Resveratrol inhibits androgen production of human adrenocortical H295R cells by lowering CYP17 and CYP21 expression and activities.
Resveratrol, a natural compound found in grapes, became very popular for its suggested protective effects against aging. It was reported to have similar positive effects on the human metabolism as caloric restriction. Recently, positive effects of resveratrol on steroid biosynthesis in cell systems and in humans suffering from polycystic ovary syndrome have also been reported, but the exact mechanism of this action remains unknown. Sirtuins seem targeted by resveratrol to mediate its action on energy homeostasis. In this study, we investigated the mechanisms of action of resveratrol on steroidogenesis in human adrenal H295R cells. Resveratrol was found to inhibit protein expression and enzyme activities of CYP17 and CYP21. It did not alter CYP17 and CYP21 mRNA expression, nor protein degradation. Only SIRT3 mRNA expression was found to be altered by resveratrol, but SIRT1, 3 and 5 overexpression did not result in a change in the steroid profile of H295R cells, indicating that resveratrol may not engage sirtuins to modulate steroid production. Previous studies showed that starvation leads to a hyperandrogenic steroid profile in H295R cells through inhibition of PKB/Akt signaling, and that resveratrol inhibits steroidogenesis of rat ovarian theca cells via the PKB/Akt pathway. Therefore, the effect of resveratrol on PKB/Akt signaling was tested in H295R cells and was found to be decreased under starvation growth conditions, but not under normal growth conditions. Overall, these properties of action together with recent clinical findings make resveratrol a candidate for the treatment of hyperandrogenic disorders such as PCOS.
Division of Pediatric Endocrinology, Department of Pediatrics and Department of Clinical Research, University of Bern, Bern, Switzerland.|Graduate School of Bern, University of Bern, Bern, Switzerland.
Nesa
N
Marti
Division of Pediatric Endocrinology, Department of Pediatrics and Department of Clinical Research, University of Bern, Bern, Switzerland.
Nadia
N
Bouchoucha
Division of Pediatric Endocrinology, Department of Pediatrics and Department of Clinical Research, University of Bern, Bern, Switzerland.
Kay-Sara
KS
Sauter
Division of Pediatric Endocrinology, Department of Pediatrics and Department of Clinical Research, University of Bern, Bern, Switzerland.
Christa E
http://orcid.org/0000-0002-4568-5504
CE
Flück
D000302:Adrenal Cortex / Q000166:cytology / Q000378:metabolism; D000728:Androgens / Q000096:biosynthesis*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line; D000072497:Cytochrome P450 Family 21 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D014176:Protein Biosynthesis / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D000077185:Resveratrol; D056566:Sirtuin 3 / Q000096:biosynthesis / Q000235:genetics; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*
D000728:Androgens; D000894:Anti-Inflammatory Agents, Non-Steroidal; D012333:RNA, Messenger; D013267:Stilbenes; D000072497:Cytochrome P450 Family 21; D013254:Steroid 17-alpha-Hydroxylase; D051057:Proto-Oncogene Proteins c-akt; C466093:SIRT3 protein, human; D056566:Sirtuin 3; D000077185:Resveratrol