Control Of Gonadotropin Release Research Articles

ELAVL1 Elevates Insights: The Ups and Downs of Regulated mRNA Translation in the Control of Gonadotropin Release.

ELAVL1 Elevates Insights: The Ups and Downs of Regulated mRNA Translation in the Control of Gonadotropin Release.

Sexual dimorphism, plasticity and genomic diversity of the paraventricular nucleus

The hypothalamic paraventricular nucleus (PVN) is the nodal point for the integration of multiple homeostatic responses. Neurons in this area display both unique and overlapping phenotypic identities and functions. They control diverse, yet related, functions, such as fluid and electrolyte homeostasis, metabolism and cardiovascular integrity, via the release of vasopressin (antidiuretic hormone) and oxytocin from the neurohypophysis and adrenocorticotrophic hormone from the adenohypophysis. Pre-autonomic fibres projecting from the PVN exert potent effects on sympathetic and parasympathic outflow from the brainstem, medulla and spinal cord, and recently, a role for those neurons in the sexual dimorphism of cardiovascular health and disease has been identified. Certainly, neurons in the PVN play important roles in the control of gonadotrophin release and thus reproductive function. Not to be overlooked is the importance of PVN neurons in behavioural functions only secondarily related to reproduction or cardiovascular status, such as thirst, sodium appetite and food intake. Over the years, the phenotypic identities of multiple cell types in the PVN have been described, and connectivity studies have elucidated their targets. New ligand–receptor pairs have been discovered based upon the interactions of peptides and their receptors in the PVN. As a result of the availability of modern molecular tools and advanced behavioural screening approaches, studies examining PVN neurons continue to reveal new insights into the integrative nature of this crucially important region of the hypothalamus. The Physiology Society-sponsored symposium entitled ‘Sexual dimorphism, plasticity and genomic diversity of the paraventricular nucleus’ held on Wednesday 26 April 2017 at Experimental Biology 2017 in Chicago, IL, USA, brought together investigators whose work addresses several of these advances. Unique insight into the genomic regulation of cells in the PVN was presented by Dr Alastair Ferguson (Loewen, 2017), and a surprising view of their ability to switch phenotypes during physiological challenges highlighted the examination of cellular function introduced by Dr Jaideep Baines. Attention then was turned to the behavioural aspects of PVN function, with the focus on sex differences described by Dr Jessica Santollo (Santolo, 2017) and the importance of chromosomal sex on cardiovascular health as illustrated by Dr Jill Barnes (Barnes, 2017). Symposium reports from those speakers are included in this issue of Experimental Physiology. The organizers acknowledge the important contributions of the speakers and the support provided by The Physiological Society.

Social status, breeding state, and GnRH soma size in convict cichlids (Cryptoheros nigrofasciatus)

Gonadotropin-releasing hormone (GnRH) expressing neurons in the preoptic area (POA) of the hypothalamus plays a key role in regulating reproductive function through the control of gonadotropin release. Several studies have illustrated the importance of the social environment in modulating the size of GnRH expressing neurons. In the African cichlid fish Astatotilapia burtoni, the size of the soma of GnRH expressing neurons in the POA varies with social status in males, and with breeding state in females. Territorial males have larger GnRH+ cells than non-territorial males, while brooder females have smaller GnRH+ cells than control females. The lek-like breeding system of A. burtoni is, however, only one type of social system within the diverse assemblage of cichlids. To gain a better understanding of GnRH neuronal plasticity in response to the changes in the social environment, we tested whether similar effects occur in the monogamous New World cichlid, the convict cichlid (Cryptoheros nigrofasciatus), a model species for the study of social behaviour. Our results indicate that, indeed GnRH expressing neuron soma size, and not cell number, varies with both male territorial status, and manipulations of female breeding state in this monogamous, biparental, New World cichlid.

