Direct Activation of Gonadotropin-Releasing Hormone Secretion Through Different Receptors to Neuroexcitatory Amino Acids

Abstract

In order to evaluate the involvement of gonadotropin-releasing hormone (GnRH) in the effects of neuroexcitatory amino acids on luteinizing hormone (LH) secretion, N-methyl-D,L-aspartate (NMDA; 30 mg/kg s.c.) was administered to 50-day-old male rats. The in vitro release of GnRH from the hypothalamus showed a maximal increase (4.6-fold) in animals sacrificed 7.5 min after NMDA injection, while serum LH levels rose concomitantly. Incubation of rat hypothalami in vitro with kainate or NMDA concentrations > 0.1 mM resulted in a dose-related release of GnRH, NMDA being twofold more potent than kainate. Quisqualate (10 mM) did not affect the release of GnRH. On a molar basis, quinolinate (50 mM), a possible endogenous ligand for NMDA receptors, was the most effective in inducing GhRH secretion (34.9 ± 4.9 pg/7.5 min, mean increment ± SEM, n= 10). The effects of kainate and NMDA were mediated through different types of receptors, since GnRH response to kainate was unchanged in the absence of glycine or in the presence of increased concentrations of Mg²⁺ (2 mM) or Ca²⁺ (5.8 mM). In contrast, the GnRH response to NMDA was reduced by Ca²⁺ (5.8 mM) and abolished in the absence of glycine or in the presence of Mg²⁺ (2 mM). In addition, DL-amino-5-phosphonopentanoic acid (AP5), a competitive antagonist of NMDA receptors, prevented the NMDA-induced release of GnRH. The permissive effect of glycine on GnRH response to NMDA was 2.7-fold more important using glycine concentrations of 0.01 µM than when concentrations >100 µM were used. Intermittent incubation with NMDA in vitro (every other 7.5-min period) did not affect the amplitude of GnRH response, while continuous exposure to NMDA resulted in an initial and transient increase in GnRH release followed by a prolonged desensitization period. It is concluded that different neuroexcitatory amino acids acting through distinct receptor types may be involved in the hypothalamic control of LH release by regulating the secretion of GnRH.

Maternal exposure to dioxin reduces hypothalamic but not pituitary metabolome in fetal rats: a possible mechanism for a fetus-specific reduction in steroidogenesis

“…This demonstration is based on the observation that perinatal exposure to TCDD either reduces the hypothalamic expression of glutamic acid decarboxylase (GAD), or alters the sex-difference in its expression in rats (Hays et al, 2002). GnRH release also needs the stimulation of neurons by glycine, aspartic acid and N-methylaspartic acid (Bourguignon et al, 1989). The present study detected a TCDD-produced reduction of the former two amino acids in the fetal hypothalamus (Table 2).…”

Release of chicken luteinising hormone-releasing hormone-I (cLHRH-I) by mediobasal hypothalamus in the cockerel: validation of an incubation system and effect of excitatory amino acids

“…Moreover, the necessity of the presence of calcium ions in the incubation medium for a response to occur showed that this release answers to the physiological mechanisms of neural secretion (Smith and Augustine, 1988 (Gay and Plant, 1987;Ondo et al, 1988) and agonists to stimulate the release of LHRH by hypothalamic tissue of rats in vitro (Bourguignon et al, 1989;Lopez et al, 1992 (1989) that NMDA is more potent than KA in eliciting the release of GnRH by incubated hypothalimi in the rat. However, the specificity of these effects in the chicken has to be further documented by the use of antagonists.…”

Influence of Neuropeptide – Glutamic Acid-Isoleucine (NEI) on LH Regulation

“…This may represent one of the mechanisms by which intracerebroventricular administration of NEI causes an increase in LH secretion (Fig. 6 E) Experiments using in vitro preparations or intracerebroventricular injections have shown that various neurotransmitters can regulate gonadotropin release [38][39][40]. One such neurotransmitters is the cocaine-and amphetamine-regulated transcript (CART) peptide, which has been shown to increase the GnRH pulse amplitude in cycling female rats and to decrease GnRH pulse intervals in prepubertal rats [41][42][43].…”

“…One such neurotransmitters is the cocaine-and amphetamine-regulated transcript (CART) peptide, which has been shown to increase the GnRH pulse amplitude in cycling female rats and to decrease GnRH pulse intervals in prepubertal rats [41][42][43]. These effects can be achieved through direct CART innervation of the GnRH neurons [39,40]. Interestingly, in the medial ZI and lateral hypothalamus, MCH/NEI neurons coexpress CART [44,46].…”