Krey L C, Kamel F
Laboratory of Neuroendocrinology, Rockefeller University, New York, NY 10021.
Mol Cell Endocrinol. 1990 Jan 22;68(2-3):85-94. doi: 10.1016/0303-7207(90)90180-g.
Dispersed, estradiol-treated, rat pituitary cells were cultured to characterize the influences of a physiologic concentration of progesterone (P, 10(-7) M) on gonadotroph responsiveness to gonadotropin-releasing hormone (GnRH). Acute (less than 6 h) P treatment enhanced and chronic (greater than 12 h) treatment suppressed both basal and GnRH-stimulated luteinizing hormone (LH) release. This modulation took place without any change in intracellular LH stores, indicating that the secretory changes are not attributable to changes in LH synthesis, and were not accompanied by similar alterations in basal or thyrotropin-releasing hormone-stimulated prolactin secretion. Moreover, the timing of these responses was fixed since a 10-fold lower P concentration produced only smaller and briefer alterations in LH release. Analyses of the temporal characteristics of effective P stimuli indicated that a brief 6 h exposure to P inhibited GnRH-stimulated LH secretion 18 h later. In contrast, P's acute actions rapidly dissipated following removal of the steroid from the culture medium. Finally, P-induced enhancement and suppression of GnRH-stimulated LH release could be blocked by appropriately timed treatments with protein synthesis inhibitors. Our findings are consistent with the hypothesis that P influences gonadotroph secretory function via the production of specific proteins.
将分散的、经雌二醇处理的大鼠垂体细胞进行培养,以研究生理浓度的孕酮(P,10⁻⁷ M)对促性腺激素细胞对促性腺激素释放激素(GnRH)反应性的影响。急性(小于6小时)P处理增强了基础和GnRH刺激的促黄体生成素(LH)释放,而慢性(大于12小时)处理则抑制了这种释放。这种调节在细胞内LH储存没有任何变化的情况下发生,表明分泌变化并非归因于LH合成的改变,并且基础或促甲状腺激素释放激素刺激的催乳素分泌也没有伴随类似的改变。此外,这些反应的时间是固定的,因为10倍低浓度的P仅对LH释放产生较小且短暂的改变。对有效P刺激的时间特征分析表明,短暂暴露于P 6小时会在18小时后抑制GnRH刺激的LH分泌。相反,从培养基中去除类固醇后,P的急性作用迅速消失。最后,适当时间用蛋白质合成抑制剂处理可阻断P诱导的GnRH刺激的LH释放增强和抑制。我们的发现与P通过产生特定蛋白质影响促性腺激素细胞分泌功能的假设一致。