The Role of Deoxycorticosterone in Adrenal Regeneration Hypertension

Gaunt, Richard A.; Gisoldi, Elvira; Smith, Neil

doi:10.1210/endo-91-4-921

Cited by 25 publications

(9 citation statements)

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“…DOC, which has mineralocorticoid activity and is elevated in untreated 11βOHD, has been assumed to be the cause of hypertension. However, DOC has only weak mineralocorticoid activity when administered to humans or animals [16,92,93]. Moreover, there is no correlation between plasma levels of DOC and severity of hypertension [10,35].…”

Section: Blood Pressurementioning

confidence: 99%

Clinical perspectives in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

2016

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Congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency is a rare autosomal recessive genetic disorder. It is caused by reduced or absent activity of 11β-hydroxylase (CYP11B1) enzyme and the resultant defects in adrenal steroidogenesis. The most common clinical features of 11 beta-hydroxylase deficiency are ambiguous genitalia, accelerated skeletal maturation and resultant short stature, peripheral precocious puberty and hyporeninemic hypokalemic hypertension. The biochemical diagnosis is based on raised serum 11-deoxycortisol and 11-deoxycorticosterone levels together with increased adrenal androgens. More than 100 mutations in CYP11B1 gene have been reported to date. The level of in-vivo activity of CYP11B1 relates to the degree of severity of 11 beta-hydroxylase deficiency. Clinical management of 11 beta-hydroxylase deficiency can pose a challenge to maintain adequate glucocorticoid dosing to suppress adrenal androgen excess while avoiding glucocorticoid-induced side effects. The long-term outcomes of clinical and surgical management are not well studied. This review article aims to collate the current available data about 11 beta-hydroxylase deficiency and its management.

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Section: Blood Pressurementioning

confidence: 99%

Clinical perspectives in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

2016

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“…This effect of DOC has been used in experimental induction of hypertension in animals, for example in regenerating enucleated adrenal in the rat. Here, the regenerating gland is relatively deficient in 11b-hydroxylase, so corticosterone production is depressed whereas DOC becomes elevated (Brown et al 1972a, Holzbauer et al 1972: 19-nor-DOC and other DOC derivatives may also be increased and implicated in the development of hypertension in these animals (Dale et al 1982, Gomez-Sanchez et al 1983. Additionally, the salt-fed DOCA-treated rat is a standard model for hypertension, and although this could be assumed to be an adjunct to its mineralocorticoid action, the effect is complex and central, and other actions are implicated (Schenk & McNeill 1992, Pinto et al 1998, Yemane et al 2010) -as indeed is also the case for aldosterone (Xue et al 2011).…”

Section: Other Actions and Doc In Other Speciesmentioning

confidence: 99%

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

Vinson¹

2011

Journal of Endocrinology

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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.

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“…This finding raises the possibility that 19-nor-DOC may be important in the pathogenesis of ARH. It is difficult (Gomez-Sanchez, C. viously utilized for DOC assay (8,9). Therefore, further studies are required to determine if the elevated plasma DOC levels, previously noted in ARH (7-9), may be explained in part by cross-reactivity with 19-nor-DOC.…”

Section: Discussionmentioning

confidence: 99%

19-Nor-Deoxycorticosterone: A Potent Mineralcocorticoid Isolated from the Urine of Rats with Regenerating Adrenals*

Gómez-Sánchez

Holland²,

Murry

et al. 1979

Endocrinology

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Adrenal regeneration hypertension (ARH) is an experimental form of low renin hypertension in the rat in which an unknown mineralocorticoid (s) appears to contribute to the pathophysiology of the hypertension. To isolate unknown mineralocorticoids, urine of castrated rats with regenerating adrenals was lowered to pH 1.0 with sulfuric acid, incubated for 24-h at room temperature, extracted with ethyl acetate, and subjected to several successive chromatographic purifications. Unknown urinary mineralocorticoid activity was identified and monitored with an aldosterone radioreceptor assay to enable isolation of approximately 1 mg of a pure unknown steroid. Direct probe mass spectrometry, gas chromatography-mass spectrometry, and nuclear magnetic resonance revealed the following characteristics of the isolated steroid: 1) a molecular weight of 316; 2) a deficit in 14 atomic mass units in comparison to deoxycorticosterone (DOC); 21-hydroxy-4-pregnene-3,20-dione) and to the corresponding dimethoxime and dimethoxime-trimethylsilyl derivatives of the unknown steroid and of DOC; and (3) nuclear magnetic resonance spectrum identical to that of DOC except for the absence of the angular C-10 methyl signal. Further characterization revealed circular dichroism of the unknown steroid almost identical to that of DOC; UV absorption maximum at 239 nm, suggesting a 4-en-3-oxo function; and positive blue tetrazolium reaction, indicating a a-ketol. These data suggested that the steroid was 19-nor-DOC. Mass spectrometry of the isolated steroid, authentic 19-nor-DOC, and their dimethoxime-trimethylsilyl derivatives substantiated this conclusion. This is the first reported identification of 19-nor-DOC as a naturally occurring steroid. However, previous bioassay data have established the mineralocorticoid potency of 19-nor-DOC to be 1.5-5.1 times that of DOC. The role of this newly isolated mineralocorticoid in adrenal regeneration hypertension and human hypertension remains to be elucidated. {Endocrinology 105: 708, 1979)

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The Role of Deoxycorticosterone in Adrenal Regeneration Hypertension

Cited by 25 publications

References 0 publications

Clinical perspectives in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

Clinical perspectives in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

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

19-Nor-Deoxycorticosterone: A Potent Mineralcocorticoid Isolated from the Urine of Rats with Regenerating Adrenals*

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