Follicle-stimulating Hormone Release Research Articles

CRF Alters the Infundibular LHRH Secretory System from the Medial Preoptic Area of Female Rats: Possible Involvement of Opioid Receptors

Corticotropin-releasing factor (CRF) is a potent factor involved in the antireproductive effects of various stressors. However, the central mechanisms by which CRF modulates the hypothalamic-pituitary-gonadal (HPG) axis are not well understood. In order to verify whether CRF is able to directly influence luteinizing hormone-releasing hormone (LHRH) secretory activity at the level of the medial preoptic area (MPOA), CRF was chronically or acutely injected bilaterally into this hypothalamic area. Ten days before the experiments, female rats were implanted with a permanent double-guide cannula which was stereotaxically positioned close to the MPOA. Chronic administration of rat CRF (rCRF) was accomplished by means of two miniosmotic pumps connected to double internal cannula. Acute bilateral infusion of rCRF into the MPOA was performed in unrestrained ovariectomized (OVX) rats and during the afternoon of proestrus. Ten minutes before rCRF treatment, antagonists of opioid receptors (mu, mu 1, or kappa) were infused bilaterally into the MPOA. Hypothalamic LHRH release as well as circulating gonadotropins were determined using a push-pull cannula implanted into the median eminence (ME), and a catheter connected to the jugular vein, respectively. Chronic rCRF treatment in the MPOA decreased (p < 0.05) plasma LH levels but did not modify follicle-stimulating hormone release in OVX rats. A significant inhibition of LH secretion was first observed 80 min after the acute rCRF infusion into the MPOA; pretreatment with nor-Binaltorphimine (antagonist of kappa-receptors) did not measurably attenuate this effect. In contrast, bilateral administration of beta-Funaltrexamine (antagonist of mu-opioid receptors) or naloxonazine (mu 1-antagonist) partially attenuated the inhibitory effect of rCRF on plasma LH levels. Similarly, injections of rCRF bilaterally into the MPOA suppressed hypothalamic LHRH release into the ME and this effect was partially reversed by a previous administration of opioid mu- or mu 1-receptor antagonists. In contrast to rCRF injection into the MPOA, administration of rCRF into the paraventricular nucleus the arcuate nucleus of the hypothalamus and directly into the ME were without significant effect on hypothalamic LHRH release in proestrus rats. In conclusion, the present data show that from among the hypothalamic sites tested, only the MPOA proved susceptible to CRF-induced alteration of LHRH neuronal activity during proestrus afternoon in rats. The release of opioids from nerve terminals located in the MPOA, which in turn binds and activates mainly type mu 1-receptors, might contribute to this inhibitory influence of CRF on LHRH release in the infundibular system.

Cocaine impairs gonadotropin secretion in oophorectomized monkeys

OBJECTIVE: Our objective was to determine whether cocaine alters gonadotropin secretion in oophorectomized monkeys.STUDY DESIGN: Oophorectomized monkeys with elevated gonadotropin levels were chronically cannulated to allow blood sampling every 15 minutes. Monkeys received either saline solution or 2 or 4 mg/kg cocaine hydrochloride as an intravenous bolus. Other oophorectomized monkeys were pretreated with either saline solution or 4 mg/kg cocaine 2 hours before bolus gonadotropin-releasing hormone administration, and plasma luteinizing hormone and follicle-stimulating hormone levels were measured every 15 minutes for 3 hours. Monkeys were also given either saline solution or 4 mg/kg of cocaine with gonadotropin-releasing hormone simultaneously, and plasma gonadotropin levels were measured every 15 minutes for 3 hours. Serum luteinizing hormone and follicle-stimulating hormone levels were measured by radioimmunoassay.RESULTS: Both doses of cocaine resulted in a significant decrease in luteinizing hormone levels compared with controls. Follicle-stimulating hormone levels were significantly decreased only with the 4 mg/kg dose of cocaine. There was no difference in luteinizing hormone and follicle-stimulating hormone responses to gonadotropin-releasing hormone in the cocaine-treated monkeys compared with saline solution-treated monkeys by using repeated-measures analysis of variance.CONCLUSION: These findings demonstrate that acute cocaine administration to oophorectomized primates inhibits basal luteinizing hormone—follicle-stimulating hormone secretion but not gonadotropin-releasing hormone—stimulated luteinizing hormone and follicle—stimulating hormone release. In the absence of an effect on gonadotropin-releasing hormone-stimulated gonadotropin release, we conclude that the impaired luteinizing hormone-follicle-stimulating hormone secretion after cocaine administration is due in part to a direct effect of cocaine on gonadotropin-releasing hormone neurons or on hypothalamic neurotransmitter modulation of gonadotropin-releasing hormone release. (AM J OBSTET GYNECOL 1992;167:1785-93.)

