ALTERATIONS IN GRANULOSA-CELL AROMATASE-ACTIVITY ACCOMPANYING PREOVULATORY FOLLICULAR DEVELOPMENT IN THE RAT OVARY WITH EVIDENCE THAT 5-ALPHA-REDUCED C-19 STEROIDS INHIBIT THE AROMATASE REACTION INVITRO
ALTERATIONS IN GRANULOSA-CELL AROMATASE-ACTIVITY ACCOMPANYING PREOVULATORY FOLLICULAR DEVELOPMENT IN THE RAT OVARY WITH EVIDENCE THAT 5-ALPHA-REDUCED C-19 STEROIDS INHIBIT THE AROMATASE REACTION INVITRO
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DOI：
10.1677/joe.0.0840409
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发表时间：
1980-01-01
影响因子：
4
通讯作者：
VANHALL, EV
中科院分区：
文献类型：
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作者：
HILLIER, SG;VANDENBOOGAARD, AMJ;VANHALL, EV
局部产生的雄激素和雌激素被认为是卵泡发育的激素调节的重要因素。在体外研究卵泡成熟度和颗粒细胞芳香化酶活性之间的关系。从成年大鼠卵巢中最大的窦状卵泡收获的颗粒细胞产生的免疫反应性雌二醇的量可以忽略不计孵育3小时时，在体外，无论当天的发情周期后，他们获得。此外，芳香化C19类固醇底物（睾酮，雄烯二酮或19-hydroxyandrostenedione）的孵育培养基中的雌二醇的生产，这是在体内达到的卵泡成熟度的水平相关的时间和浓度依赖性增加。通过使用睾酮（10-7 mol/l）作为底物测量雌二醇的产生，在阴道间情的第1天获得的颗粒细胞的芳香化酶活性仅为发情前期早晨获得的细胞所观察到的芳香化酶活性的一小部分（小于5%）。在动情间期第2天获得的细胞显示出中等水平的活性，保持约5 × 10 - 6。动情前期低于颗粒细胞。这些观察结果，因此，建立诱导或激活颗粒细胞芳香化酶活性作为一个相关的正常排卵前卵泡发育。然而，卵泡内雄激素/雌激素比例也可能受到芳香化酶反应可用的C19甾体底物的定量和/或定性改变的影响。因此，天然存在的不可芳构化的5 α-还原雄激素代谢物，5 α-二氢睾酮和5.雄烷二酮，证明是颗粒细胞芳香化酶反应的有效竞争性抑制剂。在这方面，这些具有生物活性的雄激素中的每一种都比1-烯-睾内酯（一种已建立的C19甾体芳香酶抑制剂）更有效。由于C19类固醇5 α-还原酶是一种卵巢酶，通过影响激素环境的雄激素/雌激素组成，这种酶活性的局部改变可能是排卵前卵泡发育和功能的额外决定因素。
Locally produced androgens and estrogens are thought to be important factors in the hormonal regulation of follicular development. The relationship between follicular maturity and granulosa cell aromatase activity was examined in vitro. Granulosa cells harvested from the largest antral follicles in adult rat ovaries produced negligible amounts of immunoreactive estradiol when incubated for 3 h in vitro irrespective of the day of the estrous cycle upon which they were obtained. The addition of aromatizable C19 steroid substrate (testosterone, androstenedione or 19-hydroxyandrostenedione) to the incubation medium resulted in time- and concentration-dependent increases in estradiol production which were related to the level of follicular maturity attained in vivo. By measuring estradiol production using testosterone (10-7 mol/l) as substrate, the aromatase activity of granulosa cells obtained on the 1st day of vaginal diestrus was only a fraction (less than 5%) of that observed for cells obtained on the morning of proestrus. Cells obtained on the 2nd day of diestrus displayed an intermediate level of activity which remained approximately 5 .times. lower than that of granulosa cells at proestrus. These observations, therefore, establish the induction or activation of granulosa cell aromatase activity as a correlate of normal preovulatory follicular development. However, intrafollicular androgen/estrogen ratios may also be influenced by quantitative and/or qualitative alterations in the C19 steroidal substrate available for the aromatase reaction. Thus, the naturally occurring non-aromatizable 5.alpha.-reduced androgen metabolites, 5.alpha.-dihydrotestosterone and 5.alpha.-androstanedione, proved to be potent competitive inhibitors of the granulosa cell aromatase reaction in vitro. In this respect each of these biologically active androgens was more effective than 1-ene-testololactone, an established C19 steroidal aromatase inhibitor. Since C19 steroid 5.alpha.-reductase is an ovarian enzyme, by affecting the androgenic/estrogenic composition of the hormonal milieu, local alterations in the activity of this enzyme may be an additional determinant of preovulatory follicular development and function.