title: Autophagic deficiency is related to steroidogenic decline in aged rat Leydig cells.
abstract: Late-onset hypogonadism (LOH) is closely related to secondary androgen deficiency in aged males, but the mechanism remains unclear. In this study, we found that reduced testosterone production in aged rat Leydig cells is associated with decreased autophagic activity. Primary rat Leydig cells and the TM3 mouse Leydig cell line were used to study the effect of autophagic deficiency on Leydig cell testosterone production. In Leydig cells from young and aged rats, treatment with wortmannin, an autophagy inhibitor, inhibited luteinising hormone (LH)-stimulated steroidogenic acute regulatory (StAR) protein expression and decreased testosterone production. In contrast, treatment with rapamycin, an autophagy activator, enhanced LH-stimulated steroidogenesis in Leydig cells from aged, but not young, rats. Intracellular reactive oxygen species (ROS) levels were increased in both young and aged Leydig cells treated with wortmannin but decreased only in aged Leydig cells treated with rapamycin. Furthermore, an increased level of ROS, induced by H(2)O(2), resulted in LH-stimulated steroidogenic inhibition. Finally, knockdown of Beclin 1 decreased LH-stimulated StAR expression and testosterone production in TM3 mouse Leydig cells, which were associated with increased intracellular ROS level. These results suggested that autophagic deficiency is related to steroidogenic decline in aged rat Leydig cells, which might be influenced by intracellular ROS levels.
authors.affiliation: Andrology Center, Peking University First Hospital, Peking University, Beijing 100034, China.
authors.forename: Wei-Ren
authors.initials: WR
authors.lastname: Li
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.forename: Zhi-Jie
authors.initials: ZJ
authors.lastname: Chang
authors.forename: Hua
authors.initials: H
authors.lastname: Xin
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Yan-Quan
authors.initials: YQ
authors.lastname: Zhang
authors.forename: Guang-Yong
authors.initials: GY
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Zhou
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Gong
authors.forename: Zhe-Zhu
authors.initials: ZZ
authors.lastname: Gao
authors.forename: Zhong-Cheng
authors.initials: ZC
authors.lastname: Xin
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001343:Autophagy; D000071186:Beclin-1; D015153:Blotting, Western; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D007985:Leydig Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D007986:Luteinizing Hormone / Q000502:physiology; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D010750:Phosphoproteins / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; D007986:Luteinizing Hormone