Studies of the mechanism through which sodium depletion increases aldosterone biosynthesis in man.

Bledsoe, Turner; Island, Donald P.; Liddle, Grant W.

doi:10.1172/jci105366

Cited by 54 publications

(16 citation statements)

References 20 publications

(13 reference statements)

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“…The activity at this locus is probably regulated, at least in part, by the renin-angiotensin system. Similar results with metyrapone inhibition of steroidogenesis during sodium depletion have been reported in man (27).…”

Section: Discussionsupporting

confidence: 89%

Sites of action of sodium depletion on aldosterone biosynthesis in the dog

Davis¹,

Burwell²,

Casper³

et al. 1968

J. Clin. Invest.

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A B STRA CT Secretion of cortisol, corticosterone, and aldosterone was measured in vivo in normal and sodium-depleted hypophysectomized dogs.Biogenesis of steroids was then measured in vitro with outer slices of the adrenals of the same dogs. In some studies, metyrapone or puromycin was added.In vivo, sodium depletion stimulated the production of cortisol, corticosterone, and aldosterone. In vitro, tissues from sodium-depleted animals released more aldosterone, but less corticosterone than those from sodium-replete controls.The results are interpreted to indicate that (a) biosynthesis of aldosterone is regulated at at least two sites in the biosynthetic pathway. The final conversion, that of corticosterone to aldosterone, is stimulated by sodium depletion. This effect persists for at least 3 hr while slices from sodiumdepleted dogs are incubated in vitro. Stimulation at this site is thus relatively stable in vitro; its activation by sodium depletion is not inhibited by puromycin in the dog. Stimulation at this site can explain, at least in part, the increased effectiveness of adrenocorticotropin (ACTH) on aldosterone biogenesis during sodium depletion.(b) the earlier site at which sodium depletion stimulates the secretion of aldosterone is "above" the position of desoxycorticosterone in the pathway; it is probably at the conversion of cholesterol to pregnenolone. Stimulation at this site is quickly lost during incubation of adrenal slices. It is thus A preliminary report of some of these data has been published previously (1) .

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Section: Discussionsupporting

confidence: 89%

Sites of action of sodium depletion on aldosterone biosynthesis in the dog

Davis¹,

Burwell²,

Casper³

et al. 1968

J. Clin. Invest.

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“…Other major differences between the rat and other species have been noted, in particular the poor response of the rat to angiotensin (1). Our previous studies with beef adrenal tissue have shown a relative selectivity of ACTH upon cortisol synthesis and of angiotensin and potassium upon aldosterone synthesis (3) closely paralleling the results of in vivo studies in the sheep (13), the monkey (14), and man (15)(16)(17)(18). However, differences have also been observed between other experimental models and the human (18) so that caution is advised in application of all such studies to human physiology (19).…”

Section: Studies With Increased Potassiummentioning

confidence: 69%

“…Aldosterone is increased when fluid volume is decreased, presumably through the renin-angiotensin system, which acts early in the biosynthetic pathway and increases corticosterone synthesis as well (18). The stimulation of aldosterone synthesis by a low sodium concentration noted in these in vitro studies was unique in being accompanied by a decrease in the levels of corticosterone.…”

Section: Studies With Increased Potassiummentioning

confidence: 82%

Adrenocortical steroidogenesis: studies on the mechanism of action of angiotensin and electrolytes

Saruta¹,

Cook²,

Kaplan³

1972

J. Clin. Invest.

110

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A B S T R A C T The effects of adrenocorticotropin (ACTH), angiotensins I and II, increased potassium, and decreased sodium concentrations upon steroid synthesis were examined by incubation of beef adrenal tissue slices.Angiotensin II shared with ACTH the need for calcium and an inhibition of its effect in the presence of puromycin but differed in not stimulating cyclic adenosine monophosphate (AMP). Angiotensin I was effective in steroidogenesis. The stimulation of aldosterone synthesis by increased potassium concentration was accompanied by an increased level of cyclic AMP and was inhibited in the presence of puromycin. Decreased sodium concentration stimulated aldosterone synthesis but, alone of these stimuli, simultaneously decreased corticosterone levels.It therefore appears that ACTH and potassium stimulate steroidogenesis at an early step in the biosynthetic pathway through the activation of cyclic AMP, whereas the effect of angiotensins I and II involve another mechanism and decreased sodium concentration affects a later step in steroidogenesis.

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“…The addition of ACTH had no effect on cortisol output, and this finding is consistent with the in vivo unresponsiveness to ACTH. The failure to synthesize corticosterone after incubation with ACTH may be explained by the fact that this steroid is produced by cells of the zona glomerulosa in response to angiotensin, rather than to ACTH [4,23]. The addition of 3',5'-adenosine monophosphate produced no change in cortisol production, but did produce a marked increase in corticosterone.…”

Section: Palhogenesismentioning

confidence: 99%

The Syndrome of Congenital Adrenocortical Unresponsiveness to ACTH. Report of Six Cases

et al. 1968

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Six patients with the syndrome of congenital adrenocortical unresponsiveness to ACTH are reported. This syndrome is characterized by feeding problems early in life, hypoglycemic episodes and hyperpigmentation of the skin (table I). Blood pressure and levels of electrolytes in serum were normal (table II). PPD and histoplasmin skin tests were negative, while antibodies to adrenal, thyroid, and gastric tissues were undetectable. Urinary excretion of 17-hydroxycorticosteroids and cortisol production rates were low and did not respond to administration of ACTH (table III). While receiving a low sodium diet, the patients were able to conserve sodium (figs. 2, 3 and 4) and to increase the rate of aldosterone secretion (tables IV and V).In one case, adrenal pathology showed a normal zona glomerulosa with atrophy of the zonae fasciculata and reticularis.This isolated deficiency in cortisol secretion is not due to a defect in pituitary function or a deficiency of one of the enzymes directly involved in steroid biosynthesis. The most probable pathogenesis is an abnormality at the site (or one of the sites) of ACTH action on cortisol biosynthesis. Speculation

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Studies of the mechanism through which sodium depletion increases aldosterone biosynthesis in man.

Cited by 54 publications

References 20 publications

Sites of action of sodium depletion on aldosterone biosynthesis in the dog

Sites of action of sodium depletion on aldosterone biosynthesis in the dog

Adrenocortical steroidogenesis: studies on the mechanism of action of angiotensin and electrolytes

The Syndrome of Congenital Adrenocortical Unresponsiveness to ACTH. Report of Six Cases

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