Molecular and physiological study of the artificial maturation process in European eel males: From brain to testis

European eel males can be artificially matured (1.5 IU hCG/g fish), but the regulatory mechanisms of their reproductive development are practically unknown. Spermatogenic stages (S1–S6), biometric characters [eye index (EI), gonadosomatic index (GSI), hepatosomatic index (HSI)] and sperm quality parameters (motility, viability and head spermatozoa morphometry) were analysed. Moreover, the present study evaluated the expression of GnRHs (mammal and chicken II Gonadotropin Release Hormone I) and gonadotrophins (FSHβ and LHβ) during hormonal treatment, as well as 11-ketotestosterone (11-KT) and 17,20β-dihydroxy-4-pregnen-3-one (17,20β-P) plasma levels. One week was enough to observe the S2 of gonad development, but it was necessary to reach the 7th week of treatment to obtain animals that presented the most advanced stage of development (S6). Differential regulation of the two GnRH expressions was found, supporting the main role of mGnRH in the control of gonadotrophin release. One hCG injection was enough to dramatically decrease the FSHβ expression, being close to zero during the rest of the treatment. LHβ expression and 17,20β-P registered a significant increase in the same stage of development, S3/4, confirming the role of this gonadotrophin in the last steps of maturation and 17,20β-P in the spermatozoa maturation. The 11-KT increased with GSI, and the highest 11-KT values coincided with the advanced steps of spermatogenesis prior to spermiation. Being consistent with the known role of the steroid in these processes. Furthermore, this study supports a role for 11-KT in stimulating eye growth, presenting high values when EI increased. Sperm production was obtained from the 4th week of treatment, but it was in the 8th week when a significant increase was observed in sperm quality [viability, high motility (>75%)].

Gonadotropin-releasing hormone and the control of gonadotrope function

Normal gametogenesis and steroidogenesis is highly dependent on the pulsatile release of hypothalamic GnRH that binds high-affinity receptors present at the surface of pituitary gonadotrophs thereby triggering the synthesis and release of the gonadotropins LH and FSH. The mammalian GnRH receptor displays the classical heptahelical structure of G protein-coupled receptors with, however, a unique feature, the lack of a C-terminal tail. Accordingly, it does not desensitise sensu stricto, and internalises very poorly. It is now well established that GnRH stimulation induces the activation of a complex network of transduction pathways involved in the control of gonadotropin release and subunit gene expression. Other authors and ourselves have demonstrated that the GnRH action is associated with an increased complexity regarding gene regulation/cell function. Indeed GnRH affects the GnRH receptor gene itself and a number of additional genes that include some involved in cell signalling and auto-/paracrine regulation. The fact that GnRH regulates the expression of its own receptor, together with a host of other genes typically involved in its signal transduction cascades implies alteration/auto-adaptation in gonadotropic responsiveness. Furthermore, some of these genes respond differentially depending on whether the GnRH stimulation is intermittent or permanent suggesting specific roles in the dual process of activation/desensitisation. Thus, it can be assumed that the importance of pulsatility of GnRH action is closely related to, or dependent on, the inability of the GnRH receptor to desensitise. Moreover, multiple post-receptor events are crucial for both the regulation/plasticity of gonadotropic function and the maintenance of cell integrity.

Estrogen Modulation of Mu-Opioid Receptor-Stimulated [35S]-GTP-Gamma-S Binding in Female Rat Brain Visualized by in vitro Autoradiography

The µ-opioid receptor (OR) is involved in several aspects of female reproductive neuroendocrinology, such as the control of gonadotropin release and the display of lordosis behavior. Even though the neuroendocrine events modulated by µ-ORs are steroid hormone-dependent, few studies have shown how steroid hormones such as estrogen and/or progesterone can affect µ-OR function. Therefore, the present study investigated if in vivo estrogen or estrogen plus progesterone treatment of ovariectomized (OVX) rats affects µ-OR coupling to its G proteins. We used autoradiographic analysis of agonist-stimulated [³⁵S]-GTPγS binding, in which brain sections were incubated in the presence or absence of the µ-OR agonist [D-Ala², N-Me-Phe⁴, Gly²ol]-enkephalin (DAMGO). Film images were quantified using calibrated [¹⁴C] standards. Analysis was performed in steroid-responsive hypothalamic regions such as the medial preoptic area (mPOA) and the ventromedial nucleus of the hypothalamus, as well as in non-hypothalamic brain regions. Treatment with estrogen, alone or with progesterone, significantly increased DAMGO-stimulated [³⁵S]-GTPγS binding in the mPOA when compared to control OVX animals. In addition, estrogen increased µ-OR coupling in the caudate putamen. Steroid treatment had no effect on either basal or DAMGO-stimulated binding in the other brain regions examined. These findings suggest that estrogen modulates µ-OR function in a brain region-specific fashion. This could have important implications in terms of how these hormones synchronize reproductive behavior and gonadotropin release.

