Enzymatic Oxidation and Reduction of C19-Δ5-3β-Hydroxysteroids by Hepatic Microsomes. III. Critical Period for the Neonatal Differentiation of Certain Mixed-Function Oxidases

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Abstract
The gonadal dependence of certain hepatic enzymes has been studied in neonatal and pubertal rats with 14C-dehydroepiandrosterone (DHA). Microsomes from rats of 20, 40, 70 and 105 days of age produced 7α- and 7β-OH-DHA, and 7-keto-DHA in addition to 16-oxygenated products and A5-diol. The rates of 7α-hydroxylation (nmoles min-1mg-1) characteristic of adult males had appeared at 40 days of age and progressively increased thereafter. This transformation by tissue from females decreased from the values of 20-day-old animals to a constant minimum level. The formation of 16-keto-A5-diol, 16α-0H-DHA and A5-triol was significantly reduced from normal values in 70-day-old males which had been castrated at 1, 10 or 40 days of age. The rates of production of these 16-oxygenated metabolites were proportional to the age of castration, with neonatally castrated males having the lowest rates, similar to those of intact adult females. The pubertal increase of the 7α-hydroxylase activity was also prevented by castration of day-old male rats, but not by castration at later times. These transformations of DHA (at both the C-7 and C-16 positions) in adult females were undisturbed by neonatal castration, which did not alter in either sex the rates of 17β-dehydrogenation of DHA to A5-diol. These data indicate for the first time that the testis of male rats is a prerequisite during a “critical period” of neonatal life for the expression of certain hepatic steroid mixed-function oxidase activities of adulthood. (Endocrinology94: 97, 1974)

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