Agarwal S K, Vogel K, Weitsman S R, Magoffin D A
Department of Obstetrics and Gynecology, Cedars-Sinai Burns and Allen Research Institute, Cedars-Sinai Medical Center/University of California Los Angeles School of Medicine, 90048, USA.
J Clin Endocrinol Metab. 1999 Mar;84(3):1072-6. doi: 10.1210/jcem.84.3.5543.
There is increasing evidence that leptin is a physiological link between obesity and infertility. Although leptin receptors have been demonstrated in human ovaries, there is no information regarding the effects of leptin on cells from developing ovarian follicles. To test the direct effects of leptin on human ovarian cells, granulosa cells (GC) and theca cells were isolated from the ovaries of regularly cycling women. Serum was obtained at the time of surgery, and follicular fluid was aspirated from the follicles before isolation of the ovarian cells. Leptin concentrations were similar in follicular fluid and serum. RT-PCR analysis demonstrated that the long, signaling form of the leptin receptor was expressed in both theca and GC. In cultured GC, leptin had no effect on estradiol production, alone or in the presence of FSH, but caused a concentration-related inhibition of the insulin-like growth factor I (IGF-I) augmentation of FSH-stimulated estradiol production. The effect of leptin was specific, because there was no effect on progesterone production. In cultured theca cells, leptin did not alter androstenedione production, alone or in the presence of LH. Leptin caused a concentration-related inhibition of the IGF-I augmentation of LH-stimulated androstenedione production. These data demonstrate that leptin can directly inhibit IGF-I action in ovarian theca and GC at concentrations commonly present in obese women.
越来越多的证据表明，瘦素是肥胖与不孕症之间的生理联系。尽管已在人类卵巢中证实存在瘦素受体，但关于瘦素对发育中的卵巢卵泡细胞的影响尚无相关信息。为了测试瘦素对人卵巢细胞的直接作用，从月经周期正常的女性卵巢中分离出颗粒细胞（GC）和卵泡膜细胞。手术时采集血清，在分离卵巢细胞前从卵泡中抽吸卵泡液。卵泡液和血清中的瘦素浓度相似。逆转录聚合酶链反应（RT-PCR）分析表明，瘦素受体的长信号形式在卵泡膜细胞和颗粒细胞中均有表达。在培养的颗粒细胞中，瘦素单独或在促卵泡激素（FSH）存在的情况下对雌二醇的产生没有影响，但会导致胰岛素样生长因子I（IGF-I）增强FSH刺激的雌二醇产生呈浓度相关的抑制作用。瘦素的作用具有特异性，因为对孕酮的产生没有影响。在培养的卵泡膜细胞中，瘦素单独或在促黄体生成素（LH）存在的情况下不会改变雄烯二酮的产生。瘦素会导致IGF-I增强LH刺激的雄烯二酮产生呈浓度相关的抑制作用。这些数据表明，在肥胖女性中常见的浓度下，瘦素可直接抑制卵巢卵泡膜细胞和颗粒细胞中的IGF-I作用。
