title: Inhibition of ghrelin signaling improves the reproductive phenotype of male ob/ob mouse.
abstract: OBJECTIVE
  To investigate whether ghrelin signaling is involved in the pathogenesis of male factor infertility induced by leptin deficiency.
  
  
  METHODS
  Experimental study.
  
  
  METHODS
  University academic medical center.
  
  
  METHODS
  Ten-week-old C57BL/6J mice and ob/ob mice.
  
  
  METHODS
  Western blotting, (quantitative) reverse transcription-polymerase chain reaction (qRT-PCR), immunohistochemistry, and in situ end labeling of fragmented DNA.
  
  
  METHODS
  Expression levels of ghrelin and its functional receptor growth hormone (GH) secretagogue receptor 1a (GHS-R1α) were examined by Western blotting and immunohistochemistry. Ob/ob mice were injected IP with specific GHS-R1α antagonist, and thereafter germ cell apoptosis and steroidogenic capability were assessed by TUNEL assay, (q) RT-PCR, and radioimmunoassay.
  
  
  RESULTS
  Expression of GHS-R1α 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Human Anatomy and Histology and Embryology, the Fourth Military Medical University, Xian, People's Republic of China.
authors.forename: Chu-Chao
authors.initials: CC
authors.lastname: Zhu
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Jin-Shan
authors.initials: JS
authors.lastname: Zhang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Yuan-Qiang
authors.initials: YQ
authors.lastname: Zhang
mesh_terms: D000728:Androgens / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D005298:Fertility / Q000235:genetics*; D054439:Ghrelin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D020738:Leptin / Q000172:deficiency* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D010641:Phenotype; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013737:Testis / Q000166:cytology / Q000502:physiology*; D013739:Testosterone / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
chemical_list: D000728:Androgens; D054439:Ghrelin; D020738:Leptin; D054440:Receptors, Ghrelin; D013739:Testosterone