title: TGFB1 represses the expression of SF1 and LRH1 to inhibit E2production in rat LCs.
abstract: Leydig cells (LCs) in the adult testis have been identified as the major sites of oestrogen production, which is crucial for mammalian germ cell differentiation. Our previous work showed that transforming growth factor beta 1 (TGFB1) inhibits estradiol (E2) secretion via down-regulatingCyp19gene expression in mature rat LCs. However, the mechanism remains unclear. In the present study, the effects of TGFB1 on the expression levels of steroidogenic factor 1 (SF1), liver receptor homolog 1 (LRH1), cAMP response element-binding protein (CREB) and cAMP responsive element modulator (CREM) were evaluated both in primary cultured LCs and in rat testis. The involvement of TGFB1 signalling in the regulation of SF1 and LRH1 expression was then validated by applying the inhibitor of the TGFB type 1 receptor (TGFBR1) SB431542. Moreover, the expression of CYP19 in testicular LCs was investigated and the production of E2in testicular interstitial fluid (TIF) was measured. The results showed that TGFB1 especially down-regulated the expression levels of SF1 and LRH1 both in primary cultured LCs and in rat testis. The down-regulations of TGFB1 in the production of E2in TIF and the expression of CYP19 in testicular LCs were also observedin vivoThese inhibitory effects could be reversed by TGFBR1 inhibitor SB431542. Our findings suggest that TGFB1 may act through the canonical signalling pathway involving ALK5 to restrain SF1 and LRH1 accumulation and eventually attenuateCyp19transcription and oestrogen production in LCs.
authors.affiliation: Department of Histology and EmbryologyThe Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.|Department of Traditional Chinese MedicineXijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Histology and EmbryologyThe Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Binfang
authors.initials: B
authors.lastname: Ma
authors.affiliation: Department of Histology and EmbryologyThe Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Huilian
authors.initials: H
authors.lastname: Qiao
authors.affiliation: Department of Histology and EmbryologyThe Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: He
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Histology and EmbryologyThe Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Yuhang
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Traditional Chinese MedicineXijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Traditional Chinese MedicineXijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China jingma@fmmu.edu.cn lizhenhe@fmmu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Histology and EmbryologyThe Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China jingma@fmmu.edu.cn lizhenhe@fmmu.edu.cn.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054339:Steroidogenic Factor 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013737:Testis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; C417002:NR5A2 protein, rat; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D053773:Transforming Growth Factor beta1; C515060:steroidogenic factor 1, rat; D004958:Estradiol