Immunohistochemical Localization of Type 1 11β-Hydroxysteroid Dehydrogenase in Human Tissues1

Two isozymes of 11β-hydroxysteroid dehydrogenase (11βHSD) catalyze the interconversion of hormonally active cortisol to inactive cortisone. Activity and messenger ribonucleic acid studies indicate that type 1 11βHSD (11βHSD1) is expressed in glucocorticoid target tissues such as liver, gonad, and cerebellum, where it regulates the exposure of cortisol to glucocorticoid receptors. To further understand the role of 11βHSD1 in human tissues, we have studied the localization of this isozyme using an antibody raised in sheep against amino acids 19–33 of human 11βHSD1. Western blot analyses indicated that the immunopurified antibody recognized a band of approximately 34 kDa in human liver and decidua. Immunoperoxidase studies on liver, adrenal, ovary, decidua, and adipose tissue indicated positive cytoplasmic staining for 11βHSD1. 11βHSD1 immunoreactivity was observed more intensely around the hepatic central vein, with no staining around the portal vein, hepatic artery, or bile ducts. No staining for 11βHSD1 was observed in the adrenal medulla, but 11βHSD1-immunoreactive protein was observed in all three zones of the adrenal cortex, with the most intense staining in the zona reticularis > zona glomerulosa > zona fasciculata. In the human ovary, immunoreactivity was observed in the developing oocyte and the luteinized granulosa cells of the corpus luteum. No staining was observed in granulosa cells, thecal cells, or ovarian stroma, which contrasted with the marked expression of 11βHSD2 in the granulosa cell layer. Sections of human decidua showed high expression of 11βHSD1 in decidual cells. In omental adipose tissue, 11βHSD1 immunoreactivity was observed in both stromal and adipocyte cells. Immunohistochemical localization of 11βHSD1 in human liver, adrenal, ovary, decidua, and adipose tissue using this novel antiserum provides us with a tool to investigate the role of this isozyme in modulating glucocorticoid hormone action within these tissues.