Aldosterone Production In Glomerulosa Cells Research Articles

Effects of nitric oxide on aldosterone synthesis and nitric oxide synthase activity in glomerulosa cells from bovine adrenal gland.

This study investigated the effects of two NO-releasing agents, diethylenetriamine-NO (deta-NO) and sodium nitroprusside (SNP), on basal, ACTH-, and angiotensin II (AngII)-stimulated aldosterone production in glomerulosa cells from bovine adrenal gland. NO donors inhibited basal and ACTH- or AngII-stimulated aldosterone synthesis in a concentration-dependent manner. Deta-NO and SNP also provoked a concentration-dependent stimulation of cGMP production. However, cGMP was not responsible for the inhibition of aldosterone secretion, because a cGMP analog did not reproduce the inhibitory effect. Moreover, soluble guanylyl cyclase or protein kinase G inhibitors did not revert the inhibitory effect of NO on aldosterone production. NO donors did not modify ACTH-stimulated cAMP production or AngII-stimulated PLC activity stimulation, but inhibited 22[R] hydroxycholesterol- or pregnenolone-stimulated aldosteronogenesis. NO can be synthesized in bovine glomerulosa cells because nitrite production was determined and characterization of NOS activity was also performed. Nitrite accumulation was not modified in the presence of ACTH, AngII, or other factors used to induce iNOS. NOS activity that showed a Michaelis-Menten kinetic was NADPH- and calcium-dependent and was inhibited by two competitive inhibitors, L-NAME and L-NMMA. These results show that NO inhibits aldosterone production in glomerulosa cells acting on P450scc and other P450-dependent steroidogenic enzymes, and these cells display NOS activity suggesting that NO can be produced by constitutive NOS isozymes.

α-MSH and zona glomerulosa function in the rat

The responses of rat adrenal zona glomerulosa cells to stimulation by α-MSH and ACTH and related peptides have been studied. The major findings were that: (1) α-MSH stimulated corticosterone production in glomerulosa cells from normal animals at concentrations of about 10 −10 mol/l, but other steroids, including aldosterone, were not significantly stimulated until levels of 10 −7 mol/1 were used. Peptide structure-function relationships showed that in the adrenal cortex, in contrast with other systems, ACTH 4–10 had no effect and did not block the response of glomerulosa cells to α-MSH, bisacetyl Ser 1-α-MSH, (nor-valine-12)-α-MSH, and ACTH 1–13 amide were equipotent with α-MSH, while α-MSH 1–10 had activity but was considerably less potent. α-MSH 6–13, 7–13, 8–13 and lys-11-acetyl-α-MSH were all inactive. N-formyl- N- ϵ-benzyloxycarbonyl α-MSH stimulated only at 10 −6 mol/1. 1. (2) Normalised α-MSH dose-response curves for aldosterone production in glomerulosa cells from normal rats, and corticosterone in inner zone cells were coincident. In glomerulosa cells, prior sodium depletion shifts the dose-response curve for aldosterone to the left, indicating a more sensitive response, and for corticosterone to the right. Bromocriptine treatment (which depresses the level of α-MSH in circulating plasma) and metoclopramide (which enhances it) respectively increased and decreased the sensitivity of the response of corticosterone to α-MSH in subsequently incubated glomerulosa cells, but had no effect on aldosterone. 2. (3) In contrast, normalised ACTH stimulated dose-response curves for glomerulosa corticosterone and aldosterone, and for fasciculata corticosterone production were all coincident, and were unaffected by sodium depletion, or by metoclopramide or bromocriptine pretreatment. 3. (4) Cyclic-AMP production by glomerulosa cells was stimulated by α-MSH only at levels of in excess of 10 −5 mol/1, five orders of magnitude greater than required to produce significant corticosterone stimulation. Under cyclic-AMP stimulation, the normalised responses of glomerulosa corticosterone and aldosterone, and of inner zone corticosterone were all coincident. The data suggest that α-MSH at low concentrations (< 10 −7 mol/1) interacts with a glomerulosa cell receptor which is distinct from the ACTH receptor but interacts with the ACTH receptor at concentrations greater than 10 −5 mol/1. Corticosterone production is stimulated by α-MSH in cells from normal animals at concentrations within the normal range for circulating plasma (~3 × 10 −10 mol/l), while aldosterone is stimulated by similar concentrations of α-MSH in cells from sodium depleted animals. The effects of sodium depletion are not modulated through changes in plasma α-MSH levels. At low concentrations α-MSH stimulation of glomerulosa cells is unlikely to be modulated by cyclic-AMP as second messenger.