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)
Bourguignon
J P
JP
Department of Pediatrics, University of Liège, CHU Sart Tilman, Belgium.
Gérard
A
A
Alvarez Gonzalez
M L
ML
Franchimont
P
P
D000375:Aging / Q000378:metabolism*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004702:Endocrine Glands / Q000187:drug effects / Q000254:growth & development*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014701:Veratridine / Q000494:pharmacology
D007987:Gonadotropin-Releasing Hormone; D007334:Insulin-Like Growth Factor I; D014701:Veratridine