抗孕激素RU 486对垂体促性腺细胞中孕酮作用及促黄体生成素分泌的抑制作用。
Inhibitory effects of the antiprogestin, RU 486, on progesterone actions and luteinizing hormone secretion in pituitary gonadotrophs.
作者信息
Ortmann O, Emons G, Knuppen R, Catt K J
机构信息
Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892.
出版信息
J Steroid Biochem. 1989 Feb;32(2):291-7. doi: 10.1016/0022-4731(89)90266-5.
The effects of RU 486 on the modulation of LH release by progesterone were investigated in cultured anterior pituitary cells from ovariectomized adult female rats. The inhibitory effect of progesterone on LH secretion was demonstrable in estrogen-treated pituitary cells, in which addition of 10(-6) M progesterone to cells cultured in the presence of 10(-9) M estradiol for 52 h reduced the LH response to GnRH (10(-11) to 10(-7) M). When RU 486 was superimposed upon such combined treatment with estradiol and progesterone, the suppressive effect of progesterone on GnRH-induced LH release was completely abolished. The converse (facilitatory) effect of progesterone on LH secretion was observed in pituitary cells pretreated with 10(-9) M estradiol for 48 h and then with 10(-6) M progesterone for 4 h. When RU 486 was added together with progesterone during the 4 h treatment period, the facilitatory effect of progesterone was blocked and LH release fell to below the corresponding control value. The direct effect of RU 486 on LH secretion in the absence of exogenous progesterone was evaluated in cells cultured in the absence or presence of 10(-9) M estradiol and then treated for 4 to 24 h with increasing concentrations of RU 486 (10(-12) to 10(-5) M) and stimulated with GnRH (10(-9) M) during the last 3 h of incubation. In estrogen-deficient cultures, 4 h exposure to RU 486 concentrations of 10(-6) M and above decreased the LH response to GnRH by up to 50%. In cultures pretreated with 10(-9) M estradiol, GnRH-stimulated LH responses was inhibited by much lower RU 486 concentrations, of 10(-9) M and above. After 24 h of incubation the effects of RU 486 were similar in control and estradiol-pretreated pituitary cell cultures. Thus, RU 486 alone has a significant inhibitory effect on LH secretion that is enhanced in the presence of estrogen. The antiprogestin is also a potent antagonist of both the inhibitory and the facilitatory actions of progesterone upon pituitary gonadotropin release in vitro.
在成年雌性去卵巢大鼠的培养垂体前叶细胞中，研究了RU 486对孕酮调节促黄体生成素（LH）释放的影响。在雌激素处理的垂体细胞中，可证实孕酮对LH分泌具有抑制作用，即在存在10⁻⁹ M雌二醇的情况下培养52小时的细胞中，加入10⁻⁶ M孕酮会降低LH对促性腺激素释放激素（GnRH，10⁻¹¹至10⁻⁷ M）的反应。当RU 486叠加于雌二醇和孕酮的联合处理时，孕酮对GnRH诱导的LH释放的抑制作用完全消除。在先用10⁻⁹ M雌二醇预处理48小时、然后用10⁻⁶ M孕酮处理4小时的垂体细胞中，观察到孕酮对LH分泌的相反（促进）作用。当在4小时处理期间将RU 486与孕酮一起加入时，孕酮的促进作用被阻断，LH释放降至相应对照值以下。在不存在或存在10⁻⁹ M雌二醇的情况下培养细胞，然后用浓度递增的RU 486（10⁻¹²至10⁻⁵ M）处理4至24小时，并在孵育的最后3小时用GnRH（10⁻⁹ M）刺激，评估RU 486在无外源性孕酮时对LH分泌的直接作用。在雌激素缺乏的培养物中，暴露于10⁻⁶ M及以上浓度的RU 486 4小时可使LH对GnRH的反应降低多达50%。在用10⁻⁹ M雌二醇预处理的培养物中，10⁻⁹ M及以上浓度的RU 486即可抑制GnRH刺激的LH反应。孵育24小时后，RU 486在对照和雌二醇预处理的垂体细胞培养物中的作用相似。因此，单独的RU 486对LH分泌具有显著抑制作用，在雌激素存在时这种作用增强。该抗孕激素也是孕酮在体外对垂体促性腺激素释放的抑制和促进作用的有效拮抗剂。
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