Adverse effects associated with persistent stimulation of Leydig cells with hCG in vitro.
The detrimental effects of persistent stimulation with hCG were investigated in rat Leydig cells in vitro. Significant rise in lipid peroxidation and reactive oxygen species (ROS) with concomitant attenuation in the activities of antioxidant enzymes: superoxide dismutase, catalase, and glutathione-S-transferase was observed. Transcripts for catalase and superoxide dismutase were also depleted. Subsequent to each hCG challenge, the total antioxidant capacity in the target cells also declined significantly (P < 0.05). There was an increase in cell apoptosis (23%), which was associated with a rise in caspase-3 activity, PARP cleavage, and Fas, FasL, caspase-8 expression. While Bax and Caspase-9 expression remained unchanged, Bcl-2 demonstrated a marked decline. Taken together, the above data indicate that persistent hCG stimulation of Leydig cells induced adverse effects leading to oxidative stress and apoptosis which was channeled primarily through the extrinsic pathway.
Aggarwal
Archana
A
Department of Reproductive Biomedicine, National Institute of Health & Family Welfare, Baba Gang Nath Marg, New Delhi 110067, India.
Misro
Man M
MM
Maheshwari
Ankur
A
Sehgal
Neeta
N
Nandan
Deoki
D
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000633:toxicity*; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007985:Leydig Cells / 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; D017382:Reactive Oxygen Species; D015398:Signal Transduction / Q000187:drug effects; D013268:Stimulation, Chemical; D013739:Testosterone / Q000378:metabolism
D006063:Chorionic Gonadotropin; D017382:Reactive Oxygen Species; D013739:Testosterone; D000242:Cyclic AMP