Endocrinology, Vol 136, 911-916, Copyright © 1995 by Endocrine Society

ARTICLES

Endogenous glutamate involvement in pulsatile secretion of gonadotropin- releasing hormone: evidence from effect of glutamine and developmental changes

JP Bourguignon, A Gerard, ML Alvarez Gonzalez, G Purnelle and P Franchimont
Department of Pediatrics, University of Liege, CHU Sart Tilman, Belgium.

The secretion of GnRH can be stimulated by glutamate (GLU) and GLU agonists, whereas GLU receptor antagonists inhibit GnRH. Using 6-diazo- 5-oxo-L-norleucine (DON), an inhibitor of glutaminase, we aimed to study the involvement of endogenous GLU in GnRH secretion through the effects of impaired GLU biosynthesis from its precursor glutamine (GLN). GnRH secretion by hypothalamic explants of male rats, aged 15 and 50 days, was compared, because the frequency of spontaneous GnRH secretory pulses showed a 2-fold increase between those two ages. Using explants of 50-day-old rats, GLN elicited GnRH secretion in a similar dose-related manner as GLU. DON prevented GLN-evoked secretion of GnRH, whereas the effect of GLU was not altered. DON also markedly inhibited spontaneous pulsatile secretion of GnRH and the secretory response to veratridine, a Na+ channel opener. The inhibitory effect of DON on veratridine-evoked secretion of GnRH was directly related to the duration of exposure to DON and the frequency of GnRH secretory episodes. Using explants of 15-day-old rats, GLN could elicit GnRH release, although this response was lower than GLU-evoked secretion of GnRH. The DON concentrations required for inhibition of veratridine- evoked secretion of GnRH were lower at 15 days than at 50 days. These data indicate that 1) GLU biosynthesis from GLN is a prerequisite to the physiological mechanism of pulsatile GnRH secretion; and 2) inhibition of veratridine- or GLN-induced secretion of GnRH requires higher DON concentrations after the onset of puberty than before. This suggests that glutaminase, the enzyme controlling GLU biosynthesis from GLN, shows increased activity after the onset of puberty when the frequency of pulsatile GnRH secretion is increased as well.

This article has been cited by other articles:

				M. El-Etr, Y. Akwa, E.-E. Baulieu, and M. Schumacher The Neuroactive Steroid Pregnenolone Sulfate Stimulates the Release of Gonadotropin-Releasing Hormone from GT1-7 Hypothalamic Neurons, through N-Methyl-D-Aspartate Receptors Endocrinology, June 1, 2006; 147(6): 2737 - 2743. [Abstract] [Full Text] [PDF]

				J. Masson, M. Darmon, A. Conjard, N. Chuhma, N. Ropert, M. Thoby-Brisson, A. S. Foutz, S. Parrot, G. M. Miller, R. Jorisch, et al. Mice lacking brain/kidney phosphate-activated glutaminase have impaired glutamatergic synaptic transmission, altered breathing, disorganized goal-directed behavior and die shortly after birth. J. Neurosci., April 26, 2006; 26(17): 4660 - 4671. [Abstract] [Full Text] [PDF]

				S. S. Daftary and A. C. Gore IGF-1 in the Brain as a Regulator of Reproductive Neuroendocrine Function Experimental Biology and Medicine, May 1, 2005; 230(5): 292 - 306. [Abstract] [Full Text] [PDF]

				A.-S. Parent, M.-C. Lebrethon, A. Gerard, and J.-P. Bourguignon Factors Accounting for Perinatal Occurrence of Pulsatile Gonadotropin-Releasing Hormone Secretion In Vitro in Rats Biol Reprod, January 1, 2005; 72(1): 143 - 149. [Abstract] [Full Text] [PDF]

				V. Matagne, G. Rasier, M.-C. Lebrethon, A. Gerard, and J.-P. Bourguignon Estradiol Stimulation of Pulsatile Gonadotropin-Releasing Hormone Secretion in Vitro: Correlation with Perinatal Exposure to Sex Steroids and Induction of Sexual Precocity in Vivo Endocrinology, June 1, 2004; 145(6): 2775 - 2783. [Abstract] [Full Text] [PDF]

				E. Terasawa and D. L. Fernandez Neurobiological Mechanisms of the Onset of Puberty in Primates Endocr. Rev., February 1, 2001; 22(1): 111 - 151. [Abstract] [Full Text]

				K. J. Suter, C. R. Pohl, and M. E. Wilson Circulating Concentrations of Nocturnal Leptin, Growth Hormone, and Insulin-Like Growth Factor-I Increase before the Onset of Puberty in Agonadal Male Monkeys: Potential Signals for the Initiation of Puberty J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 808 - 814. [Abstract] [Full Text]

				K. L. Keen, A. J. Burich, D. Mitsushima, E. Kasuya, and E. Terasawa Effects of Pulsatile Infusion of the GABAA Receptor Blocker Bicuculline on the Onset of Puberty in Female Rhesus Monkeys Endocrinology, November 1, 1999; 140(11): 5257 - 5266. [Abstract] [Full Text]

				E. Kasuya, C. L. Nyberg, K. Mogi, and E. Terasawa A Role of {gamma}-Amino Butyric Acid (GABA) and Glutamate in Control of Puberty in Female Rhesus Monkeys: Effect of an Antisense Oligodeoxynucleotide for GAD67 Messenger Ribonucleic Acid and MK801 on Luteinizing Hormone-Releasing Hormone Release Endocrinology, February 1, 1999; 140(2): 705 - 712. [Abstract] [Full Text]

				L. Z. Krsmanovic, N. Mores, C. E. Navarro, S. A. Saeed, K. K. Arora, and K. J. Catt Muscarinic Regulation of Intracellular Signaling and Neurosecretion in Gonadotropin-Releasing Hormone Neurons Endocrinology, October 1, 1998; 139(10): 4037 - 4043. [Abstract] [Full Text] [PDF]

				D. Vernet, J. J. Bonavera, R. S. Swerdloff, N. F. Gonzalez-Cadavid, and C. Wang Spontaneous Expression of Inducible Nitric Oxide Synthase in the Hypothalamus and Other Brain Regions of Aging Rats Endocrinology, July 1, 1998; 139(7): 3254 - 3261. [Abstract] [Full Text] [PDF]