Abstract
We showed recently (JCI, 1992, in press) that, in hypothalamic explants of prepubertal male rats (15-day-old), NMDA receptors mediated a potent inhibitory control of GnRH secretion which was no longer observable at the onset (25 days) and by the end (50 days) of puberty. Sara et al (BBRC, 1989, 151:207) suggested that GPE, the N-terminal tripeptide of IGF-I, could play a role as competitive antagonist at NMDA receptors. Using explants obtained at 15, 25 and 50 days, we studied GnRH secretion induced by 5. 10−4 M of veratridine, a depolarizing agent. This study was repeated in the absence or in the presence of increasing concentrations of IGF-I, GPE or des(1-3)IGF-I, a bioactive form of IGF-I resulting from clivage of GPE. At none of 3 studied ages, des(1-3)IGF-I showed any effect on GnRH secretion. At 25 and 50 days, IGF-I resulted in a dose-related inhibition of GnRH secretion (50 % inhibitory concentrations, IC50 : 8.10−10 and 2.10−13 M, respectively). A similar inhibition was observed using GPE (IC50 : 4.10−9 and 3.10−13 M). At 15 days, IGF-I did not result in any effect on GnRH secretion whereas GPE showed potent inhibitory action (IC50 : 1.10−13 M). At the 3 studied ages. GPE effects paralleled those of AP-5, a competitive antagonist at NMDA receptors. These data indicate that the hypothalamus is capable of degrading IGF-I into a subproduct which is a potent endogenous antagonist at NMDA receptors involved in GnRH secretion. This effect results from a developmental process in the hypothalamus since it is not observed in the immature rat. At onset of puberty, the endogenous IGF-I-derived antagonist at NMDA receptors could be involved in the disappearance of the inhibitory control of GnRH secretion. Supported by grants from FRSM (3.4574.87), Faculty of Medicine ULg and Kabi Pharmacia.
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Bourguignon, J., Gérard, A., Alvarez Gonzalez, M. et al. INHIBITION OF GnRH SECRETION BY IGF-I DEGRADATION INTO A SUB-PRODUCT ANTAGONIST ATNMDA RECEPTORS: AN EFFECT DEVELOPING AFTER ONSET OF PUBERTY. Pediatr Res 33 (Suppl 5), S29 (1993). https://doi.org/10.1203/00006450-199305001-00154
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DOI: https://doi.org/10.1203/00006450-199305001-00154