Urinary 19-Nor-Deoxycorticosterone Excretion in the Spontaneously Hypertensive Rat*

Dale, Sidney L.; Holbrook, Monika; Komanicky, Pavel; Melby, James C.

doi:10.1210/endo-110-6-1989

Cited by 43 publications

(14 citation statements)

References 23 publications

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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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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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“…19-Nordeoxycorticosterone (19-nor-DOC) could play a role, since it is a powerful mineralocorticoid that is produced in large excess in prehypertensive, young SHR. 16 Although 19-nor-DOC levels decline before the onset of hypertension, preliminary evidence suggests that this decline is associated with further oxygenation of 19-nor-DOC precursors to new 19-nor products." Therefore, further investigations of 19-nor-DOC and the 19-nor-corticosteroid pathway in SHR are warranted.…”

Section: Ultiple Factors Have Been Implicated Inmentioning

confidence: 99%

Antihypertensive effects of an aromatase inhibitor in the spontaneously hypertensive rat.

et al. 1987

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SUMMARY Recent studies from this laboratory have demonstrated that 19-nor-deoxycorticosterone, a potent mineralocorticoid, has been excreted in excess in the urine of young spontaneously hypertensive rats (SHR). Although urinary 19-nor-deoxycorticosterone levels decline before the onset of hypertension, preliminary evidence suggests that 19-nor-deoxycorticosterone is further oxygenated to other steroid products in older SHR. Since 19-hydroxylation is the essential first step in the formation of 19-nor-deoxycorticosterone from deoxycorticosterone and since the mechanism-based aromatase inhibitor 10-propargyl-androst-4-ene,3,17-dione preferentially inhibits 19-hydroxylation, this agent was administered to weanling SHR to determine whether inhibition of 19-nor-deoxycorticosterone formation could modify or prevent hypertension. Accordingly, either 10 mg of 10-propargyl-androst-4-ene,3,17-dione or vehicle (control) was injected daily for several weeks in 4.5 week-old SHR. Injection of 10-propargyl-androst-4-ene,3,17-dione reduced urinary free 19-nor-deoxycorticosterone and retarded the development of hypertension compared with the effect of vehicle injection (p< 0.05). Mean blood pressure levels in SHR receiving 10-propargyl-androst-4-ene,3,17-dione were lower than those in SHR receiving vehicle for each of the first 8 weeks of treatment (p<0.05). These data support the importance of 10-nor-corticosteroids in the pathogenesis of hypertension in SHR. (Hypertension 10: 484-487, 1987) KEY WORDS • 19-hydroxylation • mineralocorticoids • 19-nor-deoxycorticosterone M ULTIPLE factors have been implicated in the pathogenesis of hypertension in spontaneously hypertensive rats (SHR), 1 and a large body of evidence exists in the published reports on abnormal activity of the hypothalamo-pituitaryadrenal, hypothalamo-pituitary-gonadal, and hypothalamo-pituitary-thyroidal axes in these genetically preselected animals. 25 The contribution of the adrenal gland to the development of hypertension has been From the Section of Endocrinology and Metabolism

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“…Carbon-14-labeled DOC was not present in urine after f3-glucuronidase treatment. (4,5,7). Yet, the origin of the 19-nor-DOC that is found in urine of rats and humans (5, 7-10, 24, 25) is unknown.…”

Section: Methodsmentioning

confidence: 99%

“…Heretofore, investigators have quantified the amount of 19-nor-DOC that was present as the free steroid in urine of experimental animals (5,7,24) and humans (8-10, 24, 25 From these several observations, we conclude that free 19-nor-DOC in urine is formed in kidney from a precursor other than DOC or else is formed in kidney or in urine nonenzymatically from a precursor such as the 19-carboxylic acid derivative of DOC, a compound that is known to be synthesized in rat adrenal tissue in vitro (12) and, possibly, in man. This obtains since if the 19-nor-DOC that is found in urine as the free steroid were formed in tissues other than kidney, the likely metabolic fate of such a steroid would be similar to that of intravenously infused [3H] 19-nor-DOC; if not, there seems no reasonable manner by which it could reach urine as free 19-nor-DOC.…”

Section: Methodsmentioning

confidence: 99%

Origin of urinary nonconjugated 19-nor-deoxycorticosterone and metabolism of infused radiolabeled 19-nor-deoxycorticosterone in men and women.

Casey¹,

Guerami²,

Milewich³

et al. 1985

J. Clin. Invest.

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Urinary 19-Nor-Deoxycorticosterone Excretion in the Spontaneously Hypertensive Rat*

Cited by 43 publications

References 23 publications

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

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

Antihypertensive effects of an aromatase inhibitor in the spontaneously hypertensive rat.

Origin of urinary nonconjugated 19-nor-deoxycorticosterone and metabolism of infused radiolabeled 19-nor-deoxycorticosterone in men and women.

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