Evidence for an interaction between α-MSH and opioids in the regulation of gonadotropin secretion in man

Abstract

Gonadotropin secretion is inhibited by the endogenous opioids and stimulated by their antagonist naloxone. LH secretion is stimulated by α-MSH, a tridecapeptide derived from the post-translational processing of POMC. The possibility that α-MSH interacts with the opioids, as suggested by the experimental evidence, was investigated in 7 normal 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′); α-MSH (2.5 mg iv bolus); naloxone+α-MSH (2.5 mg i.v. 15′ after commencement of the naloxone infusion); naloxone+GnRH (100 µg iv 15′ after commencement of the naloxone infusion); α-MSH+GnRH (respectively 2.5 mg and 100 µg at time 0), GnRH alone (100 µg at time 0), placebo (150 nmol/l NaCl solution). The LH AUCs during both naloxone (30.3±2.7 mlU/ml.min⁻¹) and α-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 α-MSH+naloxone (37.6±2.6 mlU/ml.min⁻¹) was not significantly different from that recorded during their separate administration. GnRH injected alone, during the naloxone infusion and with α-MSH produced similar increases in LH, that were significantly higher than that observed during the other tests (AUCs: GnRH 89.4±10.6, GnRH+naloxone 100.5±9.1, GnRH+α-MSH 94.6±7.9 mlU/ml.min¹, p<0.001). Significant increase in FSH (p<0.001) was only observed during GnRH, GnRH+naloxone and GnRH+aMSH tests (AUCs: placebo 13.3±1.7; naloxone 14.7±2.5; α-MSH 15.5±2.3; α-MSH+naloxone 16.9+1.9; GnRH 19.1 ±1.1; GnRH+α-MSH 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 α-MSH and the opioids in the regulation of gonadotropin secretion, perhaps with opposing effects on a final common pathway.