Differential expression of type I adrenal steroid receptors in immune tissues is associated with tissue-specific regulation of type II receptors by aldosterone.
We examined the influence of the type I adrenal steroid receptor agonist, aldosterone, on type II adrenal steroid receptor binding in the rat spleen and thymus after adrenalectomy. In the spleen, adrenalectomy was associated with a significant up-regulation of type II receptors, which was blocked by the concurrent administration of aldosterone (1 microgram/h) via sc osmotic minipumps. Neither adrenalectomy nor aldosterone treatment altered type II receptor binding in the thymus. Despite high doses of aldosterone (10 micrograms/h), which resulted in supra-physiological blood concentrations of this hormone, there was no evidence of type II receptor decreases in spleen or thymus below receptor levels found in sham-adrenalectomized rats. The effect of aldosterone on type II receptor binding appeared to be mediated by the type I receptor, since there was no aldosterone effect on the thymus, which did not exhibit detectable levels of type I receptor binding. Moreover, there was no evidence that aldosterone competed for the type II receptor in vivo or in vitro as determined by measurements of the type II receptor dissociation constant in the spleen of adrenalectomized, aldosterone-treated animals. Since selective activation of the type I receptor occurs in the spleen under physiological conditions, these results indicate that type I receptors may play a tonic inhibitory role in type II receptor expression in immune cells which express both receptor subtypes and reside in this tissue. Furthermore, the findings suggest that there may be different mechanisms involved in the up-regulation vs. the down-regulation of type II adrenal steroid receptors, and effects mediated solely via the type I adrenal steroid receptor appear only to influence the former process.
Miller
A H
AH
Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029.
Spencer
R L
RL
Husain
A
A
Rhee
R
R
McEwen
B S
BS
Stein
M
M
D000315:Adrenalectomy; D000450:Aldosterone / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000732:Androstanols / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011987:Receptors, Steroid / Q000187:drug effects / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism*; D013950:Thymus Gland / Q000378:metabolism*
D000732:Androstanols; D011987:Receptors, Steroid; D000450:Aldosterone; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one