Magoffin D A, Erickson G F
Endocrinology. 1981 Mar;108(3):962-9. doi: 10.1210/endo-108-3-962.
The mechanism by which 17 beta-estradiol inhibits ovarian androgen biosynthesis was investigated. Immature 25-day-old rats were treated for 2 days with estradiol, after which whole ovaries were dispersed, and gonadotropin binding and cAMP and steroid hormone production were examined. When dispersed cells from untreated control ovaries were incubated with hCG (100 ng/ml), there were marked increases (10-fold) in steroid production, with the major steroids being progesterone and androstenedione. The stimulation of steroidogenesis by hCG was dose-related (ED50 = 100 pg/ml hCG). After 2 days of estradiol treatment, the maximum hCG stimulation of androstenedione, testosterone, 17 alpha-hydroxypregnenolone, and 17 alpha-hydroxyprogesterone production by ovarian cells was inhibited by 90%; pregnenolone production was unchanged, while progesterone production was increased by 30%. Time course studies showed that the stimulatory effect of hCG on androgen production was maximally inhibited (90%) after 12 h of estradiol treatment. Implanting miniestradiol capsules unilaterally under the ovarian bursa caused a 77% decrease in the hCG stimulation of androgen production by the estradiol-treated cells, while progesterone production was unchanged. hCG-stimulated steroidogenesis in the contralateral ovary was not altered. Estradiol treatment did not affect the binding capacity, the hCG stimulation of cAMP production, or the number of steroid-producing cells in the ovaries. It is concluded from these experiments that exogenous estradiol acts directly on the rat ovary to abolish the hCG stimulation of androgen production by rapidly inhibiting 17 alpha-hydroxylation.
研究了17β-雌二醇抑制卵巢雄激素生物合成的机制。对25日龄未成熟大鼠用雌二醇处理2天，之后将整个卵巢分散，并检测促性腺激素结合、环磷酸腺苷（cAMP）及类固醇激素的产生。当将未处理的对照卵巢的分散细胞与绒毛膜促性腺激素（hCG，100 ng/ml）一起孵育时，类固醇生成显著增加（10倍），主要类固醇为孕酮和雄烯二酮。hCG对类固醇生成的刺激呈剂量依赖性（半数有效剂量[ED50]=100 pg/ml hCG）。雌二醇处理2天后，卵巢细胞对hCG刺激产生雄烯二酮、睾酮、17α-羟孕烯醇酮和17α-羟孕酮的最大反应受到90%的抑制；孕烯醇酮生成未改变，而孕酮生成增加了30%。时间进程研究表明，雌二醇处理12小时后，hCG对雄激素生成的刺激作用受到最大程度抑制（90%）。在卵巢囊下单侧植入微型雌二醇胶囊，可使经雌二醇处理的细胞对hCG刺激产生雄激素的反应降低77%，而孕酮生成未改变。对侧卵巢中hCG刺激的类固醇生成未受影响。雌二醇处理不影响卵巢中促性腺激素的结合能力、hCG刺激的cAMP生成或类固醇生成细胞的数量。从这些实验得出结论，外源性雌二醇直接作用于大鼠卵巢，通过快速抑制17α-羟化作用来消除hCG对雄激素生成的刺激。
