Effects of 17 beta-hydroxy-7 alpha-methylandrost-5-en-3-one (RMI 12,936) on pregnant rabbits

A single subcutaneous injection of RMI 12,936 interrupted 8- and 15-day pregnancy in the rabbit. A dose dependent loss of embryos was observed. Higher doses of RMI 12,936 were needed to terminate pregnancy in 8-day pregnant (74% efficacy with 10 mg/kg) than in 15-day pregnant rabbits (100% efficacy with 8 mg/kg). Termination of pregnancy by RMI 12,936 was accompanied by a significant increase of progesterone (delta 4 p) in rabbits receiving 10 mg/kg RMI 12,936 on day 8 of pregnancy. On the other hand, treatment with 8 mg/kg RMI 12,936 on day 15 of pregnancy did not alter the delta 4 p levels, but induced a significant decrease in 20 alpha-dihydroprogesterone. In these two treatment groups, a consistent and highly significant increase of serum testosterone (T) was observed. The increase of T value possibly was due to a decrease in aromatizing ability of the follicles after RMI 12, 936 treatment and might have contributed towards the interruption of pregnancy. The failure of RMI 12,936-treated rabbits to ovulate even after hCG administration suggests that his compound might have lowered the sensitivity of the mature follicles to LH stimulation.