title: Low-dose testosterone treatment decreases oxidative damage in TM3 Leydig cells.
abstract: Testosterone replacement therapy has benefits for aging men and those with hypogonadism. However, the effects of exogenous testosterone on Leydig cells are still unclear and need to be clarified. In this report, we demonstrate that testosterone supplementation can reduce oxidative damage in Leydig cells. The TM3 Leydig cell line was used as an in vitro cell model in this study. Cytoprotective effects were identified with 100-nmol l⁻¹ testosterone treatment, but cytotoxic effects were found with ≥ 500-nmol l⁻¹ testosterone supplementation. Significantly reduced reactive oxygen species (ROS) generation, lipid peroxide contents and hypoxia induction factor (HIF)-1α stabilization and activation were found with 100-nmol l⁻¹ testosterone treatment. There was a 1.72-fold increase in ROS generation in the 500-nmol l⁻¹ compared to the 100-nmol l⁻¹ testosterone treatment. A 1.58-fold increase in steroidogenic acute regulatory protein (StAR) expression was found in 50-nmol l⁻¹ testosterone-treated cells (P < 0.01). Chemically induced hypoxia was attenuated by testosterone supplementation. Leydig cells treated with low-dose testosterone supplementation showed cytoprotection by decreasing ROS and lipid peroxides, increasing StAR expression and relieving hypoxia stress as demonstrated by HIF-1α stabilization. Increased oxidative damage was found with ≥ 500-nmol l⁻¹ testosterone manipulation. The mechanism governing the differential dose effects of testosterone on Leydig cells needs further investigation in order to shed light on testosterone replacement therapy.
authors.affiliation: Department of Urology, Taipei Medical University, Taipei, Taiwan, China.
authors.forename: Thomas I S
authors.initials: TI
authors.lastname: Hwang
authors.forename: Tien-Ling
authors.initials: TL
authors.lastname: Liao
authors.forename: Ji-Fan
authors.initials: JF
authors.lastname: Lin
authors.forename: Yi-Chia
authors.initials: YC
authors.lastname: Lin
authors.forename: Shu-Yu
authors.initials: SY
authors.lastname: Lee
authors.forename: Yen-Chun
authors.initials: YC
authors.lastname: Lai
authors.forename: Shu-Huei
authors.initials: SH
authors.lastname: Kao
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000187:drug effects / Q000378:metabolism; D007985:Leydig Cells / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011944:Receptors, Androgen / Q000096:biosynthesis / Q000187:drug effects; D013739:Testosterone / Q000008:administration & dosage* / Q000009:adverse effects; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; D011944:Receptors, Androgen; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone