Ghersevich S, Nokelainen P, Poutanen M, Orava M, Autio-Harmainen H, Rajaniemi H, Vihko R
Biocenter Oulu, University of Oulu, Finland.
Endocrinology. 1994 Oct;135(4):1477-87. doi: 10.1210/endo.135.4.7925110.
17 beta-Hydroxysteroid dehydrogenase (17HSD) catalyzes the reversible conversion of estrone into estradiol. The complementary DNA (cDNA) coding for rat 17HSD type 1 was cloned from a commercial rat ovarian cDNA library, using human 17HSD type 1 cDNA as a probe. The nucleotide sequence extends for 1160 basepairs (bp), including 1035 bp of open reading frame, a stop codon, and 125 bp of 3'-untranslated sequence. The cDNA encodes a protein of 344 amino acids, with a calculated molecular mass of 36,967 daltons. The overall amino acid identity and similarity between rat and human 17HSD type 1 enzymes are 68% and 80%, respectively. Immunohistochemistry and in situ and Northern hybridizations were used to study regulation of the enzyme in rat ovary in vivo. Enzyme expression was detected in granulosa cells only, whereas no expression was observed in stromal or thecal cells. The enzyme was almost undetectable in ovaries from immature hypophysectomized rats. After 2-day treatment with recombinant FSH (recFSH), an induction of 17HSD type 1 expression was observed in granulosa cells of growing antral follicles. During 5 days of diethylstilbestrol (DES) treatment, a time-dependent increase in developing follicles was observed, showing strong expression of 17HSD type 1 in granulosa cells. Treatment with recFSH for 2 days in DES-primed animals resulted in down-regulation of ovarian enzyme expression. This reduction of enzyme expression was associated with luteinization of the follicles. hCG treatment of recFSH- or DES- plus recFSH-primed animals further induced luteinization, resulting in strong down-regulation of 17HSD type 1 expression. The enzyme was not detected in corpora lutea. The data show that 17HSD type 1 expression in rat ovary is regulated by gonadotropins and estrogens. The results suggest that expression of 17HSD type 1 and that of cytochrome P450 aromatase are regulated by distinct mechanisms, and 17HSD type 1 may be down-regulated earlier than P450 aromatase during luteinization, limiting estradiol biosynthesis in luteinizing granulosa cells in rat ovary.
17β-羟类固醇脱氢酶（17HSD）催化雌酮与雌二醇之间的可逆转化。以人17HSD 1型cDNA为探针，从市售大鼠卵巢cDNA文库中克隆出编码大鼠1型17HSD的互补DNA（cDNA）。核苷酸序列延伸1160个碱基对（bp），包括1035 bp的开放阅读框、一个终止密码子和125 bp的3'非翻译序列。该cDNA编码一种含344个氨基酸的蛋白质，计算分子量为36967道尔顿。大鼠和人1型17HSD酶之间的总体氨基酸同一性和相似性分别为68%和80%。采用免疫组织化学、原位杂交和Northern杂交技术研究了该酶在大鼠卵巢中的体内调节。仅在颗粒细胞中检测到酶表达，而在基质细胞或卵泡膜细胞中未观察到表达。在未成熟垂体切除大鼠的卵巢中几乎检测不到该酶。用重组促卵泡激素（recFSH）处理2天后，在生长中的窦状卵泡的颗粒细胞中观察到1型17HSD表达的诱导。在己烯雌酚（DES）处理的5天中，观察到发育卵泡的时间依赖性增加，显示颗粒细胞中1型17HSD的强表达。在DES预处理的动物中用recFSH处理2天导致卵巢酶表达下调。酶表达的这种降低与卵泡的黄体化有关。用人绒毛膜促性腺激素（hCG）处理recFSH或DES加recFSH预处理的动物进一步诱导黄体化，导致1型17HSD表达的强烈下调。在黄体中未检测到该酶。数据表明，大鼠卵巢中1型17HSD的表达受促性腺激素和雌激素调节。结果表明，1型17HSD和细胞色素P450芳香化酶的表达受不同机制调节，并且在黄体化过程中1型17HSD可能比P450芳香化酶更早下调，限制了大鼠卵巢黄体化颗粒细胞中雌二醇的生物合成。
