Mechanism by which GnRH inhibits androgen synthesis directly in ovarian interstitial cells.
Mechanism by which GnRH inhibits androgen synthesis directly in ovarian interstitial cells.
复制标题
GnRH 直接抑制卵巢间质细胞雄激素合成的机制。
DOI：
10.1016/0303-7207(82)90108-3
复制
发表时间：
1982
影响因子：
4.1
通讯作者：
Erickson,GF
中科院分区：
文献类型：
--
作者：
Magoffin,DA;Erickson,GF
在垂体切除的未成熟大鼠卵巢细胞的原代培养物中研究了 GnRH 作用于卵巢间质细胞抑制雄激素合成的机制。在含有 LH 的确定培养基中培养的间质细胞显示类固醇产量增加了 200 倍，其中雄酮是主要代谢物（占类固醇总含量的 88%）。 GnRH (10−8M) 治疗可抑制 LH 刺激的雄酮产生 92%。 GnRH 的这种抑制作用不是由于细胞数量、细胞活力或 125 I-hCG 结合能力的变化所致。前列腺素 E2、霍乱毒素和 8-Br-环 AMP 模拟 LH 对雄酮合成的影响，并且这些增加也受到 GnRH 的抑制。 GnRH 处理培养物的代谢研究表明，LH 刺激的雄酮和 5α-雄甾烷-3α,17β-二醇减少了 90%；雄烯二酮、睾酮和DHEA下降70%； 17α-羟基孕烯醇酮和17α-羟基孕酮降低50%；孕烯醇酮没有变化；黄体酮增加了40%。总的来说，这些结果表明 GnRH 通过选择性抑制 17α-羟化酶和 C17−20 去氨酶活性，直接抑制卵巢间质细胞中的雄激素合成。
The mechanism by which GnRH acts on ovarian interstitial cells to inhibit androgen synthesis was studied in primary cultures of ovarian cells from hypophysectomized immature rats. Interstitial cells cultured in defined medium with LH showed a 200-fold increase in steroid production, of which androsterone was the principal metabolite (88% of the total steroid content). Treatment with GnRH (10−8M) inhibited LH-stimulated androsterone production by 92%. This inhibitory effect of GnRH was not due to changes in cell number, cell viability, or125I-hCG binding capacity. Prostaglandin E2, cholera toxin and 8-Br-cyclic AMP mimicked the LH effect on androsterone synthesis and these increases were also inhibited by GnRH. Metabolic studies of GnRH-treated cultures revealed that LH-stimulated androsterone and 5α-androstane-3α,17β-diol were decreased by 90%; androstenedione, testosterone and DHEA were decreased by 70%; 17α-hydroxypregnenolone and 17α-hydroxyprogesterone were decreased by 50%; pregnenolone was unchanged; and progesterone was increased 40%. Collectively, these results suggest that GnRH directly inhibits androgen synthesis in ovarian interstitial cells by selectively inhibiting the 17α-hydroxylase and C17−20desmolase activities.