title: Basic fibroblast growth factor promotes stem Leydig cell development and inhibits LH-stimulated androgen production by regulating microRNA expression.
abstract: Leydig cells are the primary source of testosterone in the testes, and their steroidogenic function is strictly controlled by the hypothalamus-pituitary-gonad axis. Emerging evidence has indicated that fibroblast growth factors play a role in regulating stem Leydig cell development and steroidogenesis, but little is known about the regulatory mechanism. Using a seminiferous tubule culture system, we demonstrated that basic fibroblast growth factor (bFGF) can promote stem Leydig cell proliferation and commitment toward differentiation in testosterone-producing Leydig cells. However, these promoting effects decreased with an increase in the bFGF dose. Previous studies have reported that bFGF inhibits luteinizing hormone (LH)-stimulated androgen production by downregulating the mRNA expression of steroidogenic genes in immature Leydig cells. However, the expression levels of 677 microRNAs did not change significantly during the LH-mediated process of testosterone synthesis. Five microRNAs (miR-29a, -29c, -142-3p, -451 and -335) were identified, and their expression in immature Leydig cells was regulated simultaneously by bFGF and LH. These results suggested that the inhibition of LH-stimulated androgen production may be modulated by a change in bFGF-mediated microRNA expression, which further impacts the signaling pathway of testosterone biosynthesis and steroidogenic gene expression.
authors.affiliation: Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, PR China; Guangdong Provincial Key Laboratory of Bioengineering Medicine, Institute of Biomedicine, Jinan University, Guangzhou 510632, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liang
authors.affiliation: Research Academy of Reproductive Biomedicine and the 2nd Affiliated Hospital, Wenzhou Medical College, Wenzhou 325027, PR China.
authors.forename: Ren-Shan
authors.initials: RS
authors.lastname: Ge
authors.affiliation: Heilongjiang Key Laboratory of Anti-fibrosis Biotherapy, Mudanjiang Medical University, Heilongjiang 157011, PR China.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, PR China.
authors.forename: Qihao
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, PR China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xiang
authors.affiliation: Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, PR China. Electronic address: tydhuang@jnu.edu.cn.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, PR China; Guangdong Provincial Key Laboratory of Bioengineering Medicine, Institute of Biomedicine, Jinan University, Guangzhou 510632, PR China. Electronic address: tjnuszj@jnu.edu.cn.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Su
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007986:Luteinizing Hormone / Q000494:pharmacology; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D012671:Seminiferous Tubules / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D035683:MicroRNAs; D016222:Fibroblast Growth Factor 2; D013739:Testosterone; D007986:Luteinizing Hormone
keywords: Basic fibroblast growth factor; Development; Leydig cells; Testosterone; microRNA