Control of Gonadotropin Release in Trout: Estrogen Receptor‐Containing Dopaminergic Neurons and Tyrosine Hydroxylase Expressiona

Annals of the New York Academy of SciencesVolume 839, Issue 1 p. 422-424 Control of Gonadotropin Release in Trout: Estrogen Receptor-Containing Dopaminergic Neurons and Tyrosine Hydroxylase Expressiona B. LINARD, B. LINARD Endocrinologie Moléculaire de la Reproduction, UPRES-A CNRS 6026, Endocrinologie Moléculaire des Poissons, UA INRA, Campus de Beaulieu, 35042 Rennes Cedex, FranceSearch for more papers by this authorT. BAILHACHE, T. BAILHACHE Endocrinologie Moléculaire de la Reproduction, UPRES-A CNRS 6026, Endocrinologie Moléculaire des Poissons, UA INRA, Campus de Beaulieu, 35042 Rennes Cedex, FranceSearch for more papers by this authorA. CHEGUILLAUME, A. CHEGUILLAUME Endocrinologie Moléculaire de la Reproduction, UPRES-A CNRS 6026, Endocrinologie Moléculaire des Poissons, UA INRA, Campus de Beaulieu, 35042 Rennes Cedex, FranceSearch for more papers by this authorI. ANGLADE, I. ANGLADE Endocrinologie Moléculaire de la Reproduction, UPRES-A CNRS 6026, Endocrinologie Moléculaire des Poissons, UA INRA, Campus de Beaulieu, 35042 Rennes Cedex, FranceSearch for more papers by this authorO. KAH, O. KAH Endocrinologie Moléculaire de la Reproduction, UPRES-A CNRS 6026, Endocrinologie Moléculaire des Poissons, UA INRA, Campus de Beaulieu, 35042 Rennes Cedex, FranceSearch for more papers by this authorP. JEGO, P. JEGO Endocrinologie Moléculaire de la Reproduction, UPRES-A CNRS 6026, Endocrinologie Moléculaire des Poissons, UA INRA, Campus de Beaulieu, 35042 Rennes Cedex, FranceSearch for more papers by this authorC. SALIGAUT, C. SALIGAUT Endocrinologie Moléculaire de la Reproduction, UPRES-A CNRS 6026, Endocrinologie Moléculaire des Poissons, UA INRA, Campus de Beaulieu, 35042 Rennes Cedex, FranceSearch for more papers by this author B. LINARD, B. LINARD Endocrinologie Moléculaire de la Reproduction, UPRES-A CNRS 6026, Endocrinologie Moléculaire des Poissons, UA INRA, Campus de Beaulieu, 35042 Rennes Cedex, FranceSearch for more papers by this authorT. BAILHACHE, T. BAILHACHE Endocrinologie Moléculaire de la Reproduction, UPRES-A CNRS 6026, Endocrinologie Moléculaire des Poissons, UA INRA, Campus de Beaulieu, 35042 Rennes Cedex, FranceSearch for more papers by this authorA. CHEGUILLAUME, A. CHEGUILLAUME Endocrinologie Moléculaire de la Reproduction, UPRES-A CNRS 6026, Endocrinologie Moléculaire des Poissons, UA INRA, Campus de Beaulieu, 35042 Rennes Cedex, FranceSearch for more papers by this authorI. ANGLADE, I. ANGLADE Endocrinologie Moléculaire de la Reproduction, UPRES-A CNRS 6026, Endocrinologie Moléculaire des Poissons, UA INRA, Campus de Beaulieu, 35042 Rennes Cedex, FranceSearch for more papers by this authorO. KAH, O. KAH Endocrinologie Moléculaire de la Reproduction, UPRES-A CNRS 6026, Endocrinologie Moléculaire des Poissons, UA INRA, Campus de Beaulieu, 35042 Rennes Cedex, FranceSearch for more papers by this authorP. JEGO, P. JEGO Endocrinologie Moléculaire de la Reproduction, UPRES-A CNRS 6026, Endocrinologie Moléculaire des Poissons, UA INRA, Campus de Beaulieu, 35042 Rennes Cedex, FranceSearch for more papers by this authorC. SALIGAUT, C. SALIGAUT Endocrinologie Moléculaire de la Reproduction, UPRES-A CNRS 6026, Endocrinologie Moléculaire des Poissons, UA INRA, Campus de Beaulieu, 35042 Rennes Cedex, FranceSearch for more papers by this author First published: 07 February 2006 https://doi.org/10.1111/j.1749-6632.1998.tb10820.xCitations: 1 a This work was supported by grants from CNRS and INRA. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume839, Issue1TRENDS IN COMPARATIVE ENDOCRINOLOGY AND NEUROBIOLOGY: FROM MOLECULAR TO INTEGRATIVE BIOLOGYMay 1998Pages 422-424 RelatedInformation