Evidence for a gonadal nonsteroidal factor that specifically inhibits release of luteinizing hormone in ewes.

Bilaterally ovariectomized ewes were used to investigate the effect of systemic administration (i.v.) of charcoal-treated aqueous luteal extracts from ovine corpora lutea on plasma concentrations of pituitary gonadotrophins. Jugular blood samples were taken every 15 min at least 5 h before (control period) and 5 h after (treatment period) injection. In Expt 1, the administration of luteal extract from corpora lutea of days 70-76 of pregnancy, but not of the extract prepared from muscular tissue, resulted in a significant decrease of mean concentrations of luteinizing hormone (LH) (P < 0.02) and frequency of LH pulses (P < 0.01). Plasma follicle-stimulating hormone (FSH) concentrations were not affected by injections of either extract. These findings provide the first demonstration of the presence of a nonsteroidal factor in the corpus luteum of midpregnancy that selectively suppresses the secretion of LH. In Expt 2, mean concentrations of LH and FSH and frequency of LH pulses were unaffected by injections of luteal extracts from ovine corpora lutea of days 10-12 of the oestrous cycle or day 15 of pregnancy. These data suggest that some factor(s), probably from the fetoplacental endocrine unit, is required to ensure the production of a significant quantity of the luteal LH-inhibiting factor after day 15 of pregnancy. In Expt 3, treatment of luteal extract from corpora lutea of day 70 of pregnancy with proteolytic enzymes destroyed the LH-inhibiting activity, suggesting the proteic nature of the luteal LH-inhibiting factor. In Expt 4, plasma concentrations of LH were not affected by injection of charcoal-treated extract prepared from fetal cotyledonary tissue of days 110-120 of pregnancy suggesting that the LH-inhibiting factor exclusively originates from the corpus luteum during pregnancy. These experiments provide the first direct evidence for the existence of a potent nonsteroidal factor of luteal origin that specifically inhibits pulsatile secretion of LH, without influencing FSH release in female animals. We propose the term LH-release-inhibiting factor (LH-RIF) to describe this activity.

Increased LH and FSH release from the anterior pituitary of ovariectomized rat, in vivo, by copper-, nickel-, and zinc-LHRH complexes

The effect of Cu 2+, Ni 2+, Zn 2+ and their complexes with LHRH on the release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) was estimated in in vivo experiments with the use of the method proposed by Ramirez and McCann. Ovariectomized, estradiol, and progesterone pretreated rats were injected intraveneously either with LHRH alone, a metal ion alone, a mixture of metal and hormone, or a metal-LHRH complex. A metal alone or a mixture of it with LHRH did not affect gonadotropin release at all or no more than LHRH alone. However, the complex of Cu 2+ with LHRH brought about a high release of LH and even higher release of FSH. This indicates that copper complex is more effective than metal-free LHRH. The nickel complex showed a similar although lesser effect. The zinc complex had similar potency to free LHRH though higher FSH-releasing ability was noticed. We conclude that copper-, nickel-, and zinc-LHRH complexes were more potent than the peptide hormone itself and promoted the FSH release in the ovariectomized, estradiol, and progesterone pretreated rats.

Abrogation by a potent gonadotropin-releasing hormone antagonist of the estrogen/progesterone-stimulated surge-like release of luteinizing hormone and follicle-stimulating hormone in postmenopausal women

Abrogation by a potent gonadotropin-releasing hormone antagonist of the estrogen/progesterone-stimulated surge-like release of luteinizing hormone and follicle-stimulating hormone in postmenopausal women

Abrogation by a potent gonadotropin-releasing hormone antagonist of the estrogen/progesterone-stimulated surge-like release of luteinizing hormone and follicle-stimulating hormone in postmenopausal women.

