De Coster, R., Wouters, W., Beerens, D., Haelterman, C, Doolaege, R., Goeminne, N.Krekels, M. Comparative effects of etomidate and its fluoro analogue, R 8110 on testicular, adrenal and ovarian steroid biosynthesis.J. vet. Pharmacol. Therap.11, 345–353.The effects, of etomidate and of its fluoro analogue, R 8110, on adrenal, testicular and ovarian steroid biosynthesis were compared using cultures of guinea‐pig adrenal, rat adrenal capsular, rat testicular and rat ovarian granulosa cells. At a concentration of 100 nM, etomidate inhibited the adrenal 11‐hydroxylation of glucocorticoid and mineralocorticoid biosyntheses, producing a decrease in Cortisol and corticosterone and an accumulation of 11‐deoxycortisol and 11‐deoxycorticosterone in guinea‐pig adrenal and rat capsular adrenal cell suspensions, respectively. At higher concentrations (>10‐6M), etomidate also inhibited ovarian oestradiol production, testicular androgen formation and ovarian progesterone synthesis. The latter action suggests an effect on ovarian aroma‐tase, on testicular 17a/17,20‐lyase activities and Finally on cholesterol side‐chain cleavage. The fluoro analogue of etomidate, R 8110, was ten times less potent as an inhibitor of 11‐hydroxylation and affected progesterone formation only slightly in adrenal cell suspensions. Testosterone production was less affected by R 8110 than by etomidate. The increase of progestins suggests that the 17a/ 17,20‐lyase activities are the most sensitive testicular enzymatic reactions to R 8110. For inhibition of ovarian oestradiol production, R 8110 was twenty times mor
展开▼