The gonadotropin-releasing hormone receptor: signals involved in gonadotropin secretion and biosynthesis

The neurohormone gonadotropin-releasing hormone (GnRH) is a decapeptide which is synthesized in the hypothalamus and released into the hypophysial portal system in a pulsatile manner. GnRH exerts its effect on the anterior pituitary gonadotrophs where it regulates the secretion and synthesis of gonadotropins (luteinizing hormone and follicle-stimulating hormone) through receptor-mediated actions. The GnRH receptor has been characterized and shown to be coupled to the formation of 'second messengers' which participate in signal transduction mechanisms. GnRH stimulation of luteinizing hormone release is a Ca2(+)-dependent process. G protein, phosphoinositide hydrolysis, protein kinase C as well as arachidonic acid and some of its metabolites were identified as possible mediators in the process.     

Differential regulation of gonadotropin subunit messenger ribonucleic acids by gonadotropin-releasing hormone pulse frequency in ewes

Changes in the frequency of GnRH and LH pulses have been shown to occur between the luteal and preovulatory periods in the ovine estrous cycle. We examined the effect of these different frequencies of GnRH pulses on pituitary concentrations of LH and FSH subunit mRNAs. Eighteen ovariectomized ewes were implanted with progesterone to eliminate endogenous GnRH release during the nonbreeding season. These animals then received 3 ng/kg body weight GnRH in frequencies of once every 4, 1, or 0.5 h for 4 days. These frequencies represent those observed during the luteal and follicular phases, and the preovulatory LH and FSH surge of the ovine estrous cycle, respectively. On day 4, the ewes were killed and their anterior pituitary glands were removed for measurements of pituitary LH, FSH, and their subunit mRNAs. Pituitary content of LH and FSH, as assessed by RIA, did not change (P greater than 0.10) in response to the three different GnRH pulse frequencies. However, subunit mRNA concentrations, assessed by solution hybridization assays and expressed as femtomoles per mg total RNA, did change as a result of different GnRH frequencies. alpha mRNA concentrations were higher (P less than 0.05) when the GnRH pulse frequency was 1/0.5 h and 1 h, whereas LH beta and FSH beta mRNA concentrations were maximal (P less than 0.05) only at a pulse frequency of 1/h. Additionally, pituitary LH and FSH secretory response to GnRH on day 4 was maximal (P = 0.05) when the pulse infusion was 1/h.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential regulation of the gonadotropin storage pattern by gonadotropin-releasing hormone pulse frequency in the ewe

The differential control of gonadotropin secretion by GnRH pulse frequency may reflect changes in the storage of LH and FSH. To test this hypothesis, ovariectomized ewes passively immunized against GnRH received pulsatile injections of saline (group 1) or GnRH analogue: 1 pulse/6 h for group 2 or 1 pulse/h for group 3, during 48 h. Immunization against GnRH suppressed pulsatility of LH release and reduced mean FSH plasma levels (3.1 +/- 0.2 vs. 2.2 +/- 0.1 ng/ml before and 3 days after immunization, respectively). Pulsatile GnRH analogue replacement restored LH pulses but not FSH plasma levels. Low and high frequencies of GnRH analogue increased the percentage of LH-containing cells in a similar way (group 1 = 6.9 +/- 0.5% vs. group 2 = 10.5 +/- 0.8%, or vs. group 3 = 9.6 +/- 0.4%). In contrast, the rise of the percentage of FSH-containing cells was greater after administration of the analogue at low frequency than at high frequency (group 1 = 3.7 +/- 0.4% vs. group 2 = 8.4 +/- 0.2%, or vs. group 3 = 5.2 +/- 0.8%). Moreover, while GnRH pulse frequency had no differential effect on FSHbeta mRNA levels, LHbeta mRNA levels were higher under high than low frequency. These data showed that the frequency of GnRH pulses can modulate the gonadotropin storage pattern in the ewe. These changes may be a component of the differential regulation of LH and FSH secretion.     

