Inhibition of Estradiol-17ß-Induced Uterine Growth by ¹, 9 Fluoro-17 Hydroxycorticosterone

¹ From the Department of Anatomy, Yale University School of Medicine, New Haven, Connecticut

Adult, albino rats of the Charles River strain, 100 days of age, weighing 190–210 gm, were bilaterally ovariectomized, and 1 week later were placed on experiments to ascertain the influence of ¹, 9 fluoro-17-hydroxycorticosterone (FF) on estradiol-17ß-induced uterine growth. The results indicate that FF when administered in a daily dosage up to 0.20 mg for 3 days did not modify the weight of the uterus of the ovariectomized rat, whereas 3 daily dosages of 0.10 µg estradiol-17ß effected an increase of approximately 85% in uterine weight. When 0.05–0.20 mg FF was injected daily, but at different sites, with 0.10 µg estradiol-17ß for the 3-day period, the response of the uterus to estradiol-17ß was markedly reduced from the estradiol-17ß-induced increase of 85% to 52% on the lowest dosage of FF down to 24% on the highest dose (0.20 mg) of FF. These experiments further indicate that the inhibition of estradiol-17ß-induced uterine growth could be partially reversed by increasing the dosage of estradiol-17ß. Comparatively, data at hand suggest that FF > 9FlF > compound F > compound E > ¹E and ¹F in inhibiting 0.10 µg estradiol-17ß on the uterus and the vagina of the ovariectomized rat. Moreover, the incorporation of an additional double bond in ring A (¹) and flourine atom in the 9 position of compound F enhances the uterine growth inhibiting activity of compound F. Of the numerous glucocorticoids and mineralocorticoids tested for ability to inhibit estradiol-17ß, FF is by far the most efficacious.