Stocco C O, Chedrese J, Deis R P
Laboratorio de Reproducción y Lactancia, CONICET, 5500 Mendoza, Argentina.
Biol Reprod. 2001 Oct;65(4):1114-9. doi: 10.1095/biolreprod65.4.1114.
A decrease in serum progesterone at the end of pregnancy is essential for the induction of parturition in rats. We have previously demonstrated that LH participates in this process through: 1) inhibiting 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity and 2) stimulating progesterone catabolism by inducing 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) activity. The objective of this investigation was to determine the effect of LH and progesterone on the luteal expression of the steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage (P450(scc)), 3beta-HSD, and 20alpha-HSD genes. Gene expression was analyzed by Northern blot analysis 24 and 48 h after administration of LH or vehicle on Day 19 of pregnancy. StAR and 3beta-HSD mRNA levels were lower in LH-treated rats than in rats administered with vehicle at both time points studied. P450(scc) mRNA levels were unaffected by LH. The 20alpha-HSD mRNA levels were not different between LH and control rats 24 h after treatment; however, greater expression of 20alpha-HSD, with respect to controls, was observed in LH-treated rats 48 h after treatment. Luteal progesterone content dropped in LH-treated rats at both time points studied, whereas serum progesterone decreased after 48 h only. In a second set of experiments, the anti-progesterone RU486 was injected intrabursally on Day 20 of pregnancy. RU486 had no effect on 3beta-HSD or P450(scc) expression but increased 20alpha-HSD mRNA levels after 8 h treatment. In conclusion, the luteolytic effect of LH is mediated by a drop in StAR and 3beta-HSD expression without effect on P450(scc) expression. We also provide the first in vivo evidence indicating that a decrease in luteal progesterone content may be an essential step toward the induction of 20alpha-HSD expression at the end of pregnancy in rats.
妊娠末期血清孕酮水平降低对大鼠分娩的启动至关重要。我们先前已证明，促黄体生成素（LH）通过以下方式参与这一过程：1）抑制3β-羟基类固醇脱氢酶（3β-HSD）活性；2）通过诱导20α-羟基类固醇脱氢酶（20α-HSD）活性来刺激孕酮分解代谢。本研究的目的是确定LH和孕酮对类固醇生成急性调节蛋白（StAR）、细胞色素P450侧链裂解酶（P450(scc)）、3β-HSD和20α-HSD基因在黄体中的表达的影响。在妊娠第19天给予LH或溶剂后24小时和48小时，通过Northern印迹分析来分析基因表达。在所研究的两个时间点，LH处理组大鼠的StAR和3β-HSD mRNA水平均低于给予溶剂的大鼠。LH对P450(scc) mRNA水平无影响。处理24小时后，LH组和对照组大鼠的20α-HSD mRNA水平无差异；然而，处理48小时后，LH处理组大鼠的20α-HSD表达相对于对照组有所增加。在所研究的两个时间点，LH处理组大鼠的黄体孕酮含量均下降，而血清孕酮仅在48小时后降低。在第二组实验中，于妊娠第20天向囊内注射抗孕酮药物RU486。RU486对3β-HSD或P450(scc)表达无影响，但处理8小时后可增加20α-HSD mRNA水平。总之，LH的溶黄体作用是通过StAR和3β-HSD表达下降介导的，而对P450(scc)表达无影响。我们还提供了首个体内证据，表明黄体孕酮含量降低可能是大鼠妊娠末期诱导20α-HSD表达的关键步骤。
