Chronic
adrenocorticotropin (
ACTH) treatment in rats leads to a fall in
aldosterone secretion (
aldosterone turn-off or "
aldosterone escape" phenomenon) with a concomitant rise in
corticosterone. To elucidate whether
ACTH-induced
aldosterone suppression is mediated by
steroid type II receptor or related to a
free-radical effect by over-synthesized
corticosterone, we examined the effects of a
glucocorticoid antagonist,
RU486, and
antioxidants dimethyl sulfoxide (
DMSO) and
vitamin E, on the
aldosterone turn-off phenomenon in rats. Each rat received daily for 5 days a different dose of
ACTH-Z (5, 10, 20 or 40 micrograms/100 g
body weight) 1 mg
RU486/100 g
body weight, 100 microliters (1.3 mmol)
DMSO/100 g
body weight or 2 mg
vitamin E/100 g
body weight with
subcutaneous injection. Plasma
steroid levels and in vitro release of
steroids from the adrenal
capsule were measured. The
ACTH-Z treatment caused a dose-dependent increase in
corticosterone and a decrease in
aldosterone in both plasma and adrenal
capsule experiments, as well as an increase in adrenal weights. For the following study 5 micrograms/100 g
body weight of
ACTH-Z was used. Administration of
RU486 alone caused no change in plasma
aldosterone level compared to controls, even though the
steroid type II receptor was blocked, as evidenced by significant increases in plasma
ACTH and
corticosterone levels. Concomitant administration of
RU486 and
ACTH-Z increased both plasma
corticosterone and
aldosterone levels (p < 0.01) but decreased adrenal
capsule corticosterone production (p < 0.05) compared to the rats treated with
ACTH-Z alone.(ABSTRACT TRUNCATED AT 250 WORDS)