Participation of the opioid system in the regulation of prolactin secretion in androgenized rats: effect of ovarian steroids

We examined the role of the opioid system on the regulation of prolactin se cretion in neonatally androgenized rats and evaluated the participation of ovarian steroids in this regulation. Androgenized rats exhibited an increas e of prolactin secretion with higher serum circulating levels in the aftern oon (1800) than in the morning (1000). The administration of the opioid ant agonist naloxone (2 mg/kg, 30 min before decapitation) reduced serum prolac tin levels in both groups. To identify the opioid receptor subtypes involve d in this regulation, opioid agonists were administered i.c.v. 15 min befor e the decapitation (1000). The mu-opioid receptor agonist DAMGO ([D-Ala(2), NMe-Phe(4), Gly(5)-ol]-enkephalin) caused a significant increase in serum prolactin concentration. The selective kappa-opioid receptor agonist U-50, 488H (trans-(+/-)-3,4-dichloro-N-[2(1-pyrrolidinyl)-cyclohexyl]-benzene ace tamide methane sulfonate salt) induced a small but significant increase in serum prolactin levels but no effect was observed after administration of t he delta-opioid agonist DPDPE ([D-Pen(2), D-Pen(5)]-enkephalin). The role o f oestradiol and the opioid system in the continuous secretion of prolactin was also study. Chronic gonadectomy (3-4 weeks) reduced serum prolactin co ncentrations measured at 1000 but the administration of naloxone had no eff ect. Three days of oestrogen treatment (2 mu g/rat in oil) restored serum p rolactin levels compared with ovariectomized animals and this effect was ab olished by naloxone treatment. Interestingly, acute ovariectomy or administ ration of tamoxifen to intact androgenized rats did not prevent the continu ous secretion of prolactin observed in these animals and naloxone treatment reduced serum prolactin levels in both groups of rats. We also examine the participation of adrenal progesterone and the endogenous opioid peptides o n the regulation of prolactin levels in androgenized rats. After adrenalect omy, no changes in serum prolactin levels (1000) were observed compared wit h the control animal and naloxone treatment significantly reduced circulati ng prolactin levels. Progesterone treatment to intact androgenized rats sig nificantly increased prolactin levels and the administration of naloxone bl ocked the stimulatory effect of the steroid. These results suggest that the opioid system play a role in the regulation of prolactin secretion in andr ogenized rats modulated by the persistence of oestrogen action. Moreover, t he presence or absence of progesterone did not modify the regulation of pro lactin secretion by the opioids. The mu- and kappa-opioid receptor subtypes are the ones involved in the modulation of pituitary prolactin secretion. (C) 1999 Elsevier Science B.V. All rights reserved.