Sesquiterpene lactone helenalin suppresses Leydig and adrenocortical cell steroidogenesis by inhibiting expression of the steroidogenic acute regulatory protein.
Helenalin is a potent anti-inflammatory and anti-neoplastic agent isolated from several plant species of the Asteracea family. Here, we have investigated the effects of helenalin on steroidogenesis activated by adrenocorticotropic hormone (ACTH) and human chorionic gonadotropin (hCG) in primary cultures of rat adrenocortical and Leydig cells. Our findings demonstrate that helenalin inhibits both ACTH- and hCG-activated steroidogenesis in these cells. This effect was already evident after 2-3 h treatment with helenalin. In contrast, steroidogenesis from 22R-OHC, a cell-permeable form of cholesterol, was not inhibited by helenalin, suggesting that the expression of the steroidogenic acute regulartory (StAR) protein might be inhibited by this compound. Indeed, helenalin attenuated StAR protein expression activated by ACTH and hCG in adrenocortical and Leydig cells as assessed by PAGE/Western analyses. This inhibitory action of helenalin on steroidogenic cell functions indicates novel mechanisms of action of this compound which may be of potential therapeutic interest. However, it also poses safety concerns relating to possible negative side-effects on anabolism and systemic stress.
Supornsilchai
Vichit
V
Department of Woman and Child Health, Pediatric Endocrinology Unit, Q2:08, Karolinska University Hospital, Stockholm, Sweden. Vichit.Supornsilchai@kbh.ki.se
Söder
Olle
O
Svechnikov
Konstantin
K
D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D003994:Bucladesine / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003345:Corticosterone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D006888:Hydroxycholesterols / Q000494:pharmacology; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010750:Phosphoproteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000737:chemistry / Q000633:toxicity*; D045789:Sesquiterpenes, Guaiane; D013739:Testosterone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013778:Tetrazolium Salts / Q000378:metabolism; D013997:Time Factors; D000098682:Steroidogenic Acute Regulatory Protein
C110656:2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium; D006063:Chorionic Gonadotropin; D006888:Hydroxycholesterols; D010750:Phosphoproteins; D012717:Sesquiterpenes; D045789:Sesquiterpenes, Guaiane; D013778:Tetrazolium Salts; D000098682:Steroidogenic Acute Regulatory Protein; C003585:22-hydroxycholesterol; D013739:Testosterone; C001329:helenalin; D003994:Bucladesine; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone