title: Interactive Effect of Corticosterone and Lactate on Regulation of Testosterone Production in Rat Leydig Cells.
abstract: The increasing intensity of exercise enhanced corticosterone and lactate production in both humans and rodents. Our previous studies also demonstrated that lactate could stimulate testosterone production in vivo and in vitro. However, the production of testosterone in response to combined corticosterone and lactate on Leydig cells, and underlying molecular mechanisms are remained unclear. This study investigated the changes in testosterone levels of Leydig cells upon exposure to lactate, corticosterone or combination of both, and revealed the detailed mechanisms. Leydig cells were isolated from rat testes, and treated with different concentrations of lactate (2.5-20 mM), cortiosterone (10-9-10-4M) and lactate plus corticosterone. The production of testosterone were assayed by radioimmunoassay, and the key molecular proteins, including luteinizing hormone receptor (LHR), protein kinase A (PKA), steroidogenic acute regulatory protein (StAR), and cholesterol P450 side-chain cleavage enzyme (P450scc) involved in testosterone production were performed by Western blot. Results showed that testosterone levels were significantly increased with lactate, while decresed with corticosterone and lactate plus corticosterone treatment. Protein expressions of LHR and P450scc were upregulated with lactate treatment. However, PKA and P450scc were downregulated by lactate plus corticosterone treatment. This downregulation was followed by decreased testoterone levels in Leydig cells. Furthermore, acetylated cAMP, which activates testosterone production was increased with lactate, but not altered by conrtiosterone. Our findings conclude that corticosterone may interfere with lactate, and restrict lactate-stimulated testosterone production in Leydig cells. J. Cell. Physiol. 232: 2135-2144, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China.
authors.forename: Chih-Chieh
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China.
authors.forename: Chien-Wei
authors.initials: CW
authors.lastname: Chen
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China.
authors.forename: Po-Han
authors.initials: PH
authors.lastname: Lin
authors.affiliation: Medical Center of Aging Research, China Medical University Hospital, Taichung, Taiwan, Republic of China.|Department of Life Sciences, National Chung-Hsing University, Taichung, Taiwan, Republic of China.
authors.forename: Jou-Chun
authors.initials: JC
authors.lastname: Chou
authors.affiliation: Medical Center of Aging Research, China Medical University Hospital, Taichung, Taiwan, Republic of China.
authors.forename: Ting-Chun
authors.initials: TC
authors.lastname: Weng
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China.
authors.forename: Cai-Yun
authors.initials: CY
authors.lastname: Jian
authors.affiliation: Aesthetic Medical Center, Department of Dermatology, Chang-Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China.|Department of Medicine, College of Medicine, Chang-Gung University, Taoyuan, Taiwan, Republic of China.
authors.forename: Sindy
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Rehabilitation, Cheng-Hsin General Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Wei-Ho
authors.initials: WH
authors.lastname: Lai
authors.affiliation: Department of Rehabilitation, Cheng-Hsin General Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Fu-Kong
authors.initials: FK
authors.lastname: Lieu
authors.affiliation: Department of Life Sciences, National Chung-Hsing University, Taichung, Taiwan, Republic of China.|Department of Physiology and Pharmacology, College of Medicine, Chang-Gung University, Taoyuan, Taiwan, Republic of China.
authors.forename: Shyi-Wu
authors.initials: SW
authors.lastname: Wang
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China.|Medical Center of Aging Research, China Medical University Hospital, Taichung, Taiwan, Republic of China.|Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan, Republic of China.|Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Paulus S
authors.initials: PS
authors.lastname: Wang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D003345:Corticosterone / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D019344:Lactic Acid / Q000494:pharmacology*; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017207:Rats, Sprague-Dawley; D011974:Receptors, LH / Q000187:drug effects / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects; D013739:Testosterone / Q000378:metabolism*
chemical_list: D011974:Receptors, LH; D019344:Lactic Acid; D013739:Testosterone; D000242:Cyclic AMP; D002786:Cholesterol Side-Chain Cleavage Enzyme; D017868:Cyclic AMP-Dependent Protein Kinases; D003345:Corticosterone