Tissue-Specific Regulation of Aromatase Cytochrome P450 (CYP19) Expression
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The conversion of androgens to estrogens is catalyzed by an enzyme complex known as aromatase, whose activity results in aromatization of the A ring of androgens, to form the phenolic A ring characteristic of estrogens with concomitant loss of the C19 angular methyl group. This enzyme complex is localized to the endoplasmic reticulum of cells in which it is expressed and consists of two components. The first is a form of cytochrome P450 known as aromatase cytochrome P450 (P450arom) (Mendelson et al. 1985; Chen et al. 1986; Kellis and Vickery 1987), the product of the CYP19 gene (Nebert et al. 1991). This heme protein is responsible for binding the C19 steroid substrate and catalyzing the concerted series of reactions leading to formation of the phenolic A ring. The second component is a flavoprotein, NADPH-cytochrome P450 reductase, which is a ubiquitous protein in the endoplasmic reticulum of most cell types and is responsible for transferring reducing equivalents from NADPH to any microsomal cytochrome P450 species with which it comes into contact. The aromatase reaction utilizes 3mol oxygen and 3mol NADPH for every mole of C19 steroid metabolized (Thompson and Siiteri 1974) (Fig. 1). There is general agreement that the first two oxygen molecules are utilized in the oxidation of the C19 angular methyl group. A growing consensus of opinion considers that the third oxygen attack is also on the C19 methyl group resulting in its loss as formic acid.
KeywordsCorpus Luteum Aromatase Activity Human Ovary Primer Extension Analysis Estrogen Biosynthesis
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