In both the rodent and primate, administration of progesterone elicits an acute surge-like release of LH in the setting of prior estrogen treatment. Whether these facilitative effects of estrogen and progesterone on gonadotropin secretion reside at pituitary or hypothalamic loci is not known. To further investigate the mechanisms by which estrogen combined with progesterone amplifies gonadotropin secretion, we studied the responses of seven estrogen-primed postmenopausal women to progesterone administration with or without cotreatment with a potent GnRH antagonist, [Ac-D2Nal1,D4ClPhe2,D3Pal3,Arg5,DGlu6(AA), DAla10]GnRH. Repetitive blood sampling for the later measurement of serum concentrations of LH, FSH, and PRL was begun 4 h before the administration of progesterone and continued for 36 h. We observed that progesterone administration after 72 h of priming with ethinyl estradiol resulted in a surge-like release of LH and FSH in all subjects. Concomitant administration of the GnRH antagonist abolished the surge-like release of both gonadotropins in all subjects. In contrast, administration of the antagonist had no effect on PRL release. These results indicate that endogenous GnRH action is an obligatory component of the progesterone-induced surge-like release of both gonadotropic hormones in the estrogen-primed human.

Total solid-phase synthesis and prolactin-inhibiting activity of the gonadotropin-releasing hormone precursor protein and the gonadotropin-releasing hormone associated peptide.

The human gonadotropin-releasing hormone precursor protein, pHGnRH (Met-23-Ile69) (preproGnRH), and three of its fragment peptides, pHGnRH (Asp14-Ile69) (gonadotropin-releasing hormone associated peptide--GAP), pHGnRH (Phe38-Ile69), and pHGnRH (Ser47-Ile69), were assembled in a stepwise solid-phase cosynthesis employing Boc/Bzl tactics and an optimized acylation schedule which included recoupling steps with hexafluoro-2-propanol to help overcome the aggregation of the pendant peptide chains of the peptidoresin during difficult couplings. Reversed-phase high-performance liquid chromatography (HPLC) purification yielded products which were characterized by analytical reversed-phase HPLC, ion-exchange chromatography, capillary zone electrophoresis, SDS-polyacrylamide gel electrophoresis, and ion-spray mass spectrometry to reveal a high degree of homogeneity. Biological characterization demonstrated that only GAP stimulated luteinizing hormone and follicle-stimulating hormone release from primary cultures of rat anterior pituitary cells, while GAP, pHGnRH (Phe38-Ile69), and preproGnRH all inhibited prolactin release, with the latter being the most potent at concentrations comparable to bromocryptine. However, only GAP and pHGnRH (Phe38-Ile69) were able to displace a labeled gonadotropin-releasing hormone agonist from binding to rat pituitary membrane preparations. This first demonstration of significant biological activity with a precursor protein also suggests that the gonadotropin-releasing and prolactin release-inhibiting functions of GAP are not mediated through the same pituitary receptors.

Effects of clomiphene citrate on pituitary luteinizing hormone and follicle-stimulating hormone release in women before and after treatment with ethinyl estradiol

To evaluate the effects of clomiphene citrate (CC) on pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release in hypoestrogenic women and in the same women after treatment with ethinyl estradiol (EE2). The study was of a prospective nature and was conducted on selected patients. Volunteer women were studied in a tertiary care public hospital. The 10 patients studied were selected on the basis of hypogonadal status (menopause, premature ovarian failure, or gonadal dysgenesis and Turner phenotype) and no hormonal treatment. Gonadotropin-releasing hormone (GnRH) was continually infused at the dose of 0.2 micrograms/min for 4 hours before and after the use of CC and/or EE2. The study was performed with the objective of determining the effect of estrogen (E) levels on the action of CC on in vivo gonadotropin release. In the presence of hypoestrogenic conditions, CC had no pituitary action. However, after EE2 treatment CC promoted greater FSH release and a significant inhibition of LH release from the pituitary. Clomiphene citrate needs a basal E level to be able to act on the pituitary. In normoestrogenic states and under GnRH stimulation, CC preferentially promotes FSH release while presenting a predominantly inhibitory effect on LH release.

Inhibin-like "antigonadotropic" activity in the ovine pineal.

