Changes in characteristics of rat adrenal glomerulosa cells under acute and chronic treatment with ACTH

Abstract

Groups of Long Evans rats were treated with 15 IU ACTH/day for 1–9 days and sacrificed at different intervals during and after treatment. Aldosterone and corticosterone plasma levels were increased above control values for the entire duration of treatment and were decreased to control values as early as 3 days posttreatment. The uptake of [125I]angiotensin II ([125I]AII) by adrenocortical glomerulosa cell suspensions was diminished by 71% at day 9 of treatment and this [125I]AII-uptake capacity slowly returned to control values after cessation of treatment (66.0% of control at day +19). The association constants at equilibrium (Ka) for AII receptors were similar in both treated (0.19 × 109 M−1 at day 9) and control (0.12 × 109 M−1) rats, whereas the number of AII-binding sites was lowered in the glomerulosa cells of treated (Nmax = 6 fmol/50 000 cells) compared with control (29 fmol) animals. In vitro cell suspensions from treated rats had, compared with controls, a lowered basal aldosterone and an increased corticosterone output. Addition of ACTH (10−8 M) to these cell suspensions showed no effect on the aldosterone or corticosterone output, whereas a significant stimulation was observed for cells obtained from control animals. Studies on rats treated 9 days and sacrificed 19 days after cessation of treatment demonstrated that the basal aldosterone and corticosterone output from zona glomerulosa cell suspensions was comparable with that of control rats; the steroid output of these cells could be further stimulated in vitro by addition of ACTH. It is concluded that the chronic ACTH treatment produced (i) a loss of AII receptor of adrenal zona glomerulosa cells, a phenomenon that was reversible 3–4 weeks posttreatment; (ii) a decreased capacity of glomerulosa cells to further respond to ACTH stimuli in vitro, suggesting either a loss of ACTH receptor by these cells or a decrease in activity of enzymes responsible for steroidogenesis, or a lack of endogenous precursor; (iii) a diminution of the thickness of the zona glomerulosa accompanied by an enlargement of the zonae fasciculate–reticularis, resulting in high circulating plasma corticosterone. This high plasma corticosterone level might well be the source of the precursor used in vivo by the zona glomerulosa to maintain the observed high plasma aldosterone level, despite the lowered overall steroidogenic capacities of these cells demonstrated by our in vitro studies.