Effects of resveratrol analogs on steroidogenesis and mitochondrial function in rat Leydig cells in vitro.
Resveratrol and its analogs are considered to be a promising drug candidate for treatment of cancer and different age-associated diseases. In the present study we have investigated the effects of resveratrol and its synthetic analogs on steroidogenesis and mitochondrial function in primary cultures of rat Leydig cells. Our findings indicate that resveratrol and its analogs structure-dependently attenuated hCG-activated steroidogenesis in Leydig cells through suppression of the expression of steroidogenic acute regulatory protein and cytochrome P450c17. 3,5-Diacetyl resveratrol was observed to modulate mitochondrial function in Leydig cells, suppressing polarization of inner mitochondrial membrane, and 3,4,4'-trimethoxystilbene stimulated the overall activity of intracellular reductases involved in the reduction of WST-1 to formazan. Thus, the inhibitory actions of resveratrol analogs on steroidogenesis in Leydig cells indicate novel mechanisms of action of these compounds, which may be of potential therapeutic interest, where suppression of androgen action is needed.
Svechnikov
Konstantin
K
Department of Woman and Child Health, Pediatric Endocrinology Unit, Q2:08, Karolinska Institute and University Hospital, SE-17176 Stockholm, Sweden. konstantin.svechnikov@ki.se
Spatafora
Carmela
C
Svechnikova
Irina
I
Tringali
Corrado
C
Söder
Olle
O
D000735:Androstenedione / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D007985:Leydig Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D013256:Steroids / Q000378:metabolism*; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
C110656:2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium; D006063:Chorionic Gonadotropin; D004791:Enzyme Inhibitors; D010750:Phosphoproteins; D013256:Steroids; D013267:Stilbenes; D013778:Tetrazolium Salts; D000098682:Steroidogenic Acute Regulatory Protein; D000735:Androstenedione; D011374:Progesterone; D013254:Steroid 17-alpha-Hydroxylase; D000077185:Resveratrol