Maintenance of Basal ACTH Levels by Corticosterone and RU28362, but not Aldosterone: Relationship to Available Type I and Type II Corticosteroid Receptor Levels in Brain and Pituitary.
This study examined the ability of three replacement doses of corticosterone, aldosterone, or RU28362 to prevent the increase in morning basal plasma ACTH levels that occurs after adrenalectomy. In addition, the effect of each of these systemic steroid treatments on available cytosolic type I and type II corticosteroid receptor binding levels in hypothalamus, pituitary and hippocampus was measured. Available corticosteroid receptor measures indicated that the low dose of corticosterone occupied type I receptors, whereas the middle and high doses of corticosterone occupied both type I and type II receptors. Each of the doses of RU28362 selectively occupied type II receptors, whereas each of the doses of aldosterone selectively occupied type I receptors. The lowest dose of corticosterone partially prevented, and the middle and high doses of corticosterone completely prevented the adrenalectomy-induced increase in ACTH. Each of the doses of RU28362 prevented the adrenalectomy-induced increase in ACTH, whereas none of the doses of aldosterone had an effect on ACTH levels. These results substantiate the in vivo corticosteroid receptor subtype selectivity of aldosterone and RU28362. In addition, these results indicate that corticosteroid activation of neural type II receptors is sufficient to maintain morning levels of basal ACTH secretion. Type I corticosteroid receptor activation in the brain may also be sufficient to maintain basal ACTH levels, but only in response to corticosterone, not in response to aldosterone.
Spencer
RL
Department of Psychology, University of Colorado, Boulder, Colorado.
Moday
HJ
Miller
AH