The effect of synthetic gestagens on progesterone formation in vitro in human corpus luteum of early pregnancy.

Abstract

Abstract Tissue derived from 26 corpora lutea of 7–14 weeks of pregnancy was incubated with pregnenolone as the substrate in different concentrations. With a concentration of 53 μmol/l progesterone was formed at a rate of 44–257 μg/g during 30 min incubation and 454–492 μg/g, respectively, in the presence of cofactors. The effect of progesterone and of nine synthetic gestagenic steroids on progesterone synthesis was as follows. Progesterone in concentrations of 5–10 μmol/l had no effect on the conversion of labelled pregnenolone (1 μmol/l) to progesterone. When progesterone was present in a concentration of 53 or 530 μmol/l, the formation of progesterone was reduced to the level of 72.3% and 22.8%, respectively, of that of the controls. Under similar conditions, dydrogesterone, lynestrenol and norethynodrel were less inhibitory than progesterone. The degree of inhibition caused by medroxyprogesterone acetate and norgestrel was comparable to that of progesterone, that of allylestrenol and megestrol acetate was slightly more marked but not proportional to the dose at the levels used. The strongest inhibition on progesterone formation was induced by Δ 4 -3-keto-19-nortestosterone derivatives, norethisterone and methylestrenolone. These steroids were already effective at the lowest concentration (6 μmol/l) used with an equimolar amount of the substrate. At the highest concentration (57 and 59 μmol/l of norethisterone and methylestrenolone, respectively) used equimolarly with 50 μg of pregnenolone as the substrate, the steroids reduced the progesterone formation to 53.3−43.6% of the control values. This inhibition was reversed to a considerable extent by the addition of NAD.