Effects of growth hormone on neuroendocrine function.

Although the role of growth hormone (GH) in the control of reproductive functions is not well understood, there is considerable evidence that the states of both GH deficiency and GH excess are typically associated with reproductive deficits. To identify the possible involvement of functional alterations in the hypothalamic-pituitary system in producing these deficits, we are studying neuroendocrine function related to reproduction in transgenic animals overexpressing GH, in animals with congenital GH deficiency, and in animals with selective immunoneutralization of GH. The results indicate that GH acts on the hypothalamus to alter dopaminergic and noradrenergic control of prolactin and gonadotropin release. Life-long elevation of GH levels outside the physiological ranges disrupts feedback control of luteinizing hormone (LH) release by gonadal streroids. Plasma LH and follicle-stimulating hormone (FSH) levels and feedback control of LH release are also abnormal in GH-deficient animals indicating that physiological levels of endogenous GH are normally involved in the control of gonadotropin release. Differences between the effects of bovine vs. human GH in transgenic mice and differential effects of GH deficiency in mice and rats should facilitate identification of the mechanisms involved in the actions of GH on the hypothalamic-pituitary system.

Inhibitory effect of 5β-pregnan-3α-ol-20-one on gonadotropin-releasing hormone gene expression in the male rat

Neuroanatomical data have documented the existence of synaptic contacts between γ-aminobutyric acid (GABA) terminals and preoptic gonadotropin-releasing hormone (GnRH) neurons in the rat anterior hypothalamus. In addition, pharmacological studies have suggested that the GABAergic system may be involved in the control of gonadotropin release. Moreover, it has been shown that some progesterone metabolites such as 5β-pregnan-3α-ol-20-one (5β3αP) are able to interact with the GABA A receptor complex. In the present study, we have investigated the effects of chronic (5 days) treatment with the GABA A-positive ligand 5β3αP (20 mg/kg body weight i.p., twice a day) or with the GABA A agonist muscimol (1 mg/kg body weight i.p., twice a day) alone or in combination on GnRH mRNA levels in the preoptic area of the male anterior hypothalamus as measured by in situ hybridization. Treatment with 5β3αP produced a 30% decrease in the number of grains overlying labelled cells, while muscimol treatment decreased the hybridization signal by 36%. The concomitant administration of 5β3αP and muscimol resulted in a 46% decrease in the GnRH mRNA levels. This inhibitory effect was completely antagonized by the concomitant administration of picrotoxin (4 mg/kg body weight i.p., twice a day). These data suggest that the GABA A receptor complex and steroids that interact positively with this GABA A receptor complex may play an important role in the regulation of GnRH biosynthesis by hypothalamic neurons.

