title: Stress triggers mitochondrial biogenesis to preserve steroidogenesis in Leydig cells.
abstract: Adaptability to stress is a fundamental prerequisite for survival. Mitochondria are a key component of the stress response in all cells. For steroid-hormones-producing cells, including also Leydig cells of testes, the mitochondria are a key control point for the steroid biosynthesis and regulation. However, the mitochondrial biogenesis in steroidogenic cells has never been explored. Here we show that increased mitochondrial biogenesis is the adaptive response of testosterone-producing Leydig cells from stressed rats. All markers of mitochondrial biogenesis together with transcription factors and related kinases are up-regulated in Leydig cells from rats exposed to repeated psychophysical stress. This is followed with increased mitochondrial mass. The expression of PGC1, master regulator of mitochondrial biogenesis and integrator of environmental signals, is stimulated by cAMP-PRKA, cGMP, and β-adrenergic receptors. Accordingly, stress-triggered mitochondrial biogenesis represents an adaptive mechanism and does not only correlate with but also is an essential for testosterone production, being both events depend on the same regulators. Here we propose that all events induced by acute stress, the most common stress in human society, provoke adaptive response of testosterone-producing Leydig cells and activate PGC1, a protein required to make new mitochondria but also protector against the oxidative damage. Given the importance of mitochondria for steroid hormones production and stress response, as well as the role of steroid hormones in stress response and metabolic syndrome, we anticipate our result to be a starting point for more investigations since stress is a constant factor in life and has become one of the most significant health problems in modern societies.
authors.affiliation: Laboratory for Reproductive Endocrinology and Signaling (LaRES), Faculty of Sciences, University of Novi Sad, Dositeja Obradovica Sq. 2, 21000 Novi Sad, Serbia.
authors.forename: Igor A
authors.initials: IA
authors.lastname: Gak
authors.affiliation: Laboratory for Reproductive Endocrinology and Signaling (LaRES), Faculty of Sciences, University of Novi Sad, Dositeja Obradovica Sq. 2, 21000 Novi Sad, Serbia.
authors.forename: Sava M
authors.initials: SM
authors.lastname: Radovic
authors.affiliation: Laboratory for Reproductive Endocrinology and Signaling (LaRES), Faculty of Sciences, University of Novi Sad, Dositeja Obradovica Sq. 2, 21000 Novi Sad, Serbia.
authors.forename: Aleksandra R
authors.initials: AR
authors.lastname: Dukic
authors.affiliation: Laboratory for Reproductive Endocrinology and Signaling (LaRES), Faculty of Sciences, University of Novi Sad, Dositeja Obradovica Sq. 2, 21000 Novi Sad, Serbia.
authors.forename: Marija M
authors.initials: MM
authors.lastname: Janjic
authors.affiliation: Laboratory for Reproductive Endocrinology and Signaling (LaRES), Faculty of Sciences, University of Novi Sad, Dositeja Obradovica Sq. 2, 21000 Novi Sad, Serbia.
authors.forename: Natasa J
authors.initials: NJ
authors.lastname: Stojkov-Mimic
authors.affiliation: Laboratory for Reproductive Endocrinology and Signaling (LaRES), Faculty of Sciences, University of Novi Sad, Dositeja Obradovica Sq. 2, 21000 Novi Sad, Serbia.
authors.forename: Tatjana S
authors.initials: TS
authors.lastname: Kostic
authors.affiliation: Laboratory for Reproductive Endocrinology and Signaling (LaRES), Faculty of Sciences, University of Novi Sad, Dositeja Obradovica Sq. 2, 21000 Novi Sad, Serbia. Electronic address: silvana.andric@dbe.uns.ac.rs.
authors.forename: Silvana A
authors.initials: SA
authors.lastname: Andric
mesh_terms: D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D006801:Humans; D007985:Leydig Cells / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology; D013739:Testosterone / Q000096:biosynthesis*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D011943:Receptors, Adrenergic, beta; D014157:Transcription Factors; D013739:Testosterone; D017868:Cyclic AMP-Dependent Protein Kinases; D006152:Cyclic GMP
keywords: Leydig cells; Mitochondrial biogenesis; PGC1; Stress; Testosterone