EVIDENCE FOR AN INTERACTION BETWEEN ALPHA-MSH AND OPIOIDS IN THE REGULATION OF GONADOTROPIN-SECRETION IN MAN

Gonadotropin secretion is inhibited by the endogenous opioids and stim ulated by their antagonist naloxone. LH secretion is stimulated by alp ha-MSH, a tridecapeptide derived from the post-translational processin g of POMC, The possibility that alpha-MSH interacts with the opioids, as suggested by the experimental evidence, was investigated in 7 norma l males aged 24-29 through the performance of seven tests: naloxone (0 .8 mg iv bolus, followed by infusion of 1.6 mg/h for 120'); alpha-MSH (2.5 mg iv bolus); naloxone+alpha-MSH (2.5 mg i.v. 15' after commencem ent of the naloxone infusion), naloxone+GnRH (100 mu g iv 15' after co mmencement of the naloxone infusion); alpha-MSH+GnRH (respectively 2.5 mg and 100 mu g at time 0), GnRH alone (100 mu g at time 0), placebo (150 nmol/l NaCl solution). The LH AUCs during both naloxone (30.3+/-2 .7 mlU/ml.min(-1)) and alpha-MSH test (32.9+/-4.6 mlU/ml.min(-1)) were significantly greater (p < 0.005) than that observed during placebo ( 16.9+/-3.6 mlU/ml.min(-1)). The LH AUC during alpha-MSH+naloxone (37.6 +/-2.6 mlU/ml.min(-1)) was not significantly different from that recor ded during their separate administration. GnRH injected alone, during the naloxone infusion and with alpha-MSH produced similar increases in LH, that were significantly higher than that observed during the othe r tests (AUCs: GnRH 89.4+/-10.6, GnRH+naloxone 100.5+/-9.1, GnRH+alpha -MSH 94.6+/-7.9 mlU/ml.min(-1), p < 0.001). Significant increase in FS H (p < 0.001) was only observed during GnRH, GnRH+naloxone and GnRH+aM SH tests (AUCs: placebo 13.3+/-1.7; naloxone 14.7+/-12.5; alpha-MSH 15 .5+/-2.3; alpha-MSH+naloxone 16.9+/-1.9; GnRH 19.1+/-1.1; GnRH+alpha-M SH 20.7+/-1.3; GnRH+naloxone 21.2+/-1.8 mlU/ml.min(-1)). These results are in line with the possibility of an interaction between alpha-MSH and the opioids in the regulation of gonadotropin secretion, perhaps w ith opposing effects on a final common pathway. (C) 1997, Editrice Kur tis.