THE KEY ROLE OF 17-BETA-HYDROXYSTEROID DEHYDROGENASES IN SEX STEROID BIOLOGY

17 beta-Hydroxysteroid dehydrogenase (17 beta-HSD) controls the last s tep in the formation of all androgens and all estrogens. This crucial role of 17 beta-HSD is performed by at least five 17 beta-HSD isoenzym es having individual cell-specific expression, substrate specificity, regulation mechanisms, and reductive or oxidative catalytic activity. Both estrogenic and androgenic 17 beta-HSD activities were found in al l 25 rhesus monkey and 15 human peripheral intracrine tissues examined . Type 1 17 beta-HSD is a protein of 327 amino acids catalyzing the fo rmation of 17 beta-estradiol from estrone. Its x-ray structure was the first to be determined among mammalian steroidogenic enzymes. Initial ly crystallized with NAD, the crystal structure of type 1 17 beta-HSD has just been determined as a complex with 17 beta-estradiol, thereby illustrating the conformation of the substrate-binding site. Type 2 17 beta-HSD degrades 17 beta-estradiol into estrone and testosterone int o androstenedione, and type 4 17 beta-HSD mainly degrades 17 beta-estr adiol into estrone and androst-5-ene-3 beta, 17 beta-diol into dehydro epiandrosterone. Types 3 and 5 17 beta-HSD, on the other hand, catalyz e the formation of testosterone from androstenedione in the testis and peripheral tissues, respectively. The various types of human 17 beta- HSD, because of their tissue-specific expression and substrate specifi city, provide each peripheral cell with the necessary mechanisms to co ntrol the level of intracellular androgens and/or estrogens, a new are a of hormonal control that we call intracrinology. (C) 1997 by Elsevie r Science Inc.