Suppression of gonadotropin secretion and prevention of ovulation in the rat by antiserum to synthetic gonadotropin-releasing hormone

Administration of an antiserum (0.10–0.25 ml/rat) to the synthetic decapeptide “luteinizing hormone releasing hormone” (LH-RH) suppressed the cyclic surge of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in proestrous rats and prevented ovulation; exogenous LH reversed the block of ovulation. Serum prolactin levels remained unaffected. In ovariectomized rats, the antiserum suppressed the elevated serum levels of both gonadotropins. These findings are compatible with the view that the synthetic decapeptide is identical with the natural hypothalamic hormone that regulates the secretion of both LH and FSH.     

Negative feedback regulation of the secretion and actions of gonadotropin-releasing hormone in males

This minireview considers the state of knowledge regarding the interactions of testicular hormones to regulate the secretion and actions of GnRH in males, with special focus on research conducted in rams and male rhesus monkeys. In these two species, LH secretion is under the negative feedback regulation of testicular steroids that act predominantly within the central nervous system to suppress GnRH secretion. The extent to which these actions of testicular steroids result from the direct actions of testosterone or its primary metabolites, estradiol or dihydrotestosterone, is unclear. Because GnRH neurons do not contain steroid receptors, the testicular steroids must influence GnRH neurons via afferent neurons, which are largely undefined. The feedback regulation of FSH is controlled by inhibin acting directly at the pituitary gland. In male rhesus monkeys, the feedback regulation of FSH secretion is accounted for totally by the physiologically relevant form of inhibin, which appears to be inhibin B. In rams, the feedback regulation of FSH secretion involves the actions of inhibin and testosterone and interactions between these hormones, but the physiologically relevant form of inhibin has not been determined. The mechanisms of action for inhibin are not known.     

Autocrine regulation of calcium influx and gonadotropin-releasing hormone secretion in hypothalamic neurons.

Gonadotropin-releasing hormone (GnRH) receptors are expressed in hypothalamic tissues from adult rats, cultured fetal hypothalamic cells, and immortalized GnRH-secreting neurons (GT1 cells). Their activation by GnRH agonists leads to an overall increase in the extracellular Ca2+-dependent pulsatile release of GnRH. Electrophysiological studies showed that GT1 cells exhibit spontaneous, extracellular Ca2+-dependent action potentials, and that their inward currents include Na+, T-type and L-type Ca2+ components. Several types of potassium channels, including apamin-sensitive Ca2+-controlled potassium (SK) channels, are also expressed in GT1 cells. Activation of GnRH receptors leads to biphasic changes in intracellular Ca2+ concentration ([Ca2+]i), with an early and extracellular Ca2+-independent peak and a sustained and extracellular Ca2+-dependent plateau phase. During the peak [Ca2+]i response, electrical activity is abolished due to transient hyperpolarization that is mediated by SK channels. This is followed by sustained depolarization and resumption of firing with increased spike frequency and duration. The agonist-induced depolarization and increased firing are independent of [Ca2+]i and are not mediated by inhibition of K+ currents, but by facilitation of a voltage-insensitive and store depletion-activated Ca2+-conducting inward current. The dual control of pacemaker activity by SK and store depletion-activated Ca2+ channels facilitates voltage-gated Ca2+ influx at elevated [Ca2+]i levels, but also protects cells from Ca2+ overload. This process accounts for the autoregulatory action of GnRH on its release from hypothalamic neurons.     

Regulation of gonadotropin secretion and number of gonadotropin-releasing hormone receptors by inhibin, activin-A, and estradiol.

