Endocrinology, Vol 121, 1209-1214, Copyright © 1987 by Endocrine Society

ARTICLES

19-Hydroxylation and aromatization of androgens in the developing rat brain

JJ Michnovicz, EF Hahn and J Fishman
Laboratory of Biochemical Endocrinology, Rockefeller University, New York 10021.

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.

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				A. Tchoudakova and G. V. Callard Identification of Multiple CYP19 Genes Encoding Different Cytochrome P450 Aromatase Isozymes in Brain and Ovary Endocrinology, April 1, 1998; 139(4): 2179 - 2189. [Abstract] [Full Text] [PDF]