THE HUMAN TYPE-II 17-BETA-HYDROXYSTEROID DEHYDROGENASE GENE ENCODES 2ALTERNATIVELY SPLICED MESSENGER-RNA SPECIES

The isozymes of the 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) gene family are responsible for the formation of the 17 beta-hydroxys teroids Delta(5)-androstene-3 beta,17 beta-diol, testosterone, 17 beta -estradiol, and dihydrotestosterone from their corresponding 17-ketost eroid precursors, thus playing a pivotal role in the formation of acti ve sex steroids in both steroidogenic and peripheral target tissues, T o clone the type II 17 beta-HSD gene, the full-length cDNA type II 17 beta-HSD was used as probe to screen a human leukocyte genomic DNA lib rary. The type II I7 beta-HSD gene contains seven exons and spans >40 kbp, The type II 17 beta-HSD gene encodes two alternatively spliced mR NAs that give rise to the previously identified type IIA 17 beta-HSD p rotein of 387 amino acids, as well as to a related 291-amino-acid type IIB 17 beta-HSD protein of unknown function, RNA blot analysis reveal ed the presence of a major 1.45-kb transcript that is abundant in plac enta and endometrium. The mRNA cap site has been localized in a region between 179 and 167 nucleotides upstream of the ATG start codon by RN ase protection and S1 nuclease mapping analyses, Cloning of the 17 bet a-HSD type II gene provides us with the tools to study its transcripti onal expression.