Soaje M, Deis R P
Laboratorio de Reproducción y Lactancia, CRICYT-CONICET, Mendoza, Argentina.
Eur J Pharmacol. 1999 Apr 23;371(1):43-9. doi: 10.1016/s0014-2999(99)00152-1.
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.
我们研究了阿片系统在新生期雄激素化大鼠催乳素分泌调节中的作用，并评估了卵巢类固醇在该调节过程中的参与情况。雄激素化大鼠的催乳素分泌增加，下午（18:00）血清循环水平高于上午（10:00）。给予阿片拮抗剂纳洛酮（2mg/kg，断头前30分钟）可降低两组大鼠的血清催乳素水平。为了确定参与该调节的阿片受体亚型，在断头前15分钟（10:00）经脑室内注射阿片激动剂。μ-阿片受体激动剂DAMGO（[D-Ala2，NMe-Phe4，Gly5-ol]-脑啡肽）可使血清催乳素浓度显著升高。选择性κ-阿片受体激动剂U-50,488H（反式-(+/-)-3,4-二氯-N-[2-(1-吡咯烷基)-环己基]-苯乙酰胺甲磺酸盐）可使血清催乳素水平有小幅但显著的升高，但给予δ-阿片激动剂DPDPE（[D-Pen2，D-Pen5]-脑啡肽）后未观察到作用。还研究了雌二醇和阿片系统在催乳素持续分泌中的作用。慢性去势（3-4周）可降低10:00时测得的血清催乳素浓度，但给予纳洛酮无作用。与去卵巢动物相比，三天的雌激素治疗（2μg/大鼠，溶于油中）可恢复血清催乳素水平，且该作用可被纳洛酮治疗消除。有趣的是，对完整的雄激素化大鼠进行急性卵巢切除或给予他莫昔芬并不能阻止这些动物中观察到的催乳素持续分泌，且纳洛酮治疗可降低两组大鼠的血清催乳素水平。我们还研究了肾上腺孕酮和内源性阿片肽在雄激素化大鼠催乳素水平调节中的参与情况。肾上腺切除后，与对照动物相比，血清催乳素水平（10:00）无变化，而纳洛酮治疗可显著降低循环催乳素水平。对完整的雄激素化大鼠进行孕酮治疗可显著提高催乳素水平，给予纳洛酮可阻断该类固醇的刺激作用。这些结果表明，阿片系统在雌激素作用持续调节的雄激素化大鼠催乳素分泌调节中发挥作用。此外，孕酮的存在与否并未改变阿片类药物对催乳素分泌的调节。μ-和κ-阿片受体亚型参与了垂体催乳素分泌的调节。
