-0.53, respectively; p<0.01). Liver T2 did not show significant correlation with serum ferritin. The variability of L/F explained only the 10.8% of the variability of pituitary T2 and of the P/F. When ferritin was added to the model it predicted only the 26.85% and the 30.8% of the variability of pituitary T2 and of the P/F, respectively. The P/F and pituitary T2 were lower in patients with hypogonadotropic hypogonadism (group 1) compared with those without pituitary dysfunction (group 2). No significant differences of L/F were found between the two groups. Hepatic iron overload evaluated by MR is a poor predictor of pituitary siderosis. The MR studies of the pituitary gland might be necessary to evaluate the pituitary iron overload. (orig.)

  15. Histology and Histochemistry of Pituitary in Siniperca kneri%大眼鳜垂体的组织学和组织化学研究

    谢碧文; 黄琪; 蒲德永; 张耀光


    [Objective] The aim was to discuss the histological structure of pituitary in Siniperca kneri. [Method] With S. kneri as tested material, the histology and histochemistry of its pituitary were studied by microscope observation. [Result] The pituitary of S. kneri was composed of neurohypophysis and adenohypophysis. The adenohypophysis divided into rostral pars distalis, proximal pars distalis and pars intermedia. The neurohypophysis was extremely developed, especially in the posterior neurohypophysis, which occupied the majority of the posterior pituitary. The adenohypophysis could distinguish 7 kinds of secretory cell types, namely, prolactin cells and adrenocorticotropic hormone cells in rostral pars distalis, growth hormone cells, gonadotropin cells and thyrotropin cells in proximal pars distalis, and melanocyte stimulating hormone cells and PAS positive cells in pars intermedia. Microvessel was very developed in ventral region of posterior pars intermedia. [Conclusion] The research provided the scientific basis for further making clear the propagation mechanism of S. kneri.%[目的] 探讨大眼鳜垂体的组织学结构.[方法] 以大眼鳜成鱼为试验材料,通过显微镜观察对其垂体的组织学、组织化学进行研究.[结果] 大眼鳜垂体由神经垂体和腺垂体两部分组成,腺垂体分为前外侧部、中外侧部和中间部.神经垂体十分发达,尤其是后腺垂体神经部,占垂体后部大部分区域;腺垂体可分辨出7种分泌细胞类型,即前外侧部的催乳激素细胞和促肾上腺皮质激素细胞,中外侧部的生长激素细胞、促性腺激素细胞和促甲状腺激素细胞,中间部的促黑色素细胞刺激激素细胞和PAS阳性细胞;中间部后方腹面边缘微血管十分发达.[结论] 该研究为进一步弄清大眼鳜的繁殖机理提供了科学依据.

  16. Feeding prepubescent gilts a high-fat diet induces molecular changes in the hypothalamus-pituitary-gonadal axis and predicts early timing of puberty.

    Zhuo, Yong; Zhou, Dongsheng; Che, Lianqiang; Fang, Zhengfeng; Lin, Yan; Wu, De


    The onset of puberty in females has been occurring earlier over the past decades, presumably as a result of improved nutrition in developed countries. However, the underlying molecular mechanisms responsible for the early attainment of puberty as a result of nutrition fortification remain largely unknown. The aim of this study was to evaluate the hormone and gene expression changes in prepubescent gilts fed a high-fat diet to investigate whether these changes could predict the early timing of puberty. Forty gilts were fed a daily basal diet (LE) or a basal diet with an additional 270 g/d or 340 g/d of fat (HE) during the prepubescent phase. Blood samples were collected during the prepubescent phase to detect hormone secretion changes in insulin-like growth factor-1, kisspeptin, estradiol, progesterone, and leptin. The gene expressions at the hypothalamus-pituitary-gonadal axis were examined on day 73 of the experiment (average age on day 177) during the prepubescent phase. An HE diet resulted in accelerated body weight gain and back-fat thickness at the P2 point compared with LE gilts during the prepubescent phase. Gilts that were fed HE diets attained puberty 12 d earlier than LE gilts, and a larger proportion of HE gilts reached puberty at day 180 or 190 of age. A postmortem analysis revealed a promoted development of the uterus and ovary tissue that was characterized by a 53.7% and 29.5% increase in the uterine and ovary weight, respectively, and an increased length of the uterine horn and oviduct tissue in HE gilts. Real-time quantitative polymerase chain reaction revealed that HE gilts had higher Kiss-1, G protein-coupled receptor 54, gonadotropin-releasing hormone and estrogen receptor α mRNA expression levels in the hypothalamic anteroventral periventricular nucleus; the leptin receptor mRNA expression level was higher in the hypothalamic arcuate nucleus and ovary tissue; the insulin-like growth factor-1 receptor expression was higher in the pituitary and

  17. Exposure to bleached kraft pulp mill effluent disrupts the pituitary-gonadal axis of white sucker at multiple sites

    Van Der Kraak, G.J.; Munkittrick, K.R.; McMaster, M.E.; Portt, C.B.; Chang, J.P. (Department of Zoology, University of Guelph, Ontario (Canada))


