Cytochrome P450c17: Regulation of Gene Expression and Enzyme Function at the Bifurcation in Steroid Hormone Synthesis

  • W. N. Kühn-Velten
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 105)


Cytochrome P450c17 is a member of the cytochrome P450 gene superfamily (Nebert et al. 1991) that is of special interest because of its functional significance, catalytic properties, and hormonal regulation. Located in the membranes of the smooth endoplasmic reticulum in steroidogenic cells, cytochrome P450c17 is the terminal substrate-binding and oxygen-activating heme protein in a monooxygenase system which is able to catalyze a two-step reaction sequence, i.e., a first oxygen- and NADPH-dependent hydroxylation of a C21 steroid (pregnenolone or progesterone) in the C17α position (yielding 17α-hydroxypregnenolone or 17α-hydroxyprogesterone), which may be (but is not necessarily) followed by a second NADPH- dependent oxygen activation and insertion resulting in a C-C bond cleavage yielding C19 steroids (dehydroepiandrosterone or androstenedione). Thus, depending on the further enzyme equipment of an endocrine active cell, the reaction intermediate can either be processed towards glucocorticoids (Cortisol and 11-deoxyCortisol) or to androgens (mainly testosterone) and estrogens (mainly estradiol). Cytochrome P450c17 therefore occupies an important position at a metabolic branchpoint (Hall 1986; Simpson and Waterman 1988). Since the discovery of cytochrome P450c17 in testicular microsomes (Menard and Purvis 1973), major methodological breakthroughs in membrane protein purification (Nakajin and Hall 1981), protein and DNA sequence analysis, heterologous gene expression, and computer-aided modeling have provided increasing information about this enzyme.


Leydig Cell Lyase Activity Steroidogenic Enzyme Microsomal Cytochrome Testis Microsome 
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© Springer-Verlag Berlin Heidelberg 1993

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  • W. N. Kühn-Velten

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