Localization of Renal 1 β-Dehydrogenase byin SituHybridization: Autocrine not Paracrine Protector of the Mineralocorticoid Receptor

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Abstract
In the kidney, 11β-dehydrogenase (11β-DH) converts the active steroid cortisol to inactive cortisone (corticosterone to 11-dehydrocorticosterone in the rat). In man, congenital and acquired deficiency of 11β-dehydrogenase are rare causes of hypertension in which cortisol acts as a potent mineralocorticoid. Observations from these clinical studies indicate that Ilj8-DH conveys specificity for the mineralocorticoid receptor in distal tubules and collecting ducts. However, while some studies do indicate 11β-DH activity in rat distal tubules and collecting ducts, immunohistochemical studies localize 11β-DH only to proximal tubules. To resolve this dilemma, we have performed in situ hybridization localization of 11β-DH mRNA in rat kidney tissue using 35S-labeled sense and antisense cRNA probes to rat 11β-DH. In contrast to our immunohistochemical studies in which 11β-DH protein was localized predominantly to proximal tubules in the inner cortex, 11β-DH mRNA was expressed in tubules in both the inner and outer cortex, most probably proximal and distal tubules, and in collecting ducts extending across the corticomedullary junction to the papillary tip. Weak hybridization was also seen in glomeruli, but no hybridization to the sense 11β-DH cRNA or to sections pretreated with RNAase-A was observed. We conclude that renal 11β-DH is suitably located to prevent access of glucocorticoid to the MR in an autocrine and not a paracrine fashion. 11β-DH in proximal tubules may protect the glucocorticoid receptor. (Endocrinology128: 2129–2135,1991)

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