Disease relevance of Deoxycorticosterone

• The uninephrectomized rat given desoxycorticosterone (DOC) provides a classic model of "sodium-dependent" hypertension [1].
• Plasma 11-deoxycorticosterone levels were manyfold elevated in three adult patients with hypertension and elevated urinary excretion levels of 17-ketosteroids but without Cushing's syndrome [2].
• Aldo and DOC markedly increased systolic BP and caused considerable (40-50%) cardiac hypertrophy; B and RU486 caused neither hypertension nor cardiac hypertrophy [3].
• 25 d after the induction of severe hypertension with deoxycorticosterone acetate and salt, proteinuria, impaired glomerular filtration rate, and extensive vascular and glomerular injury were observed in the Brown Norway donor kidneys, but not in the SHR-RT1.N kidneys [4].
• Although clinical presentations were similar to those of patients with benign adenoma, all had significantly higher concentrations of deoxycorticosterone and aldosterone and more profound hypokalemia [5].

Psychiatry related information on Deoxycorticosterone

• Inhibitory effects of various progestins and deoxycorticosterone on the rapid onset of maternal behavior induced by ovariectomy-hysterectomy during late pregnancy in rats [6].
• As compared to their appropriate controls, both experimentally (either renal or deoxycorticosterone salt) hypertensive rats and spontaneously hypertensive rats maintained a higher level of spontaneous motor activity [7].

High impact information on Deoxycorticosterone

• The adrenaline-forming enzyme (phenylethanolamine N-methyltransferase) was elevated in the A1 and A2 regions of the brainstem of 4-week-old spontaneously (genetic) hypertensive rats and in the A1 region of adult experimentally (deoxycorticosterone acetate and sodium chloride) hypertensive rats [8].
• There was a three to sixfold increase in fibronectin biosynthesis by aortic rings taken from rats treated with deoxycorticosterone/salt for 7 and 21 d, the change being more pronounced at 21 d [9].
• TGF-beta aortic mRNA levels increased up to threefold as a result of DOC/salt hypertension [10].
• Chronic blockade of endogenous atrial natriuretic polypeptide (ANP) by monoclonal antibody against ANP accelerates the development of hypertension in spontaneously hypertensive and deoxycorticosterone acetate-salt-hypertensive rats [11].
• We have studied the effects of deoxycorticosterone, arginine vasopressin, and bradykinin on net transepithelial sodium and potassium transport in isolated, perfused rat cortical collecting ducts [12].

Chemical compound and disease context of Deoxycorticosterone

• Is vasopressin involved in the pathogenesis of malignant desoxycorticosterone hypertension in rats [13]?
• Insulin or pharmacologic doses of desoxycorticosterone acetate eliminated the glucose-induced hyperkalemia [14].
• In 19 control subjects, 33 patients with essential hypertension and normal plasma renin activity (PRA) and 11 patients with low PRA, secretory rates of 18-hydroxy-11-deoxy-corticosterone (18-OH DOC), 11-deoxycorticosterone (DOC) and corticosterone were measured [15].
• The role of the sympathetic nervous system in the development of deoxycorticosterone-sodium chloride (DOCA-saline) hypertension was investigated by measuring plasma levels of norepinephrine, total catecholamines, and dopamine-beta-hydroxylase activity at intervals after the initiation of the DOCA-saline regimen [16].
• Immunologic identification of Na+,K(+)-ATPase isoforms in myocardium. Isoform change in deoxycorticosterone acetate-salt hypertension [17].

Biological context of Deoxycorticosterone

• During the third trimester of human pregnancy the concentrations of deoxycorticosterone (DOC) in maternal plasma are 4-50 times those in nonpregnant women and men [18].
• Similarly, pH values for each rat model varied inversely with blood pressure, regardless of whether increased dietary calcium intake lowered pressure (normotensive and deoxycorticosterone/saline hypertensive rats) or elevated it (2K-1C Goldblatt hypertensive rats) [19].
• The COX-2 up-regulation in ADX rats was reversed by replacement therapy with either corticosterone or deoxycorticosterone acetate [20].
• Effects of deoxycorticosterone/salt hypertension on cell ploidy in rat aortic smooth muscle cells [21].
• Infusion of RB 105 as a bolus of 25 mg/kg followed by 25 mg/kg per hr similarly decreased blood pressure and increased natriuresis in three different models of hypertension (renovascular, deoxycorticosterone acetate-salt, and spontaneously hypertensive rats) [22].

