Ghersevich S, Poutanen M, Tapanainen J, Vihko R
Biocenter Oulu, University of Oulu, Finland.
Endocrinology. 1994 Nov;135(5):1963-71. doi: 10.1210/endo.135.5.7956918.
Ovarian estradiol (E2) production is regulated by complex interaction of different hormones, such as gonadotropins, steroids, and growth factors. Despite the key role of 17 beta-hydroxysteroid dehydrogenase (17HSD) in E2 biosynthesis, little is known about its regulation in the ovary. Recently, we have characterized the structure of rat 17HSD type 1 and demonstrated that its expression is regulated by gonadotropins and diethylstilbestrol (DES) in rat ovary in vivo. In the present study, the hormonal regulation of 17HSD type 1, and the expression of cytochrome P450 aromatase were examined in parallel in cultured granulosa cells obtained from DES-primed immature rats. Under these conditions, the cells show high expression of 17HSD type 1. Both the enzyme activity and 17HSD type 1 messenger RNA expression in these cells decreased over 2 days of culture in serum-free medium. However, recombinant FSH (recFSH) partially prevented the decreases in enzyme activity and messenger RNA expression in a dose-dependent manner. This effect appears to be mediated by a cAMP-dependent pathway. In contrast to recFSH, neither estrogens (DES or E2) nor androgens (testosterone or dihydrotestosterone) alone affected expression of the enzyme in the cultured cells. However, both estrogens and androgens clearly enhanced the effect of recFSH on 17HSD type 1 expression and 17HSD activity in a dose-dependent manner. Among the growth factors, epidermal growth factor (EGF) has previously been shown to decrease the expression of cytochrome P450 aromatase and E2 biosynthesis in granulosa cells. In the present study, we found that treatment with EGF caused a marked decrease in the effect of recFSH on 17HSD type 1 expression and 17HSD activity. The fact that 17HSD type 1 expression and 17HSD activity always behaved in parallel suggests that 17HSD type 1 is the major 17HSD enzyme involved in estradiol biosynthesis in rat granulosa cells. In conclusion, these data indicate that expression of 17HSD type 1 in rat granulosa cells is under multihormonal regulation. The enzyme is regulated by FSH, via cAMP, and the effect of FSH is modulated by estrogens, androgens, and EGF.
卵巢雌二醇（E2）的产生受多种激素复杂相互作用的调节，如促性腺激素、类固醇和生长因子。尽管17β-羟类固醇脱氢酶（17HSD）在E2生物合成中起关键作用，但对其在卵巢中的调节机制知之甚少。最近，我们已对大鼠1型17HSD的结构进行了表征，并证明其表达在体内受大鼠卵巢中促性腺激素和己烯雌酚（DES）的调节。在本研究中，我们同时检测了从经DES预处理的未成熟大鼠获得的培养颗粒细胞中1型17HSD的激素调节以及细胞色素P450芳香化酶的表达。在这些条件下，细胞显示出1型17HSD的高表达。在无血清培养基中培养2天后，这些细胞中的酶活性和1型17HSD信使核糖核酸表达均下降。然而，重组促卵泡激素（recFSH）以剂量依赖的方式部分阻止了酶活性和信使核糖核酸表达的下降。这种作用似乎是由cAMP依赖途径介导的。与recFSH相反，单独的雌激素（DES或E2）和雄激素（睾酮或二氢睾酮）均未影响培养细胞中该酶的表达。然而，雌激素和雄激素均以剂量依赖的方式明显增强了recFSH对1型17HSD表达和17HSD活性的作用。在生长因子中，表皮生长因子（EGF）先前已被证明可降低颗粒细胞中细胞色素P450芳香化酶的表达和E2生物合成。在本研究中，我们发现用EGF处理可导致recFSH对1型17HSD表达和17HSD活性的作用显著降低。1型17HSD表达和17HSD活性总是平行变化这一事实表明，1型17HSD是大鼠颗粒细胞中参与雌二醇生物合成的主要17HSD酶。总之，这些数据表明大鼠颗粒细胞中1型17HSD的表达受多种激素调节。该酶受FSH通过cAMP调节，而FSH的作用受雌激素、雄激素和EGF调节。
