Relationship of 19-nor-deoxycorticosterone to other mineralocorticoids in low-renin hypertension.
(9/17)
A number of mineralocorticoids have been proposed as etiologic factors in low-renin hypertension. In this study, urinary free 19-nor-deoxycorticosterone (UF 19-nor-DOC) was compared to other mineralocorticoids--aldosterone, deoxycorticosterone (DOC), and 18-OH-DOC, in 11 low-renin hypertensive patients on a controlled diet in a metabolic unit. Results demonstrated that both UF 19-nor-DOC and tetrahydro-DOC (TH-DOC) excretion were elevated (2086 +/- 926, nl = 339-579 ng/day, and 18 +/- 7, nl = 5-15 mcg/day, respectively), and positively correlated (r = 0.95). Neither 18-OH-DOC nor aldosterone secretion rates were elevated, and neither of these hormones correlated with UF 19-nor-DOC, with exception of the supine plasma aldosterone (SPA) (r = 0.86). In conclusion, both UF 19-nor-DOC and TH-DOC were increased and positively correlated in the present series of hypertensives. This association is possibly indicative of a precursor-product relationship between DOC and 19-nor-DOC. 19-Nor-DOC, furthermore, correlated with supine plasma aldosterone (SPA), which could, in part, reflect their shared adrenocorticotropic hormone (ACTH) dependence. (+info)
Effect of metoprolol on 24-hour urinary excretion of adrenal steroids and kallikrein in patients with essential hypertension.
(10/17)
Treatment of fifteen patients with essential hypertension over four weeks using the beta 1-adrenoceptor blocking agent, metoprolol, resulted in a decrease in 24 h urinary excretion of kallikrein and aldosterone along with a decrease in plasma renin activity. There was no significant change in 24 h excretion rates of the free adrenal steroids deoxycorticosterone, 18-OH-deoxycorticosterone, corticosterone, cortisol or 18-OH-corticosterone during treatment, which were not significantly different from excretion rates of normal males, thus excluding inhibitory effects of adrenal steroids on urinary kallikrein activity. A positive correlation was found between plasma renin activity and urinary excretion of kallikrein during the control period and after 2 weeks on metoprolol, supporting the assumption of a preserved link between the renin-angiotensin-aldosterone system and the renal excretion of kallikrein in these patients. The decrease in kallikrein excretion during beta 1-adrenoceptor blockade in patients with essential hypertension may be explained by a reduction in sympathetic tone and by reduced activity of the renin-aldosterone system. (+info)
Evidence for endogenous dopaminergic control of mineralocorticoids secretion in normal subjects and in patients with hyperaldosteronism.
(11/17)
The role of endogenous dopamine (DA) in the secretion of several mineralocorticoids was studied in six normal subjects, eight patients with primary aldosteronism (PA), two patients with non-familial idiopathic hyperaldosteronism (NF-IHA), and four patients with familial IHA (F-IHA). To these subjects 10 mg metoclopramide (MCP) was administered intravenously, and plasma aldosterone (Ald), 18-OH-corticosterone (18-OH-B), 18-OH-11-deoxycorticosterone (18-OH-DOC), and DOC were measured by RIA. Further, five normal subjects were studied with MCP test after pretreatment with DA infusion (5 micrograms/kg/min over 90 min). After the administration of MCP, normal subjects showed significant increases in their plasma Ald and 18-OH-B, and slight increases in plasma 18-OH-DOC and DOC. However, no significant changes were observed in plasma ACTH, cortisol, PRA, or serum K, Na or Cl. In patients with PA and NF-IHA, plasma Ald and the three precursors were increased after administration of MCP. Especially, marked increases in plasma 18-OH-DOC were seen in PA patients. In contrast, F-IHA patients showed increases in the above mineralocorticoids except 18-OH-B. Following DA infusion in normal subjects neither basal plasma Ald secretion nor the responsivenesses to MCP were modified. These results suggest that endogenous DA plays an inhibitory role in the terminal stages of mineralocorticoids production in man. However, the degrees of the dopaminergic inhibition may be different in normal subjects and the patients with mineralocorticoids excess, and among the three groups of aldosteronism mentioned above. (+info)
Simultaneous determination of plasma 11-deoxycorticosterone, 18-hydroxy-11-deoxycorticosterone, and aldosterone in man.
(12/17)
A method for simultaneous measurement of 11-deoxycorticosterone (DOC), 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) and aldosterone using 1.0-2.0 ml of plasma has been developed. The present method consists of extracting plasma with dichloromethane, separating the DOC, 18-OH-DOC, and aldosterone from other steroids on a Sephadex LH-20 column, and quantitating each steroid by radioimmunoassay. This method was demonstrated to be sensitive, accurate and precise. In 20 normal male subjects, the mean recumbent level of DOC was 9.1 +/- 3.1 ng/100 ml, on random diet, at 0800 h. The corresponding levels of 18-OH-DOC and aldosterone were 8.2 +/- 3.9 ng/100 ml, and 6.7 +/- 2.6 ng/100 ml, respectively. Plasma levels of these three steroids were measured in several types of adrenocortical disorders associated with hypertension and hypokalemia. Patients with Cushing's syndrome due to adrenocortical hyperplasia, and 17alpha-hydroxylase deficiency had elevated DOC and 18-OH-DOC levels, but showed normal or lower aldosterone levels. Hypersecretion of DOC and 18-OH-DOC may cause the symptoms of hypertension and hypokalemia. Patients with primary aldosteronism had elevated levels of DOC and 18-OH-DOC as well as aldosterone. The former two steroids may be hyperproduced as a precursor of aldosterone. (+info)
A radioimmunoassay of plasma 18-hydroxy-11-deoxycorticosterone.
