Site of stimulation of aldosterone biosynthesis by angiotensin and potassium

Brown, Ronald D.; Strott, Charles A.; Liddle, Grant W.

doi:10.1172/jci106937

Cited by 48 publications

(14 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…If insulin also regulates adrenal K uptake, then a state of intracellular adrenal K depletion might develop in diabetic pa tients and account for the defect in aldosterone secretion. The ability of ACTH and angiotensin II to stimulate aldosterone secretion is decreased in the presence of low K concentrations (106,108), an observation consis tent with the known stimulatory effect of K on the biosynthetic pathway involving the conversion of cholesterol to deoxycorticosterone and cor ticosterone to aldosterone (107,119).…”

Section: Impaired Renin-aldosterone Axismentioning

confidence: 62%

Clinical Disorders of Hyperkalemia

DeFronzo¹,

BIa²,

Smith³

1982

Annu. Rev. Med.

View full text Add to dashboard Cite

Potassium DistributionTotal body potassium in a healthy adult is approximately 50 meqlkg body weight or about 3500 meq for a 70-kg man (1, 2). Most of this is located within cells (Figure 1), primarily muscle, at a concentration of about 150 meq/L. Only 2% of total body potassium is located in the extracellular fl uid, normally at concentrations of 3.5 -5.0 meq/L. The maintenance of this high intracellular to extracellular K concentration depends upon the Na-K ATPase pump (3, 4) as well as other fac tors, including H+ balance, plasma tonicity, and plasma insulin, epinephrine, and aldosterone concentrations (5). The large difference in potassium concentration across the cell mem brane is critical for normal cell fu nction since it is the primary determinant of the resting membrane potential. Small changes in the intracellular/ex tracellular K ratio can severely disturb neuromuscular fu nction, particu larly of the heart. A gain (or loss) fr om the extracellular space of an amount of potassium equal to only I % of the total body K content (35 meq) can cause a 50% increase (or decrease) in plasma K concentration. Such a change would have pronounced effects on neuromuscular func ti on. Like wise, redistribution of a similar amount of potassium fr om the intracellular to extracellular (or vice versa) fluid compartmen t without net gain or loss of K fr om the body, would similarly affect neuromuscular excitability. Thus, it is important that both the total amount of potassium within the body and the distribution of potassium between intracellular and extracellu lar fl uid compartments be closely regulated.In healthy man, potassium enters only via the gastrointestinal tract. Approximately 100 meq of K is ingested per day and essentially all of this is absorbed fr om the stomach and upper gastrointestinal tract. Approxi-521 0066-4219/8 2/040 1-0521 $02.00 Annu. Rev. Med. 1982.33:521-554. Downloaded from www.annualreviews.org Access provided by Haifa University on 01/05/15. For personal use only.Quick links to online content Further ANNUAL REVIEWS

show abstract

Section: Impaired Renin-aldosterone Axismentioning

confidence: 62%

Clinical Disorders of Hyperkalemia

DeFronzo¹,

BIa²,

Smith³

1982

Annu. Rev. Med.

View full text Add to dashboard Cite

show abstract

“…It seems likely that the ability to synthesize cortisol in response to angiotensin is species specific since the human adrenal does not produce cortisol in response to angiotensin infusion (25,26). However, the apparent failure of angiotensin to stimulate cortisol production in the human may be related to doses that can be safely administered to humans compared to other species.…”

Section: Discussionmentioning

confidence: 99%

Comparative Effects of Angiotensin and ACTH on Cyclic AMP and Steroidogenesis in Isolated Bovine Adrenal Cells

