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 stimulated by their antagonist naloxone. LH secretion is stimulated by alpha-MSH, a tridecapeptide derived from the post-translational processing of POMC. The possibility that alpha-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 i.v. bolus, followed by infusion of 1.6 mg/h for 120'); alpha-MSH (2.5 mg i.v. bolus); naloxone + alpha-MSH (2.5 mg i.v. 15' after commencement of the naloxone infusion); naloxone + GnRH (100 micrograms i.v. 15' after commencement of the naloxone infusion); alpha-MSH + GnRH (respectively 2.5 mg and 100 micrograms at time 0), GnRH alone (100 micrograms at time 0), placebo (150 nmol/l NaCl solution). The LH AUCs during both naloxone (30.3 +/- 2.7 mIU/ml.min-1) and alpha-MSH test (32.9 +/- 4.6 mIU/ml.min-1) were significantly greater (p < 0.005) than that observed during placebo (16.9 +/- 3.6 mIU/ml.min-1). The LH AUC during alpha-MSH + naloxone (37.6 +/- 2.6 mIU/ml.min-1) was not significantly different from that recorded 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 other tests (AUCs: GnRH 89.4 +/- 10.6, GnRH + naloxone 100.5 +/- 9.1, GnRH + alpha-MSH 94.6 +/- 7.9 mIU/ml.min-1, 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; alpha-MSH 15.5 +/- 2.3; alpha-MSH + naloxone 16.9 +/- 1.9; GnRH 19.1 +/- 1.1; GnRH + alpha-MSH 20.7 +/- 1.3; GnRH + naloxone 21.2 +/- 1.8 mIU/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 with opposing effects on a final common pathway.
Limone
P
P
Department of Internal Medicine, Regina Margherita Hospital, Torino, Italy.
Calvelli
P
P
Altare
F
F
Ajmone-Catt
P
P
Lima
T
T
Molinatti
G M
GM
D000328:Adult; D004347:Drug Interactions; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology; D006062:Gonadotropins / Q000378:metabolism*; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007986:Luteinizing Hormone / Q000097:blood / Q000187:drug effects; D008297:Male; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology*; D013739:Testosterone / Q000097:blood; D000521:alpha-MSH / Q000008:administration & dosage / Q000187:drug effects / Q000494:pharmacology*
D006062:Gonadotropins; D007987:Gonadotropin-Releasing Hormone; D009270:Naloxone; D013739:Testosterone; D000521:alpha-MSH; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone