ESTROGENIC AND ANTIESTROGENIC ACTIVITIES OF ANORDIOL - A COMPARISON OF UTERINE AND VAGINAL RESPONSES WITH THOSE OF CLOMIPHENE CITRATE

Anordiol(2 alpha,17 alpha-diethynyl-A-nor-5 alpha-androstane-2 beta,17 beta-diol) has been variously characterized as an estrogen and as an antiestrogen. To more completely understand the pharmacological proper ties of this contraceptive steroid, simultaneous responses were studie d in uterine, vaginal, and hepatic tissues. Rats received 4 daily sc i njections with either anordiol, clomiphene citrate (CC), or the vehicl e alone (C+) starting on the first day of pseudopregnancy. Uteri were traumatized on day 4 of pseudopregnancy, and rats were sacrificed 5 da ys later. A pseudopregnant group without uterine trauma served as a ne gative control (C-). Mean uterine weights per animal and cytosolic est rogen (E(c)R) and progesterone (P(c)R) receptor activities per g of DN A were all 5- to 7-fold greater in the C+ group than in the other grou ps (all p<0.05). However, anordiol and CC suppressed uterine weight wi thout suppressing the stromal proliferative response; the DNA content of the uteri of anordiol and CC-treated rats was similar to that of C rats. Vaginal tissue exhibited estrogenic responses to anordiol and C C with an increase in epithelial stratification compared to the C+ and C- groups even though no difference in levels of E(c)R/g of DNA were expressed 5 days after the last antiestrogen dose. Binding affinities and serum E(2) and progesterone (P) concentrations were not statistica lly different among the groups. In conclusion, anordiol produced respo nses in the uterus and vagina of the pseudopregnant rat which were ind istinguishable from those of CC, and, therefore, we conclude that anor diol acts on these tissues as an antiestrogen.