Gonadotropin-releasing Hormone Dendrites Research Articles

Neuroendocrine control of gonadotropin-releasing hormone: Pulsatile and surge modes of secretion.

The concept that different systems control episodic and surge secretion of gonadotropin-releasing hormone (GnRH) was well established by the time that GnRH was identified and formed the framework for studies of the physiological roles of GnRH, and later kisspeptin. Here, we focus on recent studies identifying the neural mechanisms underlying these two modes of secretion, with an emphasis on their core components. There is now compelling data that kisspeptin neurons in the arcuate nucleus that also contain neurokinin B (NKB) and dynorphin (i.e., KNDy cells) and their projections to GnRH dendrons constitute the GnRH pulse generator in mice and rats. There is also strong evidence for a similar role for KNDy neurons in sheep and goats, and weaker data in monkeys and humans. However, whether KNDy neurons act on GnRH dendrons and/or GnRH soma and dendrites that are found in the mediobasal hypothalamus (MBH) of these species remains unclear. The core components of the GnRH/luteinising hormone surge consist of an endocrine signal that initiates the process and a neural trigger that drives GnRH secretion during the surge. In all spontaneous ovulators, the core endocrine signal is a rise in estradiol secretion from the maturing follicle(s), with the site of estrogen positive feedback being the rostral periventricular kisspeptin neurons in rodents and neurons in the MBH of sheep and primates. There is considerable species variations in the neural trigger, with three major classes. First, in reflex ovulators, this trigger is initiated by coitus and carried to the hypothalamus by neural or vascular pathways. Second, in rodents, there is a time of day signal that originates in the suprachiasmatic nucleus and activates rostral periventricular kisspeptin neurons and GnRH soma and dendrites. Finally, in sheep nitric oxide-producing neurons in the ventromedial nucleus, KNDy neurons and rostral kisspeptin neurons all appear to participate in driving GnRH release during the surge.

Networking of glucagon-like peptide-1 axons with GnRH neurons in the basal forebrain of male mice revealed by 3DISCO-based immunocytochemistry and optogenetics

Glucagon-like peptide-1 (GLP-1) regulates reproduction centrally, although, the neuroanatomical basis of the process is unknown. Therefore, the putative networking of the central GLP-1 and gonadotropin-releasing hormone (GnRH) systems was addressed in male mice using whole mount immunocytochemistry and optogenetics. Enhanced antibody penetration and optical clearing procedures applied to 500–1000 µm thick basal forebrain slices allowed the simultaneous visualization of the two distinct systems in the basal forebrain. Beaded GLP-1-IR axons innervated about a quarter of GnRH neurons (23.2 ± 1.4%) forming either single or multiple contacts. GnRH dendrites received a more intense GLP-1 innervation (64.6 ± 0.03%) than perikarya (35.4 ± 0.03%). The physiological significance of the innervation was examined by optogenetic activation of channelrhodopsin-2 (ChR2)-expressing axons of preproglucagon (GCG) neurons upon the firing of GnRH neurons by patch clamp electrophysiology in acute brain slices of triple transgenic mice (Gcg-cre/ChR2/GFP-GnRH). High-frequency laser beam stimulation (20 Hz, 10 ms pulse width, 3 mW laser power) of ChR2-expressing GCG axons in the mPOA increased the firing rate of GnRH neurons (by 75 ± 17.3%, p = 0.0007). Application of the GLP-1 receptor antagonist, Exendin-3-(9-39) (1 μM), prior to the photo-stimulation, abolished the facilitatory effect. In contrast, low-frequency trains of laser pulses (0.2 Hz, 60 pulses) had no effect on the spontaneous postsynaptic currents of GnRH neurons. The findings indicate a direct wiring of GLP-1 neurons with GnRH cells which route is excitatory for the GnRH system. The pathway may relay metabolic signals to GnRH neurons and synchronize metabolism with reproduction.

