Stereological and functional investigations on isolated adrenocortical cells. III. Zona glomerulosa cells of chronically ACTH-treated rats.

Prolonged (5 day) treatment of rats with high doses of ACTH caused a significant reduction in the plasma concentration of aldosterone and a notable rise in that of corticosterone. Outer subcapsular (zona glomerulosa [ZG]) adrenocortical cells were isolated, and their morphology and secretory activity was investigated. ACTH pretreatment induced a marked hypertrophy of ZG cells which was coupled with significant increases in the volume of the mitochondrial compartment and in the surface area per cell of mitochondrial cristae and AER tubules, as well as with a striking lipid droplet depletion. Mitochondrial cristae were found to change from a tubulo-laminar to a tubulo-convolute configuration. Despite their hypertrophy, ZG cells from ACTH-pretreated rats displayed a conspicuous decrease in both basal and stimulated overall production of post-pregnenolone steroids, which was ascribed to the depletion of their stores of steroid hormone precursors (i.e. cholesterol and cholesterol esters contained in the lipid droplets). However, both basal and stimulated secretion of aldosterone was doubled, suggesting that chronic ACTH treatment induces in ZG cells an increased availability of monoxygenase II, the enzyme involved in the transformation of 18-hydroxycorticosterone into aldosterone. In the light of these findings, the drop in the plasma level of aldosterone observed in rats after prolonged treatment with ACTH is assumed to be due to an enhanced metabolism of aldosterone, possibly at the hepatic level.