Characterization and localization of human type10 17beta-hydroxysteroid dehydrogenase.
The tissue distribution, subcellular localization, and metabolic functions of human 17beta-hydroxysteroid dehydrogenase type 10/short chain L-3-hydroxyacyl-CoA dehydrogenase have been investigated. Human liver and gonads are abundant in this enzyme, but it is present in only negligible amounts in skeletal muscle. Its N-terminal sequence is a mitochondrial targeting sequence, but is not required for directing this protein to mitochondria. Immunocytochemical studies demonstrate that this protein, which has been referred to as ER-associated amyloid beta-binding protein (ERAB), is not detectable in the ER of normal tissues. We have established that protocols employed to investigate the subcellular distribution of ERAB yield ER fractions rich in mitochondria. Mitochondria-associated membrane fractions believed to be ER fractions were employed in ERAB/Abeta-binding alcohol dehydrogenase studies. The present studies establish that in normal tissues this protein is located in mitochondria. This feature distinguishes it from all known 17beta-hydroxysteroid dehydrogenases, and endows mitochondria with the capability of modulating intracellular levels of the active forms of sex steroids.
He
X Y
XY
Department of Pharmacology, New York State Institute for Basic Research in Developmental Disabilities, New York 10314, USA.
Merz
G
G
Yang
Y Z
YZ
Mehta
P
P
Schulz
H
H
Yang
S Y
SY
D015067:17-Hydroxysteroid Dehydrogenases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002384:Catalysis; D002458:Cell Fractionation; D002467:Cell Nucleus / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006066:Gonads / Q000201:enzymology; D006728:Hormones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000201:enzymology; D008297:Male; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism; D009928:Organ Specificity; D021382:Protein Sorting Signals / Q000235:genetics / Q000502:physiology; D021381:Protein Transport; D015203:Reproducibility of Results; D013256:Steroids / Q000737:chemistry / Q000378:metabolism
D006728:Hormones; D021382:Protein Sorting Signals; D013256:Steroids; D015067:17-Hydroxysteroid Dehydrogenases; D015094:3-Hydroxyacyl CoA Dehydrogenases; C108634:HSD17B10 protein, human