Rabconnectin-3\u03b1 is required for the morphological maturation of GnRH neurons and kisspeptin responsiveness

A few hundred hypothalamic neurons form a complex network that controls reproduction in mammals by secreting gonadotropin-releasing hormone (GnRH). Timely postnatal changes in GnRH secretion are essential for pubertal onset. During the juvenile period, GnRH neurons undergo morphological remodeling, concomitantly achieving an increased responsiveness to kisspeptin, the main secretagogue of GnRH. However, the link between GnRH neuron activity and their morphology remains unknown. Here, we show that brain expression levels of Dmxl2, which encodes the vesicular protein rabconnectin-3α, determine the capacity of GnRH neurons to be activated by kisspeptin and estradiol. We also demonstrate that Dmxl2 expression levels control the pruning of GnRH dendrites, highlighting an unexpected role for a vesicular protein in the maturation of GnRH neuronal network. This effect is mediated by rabconnectin-3α in neurons or glial cells afferent to GnRH neurons. The widespread expression of Dmxl2 in several brain areas raises the intriguing hypothesis that rabconnectin-3α could be involved in the maturation of other neuronal populations.

Lateral hypothalamic orexin and melanin-concentrating hormone neurons provide direct input to gonadotropin-releasing hormone neurons in the human.

Hypophysiotropic projections of gonadotropin-releasing hormone (GnRH)-synthesizing neurons form the final common output way of the hypothalamus in the neuroendocrine control of reproduction. Several peptidergic neuronal systems of the medial hypothalamus innervate human GnRH cells and mediate crucially important hormonal and metabolic signals to the reproductive axis, whereas much less is known about the contribution of the lateral hypothalamic area to the afferent control of human GnRH neurons. Orexin (ORX)- and melanin-concentrating hormone (MCH)-synthesizing neurons of this region have been implicated in diverse behavioral and autonomic processes, including sleep and wakefulness, feeding and other functions. In the present immunohistochemical study, we addressed the anatomical connectivity of these neurons to human GnRH cells in post-mortem hypothalamic samples obtained from autopsies. We found that 38.9 ± 10.3% and 17.7 ± 3.3% of GnRH-immunoreactive (IR) perikarya in the infundibular nucleus of human male subjects received ORX-IR and MCH-IR contacts, respectively. On average, each 1 mm segment of GnRH dendrites received 7.3 ± 1.1 ORX-IR and 3.7 ± 0.5 MCH-IR axo-dendritic appositions. Overall, the axo-dendritic contacts dominated over the axo-somatic contacts and represented 80.5 ± 6.4% of ORX-IR and 76.7 ± 4.6% of MCH-IR inputs to GnRH cells. Based on functional evidence from studies of laboratory animals, the direct axo-somatic and axo-dendritic input from ORX and MCH neurons to the human GnRH neuronal system may convey critical metabolic and other homeostatic signals to the reproducive axis. In this study, we also report the generation and characterization of new antibodies for immunohistochemical detection of GnRH neurons in histological sections.

Simulated GABA Synaptic Input and L-Type Calcium Channels Form Functional Microdomains in Hypothalamic Gonadotropin-Releasing Hormone Neurons

Hypothalamic gonadotropin-releasing hormone (GnRH) neurons integrate the multiple internal and external cues that regulate sexual reproduction. In contrast to other neurons that exhibit extensive dendritic arbors, GnRH neurons usually have a single dendrite with relatively little branching. This largely precludes the integration strategy in which a single dendritic branch serves as a unit of integration. In the present study, we identify a gradient in L-type calcium channels in dendrites of mouse GnRH neurons and its interaction with GABAergic and glutamatergic inputs. Higher levels of L-type calcium channels are in somata/proximal dendrites (i.e., 0-26 μm) and distal dendrites (∼130 μm dendrite length), but intervening midlengths of dendrite (∼27-130 μm) have reduced L-type calcium channels. Using uncaging of GABA, there is a decreasing GABAergic influence along the dendrite and the impact of GABA(A) receptors is dependent on activation of L-type calcium channels. This results in amplification of proximal GABAergic signals and attenuation of distal dendritic signals. Most interestingly, the intervening dendritic regions create a filter through which only relatively high-amplitude, low-frequency GABAergic signaling to dendrites elicits action potentials. The findings of the present study suggest that GnRH dendrites adopt an integration strategy whereby segments of single nonbranching GnRH dendrites create functional microdomains and thus serve as units of integration.

