Cyproterone acetate and reversal of the impaired endometrial decidualization in streptozotocin-diabetic pseudopregnant rats

Reproductive dysfunction in the female diabetic rat is associated with impaired hypothalamic-hypophyseal system, anovulation, insufficiency of ovarian steroidogenesis and spontaneous failure of pregnancy. Formation of decidua, the highly modified endometrium of pregnancy and pseudopregnancy could only be achieved when the uterus was sensitized by a sequence of oestrogen and progesterone. In this study, we examined whether the impaired expression of endometrial decidualization in the pseudopregnant rat is linked with diabetes-associated hypersecretion of testosterone. Rats were made pseudopregnant by sterile mating. Diabetes was induced by streptozotocin on day 1 p.c. Deciduogenic stimulus was given on day 5 p.c. Treatment of cyproterone acetate (10 mg kg(-1)) was scheduled from day 5 through day 9 p.c. Animals were killed on day 10 p.c, and the degree of endometrial decidual growth, plasma levels of oestradiol, progesterone, ACTH and testosterone were determined. Results showed that compared to controls there was a concomitant drop in endometrial decidual growth concurrently with impaired levels of oestradiol and progesterone in diabetic pseudopregnant rats. ACTH and testosterone levels were, however, profoundly elevated. Cyproterone acetate treatment in the diabetic pseudopregnant rat resulted in a simultaneous elevation of oestradiol and progesterone, which eventually helped the endometrial differentiation to decidua in the diabetic pseudopregnant rat parallel to controls. Present experimental data suggest that diabetes-associated impaired endometrial decidualization in the pseudopregnant rat is possibly caused by testosterone-induced oestrogen deficiency. (C) 2000 Academic Press.