SEX DIFFERENCE IN RATE OF RING A REDUCTION OF Δ4-3-KETO-STEROIDSIN VITROBY RAT LIVER12

Abstract
Homogenates of livers from adult female rats reduce Ring A of Δ4-3-ketosteroids at rates 3 to 10 times greater than those from males. This large sex difference has been observed for all substrates so far tested: aldosterone, desoxycorticosterone, hydrocortisone, cortisone, corticosterone, testosterone and progesterone. It consists of a much greater concentration of the microsomal Δ4-5α-steroid hydrogenases in the livers of females and does not involve any sex difference in availability of reduced pyridine nucleotides, nor the presence of activators in the females or inhibitors in the males. Castration increases and testosterone decreases Δ4-steroid hydrogenase activity in males. In females, neither castration nor estrogen administration had appreciable effect. However, a striking non-gonadal process leads to an increase in activity in both sexes during growth. The sex difference is still present, although diminished, in animals castrated when young—before the difference has appeared—and then allowed to grow to adulthood. The full adult sex difference consists predominantly of this non-gonadal induction of the enzymes, which is more marked in the female. A superimposed testosterone suppression of this process in the male increases the difference still further. The sex difference in hepatic steroid metabolism first appears appoximately at the time of appearance of the sex difference in adrenal cortical weights, but treatment of adult rats with corticosteroids does not significantly increase the A4-steroid hydrogenase activity in the liver if the adrenals are present. The greater capacity of the female rat to inactivate Δ4-3-keto-steroids by Ring A reduction, compared to that of the male, may cause the larger size of the adrenal cortex in the female—through greater stimulation of ACTH release by more rapid removal of circulating Δ4-3-keto-steroids from the blood. This hypothesis is strengthened by the finding of a reversed sex difference in hepatic steroid metabolism of golden hamsters, in which the males have larger adrenals than the females.

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