RESUMO
A series of physiochemical investigations confirmed that the product of chemical and enzymatic isomerization of RMI 12,936 was 7alpha-methyltestosterone. The total activity per pair of ovaries of delta5 3-ketosteroid isomerase in vitro was unchanges by RMI 12,936 pretreatment or by advancing pregnancy, significant changes in ovarian weight being accompanied by reciprocal changes in enzyme activity/mg tissue. The initial rate of isomerization of RMI 12,936 was approximately five times greater than the corresponding rate of delta5-progesterone isomerization at equal substrate concentrations. It is concluded that RMI 12,936 does not inhibit progesterone biosynthesis by alteration of delta5 3-ketosteroid isomerase activity, but that it may do so by acting as an alternative substrate for this enzyme.
PIP: The effect of RMI 12,936, a synthetic antiprogestational steroid, on ovarian steroidogenesis in rats was studied. It was confirmed that 7alpha-methyltestosterone was the major metabolite of RMI 12,936. Pretreatment with RMI 12,936 or treatment with vehicle on Day 8 of pregnancy did not significantly (p greater than .05) increase the total in vitro ovarian activity of delta(5) 3-ketosteroid isomerase. There was a significant (p less than .01) increase in ovarian weights between Days 9-15 of pregnancy in both treated and control animals, which was accompanied by a significant (p less than .01) decrease in isomerase activity per mg tissue. The initial linear rate of isomerization of RMI 12,936 was about 5 times greater than that of delta(5)-progesterone isomerization. It is suggested that RMI-12,936 does not inhibit progesterone synthesis by alteration of delta(5) 3-ketosteroid isomerase activity, though it may have this effect by serving as an alternative substrate for this enzyme.
