Antiprogestational action of 5 alpha-dihydronorethisterone

Relative binding affinities(RBA) of 5alpha-dihydronorethisterone(5alpha-DNE), R2323 and 17beta-hydroxyl-7alpha-methylandrost-5-en-3-one for rabbit uterine progesterone receptors (p-R) were found to be 20.8,37.7 and 0.65, respectively.Results obtained from the endometrial carbonic anhydrase test and uterine cytoplasmic estrogen receptors(E-R) estimation of immature rabbits showed that 5alpha-DNE had progestational and a marked antipreogestational activity. 5alpha-DNE abollshed the uterine cytoplasmic P-R decreasing action of progesterone, but did not overcome the uterine cytoplasmic P-R increasing action of estradiol. 5alpha-DNE 4 mg/kg sc on d7-9 of pregnancy in rats exerted a full antifertility effect. After progesterone 2 mg/kg the number of uterine cytoplasmic P-R decreased to approximately half of the initial value within 2 h, thereafter gradually returned to the original value at 24 h. But there was no apparent change in the uterine cytoplasmic P-R at 2 h after 5alpha-DNE 4 mg/kg. The uterine nuclear P-R of both groups increasd to a peak in 2 h,and then decreased to the control value in 6 h. 5alpha-DNE bound to cytoplasmic P-R and competed for progesterone binding sites. Because of the competitive antagonism at the uterine progesterone receptor level and its antiprogestational activity, 5alpha-DNE might be developed as a contraceptive agent.