Pecins-Thompson M, Widmann A A, Bethea C L
Division of Reproductive Sciences, Oregon Regional Primate Research Center, Beaverton 97006, USA.
Neuroendocrinology. 1996 Jun;63(6):569-78. doi: 10.1159/000127086.
Progesterone (P) stimulates prolactin secretion through a neural mechanism in estrogen (E)-primed female monkeys. Several peptides, including beta-endorphin (BE), oxytocin (OT), substance P (SP) and vasoactive intestinal polypeptide (VIP) are potential prolactin stimulatory factors and could mediate the effect of P. We hypothesized that the antagonism of a pivotal peptidergic neural system would block P-induced prolactin secretion and that the function of a pivotal peptidergic system would be altered by changes in gonadal steroid concentrations. Therefore it was of interest (1) to examine the effect of infusion of antagonists to these peptides on P-induced prolactin secretion, and (2) to determine BE, OT, SP and VIP levels in the hypothalamus of monkeys of various reproductive states. For the antagonist studies, female monkeys (n = 8) were spayed, adapted to a vest and tether remote sampling system and catheterized prior to antagonist challenges. E-primed monkeys received P injections 48 h prior to antagonist administration. Prolactin increased within 36-48 h of P injection. All antagonist challenges were administered in varying doses during the P-induced prolactin elevation and blood samples were collected every 10 min for prolactin determinations. The opiate antagonist, naloxone (n = 5), reduced serum prolactin in a dose-related manner with a mean IC50 of 1.5 +/- 0.6 micrograms/kg/min. The OT (n = 4), SP (n = 4) or VIP (n = 4) antagonists did not reduce serum prolactin in a dose-related manner. We previously reported that the hypothalamic content of OT is increased by ovarian hormones. To determine whether the hypothalamic content of BE, SP or VIP was related to gonadal status, the peptide levels in 4 hypothalamic regions of monkeys in various physiological states were measured. BE (ng/mg protein) in the medial basal hypothalamus (MBH) was significantly greater in adult females (17.7 +/- 6.9; n = 6) as compared to spayed females (0.6 +/- 0.2; n = 3) and juvenile females (1.8 +/- 1.1; n = 3). Hypothalamic content of SP in the preoptic area and mammillary bodies, but not the MBH, was significantly greater in gonadal intact females than spayed females. VIP content (pg/mg protein) was not significantly different between adult, spayed and juvenile females nor between adult and juvenile males in any hypothalamic area. Taken together these results support a pivotal role for BE in the neural regulation of P-induced prolactin secretion. The involvement of OT, SP, and VIP in a specific manner at the pituitary level is not indicated.
在经雌激素（E）预处理的雌性猕猴中，孕酮（P）通过神经机制刺激催乳素分泌。包括β-内啡肽（BE）、催产素（OT）、P物质（SP）和血管活性肠肽（VIP）在内的几种肽是潜在的催乳素刺激因子，可能介导P的作用。我们假设关键肽能神经系统的拮抗作用会阻断P诱导的催乳素分泌，并且关键肽能系统的功能会因性腺类固醇浓度的变化而改变。因此，有必要（1）研究这些肽的拮抗剂注入对P诱导的催乳素分泌的影响，以及（2）测定处于不同生殖状态的猕猴下丘脑中BE、OT、SP和VIP的水平。对于拮抗剂研究，雌性猕猴（n = 8）被摘除卵巢，适应背心和系绳远程采样系统，并在接受拮抗剂挑战前进行插管。经E预处理的猕猴在给予拮抗剂前48小时接受P注射。催乳素在P注射后36 - 48小时内升高。在P诱导的催乳素升高期间，以不同剂量给予所有拮抗剂挑战，并每10分钟采集血样用于催乳素测定。阿片类拮抗剂纳洛酮（n = 5）以剂量相关的方式降低血清催乳素，平均IC50为1.5 +/- 0.6微克/千克/分钟。OT（n = 4）、SP（n = 4）或VIP（n = 4）拮抗剂未以剂量相关的方式降低血清催乳素。我们之前报道过，卵巢激素会增加下丘脑OT的含量。为了确定BE、SP或VIP的下丘脑含量是否与性腺状态有关，测量了处于不同生理状态的猕猴4个下丘脑区域中的肽水平。成年雌性猕猴内侧基底部下丘脑（MBH）中的BE（纳克/毫克蛋白）（17.7 +/- 6.9；n = 6）显著高于摘除卵巢的雌性猕猴（0.6 +/- 0.2；n = 3）和幼年雌性猕猴（1.8 +/- 1.1；n = 3）。在视前区和乳头体中，而非MBH中，性腺完整的雌性猕猴下丘脑SP含量显著高于摘除卵巢的雌性猕猴。在任何下丘脑区域，成年、摘除卵巢和幼年雌性猕猴之间以及成年和幼年雄性猕猴之间的VIP含量（皮克/毫克蛋白）均无显著差异。综上所述，这些结果支持BE在P诱导的催乳素分泌的神经调节中起关键作用。未表明OT、SP和VIP在垂体水平以特定方式参与其中。
