PROGESTERONE INHIBITS THE INDUCTION OF AROMATASE-ACTIVITY IN RAT GRANULOSA-CELLS INVITRO
PROGESTERONE INHIBITS THE INDUCTION OF AROMATASE-ACTIVITY IN RAT GRANULOSA-CELLS INVITRO
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DOI：
10.1095/biolreprod28.5.1078
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发表时间：
1983-01-01
影响因子：
3.6
通讯作者：
VINCENT, SE
中科院分区：
文献类型：
--
作者：
FORTUNE, JE;VINCENT, SE
在孕酮循环水平较高的生殖状态下，排卵卵泡的发育受到抑制。研究了孕酮在体外对大鼠颗粒细胞分泌雌二醇的影响，以确定孕酮是否对卵泡芳香化有直接影响。从垂体切除(HPX)、己烯雌酚处理的未成熟大鼠中获得相对未分化的颗粒细胞，并从发情前期早晨的排卵前卵泡中获得分化的颗粒细胞。当HPX或发情前期细胞与FSH(300ng/ml)和睾酮(0.5μM)一起培养时，黄体酮以剂量依赖性方式抑制雌二醇的积累，但来自发情前期大鼠的颗粒细胞对黄体酮的抑制作用较不敏感。当首次通过与 FSH 一起培养 HPX 大鼠的细胞 1、2 或 3 天来诱导芳香酶时，细胞在随后 3 天的培养过程中不太容易受到孕酮的抑制作用。当细胞暴露于孕酮超过 1 天时，孕酮对雌二醇分泌的抑制作用似乎不可逆转。孕酮对 HPX 颗粒细胞的作用是特异性的，因为孕酮前体孕烯醇酮与孕酮一样具有抑制作用，而孕酮代谢物 17α-羟基孕酮则没有作用。当发情前卵泡的颗粒细胞与睾酮和分级剂量的黄体酮一起培养时，雌二醇的产生出现轻微抑制。这种抑制比存在 FSH 时观察到的抑制要小得多。黄体酮的抑制作用主要是通过 FSH 诱导芳香酶发挥作用，而不是影响现有芳香酶的功能。在存在或不存在 FSH 和/或睾酮的情况下，还用分级剂量的黄体酮培养整个发情前卵泡。在这些实验中，孕酮在培养的第一天增加了雌二醇，但在培养后期抑制了 FSH 在维持雌二醇分泌方面的作用。黄体酮对颗粒细胞产生雌二醇具有特异性且不可逆的抑制作用。分化程度较低的颗粒细胞似乎对孕酮的抑制作用更敏感。显然，体内孕酮可能通过抑制发育卵泡颗粒细胞中的芳香酶来直接抑制排卵卵泡的发育。
The development of ovulatory follicles is suppressed during reproductive states with high circulating levels of progesterone. The effects of progesterone on estradiol secretion by rat granulosa cells in vitro were investigated to determine if progesterone has direct effects on follicular aromatization. Relatively undifferentiated granulosa cells were obtained from hypophysectomized (HPX), diethylstilbestrol-treated immature rats and differentiated granulosa cells were obtained from preovulatory follicles on the morning of proestrus. Progesterone suppressed, in a dose-dependent fashion, the accumulation of estradiol when HPX or proestrous cells were cultured with FSH (300 ng/ml) and testosterone (0.5 .mu.M), but granulosa cells from proestrous rats were less sensitive to the inhibitory effects of progesterone. When aromatase was first induced in cells from HPX rats by culturing them for 1, 2 or 3 days with FSH, the cells were less susceptible to the inhibitory effects of progesterone during the subsequent 3 days of culture. The inhibitory effects of progesterone on estradiol secretion appeared irreversible when cells were exposed to progesterone for longer than 1 day. The effects of progesterone on HPX granulosa cells were specific since the progesterone precursor, pregnenolone, was as inhibitory as progesterone, while the progesterone metabolite, 17.alpha.-hydroxyprogesterone, had no effect. When granulosa cells from proestrous follicles were cultured with testosterone and graded doses of progesterone, a slight inhibition of estradiol production occurred. This inhibition was much less than that observed when FSH was present. The inhibitory effects of progesterone are exerted primarily on the induction of aromatase by FSH, rather than on the functioning of existing aromatase. Whole proestrous follicles were also cultured with graded doses of progesterone in the presence or absence of FSH and/or testosterone. In those experiments progesterone increased estradiol on the first day of culture, but inhibited the effects of FSH in maintaining estradiol secretion later in culture. Progesterone exerts a specific and irreversible inhibitory effect on estradiol production by granulosa cells. Less differentiated granulosa cells appear to be more sensitive to the inhibitory effects of progesterone. Apparently, in vivo progesterone may directly suppress development of ovulatory follicles by inhibiting aromatase in granulosa cells of developing follicles.