title: Regulation of FoxO1 transcription factor by nitric oxide and cyclic GMP in cultured rat granulosa cells.
abstract: FoxO1 is a transcription factor implicated in a multitude of physiological processes including cell cycle progression, apoptosis and insulin signaling. Recent findings indicate that FoxO1 is a key regulator during the proliferation and maturation of granulosa cells. Over the past several years, it has become evident that nitric oxide (NO) and cGMP modulate ovarian function. There has been no information, however, about whether NO-cGMP affects FoxO1 expression or about the relationship between NO-cGMP and FoxO1. In the present study, we used immunoblot analysis to determine whether NO and cGMP affect FoxO1 expression in cultured granulosa cells. Our results clearly showed that FSH suppressed FoxO1 expression in a time-dependent manner, and that NO-cGMP stimulated FoxO1 expression in cultured granulosa cells. In addition, this stimulatory effects of NO and cGMP can be blocked by FSH in cultured granulosa cells. These findings demonstrate that NO and cGMP influence FoxO1 expression possibly through antagonizing the action of FSH in cultured granulosa cells. Results of both immunoblot analysis and immunohistochemistry also show that estradiol implantation do not affect the expression of FoxO1 in rat granulosa cells as gonadotrophins do, indicating that mechanism of estradiol on granulosa cells is different from gonadotrophins. Together, our experiments suggest that expression of FoxO1 in rat granulosa cells can be regulated by gonadotrophins and the NO/cGMP signaling pathway.
authors.affiliation: Laboratory of Animal Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Li
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Jiang
authors.forename: Zhengchao
authors.initials: Z
authors.lastname: Wang
authors.forename: Gentao
authors.initials: G
authors.lastname: Liu
authors.forename: Reinhold J
authors.initials: RJ
authors.lastname: Hutz
authors.forename: Wenbin
authors.initials: W
authors.lastname: Liu
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Xie
authors.forename: Fangxiong
authors.initials: F
authors.lastname: Shi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005786:Gene Expression Regulation; D006064:Gonadotropins, Equine / Q000494:pharmacology; D006107:Granulosa Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071161:Forkhead Box Protein O1
chemical_list: D002867:Chromones; D006152:Cyclic GMP; D004958:Estradiol; D051858:Forkhead Transcription Factors; D006064:Gonadotropins, Equine; D009025:Morpholines; D009419:Nerve Tissue Proteins; D009569:Nitric Oxide; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one