Glutamatergic and GABAergic innervation of GnRH neurons in the human hypothalamus

Event Abstract Back to Event Glutamatergic and GABAergic innervation of GnRH neurons in the human hypothalamus E. Hrabovszky1*, C. S. Molnár1, I. Kallo2, B. Borsay3, L. Sarkadi3, L. Herczeg3, M. Watanabe4 and Z. Liposits1, 2 1 Hungarian Academy of Sciences, Institute of Experimental Medicine, Hungary 2 Pázmány Péter Catholic University, Department of Neuroscience, Hungary 3 University of Debrecen, Department of Forensic Medicine, Hungary 4 Hokkaido University School of Medicine, Department of Anatomy, Japan Neurosecretory projections of gonadotropin-releasing hormone (GnRH) neurons to the hypophysial portal capillaries represent the final common output way of the hypothalamus in the neuroendocrine control of reproduction. GnRH neurons receive afferent input from a variety of neurotransmitter systems which are only partly characterized in the human. In the present study we used immunohistochemical approaches to address the contribution of the amino acid neurotransmitters GABA and glutamate to the afferent regulation of human GnRH neurons. According to previous findings in rodents where GABA represents the main neurotransmitter in the afferent control of GnRH neurons, we found that vesicular GABA transporter-immunoreactive GABAergic axons abundantly innervated the cell bodies and the dendrites of human GnRH neurons. While in rats, only glutamatergic axons of the VGLUT2 phenotype innervate GnRH neurons, in human samples we observed both VGLUT1- and VGLUT2 immunoreactive afferent contacts on GnRH neurons, with a preferential accumulation on GnRH dendrites. These morphological observations implicate the classic amino acid neurotransmitters GABA and glutamate in the afferent regulation of human GnRH neurons. As in rodents, GABA-ergic and glutamatergic afferents may have important contributions to metabolic-, sex steroid-, circadian- and stress signaling to the reproductive axis. Acknowledgements Supported by: OTKA K69127, T73002 and K83710; ETT 122/2009; FP7/2007-2013 (n° 245009) Keywords: Neuroendocrinology, Neuroscience Conference: 13th Conference of the Hungarian Neuroscience Society (MITT), Budapest, Hungary, 20 Jan - 22 Jan, 2011. Presentation Type: Abstract Topic: Neuroendocrinology Citation: Hrabovszky E, Molnár CS, Kallo I, Borsay B, Sarkadi L, Herczeg L, Watanabe M and Liposits Z (2011). Glutamatergic and GABAergic innervation of GnRH neurons in the human hypothalamus. Front. Neurosci. Conference Abstract: 13th Conference of the Hungarian Neuroscience Society (MITT). doi: 10.3389/conf.fnins.2011.84.00141 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 03 Mar 2011; Published Online: 23 Mar 2011. * Correspondence: Dr. E. Hrabovszky, Hungarian Academy of Sciences, Institute of Experimental Medicine, Budapest, Hungary, hrabovszky.erik@koki.mta.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers E. Hrabovszky C. S Molnár I. Kallo B. Borsay L. Sarkadi L. Herczeg M. Watanabe Z. Liposits Google E. Hrabovszky C. S Molnár I. Kallo B. Borsay L. Sarkadi L. Herczeg M. Watanabe Z. Liposits Google Scholar E. Hrabovszky C. S Molnár I. Kallo B. Borsay L. Sarkadi L. Herczeg M. Watanabe Z. Liposits PubMed E. Hrabovszky C. S Molnár I. Kallo B. Borsay L. Sarkadi L. Herczeg M. Watanabe Z. Liposits Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

N‐methyl D‐aspartate (NMDA) receptors endow dendrites of gonadotropin releasing‐hormone (GnRH) neurons with additional active properties

Dendrites of GnRH neurons express tetrodotoxin‐sensitive voltage‐gated sodium channels and generate action potentials. Other dendrites exhibiting action potentials possess additional active properties such as NMDA‐mediated potentials. We tested the hypothesis that GnRH dendrites express R1 subunits of NMDA receptors and exhibit amplification of sub‐threshold, excitatory post‐synaptic potentials (EPSPs) via NMDA receptor activation. Immunochemistry indicated GnRH dendrites express R1 subunits. Stimulating living GnRH dendrites with simulated sub‐threshold EPSPs resulted in plateau potentials and individual action potentials. When GABAergic inputs were blocked with picrotoxin (100 μM), repetitive action potentials occurred. The NMDA receptor antagonist D‐2‐amino‐5‐phosphono‐valeric (50 μM) eliminated responses. In small diameter dendrites, NMDA receptors would have a pronounced impact. Activating simulated NMDA conductances (at 560 μm dendrite length) in our compartmental models of GnRH neurons resulted in repetitive action potentials. Activating proximal NMDA receptors (at 200 and 100 μm dendrite length) diminished the impact of NMDA receptors. Our findings indicate GnRH dendrites exhibit regionalized expression of the NMDA conductance thereby forming location‐dependent microdomains where estrogen‐sensitive GABAergic neurons can regulate local excitability.

