A relationship between adenosine 5'-triphosphate and pregnenolone syntheses by ovarian mitochondria as demonstrated with aminoglutethimide.

Aminoglutethimide, an inhibitor of pregnenolone synthesis, was used to study the relationship between oxidative phosphorylation and steroidogenesis in ovarian mitochondria. In vitro addition of aminoglutethimide to mitochondria prepared from porcine corpora lutea resulted in a decrease in oxygen uptake and an increase in the ADP to oxygen ratio, with maximal changes occurring at a concentration of 300 microM. Similar decreases in oxygen uptake were seen when aminoglutethimide was added to ovarian mitochondria from untreated and PMS gonadotropin-treated immature rats and intact and hypophysectomized mature rats. Also, aminoglutethimide increased the ADP to oxygen ratio in ovarian mitochondria from PMS gonadotropin-treated immature rats and intact mature rats. The addition of aminoglutethimide to luteal mitochondria inhibited their [4-14C]cholesterol conversion activity but increased their ATP synthesis rate by 25%. It is concluded that inhibition of ovarian mitochondrial steroidogenesis by aminoglutethimide is accompanied by both a decrease in oxygen consumption and an increase in ATP synthesis.