Dermorphin Stimulates Prolactin Secretion in the Rat

The effect of dermorphin, a new opioid peptide originally isolated from amphibian skin, on the release of prolactin (Prl) was studied in vivo and in vitro. In vivo experiments: subcutaneous administrations of different doses of dermorphin ranging from 0.1 to 5 mg/kg body weight to normal male rats induce a statistically significant, dose-related increase in serum Prl levels. Pretreatment with the specific opioid antagonist, naloxone (2 mg/kg i.p.) completely prevents the rise in serum Prl, induced by 2 mg/kg of dermorphin. In normal male rats, the intraventricular injection of 0.25 µg/kg of dermorphin is not able to induce any significant changes in serum Prl levels 10 min after injection. Serum Prl levels show a significant enhancement 30 min after the administration of this dose of dermorphin, and return to control values at 60 min. On the contrary, 1 µg/kg of dermorphin significantly elevates Prl concentrations 10 min after injection, leaving serum Prl levels unchanged 30 and 60 min after the administration. Naloxone (25 and 100 µg/kg) alone does not substantially modify serum Prl concentrations at any time interval considered. Treatment with either dose of naloxone performed together with either 0.25 or 1 µg/kg of dermorphin completely counteracts the stimulatory effect of the peptide at all time intervals in which dermorphin was active when given alone. In orchidectomized (3 weeks) rats, the intraventricular administration of dermorphin at the dose of 0.25 µg/kg appears effective in enhancing Prl levels only 30 min after treatment. No statistically significant modifications are observed at 10 and 60 min with this dose. Injection of 1 µg/kg of dermorphin significantly increases serum Prl concentrations 10, 30 and 60 min after administration. Naloxone given alone at 25 and 100 µg/kg does not cause any significant change in serum Prl concentrations. The dermorphin-induced rise in Prl levels is totally obliterated, at any time interval considered, by the simultaneous administration of either dose of naloxone. In vitro experiment: in the isolated and dispersed rat pituitary cell preparation, dermorphin, added to the medium at a concentration of 5 × 10-7M (corresponding to 400 ng/ml), does not induce any alteration in Prl output. This peptide is also unable to counteract the inhibiting effect of a continuous perfusion (1.5 h) with dopamine (5 × 10-8M) on Prl release. The present data provide the first evidence that dermorphin is able to stimulate Prl secretion in rats and may indicate that this effect is specifically mediated through opiate receptors, since the antagonist naloxone is effective in reversing the dermorphin-induced stimulation of Prl. These results also suggest that dermorphin does not influence Prl release through an action at the pituitary level, but rather through an action which takes place in the central nervous system, possibly in the hypothalamus.