Dynorphin Immunoreactive Fibers Contact GnRH Neurons in the Human Hypothalamus

Dynorphin, an endogenous opioid peptide, mediates progesterone-negative feedback on gonadotropin-releasing hormone (GnRH) neurons in other species. The role of dynorphin in humans is unclear. The objective of this study was to determine if dynorphin fibers have close contacts with GnRH neurons in humans. Dual-label immunocytochemistry was performed on postmortem human hypothalamic tissue. The majority of GnRH neurons, 87.5%, had close contacts with dynorphin fibers and multiple close contacts were common, 62.5%. There were no regional differences between the hypothalamus and preoptic area in the distribution of close contacts. More close contacts were identified on the GnRH dendrites compared to the cell bodies (P < .001), but this difference was not significant when corrected for length. In conclusion, dynorphin fibers form close contacts with GnRH neurons in humans. This neuroanatomical evidence may suggest that dynorphin has effects on GnRH regulation in humans as seen in other species.

Neuroanatomical plasticity in the gonadotropin‐releasing hormone system of the ewe: Seasonal variation in glutamatergic and γ‐aminobutyric acidergic afferents

Temperate zone animals time the onset of reproductive events to coincide with specific portions of the sidereal year. Although the neural mechanisms involved remain poorly understood, a marked annual variation in the brain's sensitivity to estradiol negative feedback is thought to mediate many of the changes in neuroendocrine hormone secretion, especially that of the gonadotropin-releasing hormone (GnRH) neurons, via neural afferents. The aim of the present study was to determine whether glutamatergic inputs to GnRH neurons in sheep vary seasonally and to expand our previous observations of seasonal changes in gamma-aminobutyric acid (GABA)-ergic inputs. Brains from adult sheep were collected during the breeding season (N = 8) or the nonbreeding season (anestrus; N = 7). Confocal microscopy and optical sectioning were used to quantify the density of labeled VGLUT2 and VGAT immunoreactivity onto GnRH neurons. The results reveal a significantly greater number of VGLUT2-ir inputs to GnRH dendrites during the breeding season vs. the nonbreeding season but no seasonal changes on GnRH cell somas. The number of VGAT-ir terminals onto GnRH dendrites was reduced in the breeding season compared with the nonbreeding season. GnRH neurons were also found to receive dual-phenotype (VGLUT + VGAT) inputs; these varied with season in a manner similar to VGAT inputs. Morphologically, the numbers of branches of proximal dendrites increased significantly in a subset of GnRH neurons located near the midline. Together these results reveal a dynamic seasonal reorganization of identified inputs onto GnRH neurons and lend additional support to the overall hypothesis that seasonal modulation of GnRH neurons involves glutamatergic and GABAergic neural plasticity.

Evidence that kisspeptin neurons in the AVPV form part of a bisynaptic pathway connecting suprachiasmatic vasopressin neurons with preoptic GnRH cells

