Pepperell J R, Behrman H R
Department of Obstetrics and Gynecology, Yale School of Medicine, New Haven, Connecticut 06510-8063.
Endocrinology. 1990 Oct;127(4):1818-24. doi: 10.1210/endo-127-4-1818.
In rat luteal cells, an increase in intracellular [Ca]i impairs luteal function similar to that of prostaglandin F2a (PGF2a). However, calcium per se is not the mediator of the antigonadotropic action of PGF2a. Thapsigargin, a plant sesquiterpene lactone, increases intracellular calcium concentration concentration ([Ca]i) in several cell types by a mechanism that involves specific inhibition of the endoplasmic reticulum Ca2(+)-ATPase. To further investigate the antigonadotropic role of [Ca]i and the mechanism of action of PGF2a in rat luteal cells, the action of thapsigargin on cellular functional responses was examined in the absence and presence of PGF2a. Thapsigargin dose dependently increased [Ca]i and inhibited cAMP accumulation and progesterone production in response to LH. The inhibitory effect of thapsigargin on cAMP accumulation was calcium dependent but in contrast, inhibition of LH-stimulated progesterone production was independent of calcium mobilization by thapsigargin. Steroidogenesis stimulated by (Bu)2cAMP was also inhibited by thapsigargin. Thus, thapsigargin mimicked some effects of PGF2a with inhibitory sites of action on both cAMP accumulation and progesterone production. Thapsigargin also blocked the mobilization of [Ca]i by PGF2a, but when coincubated with PGF2a an additive effect on inhibition of LH-stimulated progesterone production occurred. However, no additive effects of thapsigargin and PGF2a on gonadotropin-sensitive cAMP accumulation were evident. In conclusion, although thapsigargin and PGF2a may share some similar actions, their antigonadotropic effects are mediated differently.
在大鼠黄体细胞中，细胞内钙离子浓度（[Ca]i）升高会损害黄体功能，这与前列腺素F2α（PGF2α）的作用相似。然而，钙本身并不是PGF2α抗促性腺激素作用的介质。毒胡萝卜素是一种植物倍半萜内酯，它通过一种涉及特异性抑制内质网Ca2 + -ATP酶的机制，提高多种细胞类型中的细胞内钙浓度（[Ca]i）。为了进一步研究[Ca]i的抗促性腺激素作用以及PGF2α在大鼠黄体细胞中的作用机制，在有无PGF2α存在的情况下，检测了毒胡萝卜素对细胞功能反应的影响。毒胡萝卜素剂量依赖性地增加[Ca]i，并抑制促黄体生成素（LH）诱导的环磷酸腺苷（cAMP）积累和孕酮生成。毒胡萝卜素对cAMP积累的抑制作用依赖于钙，但与之相反，其对LH刺激的孕酮生成的抑制作用与毒胡萝卜素引起的钙动员无关。毒胡萝卜素也抑制了由（Bu）2cAMP刺激的类固醇生成。因此，毒胡萝卜素模拟了PGF2α的一些作用，其作用位点对cAMP积累和孕酮生成均有抑制作用。毒胡萝卜素还阻断了PGF2α引起的[Ca]i动员，但当与PGF2α共同孵育时，对LH刺激的孕酮生成产生了相加的抑制作用。然而，毒胡萝卜素和PGF2α对促性腺激素敏感的cAMP积累没有明显的相加作用。总之，虽然毒胡萝卜素和PGF2α可能有一些相似的作用，但其抗促性腺激素作用的介导方式不同。