In an attempt to define the antigonadotropic activity associated with the protein/peptide extracts of ovine pineals, melatonin- and steroid-free fractions obtained after subjecting crude ovine pineal acetone powder to soft gel chromatography were tested in three bioassay systems: (1) the conventional compensatory ovarian hypertrophy inhibition assay in rats, (2) the coupled bioassay in immature mice that enables one to distinguish factors acting at the level of the pituitary from those acting at the gonadal level, and (3) the classical in vitro pituitary cell culture assay for inhibin. The large molecular weight fraction, referred to as PI, behaved like a classical antigonadotropin as it suppressed compensatory ovarian hypertrophy following unilateral ovariectomy. Further, it not only lowered the basal and gonadotropin releasing hormone (GnRH)-stimulated release of follicle stimulating hormone (FSH) by the cultured pituitary cells, but also inhibited the human chorionic gonadotropin (hCG)-induced uterine weight gain in the coupled assay, thus acting like inhibin in these two assay systems. In addition, it showed immunological cross-reactivity with ovine testicular inhibin. The present results strongly support the view that inhibin-like activity may be the major player in what has so far been referred to as antigonadotropic activity.

The 24 h pattern of pulsatile luteinizing hormone, follicle stimulating hormone and prolactin release during the first 8 weeks of lactational amenorrhoea in breastfeeding women.

In women, breastfeeding results in a variable period of ovarian inactivity which is apparently related to suppression of the normal pulsatile release of luteinizing hormone (LH). However, pulse profiles had only been studied during the daytime. Since resumption of pulsatile LH secretion during puberty is initiated at night, the present study determined the pattern of pulsatile LH secretion in relation to that of follicle stimulating hormone (FSH) and prolactin, and suckling and ovarian activity at 4 and 8 weeks postpartum in 20 fully breastfeeding women with lactational amenorrhoea. Blood samples were withdrawn at 10 min intervals for 24 h from 0900 h to 0900 h at either 4 weeks (n = 9) or 8 weeks (n = 11) postpartum, while the mothers and babies continued their normal pattern of suckling activity. At 4 weeks postpartum, no LH pulses occurred over 24 h in six of the nine women while one (n = 1) or two (n = 2) LH pulses occurred in three of the nine women. In contrast, LH pulses were present in nine of the 11 women at 8 weeks postpartum. The pulse frequency varied considerably from two to eight pulses over the 24 h and there was no influence of the time of day or sleep on the time of the pulse release. Lactational amenorrhoea was maintained for at least 10 weeks afterwards and there was no relationship between the time of resumption of ovarian activity and the presence or absence of pulsatile LH secretion at 4 or 8 weeks postpartum.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of acute in vivo ethanol exposure on follicle stimulating hormone transcription and translation.

The impact of ethanol (EtOH) on male rodent reproduction has been well characterized for luteinizing hormone (LH) with suppression of LH release from the pituitary being reported. We have previously reported that acute ethanol (EtOH) exposure in vivo results in rapid and marked suppression of beta-LH gene expression and protein release from the pituitary. This suppression of beta-LH gene expression was unaccompanied by a change in the common alpha-subunit mRNA. To further explore the impact of ethanol on male rodent reproduction, we have expanded our studies to follicle stimulating hormone (FSH) and hypothalamic luteinizing hormone releasing hormone (LHRH) as well as of pituitary protein kinase C (PKC). Previously castrated male rats were acutely exposed to EtOH and a dramatic reduction in both serum FSH and LH levels was noted at 1.5 and 3 hr after treatment. These levels returned to saline injected control values at 6 and 24 hr. Despite the fall in serum FSH, there was no change in intrapituitary FSH content at any time point; this lack of pituitary FSH depletion in the face of a fall in serum levels is suggestive of impaired FSH release. In contrast to the fall in beta-LH steady-state mRNA levels seen previously and confirmed in the present studies, there was no change in beta-FSH steady-state mRNA at any time point suggesting that EtOH has dichotomous effects on the expression of these two gonadotropins. Pituitary PKC levels were also assessed and found to be unaffected by EtOH at any time point.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of in vitro progesterone release from caprine luteal tissues by prostaglandins E 2 and F 2a