Distribution of salmon gonadotrophin releasing-hormone in the brain and pituitary of the sea bass (Dicentrarchus labrax)

The distribution of salmon gonadotrophin-releasing hormone (sGnRH) was studied in the brain and pituitary of two-year-old immature sea bass (Dicentrarchus labrax) by means of an enzymoimmunoassay (EIA) for sGnRH and immunocytochemistry. The EIA for sGnRH is a competitive assay using a tracer made of sGnRH coupled to acetylcholinesterase from an electric eel. The separation of free and bound tracer is achieved by coating the plates with mouse anti-rabbit IgG monoclonal antibodies. Displacement curves generated by sGnRH and extracts from pituitary and different brain regions showed a good parallelism allowing the assay to be used for sGnRH measurements in this species. Although all parts of the brain contained measurable levels of sGnRH, the highest concentrations were found in the pituitary, the olfactory bulbs and the telencephalon. These data were confirmed by immunocytochemistry. Cell bodies were found in the olfactory bulbs, ventral telencephalon, preoptic region and mediobasal hypothalamus. Immunoreactive fibers could be observed in all parts of the brain including the optic tectum, the cerebellum (corpus and valvula), the vagal lobe, the medulla oblongata and the rostral spinal cord. In most cases, these fibers do not form well defined bundles; however, there was clearly a continuum of immunoreactive fibers, extending from the olfactory bulbs to the pituitary, and along which all the cell bodies described above were located. In the ventral telencephalon and the preoptic region, clear pictures of varicose positive fibers contacting immunoreactive perikarya could be observed. These data indicate that sGnRH is most likely an endogenous peptide in the brain of the sea bass, although the presence of other forms of GnRH cannot be excluded at this point. This study also demonstrates that the general organization of the GnRH systems in the sea bass is highly similar to what has been described in most freshwater teleost species, and provides basis for further studies on the neuroendocrine control of gonadotrophin release in this commercially important species.

In VivoBiological Validation and Biophysical Modeling of the Sensitivity and Positive Accuracy of Endocrine Peak Detection. II. The Follicle-Stimulating Hormone Pulse Signal*

Despite interest in the in vivo control of gonadotropin release, valid assessment of the physiological regulation of the pulsatile secretion of the gonadotropin FSH has been hampered by the uncertain validity and reliability of available FSH peak detection algorithms. Difficulties in identifying FSH peaks accurately are believed to arise in part because of the slow metabolic clearance of this glycoprotein hormone. Here, we have used two complementary strategies to test the validity of FSH pulse detection. First, by means of a computer-assisted mathematical model for simulating episodic hormone secretion, we evaluated the effects of various putative FSH secretory pulse amplitudes and half-lives on the sensitivity and positive accuracy of peak detection. Secondly, we used an in vivo primate animal model, in which presumptively true FSH pulses were evaluated independently by continuous electrophysiological monitoring of mediobasal hypothalamic multiunit activity. These two approaches allowed us to define optimal pulse analysis parameters that yield maximal sensitivity and positive accuracy for detecting FSH peaks in synthetic and biological time series. We found (as predicted intuitively) that increasing half-times of hormone disappearance decrease both the sensitivity and positive accuracy of peak detection for any given peak detection thresholds and hormone secretory amplitudes. However, adequately sampled episodic FSH time series could be analyzed for FSH pulsatility by an appropriately constrained, objective computerized algorithm with reasonable (less than 10-15%) false negative and false positive errors, such that resultant sensitivity and positive accuracy exceed 85-90%. Of interest, computer simulations and the in vivo animal model exhibited similar discriminative capabilities. We conclude that increasing half-times of hormone (e.g. FSH) removal do impair hormone peak detection sensitivity and positive accuracy. Nevertheless, gonadotropin time series can be analyzed for FSH pulsatility in a valid manner with adequately constrained false negative and false positive error rates.

