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KMID : 0356420060240010044
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Journal of Korean Andrology
2006 Volume.24 No. 1 p.44 ~ p.50
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Effect of Metformin on the Expression of Nitric Oxide Synthase in High Fat Fed Obese Rats
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Yoon Chang-Jun
Jeon Woo-Sung
Kim Yong-Woon
Moon Ki-Hak
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Abstract
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Purpose: Obesity is a well known risk factorfor erectile dysfunction, and metformin normalizes androgen levels in patients with polycystic ovary syndrome and decreases body fat and leptin concentration in normal weight men. Thus, we hypothesized that metformin may restore the neuroendocrine abnormalities associated with obesity and improve erectile dysfunction.
Materials and Methods: Obesity was induced by a high fat(HF) diet fed for 4 months, and then metformin(300 mg/kg/day) was administered for 4 weeks. Penile nitric oxide synthase(NOS) expression and luteinizing hormone (LH), follicle stimulating hormone(FSH), testosterone, leptin, corticotropin releasing factor(CRF), adrenocorticotropin (ACTH), and proopiomelanocortin(POMC) were evaluated in control and HF obese rats.
Results: Penile nNOS and eNOS were suppressed markedly, and serum leptin and FSH were increased in HF rats compared to controls. However, POMCexpression in the hypothalamus was decreased in HF rats compared to controls,despite slightly elevated cerebrospinal fluid(CSF) leptin concentration. Metformin treatment for 4 weeks restored penile nNOS and eNOS expression, decreased serum leptin, increased POMC expression in the hypothalamus, and decreased serum concentration of FSH and CRF in HF rats. Surprisingly, metformin increased CSF leptin concentration in both control and HF rats.
Conclusions: These results suggested that NOS expression was suppressed by the HF diet, but restored by metformin treatment. The effect of metformin on NOS expression resulted from not only a leptin sensitizing effect but also through a normalizing effect on levels of endocrine factors.
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KEYWORD
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Metformin, Nitric oxide synthase, Obesity
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