ESTROGEN REGULATION OF THECAL CELL STEROIDOGENESIS AND DIFFERENTIATION - THECAL CELL-GRANULOSA CELL-INTERACTIONS
ESTROGEN REGULATION OF THECAL CELL STEROIDOGENESIS AND DIFFERENTIATION - THECAL CELL-GRANULOSA CELL-INTERACTIONS
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DOI：
10.1210/endo-127-6-2918
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发表时间：
1990-12-01
期刊：
影响因子：
4.8
通讯作者：
SKINNER, MK
中科院分区：
文献类型：
--
作者：
ROBERTS, AJ;SKINNER, MK
用来自卵巢窦卵泡的细胞研究了雌激素对膜细胞类固醇生成和分化的调节。分离牛卵泡膜内细胞并在无血清条件下培养，以评估雌二醇对卵泡膜细胞产生雄烯二酮、睾酮和黄体酮的影响。雌二醇在整个 6 天的培养期内增加了鞘细胞雄激素的产生；然而，培养第3天后，雄激素产生的基础水平和刺激水平下降。雄烯二酮的积累量大约是睾酮的10倍。与雌二醇对雄激素产生的刺激作用相反，雌二醇在整个 6 天的培养期间抑制黄体酮的产生。比较雌二醇和 hCG 对小 (< 5 mm)、中 (5-10 mm) 和大 (> 10 mm) 窦卵泡的膜细胞的影响表明，对于卵泡发育所有这些阶段的细胞，雌二醇比 hCG 更大程度地刺激雄激素产生。雌二醇对小卵泡卵泡膜中雄烯二酮的刺激大于中型或大卵泡卵泡膜中的雌二醇对雄烯二酮的刺激。相反，雌二醇对孕酮的抑制作用在中型和大卵泡的膜细胞上最明显，而在小卵泡的膜细胞上不太明显。雌二醇以剂量依赖性方式刺激雄烯二酮的产生，最小有效浓度为 10-9 M，最大有效浓度为 10-7-10-6 M。雌二醇浓度大于 10-6 M 会导致刺激反应下降，并且可能对排卵前卵泡抑制鞘细胞雄激素产生并启动黄体化过程很重要。 10-9M雌二醇轻微刺激孕酮产生，而较高浓度（10-7-5×10-6M）导致孕酮产生的剂量依赖性抑制。有趣的是，雌二醇和 hCG 联合治疗鞘膜细胞对雄烯二酮产生的刺激大于相加，并且雌二醇降低了 hCG 刺激黄体酮产生的能力。观察结果表明，雌二醇可以显着改变鞘细胞产生类固醇，并支持类固醇介导的颗粒细胞和鞘细胞之间的相互作用在调节卵泡内细胞功能中发挥重要作用的假设。这些数据提供的证据表明，卵巢卵泡中可能存在局部反馈回路，卵泡膜细胞产生的雄激素被用作颗粒细胞芳构化为雌激素的底物，而雌激素反过来又可能反馈刺激卵泡膜细胞产生雄激素。获得的信息提供了对调节鞘细胞功能的机制的深入了解，并表明雌二醇可能在控制鞘细胞功能和分化中发挥重要作用。
Estrogen regulation of thecal cell steroidogenesis and differentiation was investigated with cells from ovarian antral follicles. Bovine theca interna cells were isolated and cultured in serum-free conditions to evaluate the effects of estradiol on thecal cell production of androstenedione, testosterone, and progesterone. Estradiol increased thecal cell androgen production throughout a 6-day culture period; however, the basal and stimulated levels of androgen production diminished after day 3 of culture. Androstenedione accumulation was approximately 10-fold greater than that of testosterone. In contrast to the stimulatory effects that estradiol had on androgen production, estradiol suppressed progesterone production throughout the 6-day culture period. Comparison of the effects of estradiol and hCG on thecal cells from small (< 5 mm), medium (5-10 mm), and large (> 10 mm) antral follicles demonstrated that estradiol stimulated androgen production to a greater extent than hCG with cells from all of these stages of follicle development. Estradiol stimulation of androstenedione was greater in theca from small follicles than in theca from medium or large follicles. In contrast, suppressive effects of estradiol on progesterone were most apparent on thecal cells from medium and large follicles and less apparent on theca from small follicles. Estradiol stimulated androstenedione production in a dose-dependent fashion, with a minimum effective concentration of 10-9 M and a maximum effective concentration of 10-7-10-6 M. Concentrations greater than 10-6 M estradiol resulted in a decline in the stimulatory response and may be important in the preovulatory follicle to suppress thecal cell androgen production and initiate the process of luteinization. Progesterone production was slightly stimulated by 10-9 M estradiol, whereas higher concentrations (10-7-5 .times. 10-6 M) resulted in a dose-dependent suppression of progesterone production. Interestingly, combined treatment of thecal cells with estradiol and hCG resulted in a greater than additive stimulation of androstenedione production, and estradiol decreased the ability of hCG to stimulate progesterone production. Observations demonstrate that estradiol can dramatically alter thecal cell production of steroids and support a hypothesis that steroid-mediated interactions between granulosa and thecal cells play an important role in regulating cellular function within follicles. The data provide evidence that a local feedback loop may exist in ovarian follicles, where androgens produced by thecal cells are used as a substrate for granulosa cell aromatization into estrogens, which, in turn, may feed back to stimulate thecal cell production of androgens. The information obtained provides insight into the mechanisms involved in regulating thecal cell function and indicates that estradiol may have an important role in the control of thecal cell function and differentiation.