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Nitric Oxide Mediates Inhibitory Effect of Leptin on Insulin-Like Growth Factor I Augmentation of 17ß-Estradiol Production in Human Granulosa Cells¹

Department of Reproductive Endocrinology,⁴ Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, China Department of Pharmacology and Therapeutics,⁵ Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada T2N 4N1

In the present study the authors investigated if the inhibitory effect of leptin in the ovary was mediated via nitric oxide (NO) using human granulosa cells (GCs). Human GCs were obtained from preovulatory follicles of women who underwent IVF. Reverse transcription–polymerase chain reaction (RT-PCR) demonstrated that human GCs expressed mRNA of leptin and mRNA of isoforms of leptin receptor, including one long form and two types of short forms. Exposure of human GCs to leptin at concentrations of 3–30 ng/ml for 60 min dose-dependently increased the fluorescence of 4,5-diaminofluorescein (DAF-2), an NO-sensitive dye. The effect of leptin on DAF-2 fluorescence was inhibited by pretreatment of human GCs with 100 µM nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase (NOS), indicating that the increase in DAF-2 fluorescence properly reflected the intracellular NO production. FSH (1 ng/ ml) and IGF-I (30 ng/ml) stimulated 17ß-estradiol (E₂) production in human GCs, respectively. FSH plus IGF-I induced a further increase in E₂ production. Leptin did not significantly alter basal or FSH-dependent E₂ production, but it inhibited the effect of IGF-I on E₂ production and the synergistic effect of IGF-I on FSH-stimulated E₂ production. The inhibitory effect of leptin on IGF-I argumentation of E₂ production was attenuated by pretreatment of human GCs with 100 µM L-NAME. In conclusion, leptin could induce NO production in human GCs. The inhibitory effect of leptin on IGF-I augmentation of E₂ production in human GCs was attenuated by L-NAME, strongly suggesting that NO may mediate the action of leptin in human GCs.

¹ Supported by Zhejiang Natural Science Foundation of China and the Pao Yu-Kong and Pao Zhao-long Scholarship.

² Correspondence: Jian-Zhong Sheng, Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada. FAX: 403 270 2211; jzsheng{at}ucalgary.ca

³ Correspondence: He-Feng Huang, Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, 2 Xue Shi Road, Hangzhou, Zhejiang 310006, China. FAX: 86 571 8721 8744; huanghefg{at}hotmail.com

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				A G Ricci, M P Di Yorio, and A G Faletti Inhibitory effect of leptin on the rat ovary during the ovulatory process. Reproduction, November 1, 2006; 132(5): 771 - 780. [Abstract] [Full Text] [PDF]