Le W W, Attardi B, Berghorn K A, Blaustein J, Hoffman G E
Department of Anatomy and Neurobiology, University of Maryland at Baltimore, School of Medicine, 21201, USA.
Brain Res. 1997 Dec 19;778(2):272-80. doi: 10.1016/s0006-8993(97)00971-2.
Progesterone is capable of facilitating or blocking the luteinizing hormone (LH) surge, depending on the timing of its administration. However, the precise targets of progesterone's actions are unknown. Since recent studies described the presence of a periventricular preoptic area (pePOA) neuron population afferent to LH-releasing hormone (LHRH) neurons that is co-activated to express c-Fos with LHRH neurons at the time of the LH surge, the present study was designed to determine if the pePOA neurons contain progesterone receptors (PRs) and whether progesterone inhibition is manifested by a failure of LHRH and pePOA neurons to become activated at the time of an LH surge. For progesterone facilitation, a group of immature rats each received a silastic capsule (1.57 mm i.d., 3.18 mm o.d., 1.5 cm long) containing estradiol-17beta (E2) in peanut oil (150 microg/ml) at 09.00 h on postnatal day 28 followed 24 h later by a progesterone implant (crystalline, 1.57 mm i.d., 3.18 mm o.d., 1.5 cm long). For progesterone inhibition, a second group of rats received the estrogen capsule and a progesterone capsule (3.35 mm i.d., 4.65 mm o.d., 3.0 cm long) together at 09.00 h on day 28, and 24 h later received only a blank capsule. On the afternoon of postnatal day 29, all animals were anesthetized and perfused for localization of c-Fos and LHRH, PRs alone, or c-Fos and PRs. The present studies determined that following a progesterone-inhibition paradigm, along with blockade of the LH surge, both activation of LHRH and pePOA neurons was low or absent. Staining of PRs in progesterone-facilitated and progesterone-inhibited rats indicated that the pePOA neurons contained PRs in similar patterns. Double labeling of c-Fos and PRs in progesterone-facilitated rats indicated that nearly all the c-Fos-positive neurons of the pePOA (80 +/- 4.2%) co-expressed PRs; in progesterone-inhibited rats, only 32 +/- 12% of few c-Fos-positive neurons also contained PRs. In no instance were LHRH neurons found to contain PRs. Taken together, these data suggest that both progesterone facilitation and inhibition likely involve direct actions of progesterone on the pePOA neurons, and are consistent with a role for the pePOA neurons in transducing steroid effects on LHRH neurons.
孕酮能够促进或阻断促黄体生成素（LH）峰，这取决于其给药时间。然而，孕酮作用的确切靶点尚不清楚。由于最近的研究描述了存在一群向促黄体激素释放激素（LHRH）神经元传入的室周视前区（pePOA）神经元，在LH峰时这些神经元与LHRH神经元共同被激活以表达c-Fos，因此本研究旨在确定pePOA神经元是否含有孕酮受体（PRs），以及孕酮抑制是否表现为LHRH和pePOA神经元在LH峰时未能被激活。对于孕酮促进作用，一组未成熟大鼠在出生后第28天上午9点各接受一个含有花生油中17β-雌二醇（E2）（150μg/ml）的硅橡胶胶囊（内径1.57mm，外径3.18mm，长1.5cm）；24小时后植入一个孕酮植入物（结晶状，内径1.57mm，外径3.18mm，长1.5cm）。对于孕酮抑制作用，第二组大鼠在第28天上午9点同时接受雌激素胶囊和一个孕酮胶囊（内径3.35mm，外径4.65mm，长3.0cm），24小时后仅接受一个空白胶囊。在出生后第29天下午，所有动物均被麻醉并灌注以定位c-Fos和LHRH、单独的PRs或c-Fos和PRs。本研究确定，在孕酮抑制模式下，除了阻断LH峰外，LHRH和pePOA神经元的激活均较低或未激活。对孕酮促进组和孕酮抑制组大鼠的PRs染色表明，pePOA神经元以相似的模式含有PRs。对孕酮促进组大鼠的c-Fos和PRs进行双重标记表明，pePOA中几乎所有c-Fos阳性神经元（80±4.2%）共表达PRs；在孕酮抑制组大鼠中，少数c-Fos阳性神经元中只有32±12%也含有PRs。在任何情况下都未发现LHRH神经元含有PRs。综上所述，这些数据表明，孕酮的促进和抑制作用可能都涉及孕酮对pePOA神经元的直接作用，并且与pePOA神经元在转导类固醇对LHRH神经元的作用方面的作用一致。