    Recent studies have demonstrated reproductive problems in white sucker (Catostomus commersoni) exposed to bleached kraft pulp mill effluent (BKME) at Jackfish Bay on Lake Superior. These fish exhibit delayed sexual maturity, reduced gonadal size, reduced secondary sexual characteristics, and circulating steroid levels depressed relative to those of reference populations. The present studies were designed to evaluate sites in the pituitary-gonadal axis of prespawning white sucker affected by BKME exposure. At the time of entry to the spawning stream, plasma levels of immunoreactive gonadotropin (GtH)-II (LH-type GtH) in male and female white sucker were 30- and 50-fold lower, respectively, than the levels in fish from a reference site. A single intraperitoneal injection of D-Arg6, Pro9N-Et sGnRH (sGnRH-A, 0.1 mg/kg) increased plasma GtH levels in male and female fish at both sites, although the magnitude of the response was greatly reduced in BKME-exposed fish. Fish at the BKME site did not ovulate in response to sGnRH-A, while 10 of 10 fish from the reference site ovulated within 6 hr. Plasma 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17,20 beta-P) levels were depressed in BKME-exposed fish and unlike fish at the reference site, failed to increase in response to sGnRH-A. Testosterone levels in both sexes and 11-ketostestosterone levels in males were elevated in fish from the reference site but were not further increased by GnRH treatment. In contrast, BKME-exposed fish exhibit a transitory increase in testosterone levels in response to the GnRH analog. In vitro incubations of ovarian follicles obtained from fish at the BKME site revealed depressed basal secretion of testosterone and 17,20 beta-P and reduced responsiveness to the GtH analog human chorionic gonadotropin and to forskolin, a direct activator of adenylate cyclase.

  18. Familial isolated pituitary adenomas (FIPA) and the pituitary adenoma predisposition due to mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene.

    Beckers, Albert; Aaltonen, Lauri A; Daly, Adrian F; Karhu, Auli


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

  19. Signaling pathway networks mined from human pituitary adenoma proteomics data

    Zhan Xianquan


    Full Text Available Abstract Background We obtained a series of pituitary adenoma proteomic expression data, including protein-mapping data (111 proteins, comparative proteomic data (56 differentially expressed proteins, and nitroproteomic data (17 nitroproteins. There is a pressing need to clarify the significant signaling pathway networks that derive from those proteins in order to clarify and to better understand the molecular basis of pituitary adenoma pathogenesis and to discover biomarkers. Here, we describe the significant signaling pathway networks that were mined from human pituitary adenoma proteomic data with the Ingenuity pathway analysis system. Methods The Ingenuity pathway analysis system was used to analyze signal pathway networks and canonical pathways from protein-mapping data, comparative proteomic data, adenoma nitroproteomic data, and control nitroproteomic data. A Fisher's exact test was used to test the statistical significance with a significance level of 0.05. Statistical significant results were rationalized within the pituitary adenoma biological system with literature-based bioinformatics analyses. Results For the protein-mapping data, the top pathway networks were related to cancer, cell death, and lipid metabolism; the top canonical toxicity pathways included acute-phase response, oxidative-stress response, oxidative stress, and cell-cycle G2/M transition regulation. For the comparative proteomic data, top pathway networks were related to cancer, endocrine system development and function, and lipid metabolism; the top canonical toxicity pathways included mitochondrial dysfunction, oxidative phosphorylation, oxidative-stress response, and ERK/MAPK signaling. The nitroproteomic data from a pituitary adenoma were related to cancer, cell death, lipid metabolism, and reproductive system disease, and the top canonical toxicity pathways mainly related to p38 MAPK signaling and cell-cycle G2/M transition regulation. Nitroproteins from a

  20. Fractionated stereotactic radiotherapy in the treatment of pituitary adenomas

    Kopp, C.; Theodorou, M.; Poullos, N.; Astner, S.T.; Geinitz, H.; Molls, M. [Technische Univ. Muenchen, Klinikum rechts der Isar (Germany). Klinik und Poliklinik fuer Strahlentherapie und Radiologische Onkologie; Stalla, G.K. [Max-Planck-Institut fuer Psychiatrie, Muenchen (Germany). Klinische Neuroendokrinologie; Meyer, B. [Technische Univ. Muenchen, Klinikum rechts der Isar (Germany). Neurochirurgische Klinik und Poliklinik; Nieder, C. [Nordland Hospital, Bodoe (Norway). Dept. of Oncology and Palliative Medicine; Tromsoe Univ. (Norway). Inst. of Clinical Medicine; Grosu, A.L [Freiburg Univ. (Germany). Klinik fuer Strahlenheilkunde


    Purpose: The purpose of this work was to evaluate tumor control and side effects associated with fractionated stereotactic radiotherapy (FSRT) in the management of residual or recurrent pituitary adenomas. Patients and methods: We report on 37 consecutive patients with pituitary adenomas treated with FSRT at our department. All patients had previously undergone surgery. Twenty-nine patients had nonfunctioning, 8 had hormone-producing adenoma. The mean total dose delivered by a linear accelerator was 49.4 Gy (range 45-52.2 Gy), 5 x 1.8 Gy weekly. The mean PTV was 22.8 ccm (range 2.0-78.3 ccm). Evaluation included serial imaging tests, endocrinologic and ophthalmologic examination. Results: Tumor control was 91.9 % for a median follow-up time of 57 months (range 2-111 months). Before FSRT partial hypopituitarism was present in 41 % of patients, while 35 % had anterior panhypopituitarism. After FSRT pituitary function remained normal in 22 %, 43 % had partial pituitary dysfunction, and 35 % had anterior panhypopituitarism. Visual acuity was stable in 76 % of patients, improved in 19 %, and deteriorated in 5 %. Visual fields remained stable in 35 patients (95 %), improved in one and worsened in 1 patient (2.7 %). Conclusion: FSRT is an effective and safe treatment for recurrent or residual pituitary adenoma. Good local tumor control and preservation of adjacent structures can be reached, even for large tumors. (orig.)