Cloning and expression of a novel tissue specific 17beta-hydroxysteroid dehydrogenase.
The 11beta-hydroxysteroid dehydrogenases (11betaHSD) modulate intracellular glucocorticoid levels, with 11betaHSD1 converting cortisone to cortisol mainly in the liver, and 11betaHSD2 performing the reverse reaction in sodium transporting epithelia and placenta. We have attempted to expand the 11betaHSD subfamily by isolating homologous cDNA's. Expressed Sequence Tag databases were screen with segments of the 11betaHSD1 enzyme amino acid sequence and Pan1b identified as a new member of the short chain alcohol dehydrogenase superfamily. Northern blot analysis of total RNA from human tissues showed a single band at 1.9 kb and a tissue specific pattern of expression with high levels in the liver, adrenal carcinoma, lung and small intestine, and much lower levels in the kidney, heart and placenta. Expression studies in a Chinese hamster ovary cell line (CHOP) showed that Pan1b did not metabolize glucocorticoids. However, preliminary studies on a range of substrates revealed that Pan1b acted as a dehydrogenase on 17beta-hydroxysteroids, although further kinetic analysis was confounded by large amounts of endogenous oxidoreductase activity in CHOP cells. These studies suggest the existence of a novel human 17betaHSD enzyme.
Li
K X
KX
Laboratory of Molecular Hypertension, Baker Medical Research Institute, Melbourne, Australia.
Smith
R E
RE
Krozowski
Z S
ZS
D042842:11-beta-Hydroxysteroid Dehydrogenases; D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics* / Q000378:metabolism*; D000426:Alcohol Dehydrogenase / Q000235:genetics; D000429:Alcohol Oxidoreductases; D000445:Aldehyde Oxidoreductases; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D003001:Cloning, Molecular; D006224:Cricetinae; D019992:Databases as Topic; D020224:Expressed Sequence Tags; D005260:Female; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism*; D008647:Mesocricetus; D005810:Multigene Family; D010053:Ovary / Q000166:cytology / Q000378:metabolism; D014018:Tissue Distribution
D007527:Isoenzymes; D015067:17-Hydroxysteroid Dehydrogenases; D000429:Alcohol Oxidoreductases; C118226:HSD17B11 protein, human; D006913:Hydroxysteroid Dehydrogenases; D000426:Alcohol Dehydrogenase; D042842:11-beta-Hydroxysteroid Dehydrogenases; D000445:Aldehyde Oxidoreductases