Luteal slices obtained from Day-10 cyclic, sexually mature, mixed-breed, superovulated goats were used to study the effects of prostaglandins E 2 and F 2a (PGE 2 and PGF 2a) on the release of progesterone. The goats were synchronized for estrus using a single intramuscular injection of 5 mg PGF 2a given during the mid-luteal phase of the estrous cycle. Multiple follicular growth and superovulation were induced using a treatment regiment of follicle stimulating hormone (FSH) and luteinizing hormone releasing hormone (LHRH) previously standardized in our laboratory (1). The luteal slices were treated with PGE 2 or PGF 2a at concentrations of 1 and 10 ng/ml each. Untreated luteal slices continued to release significant amounts of progesterone over the entire period of incubation (30 to 360 minutes). There was a progressive increase in progesterone accumulation following treatment with PGE 2 at both concentrations. The mean progesterone values were significantly higher in the PGE 2-treated groups at all incubation periods than in the controls. Progesterone values at 10 ng/ml were higher (P<0.05) than at 1 ng/ml. Treatment with PGF 2a decreased (P<0.05) progesterone release at 60 to 360 minutes of incubation compared with that of the corresponding controls for each incubation period. However, there appeared to be no differences (P>0.05) in mean progesterone values between the two concentrations of PGF 2a. The results of this study showed that PGE 2 enhanced the release of progesterone by caprine luteal tissues, whereas PGF 2a inhibited its release.

GnRH-stimulated LH and FSH release by perifused anoestrous red fox pituitary cells: gonadal steroid modulation

In this study, gonadotropin releasing hormone (GnRH)-stimulated luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretions in the red fox (Vulpes vulpes L.) have been studied during anoestrus using perifused dispersed pituitary cells. The objective was to compare LH and FSH responses to pulses of GnRH in lactating and non-lactating females and to examine the feedback of gonadal steroids. Our results indicate that the pituitary sensitivity to GnRH was greatly reduced in lactating females compared with non-lactating females. Treatment in vitro of cells during 24 h (short-term effect) by progesterone (P) or oestradiol (E2) induced an increase of LH and FSH release, indicating that even during anoestrus, pituitary cells are able to respond positively to gonadal steroids. In contrast, administration of P or E2 in vivo for several days by silastic capsules (long-term effect) induced a reduction of LH and FSH releases by pituitary cells in vitro. Thus, steroids act directly on the pituitary but their action is time- and dose-dependent. During anoestrus in the fox, particularly during lactation, P and E2 might exert a potent negative feedback control on pituitary secretion. In the red fox (Vulpes vulpes L.), the fact that GnRH-stimulated LH and FSH secretions are reduced in lactating females more than in non-lactating females, suggests that P (secreted in vivo during lactation, probably as a consequence of a luteotrophic action of prolactin) and E2 secreted jointly during episodic phases of oestrogenic activity, may be responsible for decreased pituitary responsiveness observed during early anoestrus. This action of gonadal steroids might occur in association with a specific role of prolactin or a suppressive effect of suckling.

A second endogenous molecular form of mammalian hypothalamic luteinizing hormone-releasing hormone (LHRH), (hydroxyproline 9)LHRH, releases luteinizing hormone and follicle-stimulating hormone in vitro and in vivo

In vitro and in vivo release of pituitary hormones were studied in the presence of (hydroxyproline 9)LHRH ((Hyp)LHRH), a newly characterized endogenous molecular form of LHRH. Results were compared to those obtained with LHRH itself. (Hyp)LHRH, as LHRH, stimulated both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release in a homothetic manner. The hydroxylated compound was, however, 24 times (in vitro) and 5 times (in vivo) less potent than LHRH. The lower activity of (Hyp)LHRH than of LHRH in the in vitro assay correlated well with a 28-fold lesser potency in a binding test using pituitary membrane preparations. The higher relative potency and the prolonged effect of (Hyp)LHRH in the in vivo test were related to a lesser susceptibility of the hydroxylated form to proteolytic degradation. Effects of LHRH and of (Hyp)LHRH were not additive, both peptides were equally able to desensitize gonadotrophs to a subsequent challenge by the other. Taken together, these observations suggest that both forms of LHRH act at the same receptor site. The lesser affinity of the hydroxylated compound is compensated to a certain extent by its higher resistance to enzymatic degradation. It is concluded that in spite of its lesser potency, (Hyp)LHRH may participate in the regulation of gonadotropins.

Influence of dopamine on the altered release of prolactin, luteinizing hormone, and follicle-stimulating hormone induced by interleukin-2 in vitro.

