“Puberty” of the Rat Liver. IV. Influence of Estrogens Upon the Differentiation of Cortisol Metabolism Induced by Neonatal Testosterone

Abstract

The influence of estrogens on the masculinizing effect of neonatal testosterone was explored at different ages by studying the in vitro metabolism of cortisol in rat liver homogenates. Enhanced formation rates of 3β- and 20β-hydroxy metabolites together with a decreased Δ4,3-keto reduction to allotetrahydrocortisol was accepted as a criterion of masculinization. Estradiol benzoate (E2B), given to normal male rats in a single sc dose of 200 μg on the 5th day of life, considerably delayed the sexual differentiation of cortisol metabolism, which normally becomes apparent in these animals between the 30th and the 40th day of life. Male features in cortisol metabolism only appeared about the 60th day of life. E2B, however, had no delaying effects when given on the 15th day of life. A group of male animals was treated similarly (200 μg E2B sc on the first or the 6th day of life) but was castrated when 120 days old and studied 4 months later. The animals injected on the first day of life did not differ from female rats similarly treated and spayed. On the other hand, the animals injected on the 6th day of life retained masculine characteristics after castration on the 120th day of life. Male rats castrated and simultaneously treated with E2B (300 μg sc) on the 6th day of life developed the cortisol metabolizing pattern with the masculine characteristics developing in the oil-injected castrated male rats. Another group of male rats was castrated on the 24th day of life. The animals developed a masculine type of cortisol metabolism. These features were completely abolished during treatment with estradiol valerate. The masculine features were only partly regained 7 months after the last estrogen injection. In female rats E2B treatment within the first days of life caused only a slight temporary increase in allotetrahydrocortisol formation. Ovariectomy in these rats caused a decrease in the formation of the latter metabolite but no difference was found between these animals and gonadectomized controls. Female rats injected with testosterone propionate within the first week of life developed and maintained many masculine features in their adult cortisol metabolism, but this only if they were gonadectomized at an early age. If not gonadectomized, the masculine characteristics did not appear and, if spayed on the 90th day of life, only minimal masculine changes developed even several months later. It is concluded that, as far as the differentiation of cortisol metabolizing enzymes is concerned, estradiol is able to counteract the organizing action of testosterone at birth as well as the expression of these neonatal testosterone effects after the 30th day of life. (Endocrinology85: 259,1969)