Involvement of Catecholaminergic Systems in the Zona incerta in the Steroidal Control of Gonadotrophin Release and Female Sexual Behaviour

Previous reports have shown that dopamine (DA) in the zona incerta (ZI) has a stimulatory effect on gonadotrophin release. We have now investigated the possibility that steroids exert their feedback effects on the release of luteinizing hormone (LH) via catecholamine systems in the ZI. Since the same steroid regimes also stimulate female sexual behaviour, the possibility that the ZI is also involved in the control of sexual activity was investigated. Lesions in the ZI increased proceptive and receptive behaviour in oestrogen-primed ovariectomised rats that exhibited a low level of lordosis in a pre-lesion test and had no effect in receptive animals. Turnover rates (TR) of DA, noradrenaline (NA) and adrenaline were measured in the ZI, preoptic area (POA), arcuate nucleus (ARC), median eminence (ME) and ventromedial nucleus in ovariectomised rats treated 54 h before with either oil, oestradiol benzoate (OB) at 5, 10 or 50 micrograms/rat, or 5 micrograms/rat OB followed by 0.5 mg/rat progesterone (P) 48 h later. The TR as measured from the decline in concentration after alpha-methyltyrosine and changes in DOPAC concentration were correlated with the effect of the steroids on plasma LH and lordotic activity. Confirming previous reports, NA turnover in the POA and ME was increased, and DA turnover in the ME was decreased by steroids when they enhanced LH release. DA turnover in the ARC and ME was reduced when lordosis behaviour increased. Treatment with OB plus P stimulated LH release and sexual receptivity and at the same time significantly increased DA and NA turnover in the ZI. There was no correlation between these parameters after OB alone. This report shows that the DA system in the ZI may mediate the stimulatory effect of P on LH release in OB-primed rats but is not involved in the feedback effects of oestradiol alone. NA activity in the ZI is increased after OB plus P and may therefore also be concerned with stimulating LH release. The ZI is involved in the control of sexual behaviour, as electrolytic lesions in this area enhance receptivity and proceptivity, but the catecholamine systems in the ZI do not appear to mediate this control.

Physiological roles of chicken LHRH-I and -II in the control of gonadotrophin release in the domestic chicken

The physiological roles of chicken LHRH-I and -II (cLHRH-I and -II) in the regulation of gonadotrophin release were investigated in the domestic chicken. Measurements of the neuropeptides, using specific radioimmunoassays, in brain sections cut in three planes or in grossly dissected brain areas, showed that cLHRH-II occurs in low amounts throughout the brain whereas cLHRH-I is most abundant in the diencephalon. Within the diencephalon, the largest amount of cLHRH-I occurred in the median eminence of the hypothalamus. The amount of cLHRH-I in the median eminence was higher (P less than 0.05) in laying than in out-of-lay hens. No cLHRH-II was detected in the median eminence in either reproductive state. The amount of cLHRH-I in the hypothalamus was increased (P less than 0.05) in cockerels at the onset of puberty and in somatically immature birds after castration. There were no correlated changes in the amounts of hypothalamic cLHRH-II measured in the same experimental samples. Active immunization of laying hens against cLHRH-I but not against cLHRH-II resulted in the complete regression of the reproductive system and a depression in the concentration of plasma LH. These observations, taken together, suggest that gonadotrophin secretion in the hen is more likely to be directly regulated by cLHRH-I than by cLHRH-II.

Opposite Effects of Central Immunoneutralization of Angiotensin II or Atrial Natriuretic Peptide on Luteinizing Hormone Release in Ovariectomized Rats

