Subcellular localization and membrane topology of 17β-hydroxysteroid dehydrogenases.

The 17β-hydroxysteroid dehydrogenases (17β-HSDs) comprise enzymes initially identified by their ability to interconvert active and inactive forms of sex steroids, a vital process for the tissue-specific control of estrogen and androgen balance. However, most 17β-HSDs have now been shown to accept substrates other than sex steroids, including bile acids, retinoids and fatty acids, thereby playing unanticipated roles in cell physiology. This functional divergence is often reflected by their different subcellular localization, with 17β-HSDs found in the cytosol, peroxisome, mitochondria, endoplasmic reticulum and in lipid droplets. Moreover, a subset of 17β-HSDs are integral membrane proteins, with their specific topology dictating the cellular compartment in which they exert their enzymatic activity. Here, we summarize the present knowledge on the subcellular localization and membrane topology of the 17β-HSD enzymes and discuss the correlation with their biological functions. • 17β-HSDs exert diverse functions, spanning from sex steroid and retinoid metabolism to fatty acid synthesis/oxidation. • 17β-HSDs are present in the cytosol, endoplasmic reticulum, lipid droplets, peroxisomes or mitochondria. • The topology of the 17β-HSDs at the endoplasmic reticulum and lipid droplets has now been resolved. • Subcellular localization and membrane topology of the 17β-HSDs is tightly correlated with their biological function. [ABSTRACT FROM AUTHOR]