Studies on Cyclic Nucleotides in the Adrenal Gland

Abstract

Effects of ACTH and calcium on cyclic AMP and steroid production by the zona fasciculata-reticularis (the decapsulated fraction) from the rat adrenal cortex have been studied. Increasing concentrations of extracellular calcium enhanced the action of ACTH on cyclic AMP and steroid production. These effects of ACTH with calcium were prevented by lanthanum, but not by tetracaine or verapamil, suggesting that ACTH stimulation may be mediated by calcium through a process not involving the tetracaine- or verapamil-vulnerable step(s) of the calcium current. High concentrations of external calcium itself increased cyclic AMP accumulation without any increase in steroidogenesis. A calcium ionophore, X537A was stimulatory for steroidogenesis but inhibitory with respect to cyclic AMP accumulation. Considered together with the findings of steroidogenic stimulation by low concentrations of ACTH without cyclic AMP increase, these results suggest that ACTH primarily increases intracellular calcium mobilization thus stimulating directly the steroidogenesis, which is independent of the cyclic AMP system. Relatively high concentrations of ACTH activate the adenylate cyclase, which depends on extracellular calcium to increase cyclic AMP levels and stimulation of steroidogenesis by the decapsulated fractions of the adrenal cortex.

Effects of ACTH and calcium on cyclic AMP production and steroid output by the zona glomerulosa of the adrenal cortex.

“…The present experiment also confirmed that an increase in cyclic AMP by calcium-deprivation occurred not in the decapsulated fraction (Shima et al, 1979) but only in the capsular. No increase in the medullary cyclic AMP of the rat adrenal gland was also observed by omission of calcium from the incubation medium (Shima et al, 1977). Rubin et al (1972) have reported on an increase in the whole adrenal cyclic AMP accumulation by removal of calcium from the medium.…”

“…Raising calcium concentrations in the medium increased cyclic AMP accumulation as seen in the decapsulated fraction (Shima et al, 1979), suggesting a stimulatory action of external calcium on the cell surface coupled to adenylate cyclase in the membrane independently of ACTH receptors. It is also of interest that unlike the decapsulated fraction, high concentrations of calcium itself were stimulatory to the capsular steroidogenesis (Fig.3).…”

“…Aldosterone production by the capsular fraction, susceptible to tetracaine or verapamil (Ffg.3and4) was quite different from corticosterone production by the decapsulated fraction, where these calcium antagonists were without effect (Shima et al, 1979). Steroidogenesis by the capsular fraction stimulated by ACTH might be in the process of calcium influx sensitive to tetracaine (Blaustein and Goldman, 1966;Feinstein and Paimre, 1967;Kwant and Seeman, 1969) or verapamil (Watanabe and Besch, 1974;Devis et al, 1975;Shapiro et al, 1977), and distinct from the cyclic AMP system.…”

“…Attempts to demonstrate an effect of angiotensin II on adrenal adenylate cyclase activity (Schorr and Ney, 1971;Goodfriend andLin, 1970: Masaka et al, 1974) or cyclic AMP levels (Saruta et al, 1972;Espiner et al, 1974) have thus far failed. Recent studies (Shima et al, 1976;Shima et al, 1977) from this laboratory have also demonstrated that angiotensin II stimulates aldosterone production by zona glomerulosa (the capsular fraction) of the rat adrenal, which is highly dependent on calcium but not cyclic AMP. Meanwhile, there is now a large body of evidence suggesting the action of ACTH on steroidogenes is is in part mediated by cyclic AMP increased during the stimulation of adrenocortical cells (Haynes, 1958;Haynes et al, 1959;Sutherland et al, 1965).…”

“…The present study was designed to examine the effects of ACTH and calcium at various concentrations on the aldosterone and cyclic AMP production of the capsular fraction in comparison with their effects on the decapsulated fraction (Shima et al, 1979) from the rat adrenal cortex. -24 (corticotropin1-24, tetracosa Corticosteroids in the medium after 90min-incubation were extracted and purified by the procedure described previously (Shima et al, 1970Shima et al, 1968.…”