IMMUNOHISTOCHEMICAL LOCALIZATION OF TYPE-1 11-BETA-HYDROXYSTEROID DEHYDROGENASE IN HUMAN TISSUES

Two isozymes of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) cat alyze the interconversion of hormonally active cortisol to inactive co rtisone. Activity and messenger ribonucleic acid studies indicate that type 1 11 beta HSD (11 beta HSD1) is expressed in glucocorticoid targ et tissues such as liver, gonad, and cerebellum, where it regulates th e exposure of cortisol to glucocorticoid receptors. To further underst and the role of 11 beta HSD1 in human tissues, we have studied the loc alization of this isozyme using an antibody raised in sheep against am ino acids 19-33 of human 11 beta HSD1. Western blot analyses indicated that the immunopurified antibody recognized a band of approximately 3 4 kDa in human liver and decidua. Immunoperoxidase studies on liver, a drenal, ovary, decidua, and adipose tissue indicated positive cytoplas mic staining for 11 beta HSD1. 11 beta HSD1 immunoreactivity was obser ved more intensely around the hepatic central vein, with no staining a round the portal vein, hepatic artery, or bile ducts. No staining for 11 beta HSD1 was observed in the adrenal medulla, but 11 beta HSD1-imm unoreactive protein was observed in all three zones of the adrenal cor tex, with the most intense staining in the zona reticularis > zona glo merulosa > zona fasciculata. In the human ovary, immunoreactivity was observed in the developing oocyte and the luteinized granulosa cells o f the corpus luteum. No staining was observed in granulosa cells, thec al cells, or ovarian stroma, which contrasted with the marked expressi on of 11 beta HSD2 in the granulosa cell layer. Sections of human deci dua showed high expression of 11 beta HSD1 in decidual cells. In oment al adipose tissue, 11 beta HSD1 immunoreactivity was observed in both stromal and adipocyte cells. Immunohistochemical localization of 11 be ta HSD1 in human liver, adrenal, ovary, decidua, and adipose tissue us ing this novel antiserum provides us with a tool to investigate the ro le of this isozyme in modulating glucocorticoid hormone action within these tissues.