Anatomical context of Deoxycorticosterone

• Intracellular erythrocyte pH was also measured in normotensive rats on different dietary calcium intakes as well as in volume-dependent deoxycorticosterone/saline and renin-dependent, 2 kidney, 1 clip (2K-1C) Goldblatt hypertensive rat models [19].
• When compared with the enzyme from control fibroblasts, the enzyme from chronic Gaucher patients (group 1) was more rapidly inactivated at 50 degrees C, had an altered pH curve, was less effectively inhibited by deoxycorticosterone-beta-glucoside, and was more effectively inhibited by deoxycorticosterone [23].
• This model is characterized hemodynamically by wide variations in cardiac output and extracellular fluid volume and metabolically, by hypokalemia, suppressed plasma renin activity, and elevated plasma deoxycorticosterone values [24].
• In the reconstituted system the hydroxylation of deoxycorticosterone sulfate proceeded at a much higher rate than in intact mitochondria, indicating that in the former case interactions between the hydrophilic substrate and P-450 were facilitated [25].
• Thus, at least two forms of cytochrome P-450, which catalyze the 11 beta- and 18-hydroxylations of deoxycorticosterone, exist in rat adrenal cortex, but aldosterone synthesis is catalyzed only by the one present in the zona glomerulosa mitochondria [26].

Associations of Deoxycorticosterone with other chemical compounds

• Addition of radiolabeled substrates to isolated adrenal cells and analysis of products by high performance liquid chromatography demonstrated a ketoconazole block between deoxycorticosterone (DOC) and corticosterone [27].
• We found a local inhibition of involution in the vicinity of deoxycorticosterone- and progesterone-release pellets while prolactin-release pellets were ineffective [28].
• P450c11 converts deoxycorticosterone to corticosterone and aldosterone, and P450scc converts cholesterol to pregnenolone [29].
• METHODS AND RESULTS: The model systems were suprarenal aortic constriction, uninephrectomized spontaneously hypertensive rats (SHR), and uninephrectomized, deoxycorticosterone-treated, saline-fed rats (DOCA salt) [30].
• beta-Aminopropionitrile, a specific inhibitor of lysyl oxidase prevented the rise in blood pressure induced by deoxycorticosterone-salt in rats [31].

Gene context of Deoxycorticosterone

• A small amount of aldosterone was synthesized from deoxycorticosterone only in cells expressing CYP11B2 cDNA [32].
• Steroid 21-hydroxylase (P450c21) is a microsomal enzyme expressed in the adrenal gland that catalyzes conversion of 17-hydroxyprogesterone and progesterone to 11-deoxycortisol and deoxycorticosterone respectively [33].
• Vascular capacitance is reduced by endothelin-1 (ET-1) in deoxycorticosterone (DOCA)-salt hypertensive rats [34].
• In deoxycorticosterone-producing adenomas (DOC, n = 2), on the other hand, CYP17 expression was extremely reduced (8 and 12% vs NL 98 +/- 4%), whereas DAX-1 expression increased markedly (350 and 360% vs NL 100 +/- 4%) [35].
• Addition of natural glucocorticoids, cortisol or corticosterone, or the mineralcorticoid, deoxycorticosterone, during the third culture week had no effect on PNMT activity [36].

Analytical, diagnostic and therapeutic context of Deoxycorticosterone

• Rats with unilateral nephrectomy were offered 1% sodium chloride as drinking fluid and were injected with desoxycorticosterone trimethylacetate (D.O.C.-T.M.A.) at weekly intervals [13].
• PHF is also found in several animal models of hypertension, including spontaneously hypertensive rats, and deoxycorticosterone acetate salt hypertensive rats [37].
• The procedure, which requires only about 24 hr, involves biospecific adsorption of the receptor to deoxycorticosterone derivatized agarose, elution with a glucocorticoid, and gel filtration [38].
• Tumor weight and time-integrated tumor volume, however, were significantly less in bilaterally adrenalectomized rats without deoxycorticosterone acetate replacement than in animals treated with deoxycorticosterone acetate [39].
• Parathyroidectomy ameliorates vascular lesions induced by deoxycorticosterone in the rat [40].

References