Hypertensive Action of 18-Hydroxydeoxycorticosterone

Oliver, Jack W.; Birmingham, Marion K.; Bartovà, A.; Li, M. P.; Chan, T. H.

doi:10.1126/science.182.4118.1249

Cited by 58 publications

(9 citation statements)

References 20 publications

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“…From the clinical point of view, elevated levels of 18OH-DOC were found in patients with primary aldosteronism and therefore, it may play a role in the formation of hypertension [59][60][61].…”

Section: Discussionmentioning

confidence: 99%

Human aldosterone synthase: Recombinant expression in E. coli and purification enables a detailed biochemical analysis of the protein on the molecular level

Hobler

Kagawa

Hutter

et al. 2012

The Journal of Steroid Biochemistry and Molecular Biology

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Section: Discussionmentioning

confidence: 99%

Human aldosterone synthase: Recombinant expression in E. coli and purification enables a detailed biochemical analysis of the protein on the molecular level

Hobler

Kagawa

Hutter

et al. 2012

The Journal of Steroid Biochemistry and Molecular Biology

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“…The aldosterone secretory rate is ordinarily normal in such patients (16). With further investigation, a number of other steroids have been implicated, including deoxycorticosterone (17), 18-hydroxy-deoxycorticosterone (18)(19)(20) or a metabolite of it (20), 16a,-18,-dihydroxy-deoxycorticosterone (21), and more recently (22) 169-hydroxy-dehydroepiandrosterone (16f-OH-DHEA)2 and 16-oxo-androstenediol. In all cases, a major problem has been to determine whether the amiiount of steroid is sufficient to account for an excess of sodium-retaining activity.…”

Section: Introductionmentioning

confidence: 99%

Aldosterone receptors and the evaluation of plasma mineralocorticoid activity in normal and hypertensive states.

Baxter¹,

Schambelan²,

Matulich³

et al. 1976

J. Clin. Invest.

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A B S T R A C T Aldosterone receptors from rat kidney slices were utilized in a competitive binding technique to analyze the contribution of various steroids to plasma "mineralocorticoid" activity and to assess their possible role in hypertension. To consider simultaneously the plasma binding, steroids were incubated with slices in undiluted plasma; competitor activities for [3H]aldosterone binding were aldosterone, 100%; deoxycorticosterone, 16.2%; cortisol, 0.4%; and 18-hydroxy-deoxycorticosterone and 18-hydroxy-corticosterone, 0.1%. These steroids were more active in buffer than plasma, suggesting that they bind to plasma and that this reduces their receptor binding. Analysis of the competition data suggests that at normal plasma concentrations, aldosterone occupies the receptors to a major extent, cortisol occupies some of the receptors, and deoxycorticosterone and 18-hydroxydeoxycorticosterone contribute little to receptor occupancy. Two steroids implicated in low-renin essential hypertension, 16i#-hydroxy-dehydroepiandrosterone and 16-oxoandrostenediol, did not have significant competitor activity.Competitor activity in plasmas from normal subjects taken at 12 noon (upright) was greater than that in those taken at 8 a.m. (supine). Since the 12 noon samThis work has been published in abstract form: 1975.

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“…This steroid has actions on electrolyte and water excretion in this species (Birmingham, MacDonald & Rochefort, 1968) and it has been implicated as a possible hypertensive agent in rats (Birmingham, Rochefort & Traikov, 1965;Rapp & Dahl, 1971) and in man (Melby, Dale & Wilson, 1971). In a recent study, unilaterally nephrectomized male rats maintained on 1% saline were injected with vehicle, corticosterone, 11-deoxycorticosterone or 18-hydroxydeoxycorticosterone 200 gg/daily for 21 days (Oliver, Birmingham, Bartova, Li & Chan, 1973). Oliver et al (1973) showed that not only 11-deoxycorticosterone but 1 8-hydroxydeoxycorticosterone contributes to the aetiology of hypertension possibly by a mechanism involving stress-induced ACTH release.…”

Section: Discussionmentioning

confidence: 99%

Structure‐activity Relationship of Various Corticosteroids on the Feedback Control of Corticotrophin Secretion

Jones

Tiptaft

1977

British J Pharmacology

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1 Several steroids occurring in the pathway of corticosteroid biosynthesis were investigated for their ability to exert a fast or delayed feedback inhibition of stress-induced release of corticotrophin. Rats were injected subcutaneously with vehicle or a steroid either 10 min (fast feedback) or 4 h (delayed feedback) before they were subjected to stress which consisted of a 2 min exposure to ether vapour. 2 Changes in plasma corticosterone concentration and in vitro corticosterone production by excised adrenal glands were used as indices of corticotrophin release. 3 Among the steroids tested only 1 lB, 21-dihydroxypregn-4-ene-3, 20-dione (corticosterone) and 1I#, 17a, 2 1-trihydroxypregn-4-ene-3, 20-dione (cortisol) inhibited the stress response 10 min after their administration. Therefore, it appears that the fast feedback mechanism is limited to steroids with a 2 1-hydroxyl and a 1 lp-hydroxyl group.4 In contrast, many steroids caused inhibition of the stress response 4 h after their administration. These steroids were corticosterone, cortisol, 21-hydroxypregn-4-ene-3, 20-dione (1 1-deoxycorticosterone), 17a, 21-dihydroxypregn-4-ene-3, 20-dione (1 l-deoxycortisol), 1 1B-hydroxypregn-4-ene-3, 20-dione (11/p-hydroxyprogesterone) and 11p, 17a-dihydroxypregn-4-ene-3, 20-dione (11p, 17a-dihydroxyprogesterone). Thus, either the 21-hydroxyl group (e.g. 1 1-deoxycorticosterone) or the 1 1,-hydroxyl group (e.g. 11/p-hydroxyprogesterone) is sufficient for delayed feedback activity. The 1 lahydroxyl group, e.g. 1 la, 17a, 21-trihydroxypregn-4-ene-3, 20-dione (1 1-epicortisol) renders the steroid inactive on both feedback mechanisms. 5 18, 21-Dihydroxypregn-4-ene-3, 20-dione (18-hydroxydeoxycorticosterone) was found to be the only steroid that is secreted by the adrenal gland of the rat in quantities sufficient to cause exaggeration of the stress-induced release of corticotrophin. This steroid has been implicated as a possible hypertensive agent, and its role in the control of corticotrophin secretion is discussed here.

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Hypertensive Action of 18-Hydroxydeoxycorticosterone

Cited by 58 publications

References 20 publications

Human aldosterone synthase: Recombinant expression in E. coli and purification enables a detailed biochemical analysis of the protein on the molecular level

Human aldosterone synthase: Recombinant expression in E. coli and purification enables a detailed biochemical analysis of the protein on the molecular level

Aldosterone receptors and the evaluation of plasma mineralocorticoid activity in normal and hypertensive states.

Structure‐activity Relationship of Various Corticosteroids on the Feedback Control of Corticotrophin Secretion

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