Inhibition of steroidogenesis by luteal cells of early pregnancy in the rat in response to in vitro administration of a gonadotropin-releasing hormone agonist.
Inhibition of steroidogenesis by luteal cells of early pregnancy in the rat in response to in vitro administration of a gonadotropin-releasing hormone agonist.
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体外给予促性腺激素释放激素激动剂后，大鼠早期妊娠黄体细胞对类固醇生成的抑制。
DOI：
10.1016/0960-0760(94)90303-4
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Sridaran,R
中科院分区：
文献类型：
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作者：
Srivastava,RK;Luu-The,V;Marrone,BL;Harris-Hooker,S;Sridaran,R
本实验室之前的研究表明，在妊娠早期或中期给大鼠体内注射促性腺激素释放激素激动剂（GnRH-Ag），通过抑制24小时内黄体黄体酮（P4）的产生，同时增加黄体脂滴，降低黄体细胞色素P450侧链切割（P450scc）酶及其mRNA含量，从而诱导抗生育作用。这些观察结果表明GnRH-Ag对黄体有直接的抑制作用。在体外实验中，我们证明了GnRH-Ag对妊娠早期大鼠黄体细胞基础P4、孕烯醇酮（P5）和20α-二氢孕酮（20α-DHP）产生的抑制作用。我们进一步研究了其对两种关键酶P450scc和3β-羟基类固醇脱氢酶（3β-HSD）的影响，这两种酶分别参与胆固醇向p5和P4的转化。我们观察到，10−4和10−7M两种剂量的GnRH-Ag在体外黄体细胞孵育12小时后，抑制了基础p4的产生；p4在孵育48 h后仍被抑制。与10−4和10−7M的GnRH-Ag孵育12 h后，黄体细胞的基础p5生成也受到抑制，但与GnRH-Ag孵育48 h后，这些细胞的p5生成并未改变。两种剂量的GnRH-Ag在黄体细胞孵育12小时后，20α-DHP的产生均受到抑制。GnRH-Ag在孵育12小时后抑制P450scc活性，并在所有时间段测量3β-HSD蛋白含量。这些结果表明GnRH对黄体甾体生成具有直接抑制作用。这种抑制是由于其对P450scc和/或3β-HSD的抑制作用，而不是由于p4代谢物的增加。
Previous studies from this laboratory have demonstrated that the administration of a gonadotropin- releasing hormone agonist (GnRH-Ag) in vivo in early or mid-pregnancy to rats induces antifertility effects by suppressing the luteal production of progesterone (P4) within 24 h with a concomitant increse in luteal lipid droplets and decreses in the luteal cytochrome P450 side chain cleavage (P450scc) enzyme and its mRNA content. These observations suggest a direct inhibitory effect of GnRH-Ag on the corpus luteum. Here we demonstrate a suppressive effect of GnRH-Ag in vitro on the basal P4, pregnenolone (P5) and 20α-dihydroprogesterone (20α-DHP) production by luteal cells obtained during early pregnancy in rats. We further studied its effect on two key enzymes, namely P450scc and 3β-hydroxysteroid dehydrogenase (3β-HSD), which participate in the conversion of cholesterol to P5amd conversion of P4, respectively. We observed that two doses of GnRH-Ag, 10−4and 10−7M, suppress the basal P4production in vitro after 12 h of incubation by luteal cells; P4remained suppessed after 48 h of incubation. Basal P5production was also suppressed after luteal cells were incubated for 12 h with 10−4and 10−7M GnRH-Ag, but incubation for 48 h with GnRH-Ag failed to alter P5production by these cells. 20α-DHP production was suppressed after incubating the luteal cells with both doses of GnRH-Ag for 12 h. GnRH-Ag inhibited P450scc activity after 12 h of incubation and 3β-HSD protein content at all time periods measured. These results suggest that GnRH exerts a direct inhibitory effect on luteal steroidogenesis. This inhibition is due to its suppressive effect on P450scc and/or 3β-HSD and not due to an increase in P4metabolites.