Comparative Activity of Naturally Occurring Estrogens on the Infantile Rat Uterus and Vagina. ∗ †

In a previous report it was shown that there is a distinct difference between estrone and estriol in their respective abilities to cause hypertrophy of the infantile rat uterus and vaginal introitus. 1 These observations have been confirmed and extended by other workers to include estradiol. 2 , 3 In this communication we have further extended these comparative studies to include, in addition to estrone, α-estra-diol, and estriol, the benzoates of estrone and estradiol and also equilen and equilenin.

The estrogens employed in this study were dissolved in olive oil so that the daily amount administered was always contained in 0.2 cc of oil. Twenty-five-day old female rats were injected subcutaneously once daily for 5 days. Twenty-four hours after the last injection, the animals were sacrificed. Body weight, uterine weight, and vaginal introitus were determined. At each concentration for each estrogen 4 or more animals were used, except in one instance (estriol at 55γ per day) when 3 animals were employed.

The comparative uterine and vaginal activities of the estrogens studied are presented in Table I and Fig. I. α-Estradiol ranked as the most active estrogen in its ability to hypertrophy the uterus and produce vaginal introitus. As small a daily dose as 0.01 μg produced a 30% increase in uterine weight and 40% vaginal introitus. The descending order of uterine activity was α-estradiol, estrone, equilin, equilenin, and estriol. The descending order of activity on the vagina was α-estradiol, estrone, equilin, with estriol and equilenin being the least active of the group and of about the same magnitude.

As previously described, the activity of estriol on the uterus is unique. Though a small dose stimulates the uterus, even a large dose (100γ) still does not hypertrophy the gland to its maximum size.