Rivest S, Plotsky P M, Rivier C
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, CA 92037.
Neuroendocrinology. 1993;57(2):236-46. doi: 10.1159/000126365.
Corticotropin-releasing factor (CRF) is a potent factor involved in the antireproductive effects of various stressors. However, the central mechanisms by which CRF modulates the hypothalamic-pituitary-gonadal (HPG) axis are not well understood. In order to verify whether CRF is able to directly influence luteinizing hormone-releasing hormone (LHRH) secretory activity at the level of the medial preoptic area (MPOA), CRF was chronically or acutely injected bilaterally into this hypothalamic area. Ten days before the experiments, female rats were implanted with a permanent double-guide cannula which was stereotaxically positioned close to the MPOA. Chronic administration of rat CRF (rCRF) was accomplished by means of two miniosmotic pumps connected to double internal cannula. Acute bilateral infusion of rCRF into the MPOA was performed in unrestrained ovariectomized (OVX) rats and during the afternoon of proestrus. Ten minutes before rCRF treatment, antagonists of opioid receptors (mu, mu 1, or kappa) were infused bilaterally into the MPOA. Hypothalamic LHRH release as well as circulating gonadotropins were determined using a push-pull cannula implanted into the median eminence (ME), and a catheter connected to the jugular vein, respectively. Chronic rCRF treatment in the MPOA decreased (p < 0.05) plasma LH levels but did not modify follicle-stimulating hormone release in OVX rats. A significant inhibition of LH secretion was first observed 80 min after the acute rCRF infusion into the MPOA; pretreatment with nor-Binaltorphimine (antagonist of kappa-receptors) did not measurably attenuate this effect. In contrast, bilateral administration of beta-Funaltrexamine (antagonist of mu-opioid receptors) or naloxonazine (mu 1-antagonist) partially attenuated the inhibitory effect of rCRF on plasma LH levels. Similarly, injections of rCRF bilaterally into the MPOA suppressed hypothalamic LHRH release into the ME and this effect was partially reversed by a previous administration of opioid mu- or mu 1-receptor antagonists. In contrast to rCRF injection into the MPOA, administration of rCRF into the paraventricular nucleus the arcuate nucleus of the hypothalamus and directly into the ME were without significant effect on hypothalamic LHRH release in proestrus rats. In conclusion, the present data show that from among the hypothalamic sites tested, only the MPOA proved susceptible to CRF-induced alteration of LHRH neuronal activity during proestrus afternoon in rats. The release of opioids from nerve terminals located in the MPOA, which in turn binds and activates mainly type mu 1-receptors, might contribute to this inhibitory influence of CRF on LHRH release in the infundibular system.
促肾上腺皮质激素释放因子（CRF）是参与各种应激源抗生殖作用的一种强效因子。然而，CRF调节下丘脑 - 垂体 - 性腺（HPG）轴的中枢机制尚未完全清楚。为了验证CRF是否能够直接影响视前内侧区（MPOA）水平的促黄体生成素释放激素（LHRH）分泌活性，将CRF双侧慢性或急性注射到该下丘脑区域。实验前10天，给雌性大鼠植入永久性双引导套管，通过立体定位使其靠近MPOA。大鼠CRF（rCRF）的慢性给药通过连接到双内套管的两个微型渗透泵来完成。在未束缚的去卵巢（OVX）大鼠和发情前期下午，将rCRF急性双侧注入MPOA。在rCRF处理前10分钟，将阿片受体拮抗剂（μ、μ1或κ）双侧注入MPOA。分别使用植入正中隆起（ME）的推挽式套管和连接颈静脉的导管来测定下丘脑LHRH释放以及循环中的促性腺激素。MPOA的慢性rCRF处理降低了（p < 0.05）OVX大鼠的血浆LH水平，但未改变促卵泡激素释放。在将rCRF急性注入MPOA后80分钟首次观察到LH分泌受到显著抑制；用nor - Binaltorphimine（κ受体拮抗剂）预处理并未显著减弱这种作用。相反，双侧给予β - Funaltrexamine（μ阿片受体拮抗剂）或纳洛酮嗪（μ1拮抗剂）可部分减弱rCRF对血浆LH水平的抑制作用。同样，将rCRF双侧注入MPOA可抑制下丘脑LHRH向ME的释放，并且先前给予阿片μ或μ1受体拮抗剂可部分逆转这种作用。与将rCRF注入MPOA不同，将rCRF注入下丘脑室旁核、弓状核以及直接注入ME对发情前期大鼠的下丘脑LHRH释放没有显著影响。总之，目前的数据表明，在所测试的下丘脑部位中，仅MPOA在大鼠发情前期下午对CRF诱导的LHRH神经元活动改变敏感。来自位于MPOA的神经末梢释放的阿片类物质，其反过来主要结合并激活μ1型受体，可能有助于CRF对漏斗系统中LHRH释放的这种抑制作用。
