Inhibition of ghrelin signaling improves the reproductive phenotype of male ob/ob mouse

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• 作者：Chu-Chao Zhu ; B.Sc.^a ; Hua Zhang ; M.D.^b ; Jin-Shan Zhang ; M.D.^a ; Zhen Li ; M.D.^a ; Jie Zhao ; B.Sc.^a ; Wei Li ; M.D. ; Ph.D.^a ; ^{liweipepeyato@yahoo.com.cn} ; Yuan-Qiang Zhang ; M.D.^a ; ^{zhangyq@fmmu.edu.cn}
• 关键词：Ghrelin ; leptin ; GHS-R1¦Á ; androgen ; ob/ob mice
• 刊名：Fertility and Sterility
• 出版年：2013
• 出版时间：1 March, 2013
• 年：2013
• 卷：99
• 期：3
• 页码：918-926
• 全文大小：1485 K

文摘

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Objective

To investigate whether ghrelin signaling is involved in the pathogenesis of male factor infertility induced by leptin deficiency.

Design

Experimental study.

Setting

University academic medical center.

Animal(s)

Ten-week-old C57BL/6J mice and ob/ob mice.

Intervention(s)

Western blotting, (quantitative) reverse transcription-polymerase chain reaction (qRT-PCR), immunohistochemistry, and in situ end labeling of fragmented DNA.

Main Outcome Measure(s)

Expression levels of ghrelin and its functional receptor growth hormone (GH) secretagogue receptor 1a (GHS-R1¦Á) were examined by Western blotting and immunohistochemistry. Ob/ob mice were injected IP with specific GHS-R1¦Á antagonist, and thereafter germ cell apoptosis and steroidogenic capability were assessed by TUNEL assay, (q) RT-PCR, and radioimmunoassay.

Result(s)

Expression of GHS-R1¦Á and its endogenous ligand ghrelin was both up-regulated in ob/ob testis. Inhibition of the ghrelin pathway restored androgen synthesis, reduced germ cell apoptosis, and thereby resulted in improved sperm production in ob/ob mice.

Conclusion(s)

Ghrelin, as an antagonistic partner of leptin in the endocrinic/paracrine circuit, may be involved in the pathogenesis of male factor infertility induced by leptin deficiency.