H2O2 at physiological concentrations modulates Leydig cell function inducing oxidative stress and apoptosis.
H(2)O(2) is one of the active reactive oxygen species secreted by macrophages that are seen closely aligned with Leydig cells in the testicular interstitium. The present study was initiated to investigate the role of H(2)O(2) on Leydig cell function in vitro at physiological concentrations. Significant decrease in both testosterone production (p < 0.05) and 3 beta-hydroxysteroid dehydrogenase activity (p < 0.05) in adult Leydig cells were observed even with H(2)O(2) at low concentrations (30 - 50 microM). H(2)O(2) exposure increased oxidative stress in Leydig cells with the rise in lipid peroxidation and fall in the activities of the antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT) & glutathione-s-transferase (GST). There was also a marginal increase (approximately 8%) in cell apoptosis accompanied by rise in FasL expression and caspase-3 activation. The above findings indicate that H(2)O(2) as a bio-molecule modulates Leydig cell function at or below physiological concentrations through a variety of actions like decrease in steroidogenic enzyme activity and increase in oxidative stress and apoptosis.
Gautam
D K
DK
Department of Reproductive Biomedicine, National Institute of Health and Family Welfare, New Mehrauli Road, Munirka, New Delhi.
Misro
M M
MM
Chaki
S P
SP
Sehgal
N
N
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D053222:Fas Ligand Protein / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D007985:Leydig Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis
D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D013739:Testosterone; D006861:Hydrogen Peroxide; D015096:3-Hydroxysteroid Dehydrogenases; D002374:Catalase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; C505410:Casp3 protein, rat; D053148:Caspase 3