Leptin impairs the synergistic stimulation by transforming growth factor-beta of follicle-stimulating hormone-dependent aromatase activity and messenger ribonucleic acid expression in rat ovarian granulosa cells.
Leptin impairs the synergistic stimulation by transforming growth factor-beta of follicle-stimulating hormone-dependent aromatase activity and messenger ribonucleic acid expression in rat ovarian granulosa cells.
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DOI：
10.1095/biolreprod61.4.1104
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发表时间：
1999-10
影响因子：
3.6
通讯作者：
R. Zachow;S. Weitsman;D. Magoffin
中科院分区：
文献类型：
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作者：
R. Zachow;S. Weitsman;D. Magoffin
瘦素阻断胰岛素样生长因子-I诱导的大鼠卵巢颗粒细胞（GC）FSH依赖性雌二醇-17 β（E（2））产生的增加为了确定瘦素的作用是否延伸到另一种FSH依赖性E（2）产生的正调节剂，研究了瘦素对转化生长因子β（TGF-β）的直接卵巢效应。逆转录聚合酶链反应表明，垂体切除大鼠的卵泡膜间质细胞（TIC）仅表达瘦素受体mRNA的非信号传导亚型（OB-Ra）。瘦素对TIC雄激素的产生没有影响。与此相反，mRNA的OB-Ra和信号转导（OB-Rb）瘦素受体亚型在GC中表达。当从26日龄大鼠获得的GC与FSH和雄烯二酮一起培养（48小时）时，雌酮（E（1））和E（2）水平均高于未处理的对照组。在FSH（0.1 IU/ml）存在下，TGF-β（10 ng/ml）分别增强E（2）和E（1）蓄积2.7倍和1.45倍。瘦素不改变基础或FSH刺激的E（2）和E（1）水平。然而，瘦素抑制TGF-β对FSH依赖的E（2）和E（1）的作用分别为39%和29%。芳香化酶细胞色素P450（P450（arom））mRNA的表达和P450（arom）的活性增加FSH和TGF-β的加入进一步增强。瘦素消除TGF-β对P450（arom）mRNA表达的影响，并使P450（arom）活性降低约27%。这些数据支持的假设，瘦素拮抗TGF-β对FSH依赖性雌激素产生的刺激作用的机制，涉及瘦素诱导的衰减P450（arom）的活性和mRNA表达在GC。
Leptin blocks the insulin-like growth factor-I-induced increase in FSH-dependent estradiol-17beta (E(2)) production by rat ovarian granulosa cells (GC) in vitro. To determine whether the leptin effect extended to another positive modulator of FSH-dependent E(2) production, the direct ovarian effects of leptin on transforming growth factor beta (TGF-beta) were investigated. Reverse transcription-polymerase chain reaction demonstrated that theca-interstitial cells (TIC) from hypophysectomized rats expressed only a nonsignal-transducing isoform (OB-Ra) of leptin receptor mRNA. Leptin had no effect on TIC androgen production. In contrast, mRNAs for OB-Ra and the signal-transducing (OB-Rb) leptin receptor isoforms were expressed in GC. When GC obtained from 26-day-old rats were cultured (48 h) with FSH and androstenedione, both estrone (E(1)) and E(2) levels increased over those in untreated controls. In the presence of FSH (0.1 IU/ml), TGF-beta (10 ng/ml) potentiated E(2) and E(1) accumulation by 2.7- and 1.45-fold, respectively. Leptin did not alter basal or FSH-stimulated E(2) and E(1) levels. However, leptin suppressed the effect of TGF-beta on FSH-dependent E(2) and E(1) production by 39% and 29%, respectively. Aromatase cytochrome P450 (P450(arom)) mRNA expression and P450(arom) activity were increased by FSH and further augmented by the addition of TGF-beta. Leptin abolished the TGF-beta effect on P450(arom) mRNA expression, and it decreased P450(arom) activity by approximately 27%. These data support the hypothesis that leptin antagonizes the stimulatory effects of TGF-beta on FSH-dependent estrogen production by a mechanism involving the leptin-induced attenuation of P450(arom) activity and mRNA expression in GC.