Commentary Human 3â-hydroxysteroid dehydrogenase: genes

Understanding of the principal pathways of steroid hormone biosynthesis was established over two decades ago through advances in steroid radio-isotopic and chromatographic techniques. When the enzymes of individual pathways could be examined in more detail, the dissection of the complex pattern of enzyme activities began. At many points, separate pathways employ precisely the same enzyme for equivalent catalytic steps, e.g. for 21-hydroxylase, 11â-hydroxylase, aromatase and several dehydro-genases (Orth et al. 1992). A further economy was found for 17á-hydroxylase and 17,20-lyase activities, which co-purify with the same P450c17 polypeptide. This enzyme was later cloned and expressed in tissue culture cells, revealing that, contrary to the enzyme in rat, human and cattle, 17á-hydroxylase cannot convert 17á-hydroxy-progesterone to androstenedione (Bradshaw et al. 1987, Fevold et al. 1989). Further complexity emerged with the existence of multiple tissue-specific forms of 5á-reductase (Wilson et al. 1993), and 3â-, 11â- and 17â-hydroxysteroid dehydrogen-ases, most of which also utilise multiple steroi