Short- and long-term effects of ACTH on the adrenal zona glomerulosa of the rat. A coupled stereological and enzymological study.
Short-term ACTH treatment provoked a decrease in volume of the lipid-droplet compartment in rat zona glomerulosa cells, and a rise in plasma and intracellular concentrations of corticosterone and aldosterone. It enhanced activities of 3 beta-hydroxysteroid dehydrogenase (3 beta HSD), 11 beta-hydroxylase (11 beta OH) and 18-hydroxylase (18OH). Long-term ACTH administration produced a hypertrophy of the zona glomerulosa and its parenchymal cells, a result of the increase in volume of the smooth endoplasmic reticulum and the mitochondrial compartment. The surface area per cell of mitochondrial inner membranes increased; the tubular cristae were transformed into a homogeneous population of vesicles. The plasma and intracellular concentrations of corticosterone further increased, whereas those of aldosterone fell below basal levels (the "aldosterone-escape" phenomenon). The activities of 3 beta HSD and 11 beta OH were enhanced, that of 180H decreased. Therefore, ACTH stimulates zona glomerulosa growth and transforms parenchymal elements into zona fasciculata cell-types. Cyanoketone nullified acute ACTH effects on plasma and intracellular concentrations of corticosterone and aldosterone, but did not affect the activities of 11 beta OH and 18OH. Chronic ACTH treatment produced similar results, although 18OH activity was not suppressed. The mechanism underlying the "aldosterone-escape" phenomenon may thus involve a rise in the intracellular concentration of corticosterone, caused by the enhanced synthesis and activation of 3 beta HSD and 11 beta OH.
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000450:Aldosterone / Q000097:blood / Q000378:metabolism*; D000818:Animals; D003345:Corticosterone / Q000097:blood / Q000378:metabolism*; D003489:Cyanoketone / Q000494:pharmacology; D019405:Cytochrome P-450 CYP11B2; D004789:Enzyme Activation; D006984:Hypertrophy; D050356:Lipid Metabolism; D008297:Male; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains; D013252:Steroid 11-beta-Hydroxylase / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000378:metabolism; D013997:Time Factors
D003489:Cyanoketone; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D015096:3-Hydroxysteroid Dehydrogenases; D013250:Steroid Hydroxylases; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase; D003345:Corticosterone