Clomiphene and tamoxifen inhibit the cholesterol side-chain cleavage enzyme activity in hen granulosa cells.
A radiochemical assay was utilized to study the inhibitory effects of clomiphene and tamoxifen on the cholesterol side-chain cleavage enzyme activity in a mitochondrial preparation of granulosa cells isolated from mature ovarian follicles of laying hens. At saturating substrate concentrations, both clomiphene and tamoxifen were able to suppress enzyme activity in a dose-related manner (IC50 1.8 X 10(-5) M). Double reciprocal plots of kinetic data show that the inhibition is mixed, exhibiting competitive kinetics at low concentrations, whereas at high concentrations, the inhibition is of a non-competitive nature. The competitive inhibition constants as determined from Dixon plots are 2 X 10(-5) M for clomiphene and 2.3 X 10(-5) M for tamoxifen. It is concluded that, in granulosa cells, clomiphene and tamoxifen directly inhibit the mitochondrial cholesterol side-chain cleavage activity. This inhibition may represent an important aspect of the mode of action of clomiphene and tamoxifen.
D000818:Animals; D002645:Chickens; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism*; D002996:Clomiphene / Q000494:pharmacology*; D003864:Depression, Chemical; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D010088:Oxidoreductases / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology*
D013629:Tamoxifen; D002996:Clomiphene; D010088:Oxidoreductases; D002786:Cholesterol Side-Chain Cleavage Enzyme