EFFECT OF NALOXONE ON THE LH RESPONSE TO INTRAVENOUSLY-INFUSED SUBSTANCE-P IN NORMAL MEN

In order to establish whether endogenous opioids modulate the LH respo nse to systemically-infused Substance P (SP), seven normal men (24-33 yr) were infused with SP (0.5 or 1.5 pmol/kg(-1)/min(-1) for 60 min), naloxone (0.0.2 mu g/kg(-1)/min(-1) for 60 min) or the combination of SP and naloxone. The lower dose of SP (0.5 pmol/kg(-1)/min(-1)) was un able to change the plasma levels of LH. The infusion of naloxone induc ed a slight, but significant increase in plasma LH concentrations (34% increase vs baseline). A similar response was found when naloxone was given together with the lower dose of SP. A striking increase in plas ma LH was observed during the infusion of the higher dose of SP (1.5 p mol/kg(-1)/min(-1)) (93% vs baseline). A slightly higher LH increase ( 111% vs baseline) was observed when naloxone plus the higher dose of S P was infused. However, the LH increment was not significantly differe nt from that observed during the infusion of SP (1.5 pmol/kg(-1)/min(- 1)) alone. These data confirm the stimulating effect of systemically-i nfused SP on LH release, without evidence of the involvement of naloxo ne-sensitive endogenous opioids in the mechanism of action of SP.