Using rat hypothalamic explants, we showed previously that activation of N-methyl-D-aspartate (NMDA) receptors was involved in the mechanism of gonadotropin-releasing hormone (GnRH) secretion. (1–3)Insulin-like growth factor I (IGF-I), the N-terminal tripeptide of IGF-I, was suggested to be a possible antagonist at NMDA receptors. Here, we study the effects of IGF-I and its subproducts, (1–3)IGF-I and (4-70)IGF-I, either given in vivo as a single subcutaneous injection or used in vitro, on the secretion of GnRH by hypothalamic explants. At the three ages studied (15, 25 and 50 days), (4–70)IGF-I does not show any effect. At 50 days, the in vivo administration or the in vitro use of IGF-I results in a dose-related inhibition of the GnRH secretion induced by veratridine, a depolarizing agent. In addition, the spontaneous pulsatile secretion of GnRH in vitro is transiently suppressed after the in vivo administration of IGF-I. (1–3)IGF-I results in an inhibitory effect similar to that of IGF-I. At 25 days, IGF-I and (1-3)IGF-I show the same effects as at 50 days though higher concentrations are required. At 15 days, IGF-I does not show any effect whereas a potent inhibition of GnRH secretion is observed using (1–3)IGF-I either in vivo or in vitro. At all ages, the effects of (1–3)IGF-I parallel those of AP-5, a competitive antagonist at NMDA receptors. We conclude that the acute systemic administration of IGF-I results in a suppression of GnRH secretion, presumably through a competitive antagonism at NMDA receptors by (1–3)IGF-I resulting from IGF-I degradation, a process developing between 15 and 25 days of age.

Keywords:
Insulin-like growth factor I, Gonadotropin-releasing hormone, N-methyl-D-aspartate, Puberty, Ontogeny
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© 1993 S. Karger AG, Basel
1993
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