resveratrol induced inhibitory ef fect on mRNA expression was uncovered in Cyp17a1, resver atrol with the highest concentration diminished Cyp17a1 mRNA ranges by 73%. Exposure of cells to simvastatin therapy decreased Cyp17a1 tran scripts by 82% and this simvastatin induced inhibitory effect on Cyp17a1 mRNA expression was fur ther enhanced to 95% inside the presence of 10 uM resveratrol. Result of simvastatin and resveratrol on steroid production To find out the effect of simvastatin alone and or res veratrol on steroid manufacturing, levels of progesterone, androstenedione and androsterone were evaluated in spent media utilizing liquid chromatography mass spec trometry. To account for the two simvastatin and resvera trol possible results about the cell quantity, the production of steroids was calculated per unit of protein in every single in dividual culture effectively and then expressed as percentage of handle cultures.
Steroid amounts are presented as per centage of manage in order to facilitate combining of the success of three separate experiments whereby in just about every experiment levels of steroids in manage selleck chemical cultures served as normalizing references. The amounts of steroids in con trol cultures were as follows, progesterone level ranged from 5,328 pg mg to 18,532 pg mg, androstenedione degree ranged from 392 pg mg to 3,112 pg mg and androsterone level ranged from 657 pg mg to 26,786 pg mg. As presented in Figure 2A, resveratrol did not have an effect on progesterone manufacturing except for any slight reduce by 20% at a concentration of three uM, whereas simvastatin appreciably decreased progesterone produc tion by 38%.
The addition of resveratrol to simvastatin taken care of the original source cultures had no significant effect in comparison with the degree observed with simvastatin alone at any of your concentrations tested. With regard to androgen production, resveratrol induced a concentration dependent inhibitory effect, on the highest concentration androstenedione levels decreased by 76%. Simvastatin alone inhibited androstenedione production by 83% and this result was enhanced by the addition of resveratrol whereby a combination of simvastatin and resveratrol at ten uM decreased andro stenedione to non detectable ranges. Within a related trend, resveratrol induced a concentration dependent reduce in androsterone levels by up to 76% at 10 uM resveratrol.
Simvastatin decreased androsterone production by 57%, whereas the addition of 10 uM resveratrol potentiated simvastatin induced inhib ition of androsterone ranges by added 25% when compared with the degree attained with simvastatin alone. Discussion This review demonstrates that in cultures of theca interstitial cells, 1 both resveratrol and simvastatin inhibit androgen manufacturing, 2 the simvastatin induced lower in androgen amounts is enhanced from the addition of resvera trol, three the co
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