SOME BIOLOGICAL ACTIVITIES OF CERTAIN PROGESTOGENS: I. 17?-HYDROXYPROGESTERONE 17-n-CAPROATE

Abstract

Immature virgin female rabbits were injected for 6 days with 5 mcg of estradiol and then treated with 4 daily doses of progesterone 17alpha-hydroxyprogesterone caproate (HPC) or 17alpha-hydroxyprogesterone (17alpha-OHP). Segments of uteri were taken on the fifth day for histological evaluation. The decrease in progestational efficacy of progesterone following 17alpha-hydroxylation was completely reversed by subsequent esterification with caproic acid which led to a potentiation of progesterone. 17alpha-OHP HPC and testosterone were administered subcutaneously daily for 20 days to immature castrated male rats. The animals were autopsied on Day 21 and organ weights were recorded. High doses of testosterone (1 mg) proved thymolytic but neither 17alpha-OHP nor HPC showed such activity. In contrast both 17alpha OHP and HPC tended to increase adrenal weights. Prostatic hypertrophy was evident following 17alpha-OHP but no androgenic activity was noted with comparable doses of HPC. Measurements of urinary sodium excretion were made in intact and adrenalectomized male rats. Animals treated with .3 mg progesterone daily for 3 days excreted more sodium than did rats given comparable doses of HPC. Pretreatment with progesteone for 3 days or 1 hour prior to the sodium load resulted in sodium retention in adrenalectomized rats. combinations of estradiol with progesterone 9alpha-fluoro-11beta-hydroxyprogesterone (FHP) 17alpha-OHP or HPC were administered to immature female mice daily for 3 days. FHP was the most potent antagonist of estradiol. Antiuterotrophic and progestational activities were virtually abolished when progesterone was hydroxylated in the 17alpha position.