Studies both in vivo and in vitro have provided evidence that LH secretion can be altered by angiotensin II (AII) or atrial natriuretic peptide (ANP); however, the physiological significance of these endogenous neuropeptides in the control of gonadotropin release is still unclear. We studied the effects of central immunoneutralization of these neuropeptides on LH and FSH release in ovariectomized rats. Antisera directed against AII or ANP were microinjected into the third cerebral ventricle (3V) of conscious, unrestrained rats with indwelling external jugular catheters and blood samples were withdrawn immediately prior to the injections and at various intervals thereafter. Plasma LH was not altered initially but by 2 h was significantly lower in the animals injected with antiserum directed against AII (AB-AII) than in controls injected with normal rabbit serum (NRS). Values remained low for 6 h. By 24 h they had returned to levels similar to those of NRS-injected controls. On the other hand, in animals injected with antiserum against ANP (AB-ANP) plasma LH levels were significantly higher than those of controls (NRS) after a delay of 4 h. Values were still significantly elevated at 24 h. There was no difference in plasma FSH concentrations between control groups (NRS) and groups injected with either AB-AII or AB-ANP. These results indicate that endogenous AII and ANP play no role in the control of FSH release, at least in ovariectomized rats but that these neuropeptides play a role in LH release which is stimulated by AII and inhibited by ANP since the immunoneutralization decreased and increased, respectively, the plasma levels of this hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of ovariectomy on luteinizing hormone concentrations in anestrous and cyclic sows.

In an effort to determine whether anestrus in swine is due to aberrant ovarian feedback control of gonadotropin release, this study contrasted the influence of ovariectomy on LH concentrations in serum of anestrous sows and in sows that returned to estrus following weaning. Blood samples were collected at 6-h intervals from 7 d prior to until 4 d after ovariectomy of 22 anestrous and 24 cyclic sows. Blood samples also were collected at 15-min intervals for 8 h at 2 d prior to and 2 d after ovariectomy. Sampling at 6-h intervals continued until 12 d after ovariectomy and additional 8-h windows of 15-min samples were taken at 7 and 12 d after ovariectomy of seven anestrous and nine diestrous sows. Mean LH concentrations and LH pulse frequencies were greater (P less than .05) 2 d after ovariectomy than 2 d prior to ovariectomy in both anestrous and diestrous sows. Mean pulse amplitude had increased by 2 d after ovariectomy in anestrous sows but did not change in cyclic sows. Baselines as determined from the mean of all LH measurements excluding pulses, remained the same in both anestrous and diestrous sows at 2 d after ovariectomy. Pulse frequency, pulse amplitude, and mean LH concentration were greater (P less than .05) in both anestrous and diestrous sows at 7 and 12 d after ovariectomy than at 2 d prior to and 2 d after ovariectomy. Pulse amplitude on d 7 and 12 after ovariectomy decreased (P less than .05) in both anestrous and diestrous sows relative to those observed at earlier times.(ABSTRACT TRUNCATED AT 250 WORDS)

Gonadotrophin-releasing activity of neurohypophysial hormones: I. Potential for modulation of pituitary hormone secretion in rats

Neurohypophysial hormones have been implicated in the control of anterior pituitary function, and oxytocin has been shown to stimulate gonadotrophin excretion and ovarian follicular development in certain species. To determine the role of neurohypophysial peptides in the control of gonadotrophin release, their actions on LH and FSH secretion were analysed in rats in vivo and in vitro. In adult female rats, administration of oxytocin during early pro-oestrus advanced the spontaneous LH surge and markedly increased peripheral LH levels at 15.00 h compared with control animals. In cultured pituitary cells from adult female rats, oxytocin and vasopressin elicited dose-related increases in LH and FSH release. Such responses were not affected by a potent gonadotrophin-releasing hormone (GnRH) antagonist that abolished GnRH agonist-induced release of LH and FSH. Oxytocin did not enhance GnRH agonist-stimulated gonadotrophin release to the same extent as it increased basal secretion, but at low concentrations of GnRH agonist the effects were additive. The gonadotrophin responses to oxytocin and vasopressin were inhibited by the specific neurohypophysial hormone antagonists, [d(CH2)5D-Ile2,Ile4,Arg8]vasopressin and [d(CH2)5Tyr (Me),Arg8]vasopressin. These results provide direct evidence that neurohypophysial hormones can stimulate gonadotrophin secretion through a receptor system distinct from the GnRH receptor. Such a mechanism could represent a complementary hypothalamic control system for long-term modulation of LH and FSH secretion by exerting a basal or tonic influence on gonadotrophin production.

