The effect of SRIF and its antagonist cyclo(7-aminoheptanonyl-Phe-D-Trp-Lys-Thr magnitude of Bzl)(SRIF-A) were studied in
sham-operated and bilaterally adrenalectomized rats bearing
ACTH- and
angiotensin II (ANG-II)-responsive adrenocortical autotransplants.
SRIF-A (10(-5) M) completely annulled SRIF (10(-6) M)-induced inhibition of ANG-II (10(-8) M)-evoked rise in
aldosterone (ALDO) secretion by both dispersed zona glomerulosa (ZG) cells and autotransplant slices. A 7-day
intraperitoneal infusion with SRIF (0.3 nmol.kg-1.min-1) significantly lowered plasma ALDO concentration (PAC) in both groups of animals, without affecting plasma
renin activity and the plasma levels of
ACTH and
corticosterone. This treatment caused a marked
atrophy of adrenal ZG and its parenchymal cells (without inducing any significant change in the zona fasciculata morphology), as well as of ZG-like cells of autotransplants. Isolated ZG cells and autotransplant slices from SRIF-infused rats evidenced a notable decrease in both their basal and maximally
ACTH- or ANG-II-stimulated ALDO production. The simultaneous infusion of rats with
SRIF-A (3 nmol.kg-1.min-1) completely reversed all these effects of SRIF. The prolonged infusion with
SRIF-A alone caused, in
sham-operated rats, a marked increase in PAC and a significant
hypertrophy of ZG and ZG cells; basal and maximally-stimulated ALDO secretion of dispersed ZG cells was also notably raised. Conversely,
SRIF-A infusion did not evoke any appreciable effect in autotransplanted rats. These findings suggest that endogenous SRIF is specifically involved in the negative control of the secretion and growth of the rat adrenal ZG. Since regenerated adrenocortical autotransplants, which are responsive to SRIF but not to
SRIF-A infusion, are completely deprived of chromaffin cells, the hypothesis is advanced that adrenal
zona medullaris may be the source of endogenous SRIF regulating ZG function.