Primary cultures of ovine pituitary cells were used to characterize the effects of inhibin and activin on the secretion of gonadotropins and on the regulation of number of GnRH receptors in the presence or absence of estradiol. Number of GnRH receptors was determined by the specific binding of a saturating dose of [125I]des-Gly10-D-Trp6-GnRH-ethylamide (GnRH-A). Recombinant human inhibin-A (rh-inhibin-A) or inhibin in porcine and bovine follicular fluid (pFF and bFF, respectively) decreased secretion of FSH in a dose-dependent manner, with maximum inhibition at an inhibin concentration of approximately 0.1 nM. Neither pFF or bFF affected secretion of LH, although rh-inhibin-A caused a modest decrease (p less than 0.05) in secretion of LH. Treatment of cells with rh-inhibin-A, bFF, or pFF approximately doubled the number of GnRH receptors. Scatchard analysis indicated that increases in GnRH-A binding were due to an increase in receptor number rather than a change in affinity. Additionally, rh-inhibin-A, at a dose that doubled numbers of GnRH receptors, increased GnRH-induced LH release above that caused by GnRH alone, indicating that the increase in receptor number leads to increased responsiveness to GnRH. Recombinant human activin-A (rh-activin-A) increased secretion of FSH but did not affect secretion of LH. Number of GnRH receptors was not affected by lower concentrations of rh-activin-A but was decreased (p less than 0.05) by 3.0 nM activin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evolution of duplicated growth hormone genes in autotetraploid salmonid fishes.

A defining character of the piscine family Salmonidae is autotetraploidy resulting from a genome-doubling event some 25-100 million years ago. Initially, duplicated genes may have undergone concerted evolution and tetrasomic inheritance. Homeologous chromosomes eventually diverged and the resulting reduction in recombination and gene conversion between paralogous genes allowed the re-establishment of disomic inheritance. Among extant salmonine fishes (e.g. salmon, trout, char) the growth hormone (GH) gene is generally represented by two functional paralogs, GH1 and GH2. Sequence analyses of salmonid GH genes from species of subfamilies Coregoninae (whitefish, ciscos) and Salmoninae were used to examine the evolutionary history of the duplicated GH genes. Two divergent GH gene paralogs were also identified in Coregoninae, but they were not assignable to the GH1 and GH2 categories. The average sequence divergence between the coregonine GH genes was more than twofold lower than the corresponding divergence between the salmonine GH1 and GH2. Phylogenetic analysis of the coregonine GH paralogs did not resolve their relationship to the salmonine paralogs. These findings suggest that disomic inheritance of two GH genes was established by different mechanisms in these two subfamilies.     

Dopaminergic regulation of gonadotropin and thyrotropin hormone secretion is altered with age.

To determine if age-related changes in glycoprotein pituitary hormone secretion are associated with alterations in dopaminergic regulation, plasma gonadotropins and TSH were measured before and after L-dopa administration in 44 young (31-44 years of age) and 42 old (64-88 years of age) healthy male participants. Plasma GH and PRL were also determined in order to examine the somatotroph and lactotrope response. In the young, following L-dopa, plasma FSH, LH and TSH were unchanged from baseline. However, in older subjects, plasma FSH was significantly increased (p less than 0.001) and a similar trend was noted for LH. Plasma TSH was significantly depressed (p less than 0.002) in older subjects only. Following L-dopa, increases in plasma GH and decreases in plasma PRL were of similar magnitude in each group. These data indicate that dopaminergic modulation of gonadotropins and TSH is altered with age.     

Differential regulation of gonadotropin-releasing hormone secretion and gene expression by androgen: membrane versus nuclear receptor activation

