MELANOCORTINS AND OPIOIDS MODULATE EARLY POSTNATAL-GROWTH IN RATS

This study was undertaken to investigate the effects of melanocortins and opioids on rat early postnatal body and organ growth. Among melano cortins tested desacetyl-alpha-melanocyte-stimulating hormone (alpha-M SH) at dosages of 0.3 and 3 mu g/g/day was effective in stimulating ne onatal growth with a weight gain of 7 and 5.6%, respectively, after 2 weeks of treatment. Likewise, a weight rise of 4.2 and 3% was obtained with 3 mu g/g/day of both alpha-MSH and Nle(4)-D-Phe(7) alpha-MSH. As far as opioids were concerned, while N-acetyl-beta-endorphin (beta-En d) was ineffective, the activity of beta-End was dependent on dosage. Indeed, newborns treated with 0.03 mu g/g/day showed a slight, but sig nificant, increase in weight, whereas a marked decrease in growth foll owed treatment with 0.3 and, mainly, 3 mu g/g/day, with a final weight loss of 3.4 and 5.5%, respectively. All melanocortins exerted a posit ive action on muscular and brain trophism and, in addition, desacetyl- alpha-MSH also induced a rise of fat deposits. On the contrary, while the 0.03 mu g/g/day beta-End dose caused an increase in muscular and b rain weight, the higher dosages of the opioid were detrimental, not on ly for muscle and brain, but also for both liver and spleen weight. A slight, although significant (P < 0.05), enhancement of serum dehydroe piandrosterone sulfate (DHEAS) level was found after the injection of 0.3 mu g/g desacetyl-alpha-MSH, whereas both the 0.3 and 3 mu g/g dose s of desacetyl-alpha-MSH and the 3 mu g/g dose of alpha-MSH determined the rise of plasma androstenedione (P < 0.05). All tested melanocorti ns and opioids failed to modify the concentrations of corticosterone. Our results suggest that melanocortins and opioids can modulate early postnatal growth in rats either by direct or indirect mechanisms.