Acute Suppression of Gonadotropin-Releasing Hormone Secretion by Insulin-Like Growth Factor I and Subproducts: An Age-Dependent Endocrine Effect

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.(ABSTRACT TRUNCATED AT 250 WORDS)