Steroid hormones induce rapid membrane receptor-mediated effects that appear to be separate from long-term genomic events. The membrane receptor-mediated effects of androgens on GT1-7 GnRH-secreting neurons were examined. We observed androgen binding activity with a cell-impermeable BSA-conjugated testosterone [testosterone 3-(O-carboxymethyl)oxime (T-3-BSA)] and were able to detect a 110-kDa protein recognized by the androgen receptor (AR) monoclonal MA1-150 antibody in the plasma membrane fraction of the GT1-7 cells by Western analysis. Further, a transfected green fluorescent protein-tagged AR translocates and colocalizes to the plasma membrane of the GT1-7 neuron. Treatment with 10 nM 5alpha-dihydrotestosterone (DHT) inhibits forskolin-stimulated accumulation of cAMP, through a pertussis toxin-sensitive G protein, but has no effect on basal cAMP levels. The inhibition of forskolin-stimulated cAMP accumulation by DHT was blocked by hydroxyflutamide, a specific inhibitor of the nuclear AR. DHT, testosterone (T), and T-3-BSA, all caused significant elevations in intracellular calcium concentrations ([Ca(2+)](i)). T-3-BSA stimulates GnRH secretion 2-fold in the GT1-7 neuron, as did DHT or T. Interestingly GnRH mRNA levels were down-regulated by DHT and T as has been reported, but not by treatment with T-3-BSA or testosterone 17beta-hemisuccinate BSA. These studies indicate that androgen can differentially regulate GnRH secretion and gene expression through specific membrane-mediated or nuclear mechanisms.     

Fish growth hormone genes: Divergence of coding sequences in salmonid fishes

Comparison of coding nucleotide sequences of the paralogous GH1 and GH2 genes, as well as of the growth hormone amino acid sequences, in the species of closely related salmonid genera Salvelinus, Oncorhynchus, and Salmo was performed. It was demonstrated that, in different groups of salmonids, the amino acid substitution rates were considerably different. In some cases, an obvious discrepancy between the divergence of growth hormone genes and phylogenetic schemes based on other methods and approaches was revealed. These findings suggest that the reason may be multidirectional selection at duplicated genes at different stages of evolution.     

Direct and indirect regulation of gonadotropin-releasing hormone neurons by estradiol

Estrogen signaling to GnRH neurons is critical for coordinating the preovulatory surge release of LH with follicular maturation. Until recently it was thought that estrogen signaled GnRH neurons only indirectly through numerous afferent systems. This minireview presents new evidence indicating that GnRH neurons are directly regulated by estradiol (E2), primarily through estrogen receptor (ER)-beta, and indirectly through E2-sensitive neurons in the anteroventral periventricular (AVPV) region. The data described suggest that E2 generally represses GnRH gene expression but that this repression is transiently overcome by indirect E2-dependent signals relayed by AVPV neurons. We also present evidence that the AVPV neurons responsible for relaying E2 signals to GnRH neurons are multifunctional gamma aminobutyric acid-ergic/glutamatergic/neuropeptidergic neurons.     

Catecholamine and blood pressure regulation by gonadotropin-releasing hormone analogs in amphibians

Analogs of gonadotropin-releasing hormone (GnRH) occur in the brain, plasma, and sympathoadrenal system of anuran amphibians. The present experiments studied the effects of GnRH and [Trp7, Leu8]-GnRH on plasma catecholamines and cardiovascular function in conscious adult bullfrogs (Rana catesbeiana) and cane toads (Bufo marinus). Both GnRH analogs elicited dose-dependent (0.1-1 nmol.kg-1) increases in arterial norepinephrine, epinephrine, and blood pressure levels when injected intravenously into toads. In bullfrogs, [Trp7, Leu8]-GnRH (1 nmol.kg-1) increased arterial norepinephrine concentration approximately 10-fold without affecting the concentrations of norepinephrine sulfate, norepinephrine glucuronide, epinephrine, epinephrine sulfate, or epinephrine glucuronide. The noradrenergic response of bullfrogs to [Trp7, Leu8]-GnRH was specific to the neurohormone because it could be inhibited by [D-pGlu1, D-Phe2, D-Trp3,6]-GnRH. The sympathomimetic activities of the GnRH analogs did not depend on changes in temperature, which occur seasonally in natural habitats, because similar noradrenergic responses were observed at 4 and 22 degrees C. GnRH and [Trp7, Leu8]-GnRH (0.01-10 nmol.kg-1) did not raise arterial blood pressure in bullfrogs despite their pressor actions in toads. This interspecific difference was remarkable because cardiovascular responses to norepinephrine, angiotensin II, and vasotocin in bullfrogs were similar to those in toads. The parallels between catecholamine and blood pressure responses suggest that epinephrine is the principal mediator of the blood pressure response to native GnRH analogs in toads. In bullfrogs, [Trp7, Leu8]-GnRH mobilizes norepinephrine but not epinephrine, and the noradrenergic effect is insufficient to raise blood pressure. These observations are consistent with a physiological role for native GnRH analogs in the regulation of the sympathoadrenal system in anuran amphibians.     