Event Abstract Back to Event Evidence that kisspeptin neurons in the AVPV form part of a bisynaptic pathway connecting suprachiasmatic vasopressin neurons with preoptic GnRH cells Imre Kalló1, 2*, Barbara Vida1, Levente Deli1, Theodosis Kalamatianos3, Erik Hrabovszky1, Alain Caraty4, Zsolt Liposits1, 2 and Coen W. Clive3 1 Institute of Experimental Medicine, Hungary 2 Pázmány Péter Catholic University, Department of Neuroscience, Faculty of Health,Medicine and Life Sciences, Hungary 3 King’s College London, United Kingdom 4 Univ Tours, INRA, France Gonadotropin releasing hormone (GnRH) secretion is under circadian regulation in rodents, but the mechanisms underlying this are poorly understood. Findings of our previous studies suggest that vasopressin (VP) neurons in the suprachiasmatic nucleus (SCN) convey signals to GnRH neurons via the anteroventral periventricular nucleus (AVPV). The AVPV contains kisspeptin (KP) neurons, which have been implicated in oestrogen’s positive feedback on GnRH release. Our studies have used confocal- and electronmicroscopy to test the hypotheses that direct contacts are made by VP-immunoreactive (IR) processes from the SCN on AVPV KP neurons and by KP-IR processes on GnRH neurons. Unlike the VP neurons in the supraoptic and paraventricular nuclei and in the bed nucleus of the stria terminalis and medial amygdala, those in the SCN are characterised by absence of galanin expression. Triple-label immunohistochemistry for VP, galanin and KP was carried out on hypothalamic sections from ovariectomised mice treated with estradiol benzoate. Confocal microscopy analysis indicated that nearly half of the KP-IR neurons in the AVPV show somatic or dendritic appositions from VP-IR varicosities lacking galanin-immunoreactivity; at the ultra-structural level, type II symmetric synapses were observed. KP-IR terminals were seen on GnRH perikarya and dendrites; these were not labelled for Neurokinin-B, markers of the KP fibers with arcuate nucleus origin. At the ultrastructural level KP-GnRH contacts displayed type I asymmetric synapses. The present results provide confocal and ultra-structural evidence which is consistent with the hypothesis that KP-IR neurons in the AVPV act as intermediaries between VP neurons in the SCN and GnRH neurons. Conference: 12th Meeting of the Hungarian Neuroscience Society, Budapest, Hungary, 22 Jan - 24 Jan, 2009. Presentation Type: Poster Presentation Topic: Homeostatic regulatory mechanisms Citation: Kalló I, Vida B, Deli L, Kalamatianos T, Hrabovszky E, Caraty A, Liposits Z and Clive CW (2009). Evidence that kisspeptin neurons in the AVPV form part of a bisynaptic pathway connecting suprachiasmatic vasopressin neurons with preoptic GnRH cells. Front. Syst. Neurosci. Conference Abstract: 12th Meeting of the Hungarian Neuroscience Society. doi: 10.3389/conf.neuro.01.2009.04.014 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 25 Feb 2009; Published Online: 25 Feb 2009. * Correspondence: Imre Kalló, Institute of Experimental Medicine, Budapest, Hungary, kallo@koki.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Imre Kalló Barbara Vida Levente Deli Theodosis Kalamatianos Erik Hrabovszky Alain Caraty Zsolt Liposits Coen W Clive Google Imre Kalló Barbara Vida Levente Deli Theodosis Kalamatianos Erik Hrabovszky Alain Caraty Zsolt Liposits Coen W Clive Google Scholar Imre Kalló Barbara Vida Levente Deli Theodosis Kalamatianos Erik Hrabovszky Alain Caraty Zsolt Liposits Coen W Clive PubMed Imre Kalló Barbara Vida Levente Deli Theodosis Kalamatianos Erik Hrabovszky Alain Caraty Zsolt Liposits Coen W Clive Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Direct innervation of GnRH neurons by encephalic photoreceptors in birds.

In nonmammalian vertebrates, photic cues that regulate the timing of seasonal reproductive cyclicity are detected by nonretinal, nonpineal deep brain photoreceptors. It has long been assumed that the underlying mechanism involves the transmission of photic information from the photoreceptor to a circadian system, and thence to the reproductive axis. An alternative hypothesis is that there is direct communication between the brain photoreceptor and the reproductive axis. In the present study, light and confocal microscopy reveal that gonadotropin releasing hormone (GnRH) neurons and processes are scattered among photoreceptor cells (identified by their opsin-immunoreactivity) in the lateral septum (SL). In the median eminence (ME), opsin and GnRH immunoreactive fibers overlap extensively. Single and double label ultrastructural immunocytochemistry indicate that in the SL and preoptic area (POA), opsin positive terminals form axo-dendritic synapses onto GnRH dendrites. In the ME, opsin and GnRH terminals lie adjacent to each other, make contact with tanycytes, or terminate on the hypophyseal portal capillaries. These results reveal thatbrain photoreceptors communicate directly with GnRH-neurons; this represents a means by which photoperiodic information reaches the reproductive axis.

