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

Abstract

We examined the role of the opioid system on the regulation of prolactin secretion in neonatally androgenized rats and evaluated the participation of ovarian steroids in this regulation. Androgenized rats exhibited an increase of prolactin secretion with higher serum circulating levels in the afternoon (1800) than in the morning (1000). The administration of the opioid antagonist naloxone (2 mg/kg, 30 min before decapitation) reduced serum prolactin levels in both groups. To identify the opioid receptor subtypes involved in this regulation, opioid agonists were administered i.c.v. 15 min before the decapitation (1000). The mu-opioid receptor agonist DAMGO ([D-Ala2, NMe-Phe4, Gly5-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 acetamide methane sulfonate salt) induced a small but significant increase in serum prolactin levels but no effect was observed after administration of the delta-opioid agonist DPDPE ([D-Pen2, D-Pen5]-enkephalin). The role of oestradiol and the opioid system in the continuous secretion of prolactin was also study. Chronic gonadectomy (3-4 weeks) reduced serum prolactin concentrations measured at 1000 but the administration of naloxone had no effect. Three days of oestrogen treatment (2 microg/rat in oil) restored serum prolactin levels compared with ovariectomized animals and this effect was abolished by naloxone treatment. Interestingly, acute ovariectomy or administration of tamoxifen to intact androgenized rats did not prevent the continuous 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 on the regulation of prolactin levels in androgenized rats. After adrenalectomy, no changes in serum prolactin levels (1000) were observed compared with the control animal and naloxone treatment significantly reduced circulating prolactin levels. Progesterone treatment to intact androgenized rats significantly increased prolactin levels and the administration of naloxone blocked the stimulatory effect of the steroid. These results suggest that the opioid system play a role in the regulation of prolactin secretion in androgenized rats modulated by the persistence of oestrogen action. Moreover, the presence or absence of progesterone did not modify the regulation of prolactin secretion by the opioids. The mu- and kappa-opioid receptor subtypes are the ones involved in the modulation of pituitary prolactin secretion.