Interleukin-2 (IL-2) alters the release of anterior pituitary hormones at femtomolar concentrations from hemipituitaries incubated in vitro. This cytokine significantly lowered luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and stimulated prolactin (PRL) release, thus demonstrating a reciprocal action of the lymphokine on lactotrophs and gonadotrophs. Since dopamine (DA) is a powerful inhibitor of PRL release, in the present experiments were evaluated possible dose dependent effects of DA on IL-2-induced alterations of the release of PRL, LH, and FSH. Hemipituitaries were incubated with varying concentrations of DA, a combination of IL-2 plus DA, or a combination of haloperidol (1 x 10(-5) M) with DA for 1 h, followed subsequently by incubation with medium containing only high potassium (K+) to study the effects on depolarization-induced hormone release. DA induced a dose-related, significant lowering of the basal PRL release with a minimal effective dose (MED) of less than 19 nM. The depolarization-induced PRL release was also inhibited, but the MED was 100-fold higher than the MED to inhibit basal PRL release. DA at much higher concentrations (30, 60, and 90 microM) significantly reduced pituitary PRL content. The addition of 0.187, 3.75, 15, or 60 microM DA to IL-2-induced PRL release. IL-2 (10(-15) M) produced a significant decrease in LH and FSH release. The combination of 3.75 or 15 microM DA plus IL-2 failed to alter the IL-2 suppressed LH release, whereas the addition of 0.187 microM DA to IL-2 blocked its suppressive influence, and 60 microM DA added to Il-2 produced an additive inhibitory effect. Thus, the interaction of IL-2 and DA is biphasic on LH release. The significant reduction of FSH release induced by IL-2 was blocked in the presence of 0.187, 3.75, 15, or 60 microM DA. DA alone at relatively high concentrations of 30, 60, and 90 microM suppressed basal LH and FSH release. The effects of DA on PRL, LH, and FSH at all doses tested were blocked by the DA receptor blocker, haloperidol which by itself at the concentration tested (1 x 10(-5) M) had no effect. Thus, the actions of DA at all concentrations tested appear to be mediated via DA receptors. In conclusion, DA was capable of blocking the stimulatory action of IL-2 on PRL release and its inhibitory action on FSH release by a DA receptor mediated action.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of the ovary, sucking stimulus and season on the pattern of LH and FSH release in the female tammar, Macropus eugenii.

The sequential effects of removal of the corpus luteum, removal of the non-luteal ovary and sucking stimulus and the effects of season of the year on the release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) have been determined in the tammar wallaby, Macropus eugenii. Plasma concentrations of LH and FSH were measured at 15 min intervals for 6 h in eight animals at four successive times in the breeding season (lactational quiescence); (A) while they were intact and lactating, (B) 10 days after removal of the ovary bearing the quiescent corpus luteum, (C) 21 days after bilateral ovariectomy and (D) 21 days after removal of the sucking stimulus, and (E) in the following non-breeding season (seasonal quiescence). Single blood samples were taken twice weekly during lactational quiescence. In the presence of ovarian tissue, basal concentrations of LH were low (0.94 ng mL-1) with pulses of low magnitude (1.3 ng mL-1) and low frequency (1.4 pulses per 6 h). There was no response to luteectomy but all three parameters increased after bilateral ovariectomy. Removal of the sucking stimulus affected the LH pulse frequency but seasonal differences were not evident. The pattern of release of FSH was not pulsatile. There was no response to luteectomy in basal concentrations of FSH but these rose significantly after bilateral ovariectomy (P less than 0.001) in lactational quiescence. There was no effect of removing the sucking stimulus but in seasonal quiescence concentrations were higher. The results indicate that non-luteal ovarian tissue is essential for the negative-feedback effects on LH and FSH secretion, that the pattern of release of LH, but not FSH, is pulsatile, and that there is no marked seasonal change in hypothalamo-hypophysial activity.

Inhibitory effects of the new bombesin receptor antagonist RC-3095 on the luteinizing hormone release in rats.

The effects of bombesin receptor antagonist RC-3095 and gastrin-releasing peptide [GRP (14-27)] on basal luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels, as well as on the release of LH and FSH in response to LH-releasing hormone, were studied in normal and castrated male rats. We also examined the release of LH and FSH after intracerebroventricular injection of RC-3095 under different types of anesthesia (urethane, sodium pentobarbital, Metofane). Following injection of 10 micrograms RC-3095 into the lateral brain ventricle, serum LH levels were rapidly and significantly (p < 0.001) lowered. This effect lasted for at least 60 min and was not affected by the type of anesthetic used. Serum FSH levels were not affected by intracerebroventricular administration of RC-3095 or GRP (14-27), indicating different central control mechanisms between LH and FSH release. The suppressive effect of RC-3095 on LH release could be completely prevented by prior intracerebroventricular administration of GRP (14-27) at a dose of 1 micrograms, but intravenous administration of either peptide RC-3095 or GRP (14-27) did not change the basal levels of LH, FSH, and testosterone. The pituitary LH response to LH-releasing hormone was also not modified by intravenous administration of RC-3095. These results indicate that bombesin-like peptides might be involved in control of LH release from the pituitary by an action on the CNS which is mediated by specific bombesin receptors.