Interactions between Vasopressin- and Gonadotropin-Releasing-Hormone-Containing Neuroendocrine Neurons in the Monkey Supraoptic Nucleus

Vasopressin (VP) is a hypophysiotropic hormone which is also implicated in the control of gonadotropin-releasing hormone (GnRH) secretion. We examined whether VP- and GnRH-immunoreactive (-IR) elements interact directly in the supraoptic nucleus (SON) of cynomolgus monkeys. Neuroendocrine (NEU) neurons in 4 juveniles were retrogradely labeled from the median eminence with wheat germ agglutinin apohorseradish peroxidase conjugated to gold before aldehyde perfusion. Frontal vibratome sections were immunostained for GnRH with peroxidase-antiperoxidase (PAP) and for VP with 5- or 15-nm gold. Many of the GnRH-IR and more than half the VP-IR cell bodies in the SON were NEU. VP-IR elements formed axodendritic and axosomatic symmetrical synapses with one another. In addition, VP-IR boutons also synapsed with NEU GnRH-IR neurons. Although GnRH axon terminals and dendrites contacted VP-IR dendrites and NEU cell bodies, we were unable to find convincing examples of GnRH/VP synapses through serial sections, perhaps due to the use of PAP-diaminobenzidine as the GnRH (afferent) immunolabel. In summary, our study demonstrates anatomical synapses between VP-IR and other VP and GnRH-IR neurons in the SON, in which postsynaptic VP or GnRH cell bodies were NEU. On the other hand, reciprocal GnRH/VP contacts but no true synapses were seen. However, the results suggest coordinated roles for VP and GnRH in NEU control of gonadotropin secretion. Whether VP itself and/or coexistent neuroeffectors act directly on NEU GnRH secretion remains to be determined. As such, VP neurons could help coordinate suppression of gonadotropins and augmentation of glucocorticoids during the stress response in primates.

Beta-Endorphin and gonadotropin-releasing hormone synaptic input to gonadotropin-releasing hormone neurosecretory cells in the male rat.

Physiological and pharmacological evidence has suggested that both endogenous opiates and gonadotropin-releasing hormone (GnRH) itself can act centrally to exert a tonic inhibition on gonadotropin secretion via an inhibition of the neurosecretion of GnRH. To determine if the effects of these two peptides might be mediated via a direct synaptic input to the GnRH neuron, we undertook a double label ultrastructural study. We were able to localize in the same tissue section beta-endorphin and GnRH. Analysis of serial sections through GnRH perikarya and dendrites in the male rat diagonal band/preoptic area revealed that almost 10% of the synapses impinging on the GnRH neuron contained beta-endorphin; an additional 10% of the terminals contained GnRH. These data provide anatomical evidence in support of both a direct modulation of GnRH release by opiates and of the presence of an ultrashort feedback loop.

Quantitative analysis of synaptic input to gonadotropin-releasing hormone neurons in normal mice and hpg mice with preoptic area grafts

Mutant hypogonadal ( hpg) mice with a truncated gene for the precursor to gonadotropin-releasing hormone (GnRH) show certain aspects of recovery of reproductive function after receiving grafts of normal preoptic area into the third ventricle. We have previously shown that GnRH neurons from within the grafts can innervate the appropriate neural-hemal target in the host. To determine if in turn these exogenously derived neurons receive a synaptic input comparable to the GnRH neurons in the normal aminal we ahve now carried out a quantitative ultrastructural analysis to compare the synaptic input to GnRH neurons in the normal preoptic area and in the grafts. In almost all cases GnRH cells or dendrites in normal brains and within the grafts received a synaptic input. In normal animals, input to GnRH dendritic profiles was significantly greater ( P < 0.001) than to the somatic plasma membrane and this trend was also observed within the grafts though the difference was not statistically significant. In addition, no statistically significant difference was found between the input to GnRH structures within the grafts and in normal preoptic area. However, a substantial variability in input among grafted animals was evident which was not observed in normal animals. The sources of variability within the grafts are discussed and we suggest that the deficiencies and differences that exist in regulation of gonadotropin secretion among grafted hpg animals may be reflected in aberrant synaptic input.