11 Beta-hydroxysteroid dehydrogenase type 2 in the postnatal and adult rat brain.
11 Beta-hydroxysteroid dehydrogenase (11 beta-HSD) catalyses the interconversion of active corticosterone and inert 11-dehydrocorticosterone. The recently discovered type 2 isozyme (11 beta-HSD-2) is a high affinity, NAD-dependent, exclusive 11 beta-dehydrogenase, which rapidly inactivates glucocorticoids. Thus the enzyme generates aldosterone-selectivity for intrinsically non-selective mineralocorticoid receptors in vivo as well as excluding glucocorticoids from glucocorticoid receptors, the latter being particularly important during development. Aldosterone exerts selective central effects upon salt appetite and blood pressure whilst glucocorticoids have potent effects upon postnatal neurogenesis and brain remodelling. We examined 11 beta-HSD-2 expression during postnatal ontogeny and in adult rat brain. High 11 beta-HSD-2 mRNA expression was found specifically in the postnatal thalamus and the external granule cell layer of the cerebellum. Expression peaked at the end of the first postnatal week and declined rapidly thereafter. Postnatal brain showed considerable activity of high affinity 11 beta-HSD-2 which paralleled expression of 11 beta-HSD-2 messenger ribonucleic acid (mRNA). Adult brain showed high 11 beta-HSD-2 mRNA expression limited to the subcommissural organ, with lower expression in the ventromedial nucleus of the hypothalamus, amygdala, locus coeruleus and nucleus tractus solitarius. These discrete areas are compatible with proposed selective central actions of aldosterone on blood pressure (subcommissural organ, nucleus tractus solitarius) and salt appetite (ventromedial nucleus, amygdala). In contrast, early postnatal 11 beta-HSD-2 coincides with glucocorticoid receptor rather than mineralocorticoid receptor expression, and areas of expression are among the regions where glucocorticoids have been demonstrated to have profound effects upon neuronal division, growth and maturation.
Robson
A C
AC
Molecular Endocrinology, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, Scotland, UK.
Leckie
C M
CM
Seckl
J R
JR
Holmes
M C
MC
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001921:Brain / Q000201:enzymology* / Q000254:growth & development; D001923:Brain Chemistry; D002531:Cerebellum / Q000737:chemistry; D004789:Enzyme Activation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006913:Hydroxysteroid Dehydrogenases / Q000032:analysis*; D007031:Hypothalamus / Q000737:chemistry; D007527:Isoenzymes / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013788:Thalamus / Q000737:chemistry
D007527:Isoenzymes; D012333:RNA, Messenger; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases