Neonatal imprinting of liver microsomal hydroxylation and reduction of steroids.

The metabolism of 4-[4-Wlandrostene-3,17-dione, 4-[4r4C]pregnene-3,20-dione, 5&-[4-r4C]androstane-3cr,l7P-diol, 4,16-[70+~H]androstadien-3-one, [4-W]cholesterol, and 7~ hydroxy-4-[6P-3H]cholesten-3-one was studied in the microsomal fraction of livers from adult male and female rats which had been castrated neonatally or postpubertally. The effect of testosterone propionate treatment on postpubertally castrated male and female rats was also studied with respect to the hepatic microsomal metabolism of the mentioned steroid substrates. It was found that the different microsomal enzyme activities could be grouped into three categories according to their specific characteristics. One category of enzymes (represented by the 2/3-hydroxylase active on Scr-androstane-3oc, 17p dial, the 6@ hydroxylase active on 4 androstene 3, 17-dione and 4-pregnene-3,20-dione, and the 18-hydroxylase active on Sa-androstane-3a, 17/3-diol) was more active in male than in female rats. This sexual difference was completely abolished both by postpubertal and neonatal testectomy. The activities of the enzymes in this group were stimulated by treatment with testosterone propionate. A second category of enzymes (the 2c+hydroxylase active on 4-pregnene3,20-dione and 50c-androstane-3a, 17@-diol, the 16ac-hydroxylase active on 4-androstene-3, I7-dione, the A1W19 steroid epoxidase active on 4,16-androstadien-3-one, and the 17P-hydroxysteroid reductase active on 4-androstene3,17-dione) was generally much more active in male than in female rats. Only neonatal testectomy completely abolished this sexual difference, whereas postpubertal testectomy reduced but did not abolish the differences in enzyme activities between male and female rats. Testosterone propionate treatment led to increased activities of these enzymes. The third category of enzymes (the 7oc-hydroxylase active on 4-androstene-3,1’7-dione and cholesterol, the 12oc-hydroxylase active on 7ar-hydroxy-4-cholesten-3-one, and the 1609 hydroxylase active on 4-pregnene-3,20-dione) was generally slightly more active in female than in male rats. The activities of the enzymes in this group were not significantly afIected by neonatal or postpubertal gonadectomy or by treatment with testosterone propionate.