17beta-hydroxysteroid dehydrogenases: physiological roles in health and disease.

Androgens and estrogens play crucial roles in the growth and development of sex organs. Interconversion of these hormones between biologically active and inactive forms is catalyzed by 17beta-hydroxysteroid dehydrogenase (17beta-HSD) isozymes. Aberrations in the regulation or expression of the various 17beta-HSD isoforms has been implicated in the genesis/progression of hormonally dependent cancers of various tissues, including ovary, breast and prostate; in the predisposition of women with upper body obesity to several types of diseases, such as non-insulin dependent diabetes mellitus; and in the abnormal development of sexually ambiguous individuals, as seen in 17beta-HSD-deficient male pseudohermaphrodites. Of the five known 17beta-HSD isozymes, deleterious mutations in the type 3 isoform were found to give rise to male pseudohermaphroditism. The 16 mutations characterized to date include 12 missense mutations, three splice junction mutations, and one small deletion that results in a downstream premature stop codon. 17beta-HSD has also been studied in other species. The most notable species difference observed is the placental expression in humans of the 17beta-HSD type 1 isoform.