Regulation of Reproductive Activity by Steroid Hormone Metabolizing Enzymes

20 α-羟基类固醇脱氢酶（20 α-HSD）将孕酮分解代谢成生物学上无活性的20 α-二氢孕酮，并在类固醇代谢中起重要作用，孕酮对实现和维持妊娠起关键作用，并且是多种类固醇激素的主要前体。特别是在啮齿类动物中，黄体中这种酶活性的增加导致外周孕酮水平的快速下降，这种机制使啮齿类动物能够实现非常短的排卵周期（每个周期约4天）。通过催乳素（PRL）抑制20 α-HSD活性的增加，实现并维持啮齿动物的妊娠。本研究从细胞水平和分子水平对20 α-HSD及其活性调控机制进行了研究，主要结果如下：1）卵巢20 α-HSD完全纯化; 2）卵巢20 α-HSD有两种类型，分子量相近（33，000），离子强度不同; 3）获得了抗20 α-HSD的抗血清，结果表明：PRL对20 α-HSD的抑制作用是通过黄体巨噬细胞分泌的转化生长因子-β（TGF-β）介导的; 5）制备大鼠卵巢cDNA文库，获得20 α-HSD cDNA克隆。

20a-hydroxysteroid dehydrogenase (20alpha-HSD) catabolizes progesterone, which plays a crucial role to achieve and maintain pregnancy and is a major precursor of several steroid hormones, into biologically inactive 20a-dihydroprogesterone and plays important roles in steroid metabolism. Especially in rodents, the increase of this enzyme activity in the corpus luteum causes the rapid decrease of peripheral progesterone levels and this mechanism enable rodents to actualize very short ovulation cycle (about 4 days per a cycle). Pregnancy of the rodents is achieved and maintained by the inhibition of this increase in 20alpha-HSD activity by prolactin (PRL). In this research, we studied about this enzyme and the mechanism of the regulation of the activity at cellular and molecular level, and the results are as follows.1) Ovarian 20alpha-HSDs were completely purified 2) There are two types of 20alpha-HSD with very close molecular weight (33,000) and with different ionic strengths.3) Anti-20alpha-HSD antiserum were obtained, and cellular and intracellular localization was analyzed by immunocytochemi story and western blotting.4) We found that suppressive action of PRL on the enzyme activity is mediated by transforming growth factor-beta (TGF-beta) which is produced by luteal macrophages.5) cDNA library of rat ovary was prepared to get clone of 20alpha-HSD cDNA.