Distinct ontogeny of glucocorticoid and mineralocorticoid receptor and 11 beta-hydroxysteroid dehydrogenase types I and II mRNAs in the fetal rat brain suggest a complex control of glucocorticoid actions

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Abstract

Glucocorticoids (GCs) act via intracellular mineralocorticoid (MR) and glucocorticoid receptors (GR), However, it has recently been recognized that GC access to receptors is determined by the presence of tissue-specific 11 beta-hydroxysteroid dehydrogenases (11 beta-HSDs) that catalyze the interconversion of active corticosterone and inert 11-dehydrocorticosterone. 11 beta-HSD type 1 (11 beta-HSD1) is a bidirectional enzyme in vitro that acts predominantly as a reductase (regenerating corticosterone) in intact neurons. In contrast, 11 beta-HSD type 2 (11 beta-HSD2) is a higher affinity exclusive dehydrogenase that excludes GCs from MR in the kidney, producing aldosterone-selectivity in vivo. We have examined the ontogeny of 11 beta-HSD mRNAs and enzyme activity during prenatal brain development and correlated this with GR and MR mRNA development. These data reveal that (1) 11 beta-HSD2 mRNA is highly expressed in all CNS regions during midgestation, but expression is dramatically reduced during the third trimester except in the thalamus and cerebellum; (2) 11 beta-HSD2-like activity parallels closely the pattern of mRNA expression; (3) 11 beta-HSD1 mRNA is absent from the CNS until the the third trimester, and activity is low or undectectable; and (4) GR mRNA is highly expressed throughout the brain from midgestation, but MR gene expression is absent until the last few days of gestation. High 11 beta-HSD2 at midgestation may protect the developing brain from activation of GR by GCs. Late in gestation, repression of 11 beta-HSD2 gene expression may allow increasing GC activation of GR and MR, permitting key GC-dependent neuronal and glial maturational events.

Original languageEnglish
Pages (from-to)2570-2580
Number of pages11
JournalJournal of Neuroscience
Volume18
Issue number7
Publication statusPublished - 1 Apr 1998

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