Mammalian 17β-hydroxysteroid dehydrogenases (17β-HSDs) catalyze the final steps in male and female sex hormone biosynthesis. In the Leydig cells in the testis, 17β-HSD converts androst-4-ene-3,17-dione into the male sex hormone testosterone. In the ovary and placenta, 17β-HSD converts estrone (a weak estrogen) into 17β-estradiol (a potent estrogen) (Fig. 1).
Deficiencies in testicular 17β-HSD have been associated with pseudohermaphroditism (Gross et al. 1986, Wilson et al. 1987, 1988, Farkas & Rosler 1993, Geissler et al. 1994), implicating the importance of this enzyme in testosterone production. It follows that inhibition of this enzyme could block androgen biosynthesis and androgen action. On this basis, selective inhibitors of testicular 17β-HSD have the potential to prevent the growth of androgen-dependent tumors, e.g. benign hyperplasia and cancer of the prostate. Moreover, effective inhibitors could be used as adjuvants to enhance the efficacy of androgen receptor antagonists.
In human breast tissue, 17β-HSD is responsible