Control of gonadotropin release in the Atlantic croaker ( Micropogonias undulatus): Evidence for lack of dopaminergic inhibition

Gonadotropin (GTH) secretion is known to be under inhibitory dopaminergic control in several species of fish. To investigate whether this is also the case in the Atlantic croaker (Micropogonias undulatus), juvenile and adult croaker were treated with a gonadotropin-releasing hormone analog (des-Gly10D-Ala6Pro9 n ethylamide luteinizing hormone-releasing hormone (LHRHa), 1-100 ng/g body wt) in combination with various dopaminergic drugs (1-20 mg/kg body wt). None of the dopamine antagonists tested, metoclopramide, pimozide, haloperidol, and domperidone, were able to increase plasma GTH levels above those induced by treatment with LHRHa alone and in some cases the gonadotropin response to LHRHa was reduced. The dopamine agonists bromocriptine and apomorphine either had no effect on the normal response to LHRHa or increased it. None of the drugs tested had any detectable effect on GTH levels in the absence of LHRHa. These results provide evidence for a lack of dopaminergic inhibition in the control of GTH secretion in the Atlantic croaker.

Lysine-vasopressin does not affect basal and LH-RH-stimulated LH and FSH release during the menstrual cycle of normal women.

In order to test possible effects of lysine-vasopressin (LVP) on basal and LH-RH-stimulated LH and FSH release, an intravenous bolus of LVP (0.06 IU/kg body weight) was injected alone or 10 min before LH-RH (100 micrograms i.v.) in 33 normal women in the follicular, periovulatory and luteal phase of their menstrual cycle. The administration of LVP modified neither the basal secretion of the gonadotropins nor the LH-RH-induced LH and FSH release. These data suggest that in humans, vasopressin is not involved in the control of gonadotropin release at the level of the anterior pituitary.

Dopaminergic neurones in the zona incerta exert a stimulatory control on gonadotrophin release via D1 dopamine receptors.

The zona incerta (ZI) is a site of dopamine nerve terminals and part of the incertohypothalamic tract (I-H). Previous findings indicate that dopamine in the ZI has a stimulatory control on the release of luteinizing hormone (LH) and occurrence of ovulation. The effect of acute administration into anaesthetised rats of selective D1 and D2 dopamine agonists and antagonists injected into the ZI on plasma luteinizing hormone (LH) and on the occurrence of ovulation has now been investigated. It was found that bilateral injections on the day of pro-oestrus of a selective D1 antagonist, Sch 23390, inhibited ovulation at 10 micrograms/side/rat. Unilateral injections of a selective D1 agonist, SKF 38393, at 10 micrograms/rat stimulated a significant rise in plasma LH concentration in ovariectomised oestrogen-primed rats, and this was partially reversed by systemic pre-treatment with Sch 23390. The selective D2 agonist, LY 171555, and D2 antagonists, sulpiride and domperidone, had no effect on plasma LH levels or ovulation. This indicates that D1 receptors (but not D2 receptors) in the ZI are involved in the control of gonadotrophin release and may have a physiological function in reproductive processes.

Diagnostic and Therapeutic Uses of Gonadotropin-Releasing Hormone

Fourteen years ago independent investigations regarding the hypothalamic control of gonadotropin release were simultaneously concluded by two research teams. 1,2 These reports presented the isolation and synthesis of a hypothalamic decapeptide now known as gonadotropin-releasing hormone (GnRH) (also known as luteinizing hormone-releasing hormone [LH-RH] or gonadorelin). When given parenterally to humans, this compound results in stimulation of release of the anterior pituitary gonadotropic hormones, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). In 1978 the significance of this accomplishment was recognized by the award of the Nobel Prize for Medicine to the heads of the two research teams. Since its discovery GnRH has been widely used as a reproductive endocrine probe to aid our understanding of basic control mechanisms involved in gonadal function in humans. Additionally, GnRH has been extensively used as a diagnostic tool for men and women with gonadal dysfunction; more recently it has also been utilized as a