Relative occupation of type-I and type-II corticosteroid receptors in rat brain following stress and dexamethasone treatment: functional implications

J M Reul, F R van den Bosch, E R de Kloet

Research output: Contribution to journalArticle (Academic Journal)peer-review

315 Citations (Scopus)

Abstract

The rat brain contains two receptor systems for corticosterone: the type-I corticosterone-preferring receptor and the classical type-II glucocorticoid receptor. The two receptor populations can be distinguished in binding studies with the 'pure' synthetic glucocorticoid 11 beta,17 beta-dihydroxy-6-methyl-17 alpha (1-propynyl)-androsta-1,4,6-trione-3-one (RU 28362). In-vitro autoradiography and quantitative image analysis showed that the type-I receptor was localized almost exclusively in the hippocampus, whereas the type-II receptor extended throughout the brain, with the highest levels in the nucleus paraventricularis, nucleus supraopticus and in the thalamic, amygdaloid, hippocampal and septal regions. Unoccupied type-I and type-II receptor sites, as measured in vitro by cytosol binding of 3H-labelled steroids, displayed a large difference in the rate of appearance after adrenalectomy. The availability of type-I receptors exhibited a marked increase, reaching maximal levels within 4-7 h, and then remained constant until 2 weeks after adrenalectomy. The availability of type-II receptors did not change considerably during the first 24 h after adrenalectomy, but displayed a large increase in capacity during the subsequent 2 weeks. After adrenocortical activation as a consequence of exposure to a novel environment, plasma concentrations of corticosterone increased to reach a peak of 811 nmol/l after 30 min and attained the basal concentration (43 nmol/l) after 240 min. During this time, occupation of type-I receptors increased from 77.8% at 0 min to 97% at 30-60 min and then declined to 84.8% after 240 min. Occupation of the type-II receptors was 28.1% at 0 min, 74.5% after 30 min and 32.8% after 240 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Original languageEnglish
Pages (from-to)459-67
Number of pages9
JournalJournal of Endocrinology
Volume115
Issue number3
Publication statusPublished - Dec 1987

Keywords

  • Adrenalectomy
  • Animals
  • Brain
  • Corticosterone
  • Dexamethasone
  • Male
  • Rats
  • Rats, Inbred Strains
  • Receptors, Glucocorticoid
  • Receptors, Steroid
  • Stress, Physiological

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