title: Evidence for an interaction between alpha-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 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.
authors.affiliation: Department of Internal Medicine, Regina Margherita Hospital, Torino, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Limone
authors.forename: P
authors.initials: P
authors.lastname: Calvelli
authors.forename: F
authors.initials: F
authors.lastname: Altare
authors.forename: P
authors.initials: P
authors.lastname: Ajmone-Catt
authors.forename: T
authors.initials: T
authors.lastname: Lima
authors.forename: G M
authors.initials: GM
authors.lastname: Molinatti
mesh_terms: 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*
chemical_list: D006062:Gonadotropins; D007987:Gonadotropin-Releasing Hormone; D009270:Naloxone; D013739:Testosterone; D000521:alpha-MSH; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone