Influence of cyproterone acetate on sexual differentiation of male guinea pigs.

Abstract

Pregnant guinea pigs were treated with cyproterone acetate from the 15th to the 40th day p.c. The dosage was 50, 75 and 100 mg/kg/day. On the 46th day p.c. the internal and external genitalia of untreated female and male foetuses and of male foetuses from treated mothers were prepared and histologically examined. Some fetuses, whose mothers had been treated from the 25th to the 45th day p.c. with a daily dose of 50 mg/kg cyproterone acetate, were allowed to grow up and an adult male animal was dissected. Neither the differentiation of the gonads, the descent of the testes nor the regression of the Mullerian ducts could be influenced by cyproterone acetate. The Wolffian ducts and the seminal vesicles regularly showed signs of a clear regression. In isolated cases their development was completely inhibited by the antiandrogen. The size of the prostate and the bulbo-urethral gland was much reduced in comparison to those of male control animals. However, it was not possible to induce complete regression of these gland complexes. The course of the urethra in the region of the pelvis and phallus and the anatomical form of the external genital organs of male guinea pig fetuses showed clear signs of feminization under the influence of cyproterone acetate. The formation of a vagina could not be induced. It was possible to evaluate the influence of endogenous androgens on critical phases of intrauterine sexual differentiation for the guinea pig. The possibility that cyproterone acetate also has an inherent androgenic effect and the probable existence of species-specific androgens and organ-specific androgen receptors were also discussed. Since the differentiation of the gonads, the descent of the testes and the regression of the Mullerian ducts cannot be influenced by cyproterone acetate administration even several days before the start of the histologically detectable differentiation of these tissues, the results again lead to the assumption that, apart from androgens, at least one other sexual inductor exists which is responsible for the complete sexual differentiation of the genital organs to the male or female type.