The Human Type II 17β-Hydroxysteroid Dehydrogenase Gene Encodes Two Alternatively Spliced mRNA Species

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Abstract
The isozymes of the 17β-hydroxysteroid dehydrogenase (17β-HSD) gene family are responsible for the formation of the 17β-hydroxysteroids ▲5-androstene-3β,17β-diol, testosterone, 17β-estradiol, and dihydrotestosterone from their corresponding 17-ketosteroid precursors, thus playing a pivotal role in the formation of active sex steroids in both steroidogenic and peripheral target tissues. To clone the type II 17β-HSD gene, the full-length cDNA type II 17β-HSD was used as probe to screen a human leukocyte genomic DNA library. The type II 17β-HSD gene contains seven exons and spans >40 kbp. The type II 17β-HSD gene encodes two alternatively spliced mRNAs that give rise to the previously identified type IIA 17β-HSD protein of 387 amino acids, as well as to a related 291-amino-acid type IIB 17β-HSD protein of unknown function. RNA blot analysis revealed the presence of a major 1.45-kb transcript that is abundant in placenta and endometrium. The mRNA cap site has been localized in a region between 179 and 167 nucleotides upstream of the ATG start codon by RNase protection and SI nuclease mapping analyses. Cloning of the 17β-HSD type II gene provides us with the tools to study its transcriptional expression.