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

in Journal of Endocrinology
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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 11β,17β-dihydroxy-6-methyl-17α (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. Injection of dexamethasone (25 μg/100 g body wt) at 08.00 h resulted in suppression of basal plasma concentrations of corticosterone and prevented the circadian-driven rise in circulating corticosterone. Occupation of type-I receptors did not change considerably as a result of injection of dexamethasone, but occupation of type-II receptors was markedly increased till 16.00 h compared with that after injection of vehicle.

It was concluded that the type-I and type-II receptors are not only localized differently in the rat brain, but also exhibit a striking difference in occupation after manipulation of the pituitary-adrenocortical system. The data further support the concept of a type-I receptor-mediated tonic activating influence and a type-II receptor-mediated feedback action of corticosterone on brain function.

J. Endocr. (1987) 115, 459–467

 

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