Leptin inhibits steroid biosynthesis by human granulosa-lutein cells
Leptin inhibits steroid biosynthesis by human granulosa-lutein cells
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DOI：
10.1055/s-2001-15419
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发表时间：
2001-06-01
影响因子：
2.2
通讯作者：
Bernasconi, S
中科院分区：
文献类型：
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作者：
Ghizzoni, L;Barreca, A;Bernasconi, S
缺乏瘦素分泌会损害ob/ob小鼠的生殖功能和生育能力，当给予瘦素时，小鼠的血清黄体生成素水平会上升，并变得有生育能力。最近，在卵巢中发现了长而活跃的瘦素受体亚型。这表明瘦素也可能表现出与性腺直接相关的活动。为了验证这一点，我们研究了分级剂量的人瘦素对体外受精妇女卵泡液中的人颗粒黄体细胞培养液中雌二醇(E-2)和孕酮(P-4)浓度的影响。我们还检测了基础状态下这些细胞中类固醇合成急性调节蛋白(STAR)、芳香化酶和细胞色素P45017α(CyP17mRNA)的表达，在瘦素作用下，随着hLeptin浓度的增加(10(-11)-10(-7)mol/L)，细胞孵育24小时后，细胞中雌二醇水平显著下降。当hLeptin浓度为10(-9)m ol/L时，E-2产量最大下降30%，而培养液中P-4水平不受瘦素的影响，当hLeptin(10-9m ol/L)与浓度增加的肝癌(1.25-10mIU/m l)、胰岛素样生长因子-II(15-50 ng/m l)或1-6脱脂细胞间生长因子-II(desIGF-II)共同孵育时，颗粒细胞黄体生成素对STAR、芳香化酶和细胞色素P17m RNA的表达无明显影响；15-60 ng/ml)，但不改变不同刺激引起的E_1浓度升高。我们认为，瘦素抑制人颗粒-黄体细胞分泌E-2，但不影响hCG和IGFS对这些细胞的刺激作用。瘦素可能通过干扰基础C/P17和/或芳香酶合成的翻译或翻译后步骤和/或酶的激活，在未刺激的人卵巢类固醇合成中发挥次要但直接的调节作用。
Absence of leptin secretion compromises reproductive function and fertility in the ob/ob mouse which, when given leptin, shows a rise in serum LH levels and becomes fertile. Recently, the long and active isoform of the leptin receptor was detected in the ovary. indicating that leptin may also show direct gonad-related activity. To examine this, we studied the effect of graded doses of human leptin on estradiol (E-2) and progesterone (P-4) concentrations in the culture media of human granulosa-lutein cells obtained from follicular fluid of women undergoing in vitro fertilization. We also evaluated the mRNA expression of steroidogenic acute regulatory protein (StAR), aromatase, and cytochrome P450 17 alpha (CYP17) in these cells at baseline and after exposure to leptin, Estradiol levels were significantly decreased in the media 24 hours after incubation of the cells with increasing hLeptin concentrations (10(-11) -10(-7) mol/l). The maximal 30 % decrease in E-2 production was caused by the 10(-9) mol/l hLeptin concentration; however, P-4 levels in the media were not influenced by leptin, Exposure of granulosa-lutein cells to 10-9 mol/l hLeptin did not produce any measurable changes on StAR, aromatase, or CYP17 mRNA expression, When hLeptin (10(-9) mol/l) was co-incubated with increasing concentrations of hCC (1.25-10 mIU/ml), IGF-II (15-50 ng/ml) or 1-6 desaminated ICF-II (desIGF-II; 15-60 ng/ml), it did not modify the elevation of E, concentrations caused by each of the different stimuli, We conclude that leptin suppresses E-2 secretion by human granulosa-lutein cells but does not impair the stimulatory effects of hCG and IGFs on these cells. Leptin may play a minor, but direct regulatory role on unstimulated human ovarian steroidogenesis by interfering with either the translational or post-translational steps of the baseline C/P17 and/or aromatase synthesis and/or the activation of the enzymes.