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Am J Physiol Endocrinol Metab 275: E124-E131, 1998;
0193-1849/98 $5.00
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Vol. 275, Issue 1, E124-E131, July 1998

Steroid specificity of the putative DHB receptor: evidence that the receptor is not 11beta HSD

Karen E. Sheppard1, Karen Khoo2, Zygmunt S. Krozowski1, and Kevin X. Z. Li1

1 Baker Medical Research Institute, Melbourne, Victoria 8008; and 2 Department of Pathology and Immunology, Monash University Medical School, Prahran, Victoria, Australia 3181

Recently, we identified a novel putative nuclear receptor in colonic crypt cells distinct from both mineralocorticoid receptor and glucocorticoid receptor, with high affinity for 11-dehydrocorticosterone (11-DHB) (33). In the present study, competitive nuclear binding assays demonstrated that this site has a unique steroid binding specificity that distinguishes it from other steroid receptors. Western blot analysis showed the presence of 11beta -hydroxysteroid dehydrogenase-2 (11beta HSD2) but not 11beta HSD1 in colonic crypt cells and showed that 11beta HSD2 was present in the nuclear pellet. Differences in steroid specificity between the putative DHB receptor and inhibition of 11beta HSD activity indicate that binding is not to the enzyme. Furthermore, modified Chinese hamster ovary cells transfected with the 11beta HSD2 gene express nuclear 11beta HSD2 but not a nuclear DHB binding site. In conclusion, these data support the existence of a novel nuclear DHB receptor in rat colon that is distinct from the classic steroid receptors and from both 11beta HSD1 and 11beta HSD2.

11-dehydrocorticosterone; 11beta -hydroxysteroid dehydrogenase; glucocorticoid; mineralocorticoid; nuclear receptor; colon


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