(13/17)
A radioimmunoassay for the measurement of plasma 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) has been developed. The antiserum for 18-OH-DOC was produced in rabbits immunized with 18-OH-DOC-3-(0-carboxymethyl) oxime-bovine serum albumin. This antiserum was used at a final dilution of 1:40,000 and the main cross reactants were aldosterone at 29.4%, 18-hydroxy-corticosterone at 4.9% and 11-deoxycorticosterone at 3.6%. Silica gel column chromatography (7 X 30 mm, toluene saturated with propylene glycol: dichloromethane, 95:5) and Sephadex LH-20 column chromatography (7 X 60 mm, benzene: methanol, 85:15) were employed for the separation of these cross reactants. The sensitivity was 10pg and the method blank was consistently negligible. The intra- and inter-assay precision was 11.3% and 14.8%, respectively. (+info)
19-Hydroxylation of 18-hydroxy-11-deoxycorticosterone catalyzed by cytochrome P-45011 beta of bovine adrenocortex.
(14/17)
When 18-hydroxy-11-deoxycorticosterone was incubated with adrenocortical mitochondria fortified by adding exogenously adrenodoxin reductase and adrenodoxin in the presence of an NADPH-generating system, the steroid was converted to two products which were separated by high performance liquid chromatography. The retention time of one product was identical with that of 18-hydroxycorticosterone, an expected product of 11 beta-hydroxylation, whereas the retention time of the other was not coincident with those of any other corticosteroids examined. Production of the unidentified substance was also shown when 18-hydroxy-11-deoxycorticosterone was incubated with purified cytochrome P-45011 beta and its electron transport system. The ratio of the two products was always constant, even when various incubation conditions were employed with regard to reaction time, the substrate concentration, and the cytochrome concentration. Structural determination of the unidentified product was conducted by mass spectrometry and 1H NMR spectrometry. The results of these analyses indicated that the substance was 18,19-dihydroxy-11-deoxycorticosterone, a hitherto unreported corticosteroid. (+info)
Plasma concentrations of 18-hydroxy-11-deoxycorticosterone and 18-hydroxycorticosterone simultaneously measured in normal subjects and adrenocortical disorders.
(15/17)
A method for the simultaneous measurement of 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) and 18-hydroxycorticosterone (18-OH-B) in human peripheral plasma has been developed. The present method consists of extracting plasma with dichloromethane, separating the 18-OH-DOC and 18-OH-B from other steroids on a Sephadex LH-20 column and quantitating each steroid by radioimmunoassay. The mean plasma level of 18-OH-DOC at 8:00 a.m. was 8.2 +/- 3.9 ng/100 ml (mean +/- S.D.) in normal males. It was 7.8 +/- 2.6 ng/100 ml in the follicular phase of normal females and 11.5 +/- 2.8 ng/100 ml in the luteal phase. The corresponding level of 18-OH-B in normal males was 10.3 +/- 4.2 ng/100 ml and in the follicular and luteal phases of normal females was 12.4 +/- 4.5 ng/100 ml and 13.8 +/- 4.1 ng/100 ml, respectively. No sex differences nor difference between the phases of the menstrual cycle was confirmed. Plasma levels of the two steroids were not rarely high in patients with Cushing syndrome due to adrenocortical hyperplasia and carcinoma, primary aldosteronism, idiopathic hyperaldosteronism and congenital 17 alpha-hydroxylase deficiency, while they were usually within the normal range in cases of Cushing syndrome due to adrenocortical adenoma. These steroid levels were significantly low in patients with Addison's disease. (+info)
Adrenal tumor producing 11-deoxycorticosterone, 18-hydroxy-11-deoxycorticosterone and aldosterone.
(16/17)
A case of adrenal tumor producing 11-deoxycorticosterone, 18-hydroxy-11-deoxycorticosterone and aldosterone is reported. A 55-year-old woman had hypertension, hypokalemia, low plasma renin activity and an adrenal tumor. The plasma level of aldosterone was normal, and the levels of 11-deoxycorticosterone and 18-hydroxy-11-deoxycorticosterone were extremely high. After the tumor removal, the plasma level of aldosterone decreased and plasma levels of 11-deoxycorticosterone and 18-hydroxy-11-deoxycorticosterone were normalized. The tumor was benign adenoma and the production of steroid hormones was under control of adrenocorticotropic hormone. The enzyme activity of 21-hydroxylation in the tumor was elevated and that of 11 beta-hydroxylation was decreased compared with the adjacent tissue. (+info)