On the mechanism of action of adrenocortical steroids: cortisol and aldosterone enhance guanylate cyclase activity
Vesely, D.L.
Journal of Pharmacology and Experimental Therapeutics 214(3): 561-566
1980
ISSN/ISBN: 0022-3565 PMID: 6105205 Document Number: 166399
Both glucocorticoids and cGMP stimulate RNA and protein synthesis. Because of cGMP and glucocorticoids seem to have similar actions, the objective was to determine if glucocorticoids might have part of their mechanisms of action through stimulation of guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), E.C. 4.6.1.2], the enzyme that catalyzed the formation of cGMP and GTP. Cortisol and the synthetic steroids prednisone, prednisolone and triamcinolone increased guanylate cyclase activity 2- to 4-fold in rat liver, kidney, heart, lung, spleen, ileum and cerebrum in vitro at a concentration of 1 nM. Dose-response curves revealed that maximal stimulation of guanylate cyclase activity was seen at a concentration of 1 pM when these 4 steroids and nonstimulated levels were reached when their concentrations were decreased to 0.01 pM. Aldosterone and its immediate precursors, corticosterone and 11-deoxycorticosterone, enhanced guanylate cyclase activity 2- to 3-fold in the same tissues at 1 nM concentration. The dose-response curves for these steroids were different from the glucocorticoids in that maximal stimulation was seen at 0.1 nM with aldosterone and its precursors and nonstimulated levels were seen at 0.01 nM. These precursors are generated from cholesterol which had no effect itself on guanylate cyclase activity. Mn was necessary for the maximal enhancement of guanylate cyclase by cortisol or aldosterone. Guanylate cyclase may play a role in the mechanism of action of both steroid hormones.