Krey L C, Kamel F
Laboratory of Neuroendocrinology, Rockefeller University, New York, NY 10021.
Mol Cell Endocrinol. 1990 Mar 26;70(1):21-9. doi: 10.1016/0303-7207(90)90055-d.
Dispersed estradiol-treated rat pituitary cells were used to characterize progesterone (P) modulation of luteinizing hormone (LH) secretion in response to a variety of pharmacologic secretagogues which influence cell biochemistry. Acute (less than 3 h) and chronic (24 h) exposures to P prior to secretagogue challenge respectively enhanced and inhibited Ca2+ ionophore (A23187)-stimulated and gonadotropin-releasing hormone (GnRH)-stimulated LH release in similar quantitative fashion without any effect on concurrent prolactin release. Similar responses were also noted with cholera toxin-stimulated secretion. However, when protein kinase C activators such as phorbol esters and dioctanoylglycerol were used to trigger LH release, chronic exposure to P did not inhibit, but rather enhanced, LH release. Again, P had no effect on prolactin release. 'Washout' studies indicated that chronic treatments with P would suppress LH secretion stimulated by these compounds, but only when the steroid was cleared from the cells 4 h beforehand. These studies provide further evidence that P specifically modulates gonadotroph secretory function via mechanisms which bypass GnRH receptors. Moreover, they suggest that P exerts many different actions within the gonadotroph and question the role of protein kinase C in GnRH action.
使用经分散雌二醇处理的大鼠垂体细胞来表征孕酮（P）对促黄体生成素（LH）分泌的调节作用，该调节作用是针对多种影响细胞生物化学的药理促分泌剂而言的。在促分泌剂刺激之前，分别对P进行急性（少于3小时）和慢性（24小时）暴露，以相似的定量方式分别增强和抑制钙离子载体（A23187）刺激的和促性腺激素释放激素（GnRH）刺激的LH释放，而对同时发生的催乳素释放没有任何影响。在霍乱毒素刺激的分泌中也观察到类似的反应。然而，当使用蛋白激酶C激活剂如佛波酯和二辛酰甘油来触发LH释放时，长期暴露于P并不会抑制而是增强LH释放。同样，P对催乳素释放没有影响。“洗脱”研究表明，用P进行慢性处理会抑制这些化合物刺激的LH分泌，但前提是该类固醇要提前4小时从细胞中清除。这些研究提供了进一步的证据，表明P通过绕过GnRH受体的机制特异性调节促性腺激素细胞的分泌功能。此外，它们表明P在促性腺激素细胞内发挥多种不同作用，并对蛋白激酶C在GnRH作用中的作用提出质疑。
