M. W. Burrill

Experimental Intersexuality: Modification of Sexual Development of the White Rat with a Synthetic Estrogen

The authors have previously reported on the modifications of embryonic sexual development obtained by injecting large doses of estrogens into pregnant rats. 1 2 3 The naturally occurring alpha estradiol and its diesterified derivative, estradiol dipropionate, were used in this work. Diethyl stilboestrol (4,4′ dihydroxy-alpha-beta-diethylstilbene), which is chemically somewhat dissimilar to the naturally occurring estrogens, has been shown to possess many of their functions such as vaginal cornification, growth of the uterus and mammary glands, 4 inhibition of lactation, 5 restoration of pituitary castration changes, 6 prevention of implantation of fertilized ova 7 and inhibition of the effects of progesterone on the uterus. 7 It seemed of interest to determine if this synthetic substance would have the ability of the natural estrogens to modify embryonic sexual development. Accordingly 40 pregnant rats were given large doses of diethyl stilboestrol† subcutaneously in oil solution. Administration was started in all cases on the 12th or 13th days of pregnancy and continued until the 20th or 21st day, or until resorption of the pregnancies was evident. Twelve of these treated animals carried their pregnancies to term (22nd day of pregnancy). The total dosage these animals received varied from 12 to 42 mg. Eighteen male and 28 female offspring were obtained. The findings in these newborn are essentially identical with those obtained with the natural estrogens. The external genitalia of both males and females are of the female type and nipples are present in all. Normally nipples are never found in the males of our colony and do not appear in the female until the 2nd to 4th day post partum. In the female offspring the uteri are large and distended, the ovarian capsule does not develop and the gonads are bare.

Estrogen-Induced Hypospadias in the Female Rat.∗:

Summary The administration of very large doses of estrogens to pregnant rats has caused a permanent hypospadias and lack of development of the most caudal portion of the vagina, in the female offspring. The abnormality represents an arrest of development so that conditions similar to those found in the 21-day fetus are retained.

Twenty-four hour response to androgens in the immature male rat.

Summary Twenty-four hours after the administration of testosterone propionate to the immature male rat there is an increase in the weights of the prostate and seminal vesicle. This weight increment is proportional to the dosage used.