The ovary of humans and nonhuman primates is innervated by sympathetic and sensory neurons of the peripheral nervous system. Recent studies demonstrated that the density of the sympathetic innervation to the rhesus monkey ovary is developmentally regulated, with adult density being attained around the time of puberty. In the present study, we used an immunocytochemical approach to obtain insights into the cell-cell signaling mechanisms that may contribute to the functional maintenance of this innervation. Because sympathetic neurons of the peripheral nervous system require target-derived neurotropins for their survival and function, experiments were conducted to determine if one of the receptors recognized by neurotropins is expressed in fibers innervating the primate ovary. A monoclonal antibody to the human low-affinity nerve growth factor (NGF) receptor, termed p75 NGFR because of its molecular weight, demonstrated the presence of this receptor in nerve fibers innervating the ovarian vasculature, interstitial tissue, and developing follicles of the gland. In addition, as shown in rodents, p75 NGFR immunoreactivity was detected in nonneuronal, endocrine cells of the ovary, specifically the thecal cell layer of developing follicles. Unexpectedly, however, the monkey ovary was also found to contain a network of small p75 NGFR immunoreactive cells distributed throughout the ovarian medulla and cortex. These cells, identified as such by confocal microscopy, had a neural-like appearance and displayed both neurofilament and neuron-specific enolase immunoreactivity. They appeared to be densely interconnected and were seen innervating the ovarian vasculature, the thecal cell layer of follicles, and, occasionally, primordial follicles. Double immunohistochemical procedures demonstrated that a subpopulation of these intraovarian, p75 NGFR-bearing neuron-like cells are catecholaminergic, as determined by their immunoreactivity to antibodies to tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis. RNA blot hybridization revealed the presence of p75 NGFR messenger RNA in the monkey ovary, thus demonstrating the ability of the gland to synthesize the receptors. These results demonstrate that the primate ovary contains an intrinsic network of neuron-like cells. Because such a neuronal network has not been detected in rodents or other non-primate species, it would appear that its presence in the primate ovary may have evolutionary significance.

This study utilized a newly developed antiserum, specific for lamprey gonadotropin-releasing hormone III (l-GnRH-III), to determine the following: in which regions of the rat hypothalamus the neuronal perikarya producing l-GnRH-III are localized; and whether this peptide, known to selectively induce follicle-stimulating hormone release, is coexpressed in neurons containing mammalian luteinizing hormone-releasing hormone (m-LHRH). Double-label immunocytochemistry was performed by using an l-GnRH-III polyclonal antiserum and an LHRH monoclonal antiserum. Immunopositive neurons for l-GnRH-III, m-LHRH, or neurons coexpressing both peptides were detected within the organum vasculosum lamina terminalis (OVLT) region of the preoptic area (POA). Caudal to the OVLT, l-GnRH-III-positive neurons were also observed dorso-medially, above the third ventricle in the medial POA. The m-LHRH neurons were not observed in this area. The lateral POA region contained neurons positive for both peptides along with single-labeled neurons for each peptide. Importantly, neurons that expressed l-GnRH-III, m-LHRH, or both peptides were also detected in the ventral regions of the rostral hypothalamus, dorsolateral to the borders of the supraoptic nuclei. In both of these latter areas, neurons containing l-GnRH-III were slightly dorsal to neurons containing only m-LHRH. The l-GnRH-III perikarya and fibers were eliminated by absorption of the primary antiserum with l-GnRH-III, but not by l-GnRH-I, chicken-GnRH-II, or m-LHRH. These results indicate that, unlike other isoforms of GnRH found in the mammalian brain, l-GnRH-III neurons not only are observed in regions that control follicle-stimulating hormone release but also are colocalized with m-LHRH neurons in areas primarily controlling LH release. These findings suggest an interrelationship between these two peptides in the control of gonadotropin secretion.

Objective: Activation of the epidermal growth factor receptor (EGF-R) stimulates prepubertal luteinizing hormone-releasing hormone (LHRH) release, which in turn induces luteinizing hormone (LH) secretion. Although ethanol (ETOH) diminishes LHRH secretion and delays the onset of female puberty, its actions following EGF-R activation are unknown. We therefore investigated the effects of ETOH on EGF-induced LHRH and LH release, both in vivo and in vitro. Method: Basal blood samples were taken every 15 minutes from immature female rats, which then received ETOH (3 g/kg) or saline by gastric gavage. After a 90-minute ETOH absorption period, a single blood sample was drawn from each rat. Finally, EGF (200 ng/3 microl) was injected into the third ventricle of all animals and postinjection samples were drawn every 15 minutes. A similar experimental design was performed except no blood samples were taken. After ETOH exposure, EGF was administered, and 45 minutes later the animals were killed and their medial basal...

Mammalian puberty requires complex interactions between glial and neuronal regulatory systems within the hypothalamus that results in the timely increase in the secretion of luteinizing hormone releasing hormone (LHRH). Assessing the molecules required for the development of coordinated communication networks between glia and LHRH neuron terminals in the basal hypothalamus, as well as identifying substances capable of affecting cell-cell communication are important. One such pathway involves growth factors of the epidermal growth factor (EGF) family that bind to specific erbB receptors. Activation of this receptor results in the release of prostaglandin-E₂ (PGE₂) from adjacent glial cells, which then acts on the nearby LHRH nerve terminals to elicit release of the peptide. Another pathway involves novel genes which synthesize adhesion/signaling proteins responsible for the structural integrity of bi-directional glial-neuronal communication. In this review, we will discuss the influence of these glial-neuronal communication pathways on the prepubertal LHRH secretory system, and furthermore, discuss the actions and interactions of alcohol on these two signaling processes.