Yu F H, Yun Y W, Yuen B H, Moon Y S
Department of Obstetrics and Gynaecology, University of British Columbia, Grace Hospital, Vancouver, Canada.
Can J Physiol Pharmacol. 1991 Feb;69(2):185-90. doi: 10.1139/y91-027.
Immature female rats treated with superovulatory doses of pregnant mare serum gonadotropin (PMSG) were used to study the effects of the antiandrogen hydroxyflutamide on steroid production, particularly the biologically active androgens, in two experiments. In the first experiment, animals were given either 5 mg hydroxyflutamide or vehicle alone at 30 and 36 h following 40 IU PMSG. Compared with the vehicle group, hydroxyflutamide treatment significantly reduced the percentage of degenerate oocytes recovered from oviducts (p less than 0.05). Serum levels of testosterone and androstenedione, and their aromatized product 17 beta-estradiol, significantly decreased (p less than 0.05) in the hydroxyflutamide-treated group; however, nonaromatizable androgen, 5 alpha-dihydrotestosterone, was not affected. In the second experiment, ovaries obtained 48 h after stimulation with 4 or 40 IU PMSG were incubated with and without hydroxyflutamide (10(-5) M) and (or) testosterone (10(-7) M) to study [4-14C]pregnenolone metabolism to major steroids. In 40 IU stimulated ovaries, hydroxyflutamide significantly decreased the metabolism of pregnenolone to progesterone (p less than 0.01) and androstenedione (p less than 0.01), while the production of 17 beta-estradiol increased significantly (p less than 0.05); however, pregnenolone conversions to testosterone and 5 alpha-dihydrotestosterone were not affected. Testosterone completely reversed the hydroxyflutamide-induced alteration of pregnenolone metabolism. In contrast, there was no difference in the pregnenolone conversion patterns between untreated and hydroxyflutamide or hydroxyflutamide plus testosterone groups in 4 IU stimulated ovaries. Present results confirm our previous finding that hydroxyflutamide decreases the percentage of abnormal oocytes recovered from superovulating rats and indicates that this hydroxyflutamide effect may be partly mediated by altered ovarian steroidogenesis following inhibition of androgen binding in the ovary.
在两项实验中，使用用超排卵剂量的孕马血清促性腺激素（PMSG）处理的未成熟雌性大鼠来研究抗雄激素羟基氟他胺对类固醇生成的影响，特别是对生物活性雄激素的影响。在第一项实验中，在给予40 IU PMSG后的30和36小时，给动物单独注射5毫克羟基氟他胺或赋形剂。与赋形剂组相比，羟基氟他胺处理显著降低了从输卵管回收的退化卵母细胞的百分比（p<0.05）。羟基氟他胺处理组的血清睾酮和雄烯二酮水平及其芳香化产物17β-雌二醇显著降低（p<0.05）；然而，不可芳香化的雄激素5α-二氢睾酮不受影响。在第二项实验中，将在4或40 IU PMSG刺激后48小时获得的卵巢与有或没有羟基氟他胺（10^-5 M）和（或）睾酮（10^-7 M）一起孵育，以研究[4-14C]孕烯醇酮向主要类固醇的代谢。在40 IU刺激的卵巢中，羟基氟他胺显著降低了孕烯醇酮向孕酮（p<0.01）和雄烯二酮（p<0.01）的代谢，而17β-雌二醇的生成显著增加（p<0.05）；然而，孕烯醇酮向睾酮和5α-二氢睾酮的转化不受影响。睾酮完全逆转了羟基氟他胺诱导的孕烯醇酮代谢改变。相比之下，在4 IU刺激的卵巢中，未处理组与羟基氟他胺组或羟基氟他胺加睾酮组之间的孕烯醇酮转化模式没有差异。目前的结果证实了我们之前的发现，即羟基氟他胺降低了从超排卵大鼠中回收的异常卵母细胞的百分比，并表明这种羟基氟他胺效应可能部分是由卵巢中雄激素结合受到抑制后卵巢类固醇生成的改变介导的。
