19-Hydroxylation and aromatization of androgens in the developing rat brain.
Androgen aromatization in the human placenta proceeds through two successive hydroxylations at C-19, the products of which are then virtually completely converted to estrogens. In the neonatal rat brain, however, 19-hydroxylation has been shown to exceed significantly subsequent aromatization, suggesting that formation of 19-hydroxylated androgen metabolites might be important in brain differentiation in this species. Using [19-3H3]androstenedione, we found that the surplus activity of 19-hydroxylase relative to aromatase was independent of age, sex, and androgen substrate concentration, despite 100-fold differences in tissue aromatase activity during the course of development. In addition, the surplus 19-hydroxylation was not affected by several agents which otherwise decreased or increased the activity of the aromatase enzyme, including metyrapone, KCN, and cytochrome P-450 reductase, the latter indicating that the failure of the 19-hydroxylated products to proceed to aromatization was not due to a deficit of reducing equivalents. 19-Hydroxylation of androgens in the rat brain is a quantitatively significant metabolic pathway in this tissue, although present data do not confirm the existence of a steroid C-19 hydroxylase in the brain separate from that involved in aromatization.
D000728:Androgens / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism*; D001141:Aromatase / Q000378:metabolism*; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism; D006900:Hydroxylation; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000728:Androgens; D001141:Aromatase