Effect of ACTH or zinc treatment on plasma aldosterone and corticosterone levels and on the in vitro steroid output from adrenocortical cells.

We have studied the effect of in vivo treatment with two forms of ACTH (Synacthen and Duracton) and of zinc hydroxide on plasma corticosteroid levels from adult Long Evans female rats. The corticosteroid output by isolated zona glomerulosa cells in vitro was also studied. Dose-response experiments showed that, after 2 days of treatment, Synacthen caused a 2.5- and 25.9-fold increase in plasma aldosterone and corticosterone levels, respectively, while maximal increases of 1.7- and 5.6-fold were obtained following treatment with Duracton. In contrast to elevated plasma steroid levels, the basal aldosterone and corticosterone output by isolated zona glomerulosa cells was significantly decreased for all doses of Synacthen administered. The 8 IU/day treatment with Synacthen produced an 86% diminution of aldosterone output while a treatment of 32 IU/day with Duracton gave only a 48.8% decrease. Concomitantly the Synacthen treatment provoked a high mitotic response in the zona glomerulosa cells (fivefold over control). A 2-week treatment with Synacthen resulted in elevated plasma aldosterone and corticosterone levels and produced a 92% diminution of aldosterone output by isolated zona glomerulosa cells. The aldosterone and corticosterone output from these cells was not enhanced by the addition of ACTH in the incubation media; zona glomerulosa cells of animals treated with Synacthen were no longer responsive to ACTH stimulation in vitro. The effect of a 2-day treatment with zinc hydroxide on plasma aldosterone and corticosterone levels and on steroid output by isolated adrenocortical cells was different from that of Synacthen. This meant that zinc was not the active principle of the Synacthen preparation. Our results indicate that long-term treatment with ACTH provokes profound functional changes at the adrenocortical zona glomerulosa level.