Hisahiko Sekihara

Amplification of the action of subthreshold doses of aldosterone by 19-Hydroxyandrost-4-ene-3, 17-dione

Abstract Mineralocorticoid activity of 19-hydroxyandrost-4-ene-3, 17-dione was evaluated by mineralocorticoid bioassays using adrenalectomized rats. 19-Hydroxyandrost-4-ene-3, 17-dione was devoid of mineralocorticoid activity. However, it caused a significant decrease in urinary Na K ratio and Na excretion and a significant increase in urinary K excretion when it was administered simultaneously with subthreshold doses of aldosterone. The results demonstrate that 19-hydroxyandrost-4-ene-3, 17-dione amplified the action of subthreshold doses of aldosterone.

19-HYDROXYANDROSTENEDIONE: A POTENT HYPERTENSINOGENIC STEROID IN MAN

The hypertensinogenic effects of 19-hydroxyandrostenedione (19-OH-A-dione), which we reported as an amplifier of the action of aldosterone on the basis of the results obtained in bioassays using adrenalectomized rats, were evaluated in intact rats with both adrenals and kidneys. The administration of 19-OH-A-dione to the rats caused sodium retention and the 19-OH-A-dione treated rats developed high blood pressure, suppressed plasma renin activity and low plasma aldosterone, corticosterone and deoxycorticosterone concentrations. The hypertensinogenic potency of 19-OH-A-dione was incomparably higher than that of DOCA. The results indicate that 19-OH-A-dione is a potent hypertensinogenic steroid and causes the hypertensive state similar to mineralocorticoid excess. The evaluation of 19-OH-A-dione concentrations in human plasma revealed that 19-OH-A-dione is present in human peripheral circulation. It appears to be secreted by the adrenal cortex under the control of ACTH and the renin-angiotensin system. Plasma 19-OH-A-dione concentrations in patients with normal renin essential hypertension and low renin essential hypertension are higher than those in control subjects. 19-OH-A-dione is a newly recognised hypertensinogenic steroid in man.

Evidence that 19-hydroxyandrostenedione is secreted by the adrenal cortex and is under the control of ACTH and the renin-angiotensin system in man

Abstract Plasma 19-hydroxyandrostenedione (19-OH-A-dione) concentrations in man were evaluated using a specific and sensitive radioimmunoassay. Plasma 19-OH-A-dione concentrations (mean ± SE) in normal subjects are 151 ± 14 pg/ml (n=13) in males and 141 ± 9 pg/ml (n=14) in females. Plasma 19-OH-A-dione (mean ± SE) rises significantly during ACTH stimulation (116 ± 25 pg/ml vs 288 ± 38 pg/ml; P

19-Norandrost-4-ene-3, 17-dione amplifies the action of aldosterone only in sodium-loaded conditions: Evidence for a new class of amplifiers of aldosterone

Abstract The amplification effect of 19-norandrost-4-ene-3, 17-dione (19-nor-A-dione) on aldosterone in normal and sodium-loaded conditions was evaluated using adrenalectomized rats fed a normal or high sodium diet. The administration of 19-nor-A-dione in normal or sodium-loaded conditions did not cause any significant change in urinary Na K ratio. The simultaneous administration of subthreshold doses of aldosterone and 19-nor-A-dione in normal conditions also did not cause any significant change in urinary Na K ratio. However, the simultaneous administration of subthreshold doses of aldosterone and 19-nor-A-dione in sodium-loaded conditions caused a significant decrease in urinary Na K ratio. The decrease in urinary Na K ratio was caused by a decrease in urinary Na excretion. These results demonstrate that 19-nor-A-dione, which did not amplify the action of aldosterone in normal conditions, amplified the action of subthreshold doses of aldosterone in sodium-loaded conditions. 19-Nor-A-dione is considered to be an amplifier of aldosterone which works only in sodium-loaded conditions.

A radioimmunoassay for serum 11-deoxy-17-ketosteroids

A simplified method for evaluating serum 11-deoxy-17-ketosteroids (11- deoxy-17-KS) equivalent to dehydroepiandrosterone sulfate (DHEAS) has been developed without solvolysis and chromatography. Blood serum or plasma (5 mu l) was added to 1 ml of ethanol, mixed, and centrifuged, and 10 or 20 mu l of the supernatant was evaporated to dryness and incubated with anti-11-deoxy-17-KS antiserum obtained by immunizing a rabbit with DHEA-3.O. CO-BSA which was prepared from DHEA-3.O.COCl and containing DHEAS-7

Ouabain causes kaliuresis and works synergistically with aldosterone in vivo

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5α-dihydro-11-deoxycorticosterone as a mineralocorticoid agonist and antagonist: Evidence for a weak mineralocorticoid as an antagonist of potent mineralocorticoids

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19-oxoandrost-4-ene-3, 17-dione amplifies the action of aldosterone

H, pepsin-treated human immune serum globulin and bovine serum albumin. Ammonium sulfate was used to separate free from bound DHEAS-7

Plasma 19‐hydroxyandrostenedione is elevated in patients with high renin essential hypertension

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