cyproterone and Feminization

Topics: Adult; Cyproterone; Cyproterone Acetate; Female; Feminization; Fetus; Humans; Maternal-Fetal Exchange; Pregnancy

Mammary tissue of male rats "feminized" by in utero treatment with cyproterone acetate, accrues the capacity to convert circulating androgens to estrogens at the mammary tissue level in adult life. DMBA-induced mammary tumorigenesis was studied in these feminized males to find out whether or not this altered steroid metabolism leading to heightened estrogenicity would increase mammary tumor yield when compared to that seen in normal males, where such conversion is significantly low. Results on the incidence of mammary tumors, tumor pathology and latency period of tumor appearance in these 2 groups, however, do not differ significantly. From observations on mammary morphology of these feminized males it appears that in vivo conversion of testosterone to estrogen probably is not total and that the available testosterone inhibits tumor induction.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Benz(a)Anthracenes; Cyproterone; Female; Feminization; Male; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Pregnancy; Rats; Testosterone

The metabolism of (4-14C)4-androstene-3,17-dione, (4-14C)5alpha-androstane-3alpha, 17beta-diol and (1,2-3H)5alpha-androstane-3alpha, 17beta-diol 3,17-disulphate was studied using the microsomal fraction and the metabolism of (4-14C)4-androstene-3,17-dione was studied using the 105 000 g supernatant fraction of liver from male and female rats aged 5 months that had been treated with cyproterone acetate before (from day 13 of pregnancy) and after birth (until 3 weeks of age). Nearly all sex-dependent enzyme activities in the treated male rats were changes in a direction characteristic of female rats: 5alpha-reductase active on 4-androstene-3,17-dione increased in activity whereas 3beta- and 17alpha-hydroxysteroid reductases and 6beta- and 16alpha-hydroxylases active on 4-androstene-3,17-dione and 2alpha-, 2beta- and 18-hydroxylases active on 5alpha-androstane-3alpha,17beta-diol decreased in activity. Enzyme activities not under gonadal control, i.e. 3alpha- and 17beta-hydroxysteroid reductases active on 4-androstene-3,17-dione and 7alpha-hydroxylase active on both 4-androstene-3,17-dione and 5alpha-androstane-3alpha, 17beta-diol, were not affected by cyproterone acetate. The liver enzyme activities in treated female rate were generally not affected although significant effects were noted in two cases; in one of these (17alpha-hydroxysteroid reductase) a testosterone-like effect was observed. The results obtained are probably best explained in the following way: treatment with theanti-androgen during the neonatal period results in less efficient imprinting of the hypothalamo-hypophysial system leading to less pronounced masculine setting of sex-dependent enzyme levels and also to a relative androgen unresponsiveness. It is suggested that the biochemical methods used in the degree of neonatal sexual differentiation of the hypothalamo-hypophysial system than biological and psychological methods previously available.

Topics: Androstanes; Androstenedione; Animals; Animals, Newborn; Cesarean Section; Chromatography, Gel; Chromatography, Thin Layer; Cyproterone; Feminization; Hydroxysteroid Dehydrogenases; Hydroxysteroids; Liver; Male; Microsomes, Liver; Mixed Function Oxygenases; Oxidoreductases; Rats; Scrotum; Sex Factors

Topics: Androgen Antagonists; Animals; Animals, Newborn; Castration; Cerebral Cortex; Corpus Luteum; Cyproterone; Estradiol; Female; Feminization; Hydroxysteroid Dehydrogenases; Hypothalamus; In Vitro Techniques; Leydig Cells; Male; Ovarian Cysts; Ovary; Pituitary Gland; Pregnadienes; Rats; Testis; Testosterone; Tritium