Alterations in gonadotropin-releasing hormone-dependent gonadotropin secretion in rats with polycystic ovaries.

A single injection of estradiol valerate (EV) to adult female rats induces a persistent anovulatory polycystic ovarian (PCO) condition. During the 8-20-wk interval following EV treatment, this condition is associated with a selective compromise of LH release, decreased pituitary content of LH, and decreased GnRH-stimulated LH secretion. A marked increase in mean plasma concentrations of LH and enhanced LH response to GnRH occur after 20 wk post-EV treatment. Despite this apparent improvement, the PCO condition remains unchanged. The present study was undertaken to elucidate the underlying causes for these spontaneous improvements in LH parameters. We reasoned that these changes may be the result of alterations in 1) pituitary GnRH receptor levels; or 2) the mode of LH secretion, i.e. GnRH-dependent versus GnRH-independent; or 3) post-GnRH receptor events. Hence, we assessed pituitary GnRH receptor concentration as well as the pituitary content of LH and FSH in rats with PCO of 9 wk and 22 wk duration. To examine the possibility of a change in the mode of LH secretion, we examined the effects of in vivo suppression of LH secretion by treatment with a GnRH antagonist [N-Ac-D-Nal1, D-Phe2,3, D-Arg6, Phe7, D-Ala10]-GnRH (GnRH-ANTAG) in the same groups of animals. Mean pituitary weights were greater in the 9-wk-PCO than in the 22-wk-PCO animals. The pituitary concentration of GnRH receptors (on either a weight or milligram pituitary-membrane protein basis) was similar in the 9-wk- and 22-wk-PCO animals. Pituitary LH and FSH contents, however, were significantly higher (5-fold and 2-fold, respectively) in 22-wk-PCO rats compared to the 9-wk-PCO animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Detailed examination of the mechanism and site of action of progesterone and corticosteroids in the regulation of gonadotropin secretion: hypothalamic gonadotropin-releasing hormone and catecholamine involvement.

