Document Detail

Nitric oxide mediates inhibitory effect of leptin on insulin-like growth factor I augmentation of 17beta-estradiol production in human granulosa cells.
MedLine Citation:
PMID:  15371274     Owner:  NLM     Status:  MEDLINE    
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 microM 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 17beta-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 microM 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.
He-Feng Huang; Bo Wang; Xiao-Fu Yang; Qiong Luo; Jian-Zhong Sheng
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-09-15
Journal Detail:
Title:  Biology of reproduction     Volume:  72     ISSN:  0006-3363     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2004-12-21     Completed Date:  2005-07-19     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  102-6     Citation Subset:  IM    
Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, China.
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MeSH Terms
Cells, Cultured
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Estradiol / metabolism*
Fluorescein / analysis,  metabolism
Follicle Stimulating Hormone / pharmacology
Gene Expression Regulation / drug effects
Granulosa Cells / drug effects,  metabolism*
Insulin-Like Growth Factor I / metabolism*,  pharmacology
Leptin / genetics,  metabolism,  pharmacology*
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide / metabolism*
Nitric Oxide Synthase / antagonists & inhibitors,  metabolism
Receptors, Cell Surface / drug effects,  genetics,  metabolism
Receptors, Leptin
Reg. No./Substance:
0/4,5-diaminofluorescein; 0/Enzyme Inhibitors; 0/Leptin; 0/Receptors, Cell Surface; 0/Receptors, Leptin; 0/leptin receptor, human; 10102-43-9/Nitric Oxide; 2321-07-5/Fluorescein; 50-28-2/Estradiol; 50903-99-6/NG-Nitroarginine Methyl Ester; 67763-96-6/Insulin-Like Growth Factor I; 9002-68-0/Follicle Stimulating Hormone; EC Oxide Synthase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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