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

Capsule:
Ghrelin signaling is involved in the reproductive phenotype of ob/ob mouse.

Authors:
Chu-Chao Zhu, B.Sc., Hua Zhang, M.D., Jin-Shan Zhang, M.D., Zhen Li, M.D., Jie Zhao, B.Sc., Wei Li, M.D., PhD., Yuan-Qiang Zhang, M.D.

Volume 99, Issue 3, Pages 918-926, 1 March 2013

Abstract:

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

Design:
Experimental study.

Setting:
University academic medical center.

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

Interventions:
Western blotting, (quantitative) reverse transcription–polymerase chain reaction, immunohistochemistry and in situ end labeling of fragmented DNA.

Main Outcome Measure(s):
Expression levels of ghrelin and its functional receptor GHS-R1α were examined by western blotting and immunohistochemistry. Ob/ob mice were injected intraperitoneally with specific GHS-R1α antagonist and thereafter germ cell apoptosis and steroidogenic capability were assessed by TUNEL assay, (q)PCR and radioimmunoassay.

Result(s):
Expression of growth hormone (GH) secretagogue receptor 1a (GHS-R1α) and its endogenous ligand ghrelin was both up-regulated in ob/ob testis. Inhibition of 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 infertility induced by leptin deficiency.

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