11Beta‐Hydroxysteroid Dehydrogenase Messenger Ribonucleic Acid Expression, Bioactivity and Immunoreactivity in Rat Cerebellum

Abstract

11 [GHydroxysteroid dehydrogenase (1 1P-OHSD) metabolizes corticosterone to inactive 1 1-dehydrocorticosterone and thus protects non-specific mineralocorticoid receptors from exposure to corticosterone in the kidney in vivo. Clearly, 11P-OHSD might also regulate corticosterone access to glucocorticoid receptors. We have investigated cerebellum, a tissue with high glucocorticoid receptor, but very low mineralocorticoid receptor levels and have shown marked 11p-OHSD bioactivity with similar co-substrate requirements and inhibition kinetics to the renal enzyme. 11p-OHSD messenger ribonucleic acid was expressed in cerebellum and was localized in Purkinje and granule cells. This distribution was confirmed immunohistochernically. Thus, we provide evidence for lip-OHSD in cerebellum and suggest that it may regulate the access of corticosterone to glucocorticoid receptors in addition to mineralocorticoid receptors.

11β-Hydroxysteroid dehydrogenase inhibition improves cognitive function in healthy elderly men and type 2 diabetics

“…The highest signal, as in rodent brain, came from cerebellum (52). In contrast, 11␤-HSD2 mRNA was not detected in these regions of the human CNS, again paralleling data in the adult rat brain, where 11␤-HSD2 is confined to a few discrete mid-and hind-brain nuclei (34,53) that may subserve central control of blood pressure and salt appetite (54), phenomena sensitive to aldosterone but not glucocorticoids.…”

“…In contrast, 11␤-HSD2 mRNA was not detected in these regions of the human CNS, again paralleling data in the adult rat brain, where 11␤-HSD2 is confined to a few discrete mid-and hind-brain nuclei (34,53) that may subserve central control of blood pressure and salt appetite (54), phenomena sensitive to aldosterone but not glucocorticoids. In the rat brain, 11␤-HSD1 mRNA, protein, and enzyme activity parallel each other fairly closely (52). 11␤-HSD activity was detected in both human cerebellum and hippocampus, with higher activity in cerebellar homogenates, suggesting that this may also be the case in humans.…”

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

“…However, the reason early studies failed to find ex vivo 11␤-HSD activity in brain homogenates is probably due to lower levels of endogenous NADP(H) in brain than liver (215,232). Exogenous cofactor reveals the activity (477,478). 11␤-HSD1 mRNA, immunoreactivity, and bioactivity have been repeatedly shown in hippocampus and myriad other CNS regions.…”

“…In addition, 11␤-HSD1 mRNA and protein/enzyme activity occur in adipose tissues (100), vasculature (747), ovary (68), testis (in some species including human and rat; Refs. 558, 695), but not mouse or squirrel monkey (486, 571), brain (380,477,478), uterus (103), placenta (notably in the decidua) (734), immune and inflammatory cells (231), skeletal muscle (767), and heart (747). 11␤-HSD1 is not expressed in fetal life until late in gestation when levels are greatest in organs where glucocorticoid activity is required for late maturation prior to birth, notably lung and liver (662).…”

“…More recent antisera also yield additional bands (738). Their use to localize 11␤-HSD1 by immunocytochemistry remains complicated by issues of specificity, although preabsorption with purified antigen suggests this may be feasible in specific tissues (477). Similar caveats apply to commercially available antisera, generally raised to peptides rather than the purified or recombinant proteins.…”