Peytremann¹,

Nicholson²,

Brown³

et al. 1973

J. Clin. Invest.

Self Cite

View full text Add to dashboard Cite

A B S T R A C T The comparative effects of angiotensin II and adrenocorticotropic hormone (ACTH) on cyclic AMP and steroidogenesis were investigated employing isolated bovine adrenal cells from the zona fasciculata. Like ACTH, angiotensin produced a prompt increase in cyclic AMP which preceded the increase in corticosteroid production. Although this increase in cyclic AMP was small when compared to that induced by ACTH, it correlated with the amount of steroidogenesis. This observation is consistent with the view that cyclic AMP is the intracellular mediator of the steroidogenic action of angiotensin.Angiotensin acted synergistically with ACTH on cyclic AMP levels. This synergism was not explained by inhibition of phosphodiesterase activity. Unlike ACTH, angiotensin failed to stimulate adenylate cyclase in broken cell preparations. The observations suggest that more than one mechanism may be involved in effects of ACTH and angiotensin on cyclic AMP levels. 'Abbreviations used in this paper: ACTH, adrenocorticotropic hormone; KRBG, Krebs-Ringer bicarbonate huffer; MIX, genesis through activation of the adenylate cyclase system (1, 2); however, relatively little attention has been focused on the mechanism of action of angiotensin on steroid biosynthesis. Angiotensin has been shown to induce aldosterone synthesis in man (3, 4) and in sheep with adrenal transplants (5), and to stimulate cortisol as well as aldosterone synthesis in isolated bovine adrenals (6, 7) and in the hypophysectomized dog (8, 9). However, attempts to demonstrate an effect of angiotensin on adrenal adenylate cyclase activity (10, 11) or cyclic AMP levels (12) have thus far been unsuccessful. INTRODUCTIONIn the present study, we have compared the effects of angiotensin and ACTH on adrenal cyclic AMP and steroidogenesis in vitro, utilizing isolated cells from the bovine zona fasciculata. Our results demonstrate that angiotensin increases cyclic AMP levels in cells from the zona fasciculata, and they are consistent with the view that the steroidogenic action of angiotensin in fasciculata cells is mediated through cyclic AMP. METHODS Materials. Lot H of the United States Pharmacopeiacorticotropin Reference Standard was used throughout this study. In order to express the doses of ACTH on a molar basis it was assumed that each ampule of the standard contained 1.5 i.v. U (13,14) and that each unit of activity was equivalent to 10 Ag of ACTH (2 X 10-9 mol) (15). Asparaginyl'-valyl' angiotensin II was purchased from Ciba Corp., Summit, N. J. 1 jug is equivalent to 10-' mol.Appropriate dilutions of angiotensin and ACTH were made in acid-albumin-saline (0.6 ml 12N HCl, 1 g bovine albumin, and 8.5 g NaCl/liter of water). Twice crystallized trypsin and bovine serum albumin (BSA) (Cohn fraction V) were obtained from Sigma Chemical Co., St. Louis, Mo. Lima bean trypsin inhibitor was from Worthington Biochemical Corp., Freehold, N. J. 1-Methyl-3-isobutylxanthine (SC 2964) was kindly provided by the G. Sayers, Swallow, and Giordano (17). Eight calf adrenals w...

show abstract

“…(Harris et al 1967), and its plasma concentration is typically 200-400 pmol/l (Brown & Strott 1971, Oddie et al 1972, Schoneshofer et al 1975. Its secretion may be enhanced by ACTH and by angiotensin II and potassium ions, suggesting both a zona fasciculata and a zona glomerulosa origin (Brown et al 1972b), and it is also inevitably enhanced in conditions in which 11b-hydroxylase (CYP11B1) has reduced activity. These may be as a result of defects in the enzyme, resulting in the relatively rare saltretaining form of congenital adrenal hyperplasia (CAH), or as a result of treatment of adrenocortical excess with an 11b-hydroxylase inhibitor such as metyrapone or etomidate (Harris et al 1967, Weber et al 1993.…”

Section: Effects Of Doc In Manmentioning

confidence: 99%

The mislabelling of deoxycorticosterone: making sense of corticosteroid structure and function

Vinson¹

2011

Journal of Endocrinology

View full text Add to dashboard Cite

Over the 70 or so years since their discovery, there has been continuous interest and activity in the field of corticosteroid functions. However, despite major advances in the characterisation of receptors and coregulators, in some ways we still lack clear insight into the mechanism of receptor activation, and, in particular, the relationship between steroid hormone structure and function remains obscure. Thus, why should deoxycorticosterone (DOC) reportedly be a weak mineralocorticoid, while the addition of an 11b-hydroxyl group produces glucocorticoid activity, yet further hydroxylation at C18 leads to the most potent mineralocorticoid, aldosterone? This review aims to show that the field has been confused by the misreading of the earlier literature and that DOC, far from being relatively inactive, in fact has a wide range of activities not shared by the other corticoids. In contrast to the accepted view, the presence of an 11b-hydroxyl group yields, in corticosterone or cortisol, hormones with more limited functions, and also more readily regulated, by 11b-hydroxysteroid dehydrogenase. This interpretation leads to a more systematic understanding of structure-function relationships in the corticosteroids and may assist more rational drug design.

show abstract

Site of stimulation of aldosterone biosynthesis by angiotensin and potassium

Cited by 48 publications

References 21 publications

Clinical Disorders of Hyperkalemia

Clinical Disorders of Hyperkalemia

Comparative Effects of Angiotensin and ACTH on Cyclic AMP and Steroidogenesis in Isolated Bovine Adrenal Cells

The mislabelling of deoxycorticosterone: making sense of corticosteroid structure and function

Contact Info

Product

Resources

About