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Factors Accounting for Perinatal Occurrence of Pulsatile Gonadotropin-Releasing Hormone Secretion In Vitro in Rats¹

Developmental Neuroendocrinology Unit, Research Center of Cellular and Molecular Neurosciences (CNCM), University of Liege, 4000 Liege, Belgium

Our aim was to study the inhibitory and facilitatory factors possibly accounting for the undetectable activity of the GnRH pulse generator in late fetal life in vitro and its awakening in early postnatal life. Gamma aminobutyric acid (GABA_A) receptor antagonism using SR 95 531 did not cause any secretory pulse in fetal explants, whereas a significant stimulation of GnRH pulse frequency was obtained at 5 and 15 days. GnRH secretory response to repeated N-methyl-D-aspartate (NMDA) stimulation showed progressive disappearance, indicating that the inhibitory autofeedback was operating. GnRH release caused by glutamine was respectively 9% and 20% of that evoked by glutamate in fetal and 5-day-old rats whereas both amino acids were equally active at 15 days. Explants obtained after cesarean section performed at onset of labor did not show any secretory pulse, while pulses could be observed with explants obtained 2 h after vaginal delivery. Incubation of fetal explants with oxytocin (10^–8 M) or prostaglandin E₂ (PGE₂) (10^–6 M) resulted in occurrence of GnRH secretory pulses. A facilitatory effect of the oxytocin was shown to persist on Days 1, 5, and 15 and inhibitory effects of an oxytocin receptor antagonist provided some evidence of endogenous oxytocin involvement. We conclude that, in the fetal rat hypothalamus, GnRH inhibitory autofeedback and GABAergic inputs do not account for the absence of pulsatile GnRH secretion in vitro. A low rate of glutamate biosynthesis from glutamine is a possibly limiting factor. Oxytocin and PGE₂ can play a facilitatory role in the postpartal occurrence of pulsatile GnRH secretion.

¹ Supported by the FRSM (grant 3.4515.01), the Belgian Study Group for Pediatric Endocrinology, and the Faculty of Medicine at the University of Liege. A.S.P. is a research fellow of the Belgian "Fonds National de la Recherche Scientifique" (FNRS).

² Correspondence: Jean-Pierre Bourguignon, Division of Paediatric and Adolescent Medicine, CHU Sart Tilman, B-4000 Liege, Belgium. FAX: 00 324 366 7246; jpbourguignon{at}ulg.ac.be

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