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Regulated expression by PPARα and unique localization of 17β‐hydroxysteroid dehydrogenase type 11 protein in mouse intestine and liver
Author(s) -
Yokoi Yasuhide,
Horiguchi Yuka,
Araki Makoto,
Motojima Kiyoto
Publication year - 2007
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2007.06005.x
Subject(s) - endoplasmic reticulum , subcellular localization , peroxisome , lipid droplet , biology , hydroxysteroid dehydrogenase , receptor , small intestine , cytoplasm , peroxisome proliferator activated receptor , microbiology and biotechnology , biochemistry , dehydrogenase , enzyme
17β‐Hydroxysteroid dehydrogenase type 11 (17β‐HSD11) is a member of the short‐chain dehydrogenase/reductase family involved in the activation and inactivation of sex steroid hormones. We recently identified 17β‐HSD11 as a gene that is efficiently regulated by peroxisome proliferator‐activated receptor‐α PPARα in the intestine and the liver [Motojima K (2004) Eur J Biochem 271 , 4141–4146]. In this study, we characterized 17β‐HSD11 at the protein level to obtain information about its physiologic role in the intestine and liver. For this purpose, specific antibodies against 17β‐HSD11 were obtained. Western blotting analysis showed that administration of a peroxisome proliferator‐activated receptor‐α agonist induced 17β‐HSD11 protein in the jejunum but not in the colon, and to a much higher extent than in the liver of mice. A subcellular localization study using Chinese hamster ovary cells and green fluorescent protein‐tagged 17β‐HSD11 showed that it was mostly localized in the endoplasmic reticulum under normal conditions, whereas it was concentrated on lipid droplets when they were induced. A pulse‐chase experiment suggested that 17β‐HSD11 was redistributed to the lipid droplets via the endoplasmic reticulum. Immunohistochemical analysis using tissue sections showed that 17β‐HSD11 was induced mostly in intestinal epithelia and hepatocytes, with heterogeneous localization both in the cytoplasm and in vesicular structures. A subcellular fractionation study of liver homogenates confirmed that 17β‐HSD11 was localized mostly in the endoplasmic reticulum when mice were fed a normal diet, but was distributed in both the endoplasmic reticulum and the lipid droplets of which formation was induced by feeding a diet containing a proliferator‐activated receptor‐α agonist. Taken together, these data indicate that 17β‐HSD11 localizes both in the endoplasmic reticulum and in lipid droplets, depending on physiologic conditions, and that lipid droplet 17β‐HSD11 is not merely an endoplasmic reticulum contaminant or a nonphysiologically associated protein in the cultured cells, but a bona fide protein component of the membranes of both intracellular compartments.