Genomic organization and DNA sequences of human 17β‐hydroxysteroid dehydrogenase genes and flanking regions

Abstract

(Received June 18, 1YY2) -EJB 92 0852Genomic 17~-hydroxysteroid-dehydrogenase (1 7-HSD) clones were isolated from a human leucocyte genomic library using cDNA encoding human placental 17-HSD as a probe. The overlapping fragments spanned more than 21 kbp containing the duplications, 6.2 kbp of each, as well as 7 kbp upstream and 1.6 kbp downstream from the duplicated sequences. 17 complete and eight partial A h elements were clustered in this area, covering about 30% of the region, including the borders of the duplications. Each duplication contained a 17-HSD gene and a conserved region of 1.56 kbp with 98% intercopy similarity. The exon structure of the 17-HSD gene I1 corresponded to the known cDNA species, but both genes contained a possible promoter region with TATA, GC and inverse CAAT boxes. The 5' flanking regions contained sequences similar to thc consensus sequences of cis-acting elements, defined as regulators of 17-HSD gene expression. These putative sequences included estrogen and progesterone/glucocorticoid-response elements and a cyclic-AMP regulatory element.Estrogens play a key role in the development, growth and function of hormone-dependent tissues in women. 178-Hydroxysteroid dehydrogenase (17-HSD) is involved in the regulation of estrogen action by catalyzing the reversible reaction between estradiol and the less-active estrone. 17-HSD and/or its isozymes also catalyze interconversions of other neutral and phenolic 17-hydroxysteroids and 17-ketosteroids.

Molecular Cloning of Mouse 17β‐Hydroxysteroid Dehydrogenase Type 1 and Characterization of Enzyme Activity

“…Comparison of the B1 sequence in mouse 17P-HSD type-I cDNA with B1 consensus sequences showed that it differs from a tlpical B1 sequence as a result of deletion of 30 bp in the middle of the region. Rat 17P-HSD type-1 cDNA contains a B1-like sequence similar to that in mouse cDNA (Ghersevich et al, 1994a,, but the Alu sequence in the 3' end of human cDNA (Peltoketo et al, 1992) is in the opposite orientation compared with the B1 sequence in mice and rats. Thus, the murine B1 sequence may be a remnant of a retropositional insertion into the 17/i-HSD type-1 gene before the divergence of these rodent species.…”

Molecular Endocrinology of Hydroxysteroid Dehydrogenases*

“…The 5Ј-flanking regions contained consensus sequences for cis-acting elements that may function as regulators of 17␤-HSD gene expression. These sequences included estrogen, progesterone, and glucocorticoid response elements and a cAMP response element (67). No functional studies on the 17␤-HSD type I gene promoter have been reported.…”

Intracrinology: role of the family of 17 beta-hydroxysteroid dehydrogenases in human physiology and disease

“…The molecular structure of a human type 1 17 -HSD cDNA and its corresponding gene, which encodes a predicted protein of 327 amino acids, was the first to be elucidated (Peltoketo et al 1988, Luu-The et al 1989, Peltoketo et al 1992). This enzyme is a member of the short-chain alcohol dehydrogenase superfamily.…”