Neuropeptides in the Amphibian Brain

Publisher Summary This chapter focuses on neuropeptides in the amphibian brain emphasizing neuroendocrine relations. Neuropeptides are synthesized as multiple molecular variants, and they may play different roles in various organisms. An analysis of the distribution of neuropeptides in vertebrates and their phenotypic plasticity, especially during development, leads to an understanding of the basic neurochemical organization but, at the same time, gives an appreciation of the wide diversity among species. The neuroendocrine and immunological functions exerted by neuropeptides constitute a fundamental link with other homeostatic systems that permit adaptation to a changing environment. Gonadotropin-releasing hormone (GnRH) is a decapeptide amide originally identified in the brain of a pig for its ability to stimulate the release of gonadotropins, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) from the anterior pituitary. The main groups of GnRH-secreting perikarya are located within the telencephalon from the olfactory bulb to the septum. The distribution of GnRH cell bodies and fibers corresponds to the course of the olfactory nervus terminalis, which is a small cranial nerve made of fibers and associated cells that form glanglion-like clusters. In addition, GnRH stimulates the synthesis and release of gonadotropins from the amphibian pituitary. Mammalian GnRH—added in vitro to interrenal gland from male and female Rana esculenta —induces a significant increase in prostaglandin F 2 concentrations.

LH-RH antagonists: state of the art and future perspectives.

Luteinizing hormone-releasing hormone (LH-RH) is produced in hypothalamic nuclei, travels via the portal blood to the anterior pituitary, and acts on gonadotropic cells by inducing the synthesis and release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The gonadotropic hormones, in turn, regulate gonadal steroid production and gametogenesis. Reproductive functions, therefore, are critically dependent on LH-RH whose stimulatory effects are determined by its pulsatile release pattern (Knobil 1980) and by the availability of high-affinity binding sites at the pituitary site (Clayton and Catt 1981). Consequently, interference with the binding of native LH-RH to its pituitary receptors will provoke alterations of gonadal functions.KeywordsGnRH AgonistGnRH AntagonistHormone AntagonistAndrogen SubstitutionThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Electron microscopic identification of luteinizing hormone-releasing hormone-immunoreactive neurons in the medial olfactory placode and basal forebrain of embryonic mice

Luteinizing hormone-releasing hormone is a decapeptide found in the brain and nose of all vertebrates that have been examined by immunocytochemical procedures with antiserum to luteinizing hormone-releasing hormone. It regulates the release of both luteinizing hormone and follicle-stimulating hormone from the gonadotropes of the anterior pituitary gland and promotes mating behavior. After about 11 days of embryogenesis in mice, luteinizing hormone-releasing hormone-immunoreactive cells are detected by immunocytochemical procedures in the medial olfactory placode, in the primordium of the vomeronasal organ. As they leave the olfactory placode, they run under the epithelial layer of the nasal septum associated with vomeronasal and terminalis nerves. Clustered, they stream toward the primordium of the olfactory bulb, passing along its ventromedial surface. Eventually, the largest numbers reach the septal and preoptic areas of the brain. Electron microscopic immunocytochemistry showed that luteinizing hormone-releasing hormone-immunoreactive product is accumulated just outside the nuclear envelope and in the lumen of rough endoplasmic reticulum adjacent to the cell nucleus of cells in and adjacent to the olfactory placode. As luteinizing hormone-releasing hormone-immunoreactive neurons migrate, they assume a fusiform shape and the immunoreaction product extends from the area around the nucleus throughout the cytoplasm, notably in processes which extend toward the direction of migration. Before and during migration, luteinizing hormone-releasing hormone was not detected in the Golgi apparatus or neurosecretory granules. It is inferred that as far as ultrastructural evidence is concerned, these neurons do not have a secretory function before they attain their target organs.