Progesterone and certain corticosteroids, such as deoxycorticosterone (DOC) and triamcinolone acetonide (TA), can stimulate gonadotropin surges in rats. The mechanism of these steroids could involve a pituitary or hypothalamic site of action, or both. Progesterone and TA did not alter the ability of GnRH to release LH or FSH either before, during, or after the gonadotropin surge induced by these steroids in estrogen-primed ovariectomized female rats. Furthermore, progesterone, TA and DOC were unable to induce a gonadotropin surge in short-term estrogen-primed castrated male rats. These results suggested a hypothalamic rather than a pituitary site of action of progesterone and corticosteroids in the release of gonadotropins. Since progestin and corticosteroid receptors are present in catecholamine neurons, a role for catecholamine neurotransmission in progesterone and corticosteroid-induced surges of LH and FSH in estrogen-primed ovariectomized rats was examined. Catecholamine synthesis inhibitors and specific alpha 1 (prazosin), alpha 2 (yohimbine), and beta (propranolol) receptor antagonists were used to determine the role of catecholamine neurotransmission in the steroid-induced surges of LH and FSH. Both of the catecholamine synthesis inhibitors, alpha-methyl-p-tyrosine HCl (alpha-MPT), a tyrosine hydroxylase inhibitor, and sodium diethyldithiocarbamate (DDC), an inhibitor of dopamine-beta-hydroxylase, attenuated the ability of progesterone, TA, and DOC to induce LH surges when administered 3 h and 1 h, respectively, before the steroid. DDC also suppressed the ability of progesterone, TA, and DOC to induce FSH surges. Rats treated with alpha-MPT had lower mean FSH values than did steroid controls, but the effect was not significant. Both the alpha 1 and alpha 2 adrenergic antagonists, prazosin and yohimbine, significantly suppressed the ability of progesterone, TA, and DOC to induce LH and FSH surges. In contrast, the beta adrenergic receptor blocker, propranolol, had no effect upon the ability of progesterone, TA, or DOC to facilitate LH and FSH secretion. Finally, the stimulatory effect of progesterone and TA upon LH and FSH release was found to be blocked by prior treatment with a GnRH antagonist, further suggesting hypothalamic involvement. In conclusion, this study provides evidence that the stimulation of gonadotropin release by progesterone and corticosteroids is mediated through a common mechanism, and that this mechanism involves the release of GnRH, most likely through catecholaminergic stimulation. Furthermore, catecholamine neurotransmission, through alpha 1 and alpha 2 but not beta receptor sites, is required for the expression of progesterone and corticosteroid-induced surges of LH and FSH in estrogen-primed ovariectomized rats.     

Effect of vitamin A deficiency upon gonadotropin response to gonadotropin-releasing hormone

There is a monotypic change in basal serum gonadotropin levels following retinol treatment of chronically vitamin A-deficient (VAD) male rats. The present study was undertaken to investigate the hypothesis that the specific increase in serum follicle-stimulating hormone (FSH) represents a change in gonadotrope responsiveness to gonadotropin-releasing hormone (GnRH). To this end, a test dose of GnRH was given to VAD rats pre-, 5 days post-, and 10 days postreplacement of vitamin A (PVA). In VAD rats, basal serum FSH and luteinizing hormone (LH) levels were higher than those of controls. Increased LH/testosterone ratios, both in basal levels and in the secretory response to GnRH, suggested Leydig cell hyporesponsiveness in VAD animals. Both the FSH and LH responses to GnRH were maximal at 1 h, declining thereafter. Although the absolute increments in FSH and LH 1 h after GnRH in VAD rats were greater than in controls, the percent increase in FSH tended to be lower in VAD rats and to increase after vitamin A replacement. The specific enhancement of FSH release PVA became evident only when assessing total secretion of FSH and LH after GnRH. Luteinizing hormone response to GnRH increased PVA, but not significantly, while FSH secretion after GnRH increased both 5 and 10 days PVA, times during which basal FSH levels were also increasing. These changes in FSH secretion could not be attributed either to increases in endogenous GnRH or to changes in testosterone or estradiol levels. Basal serum androgen binding protein levels, elevated in VAD animals, did not respond to the acute increases in FSH after GnRH and remained high PVA, suggesting no acute change in Sertoli cell function. Thus, the PVA increase in FSH secretion unmasks a partial inhibition of the gonadotrope present in the retinol-deficient, retinoic acid-fed male rat.     

A suppression of gonadotropin secretion by cortisol in castrated male rhesus monkeys (Macaca mulatta) mediated by the interruption of hypothalamic gonadotropin-releasing hormone release

