Wiltbank M C, Diskin M G, Niswender G D
Colorado State University Department of Physiology, Fort Collins 80526.
J Reprod Fertil Suppl. 1991;43:65-75.
Our current working hypothesis for the intracellular mechanism of action for LH and PGF-2 alpha is shown in Fig. 8. Luteinizing hormone appears to act primarily on the small luteal cell through the cAMP/protein kinase A effector system and thereby stimulates secretion of progesterone. Activation of the protein kinase C effector pathway is inhibitory to progesterone secretion from stimulated small luteal cells but it is not clear which hormones, if any, activate this effector system. Results from studies in whole animals suggest that LH may also stimulate differentiation of small luteal cells into large luteal cells (Donaldson & Hansel, 1965; Farin et al., 1988). Although there are LH receptors on large luteal cells, LH treatment does not stimulate progesterone secretion and does not appear to activate any of the second messenger pathways which we have examined. Prostaglandin F-2 alpha appears to act on the large luteal cell through free intracellular calcium and protein kinase C effector systems. Apparently, PGF-2 alpha-induced activation of protein kinase C results in the acute inhibition of progesterone production seen in the first 8 h after PGF-2 alpha treatment. The cytotoxic effects of PGF-2 alpha on the large luteal cell (Fitz et al., 1984; Braden et al., 1988) may be caused by a sustained elevation in free intracellular calcium concentrations. No direct effects of PGF-2 alpha on small luteal cells have been detected (no inhibition of progesterone production, no activation of protein kinase C, no increase in free intracellular calcium), which is consistent with an absence of high affinity PGF-2 alpha receptors on this cell type. The cytotoxic effects of PGF-2 alpha on small luteal cells and endothelial cells (Braden et al., 1988) may be caused by decreases in luteal blood flow (Niswender et al., 1975; Wiltbank et al., 1990b), actions of cytotoxic agents released by large luteal cells, or increases in cytotoxic white blood cells (Murdoch, 1987; Bagavandoss et al., 1988).
我们目前关于促黄体生成素（LH）和前列腺素F-2α（PGF-2α）细胞内作用机制的工作假设见图8。促黄体生成素似乎主要通过环磷酸腺苷/蛋白激酶A效应系统作用于小黄体细胞，从而刺激孕酮分泌。蛋白激酶C效应途径的激活对受刺激的小黄体细胞分泌孕酮具有抑制作用，但尚不清楚是哪种激素（如果有的话）激活了该效应系统。对完整动物的研究结果表明，促黄体生成素也可能刺激小黄体细胞分化为大黄体细胞（唐纳森和汉塞尔，1965年；法林等人，1988年）。尽管大黄体细胞上有促黄体生成素受体，但促黄体生成素处理并不会刺激孕酮分泌，也似乎不会激活我们所研究的任何第二信使途径。前列腺素F-2α似乎通过细胞内游离钙和蛋白激酶C效应系统作用于大黄体细胞。显然，PGF-2α诱导的蛋白激酶C激活导致PGF-2α处理后最初8小时内孕酮生成的急性抑制。PGF-2α对大黄体细胞的细胞毒性作用（菲茨等人，1984年；布雷登等人，1988年）可能是由细胞内游离钙浓度的持续升高引起的。尚未检测到PGF-2α对小黄体细胞有直接作用（对孕酮生成无抑制作用，蛋白激酶C无激活，细胞内游离钙无增加），这与该细胞类型上缺乏高亲和力的PGF-2α受体一致。PGF-2α对小黄体细胞和内皮细胞的细胞毒性作用（布雷登等人，1988年）可能是由于黄体血流量减少（尼斯文德等人，1975年；威尔特班克等人，1990b）、大黄体细胞释放的细胞毒性因子的作用或细胞毒性白细胞增加（默多克，1987年；巴加万多斯等人，1988年）所致。
