Endocrinology, Vol 127, 873-881, Copyright © 1990 by Endocrine Society

ARTICLES

Maturation of the hypothalamic control of pulsatile gonadotropin- releasing hormone secretion at onset of puberty. I. Increased activation of N-methyl-D-aspartate receptors

JP Bourguignon, A Gerard, J Mathieu, A Mathieu and P Franchimont
Department of Pediatrics, University of Liege, Belgium.

In the male rat the timing of puberty can be estimated by the rapid increase in testicular weight occurring between 25-50 days of age. We found that elongated spermatids, the most mature germ cells identified using flow cytometry, were first seen at 25 days (4% of the testicular cells), while an adult proportion (63%) was attained by 45 days of age. We have shown previously that hypothalamic explants could release GnRH in a pulsatile fashion at a frequency increasing around the age of 25 days, thus consistent with the time of onset of puberty. Since pulsatile GnRH secretion could be suppressed by MK-801, a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptor activation, we postulated that an increased activation of those receptors could be involved in the neuroendocrine mechanism that activates pulsatile GnRH secretion at the onset of puberty. Such a concept was supported by the NMDA-induced release of GnRH, which was observed using 1 mM NMDA at 25 days, while a dose of 20-50 mM was required at 15 or 50 days of age. MK-801 could provide an index of NMDA receptor activation, since the antagonistic effect of MK-801 is use dependent. This particular property was confirmed by the inability of MK-801 (5 pM) to block the depolarization (veratridine)-induced release of GnRH in the presence of 0.001 mM NMDA, while partial or complete suppression was obtained in the presence of 0.1 and 10 mM NMDA, respectively. Using explants obtained at 5, 10, 15, 20, 25, 30, 35, and 50 days of age, the lowest concentrations of MK-801 that blocked the veratridine-induced release of GnRH were, respectively, 10(7), 10(7), 10(7), 10(3), 10, 10(2), 10(4), and 10(8) pM. In contrast, there was no age-related difference in sensitivity to the inhibitory effect of Mg2+, a noncompetitive NMDA receptor antagonist which is not use dependent. The pulsatile secretion of GnRH occurred at a similar frequency at 25 and 50 days of age (4.7 and 5.4 pulses/3.5 h, respectively) but it was suppressed by a lower MK-801 concentration at 25 days (10(4) pM) than at 50 days (10(8) pM). These data indicate that the NMDA receptors involved in the control of pulsatile GnRH secretion are markedly and transiently activated around the time of onset of puberty in the male rat.

This article has been cited by other articles:

				A.-S. Parent, G. Rasier, V. Matagne, A. Lomniczi, M.-C. Lebrethon, A. Gerard, S. R. Ojeda, and J.-P. Bourguignon Oxytocin Facilitates Female Sexual Maturation through a Glia-to-Neuron Signaling Pathway Endocrinology, March 1, 2008; 149(3): 1358 - 1365. [Abstract] [Full Text] [PDF]

				G. Rasier, A.-S. Parent, A. Gerard, M.-C. Lebrethon, and J.-P. Bourguignon Early Maturation of Gonadotropin-Releasing Hormone Secretion and Sexual Precocity after Exposure of Infant Female Rats to Estradiol or Dichlorodiphenyltrichloroethane Biol Reprod, October 1, 2007; 77(4): 734 - 742. [Abstract] [Full Text] [PDF]

				B. M. Windsor-Engnell, E. Kasuya, M. Mizuno, K. L. Keen, and E. Terasawa An increase in in vivo release of LHRH and precocious puberty by posterior hypothalamic lesions in female rhesus monkeys (Macaca mulatta) Am J Physiol Endocrinol Metab, April 1, 2007; 292(4): E1000 - E1009. [Abstract] [Full Text] [PDF]

				E. Terasawa Postnatal remodeling of gonadotropin-releasing hormone I neurons: toward understanding the mechanism of the onset of puberty. Endocrinology, August 1, 2006; 147(8): 3650 - 3651. [Full Text] [PDF]

				E. C. Cottrell, R. E. Campbell, S.-K. Han, and A. E. Herbison Postnatal Remodeling of Dendritic Structure and Spine Density in Gonadotropin-Releasing Hormone Neurons Endocrinology, August 1, 2006; 147(8): 3652 - 3661. [Abstract] [Full Text] [PDF]

				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]

				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]

				G. A. Dissen, R. K. Dearth, H. M. Scott, S. R. Ojeda, and W. L. Dees Alcohol Alters Luteinizing Hormone Secretion in Immature Female Rhesus Monkeys by a Hypothalamic Action Endocrinology, October 1, 2004; 145(10): 4558 - 4564. [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]

				L. E. Claypool, E. Kasuya, Y. Saitoh, F. Marzban, and E. Terasawa N-Methyl D,L-Aspartate Induces the Release of Luteinizing Hormone-Releasing Hormone in the Prepubertal and Pubertal Female Rhesus Monkey as Measured by in Vivo Push-Pull Perfusion in the Stalk-Median Eminence Endocrinology, January 1, 2000; 141(1): 219 - 228. [Abstract] [Full Text] [PDF]

				C. Yamanaka, M. C. Lebrethon, E. Vandersmissen, A. Gerard, G. Purnelle, M. LeMaitre, S. Wilk, and J. P. Bourguignon Early Prepubertal Ontogeny of Pulsatile Gonadotropin-Releasing Hormone (GnRH) Secretion: I. Inhibitory Autofeedback Control through Prolyl Endopeptidase Degradation of GnRH Endocrinology, October 1, 1999; 140(10): 4609 - 4615. [Abstract] [Full Text]

				M. M. Adams, R. A. Flagg, and A. C. Gore Perinatal Changes in Hypothalamic N-Methyl-D-Aspartate Receptors and Their Relationship to Gonadotropin-Releasing Hormone Neurons Endocrinology, May 1, 1999; 140(5): 2288 - 2296. [Abstract] [Full Text]

				L. Z. Krsmanovic, A. J. Martinez-Fuentes, K. K. Arora, N. Mores, C. E. Navarro, H.-C. Chen, S. S. Stojilkovic, and K. J. Catt Autocrine Regulation of Gonadotropin-Releasing Hormone Secretion in Cultured Hypothalamic Neurons Endocrinology, March 1, 1999; 140(3): 1423 - 1431. [Abstract] [Full Text]

				J.-P. Bourguignon, J. Jaeken, A. Gerard, and F. de Zegher Amino Acid Neurotransmission and Initiation of Puberty: Evidence from Nonketotic Hyperglycinemia in a Female Infant and Gonadotropin-Releasing Hormone Secretion by Rat Hypothalamic Explants J. Clin. Endocrinol. Metab., June 1, 1997; 82(6): 1899 - 1903. [Abstract] [Full Text] [PDF]