Four orchidectomized rhesus monkeys (3-3.5 yr of age) were treated for 62 days with daily i.m. injections of hydrocortisone acetate (HCA) at a dose of 10-20 mg/(kg BW X day), and blood samples were obtained daily or every other day before, during, and after treatment. Hydrocortisone acetate injections resulted in a progressive rise in mean plasma cortisol from basal concentrations of 17-35 micrograms/100 ml prior to initiation of steroid treatment to approximately 150 micrograms/100 ml 5 wk later. When serum cortisol concentrations reached 100 micrograms/100 ml, 3-4 wk after the initiation of HCA treatment, circulating luteinizing hormone (LH) and follicle-stimulating hormone (FSH) began to decline, reaching nondetectable concentrations 35 days later. Withdrawal of HCA resulted in a return in plasma cortisol concentrations to pretreatment control levels, which was associated with a complete restoration of gonadotropin secretion. In 2 animals, administration of an intermittent i.v. infusion of gonadotropin-releasing hormone (GnRH) (0.1 micrograms/min for 3 min once every hour), which appears to stimulate the gonadotropes in a physiologic manner, reversed the cortisol-induced inhibition of gonadotropin secretion, restoring circulating LH and FSH concentrations to within 80-100% of control. These results suggest that, in the rhesus monkey, the major site of the inhibitory action of cortisol on gonadotropin release resides at a suprapituitary level and is mediated by interruption of hypothalamic GnRH release.     

Negative feedback regulation of gonadotropin secretion by androgens in fetal rhesus macaques

Previously we described sex differences in circulating gonadotropin concentrations (greater in females) in fetal rhesus macaques, and demonstrated that these sex differences relate, at least in part, to the negative feedback actions of testicular secretions. A fully functional gonadal-hypothalamic-pituitary feedback relationship is present as early as Day 100 of gestation in fetal males because castration at this time results in a dramatic increase (greater than 10-fold) in fetal luteinizing hormone (LH) concentrations. Although short-term (6-h) treatment of fetuses with testosterone (T) 3 wk after gonadectomy (GX) does not lower LH levels in males, it is completely effective in females. These data suggest that either T is not the primary testicular factor responsible for feedback suppression of LH in fetal males, or the hypothalamic-pituitary axis becomes insensitive to T after GX. To determine if immediate treatment with T after GX is effective in maintaining LH levels, we gonadectomized five fetal rhesus males on Days 98-104 of gestation and immediately implanted crystalline-T-containing intraabdominal Silastic capsules. An additional five fetuses were treated with the nonaromatizable androgen dihydrotestosterone (DHT). Umbilical arterial samples for hormone analysis were obtained prior to GX and again approximately 3 wk later. Serum from control males (n = 11) castrated in utero on Day 100 of gestation contained significantly greater concentrations of LH and follicle-stimulating hormone (FSH) 3 wk after the operation than before GX. Five sham-operated male fetuses did not have elevated levels of either LH or FSH in their serum on Day 120 of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Seasonal changes of gonadotropin-releasing hormone secretion in the ewe.

A sustained volley of high-frequency pulses of GnRH secretion is a fundamental step in the sequence of neuroendocrine events leading to ovulation during the breeding season of sheep. In the present study, the pattern of GnRH secretion into pituitary portal blood was examined in ewes during both the breeding and anestrous seasons, with a focus on determining whether the absence of ovulation during the nonbreeding season is associated with the lack of a sustained increase in pulsatile GnRH release. During the breeding season, separate groups (n = 5) of ovary-intact ewes were sampled during the midluteal phase of the estrous cycle and following the withdrawal of progesterone (removal of progesterone implants) to synchronize onset of the follicular phase. During the nonbreeding season, another two groups (n = 5) were sampled either in the absence of hormonal treatments or following withdrawal of progesterone. Pituitary portal and jugular blood for measurement of GnRH and LH, respectively, were sampled every 10 min for 6 h during the breeding season or for 12 h in anestrus. During the breeding season, mean frequency of episodic GnRH release was 1.4 pulses/6 h in luteal-phase ewes; frequency increased to 7.8 pulses/6 h during the follicular phase (following progesterone withdrawal). In marked contrast, GnRH pulse frequency was low (mean less than 1 pulse/6 h) in both groups of anestrous ewes (untreated and following progesterone withdrawal), but GnRH pulse amplitude exceeded that in both luteal and follicular phases of the estrous cycle.(ABSTRACT TRUNCATED AT 250 WORDS)