Mineralocorticoid and renal receptor binding activity of 21-deoxyaldosterone.
Since several aldosterone metabolites are known to be active, we have assessed the mineralocorticoid biological and renal receptor binding activities of the aldosterone metabolites, 21-deoxyaldosterone (21-deoxy-Aldo), 21-deoxytetrahydroaldosterone (21-deoxy-THAldo), and 3 alpha, 5 beta-tetrahydroaldosterone (THAldo). We synthesized these steroids by bioreduction of aldosterone with intestinal bacteria. Mineralocorticoid agonist activity of 21-deoxy-Aldo, 21-deoxy-THAldo and THAldo, determined by bioassay using adrenalectomized rats, was 1-5%, less than 0.01%, and 0.1-0.5% that of aldosterone, respectively. 21-Deoxy-Aldo showed no antagonist activity. The relative affinity in competing with [3H]aldosterone for binding to mineralocorticoid receptors in adrenalectomized rat kidney cytosols was 94%, less than 0.01%, and less than 0.01% that of aldosterone. The relative binding affinity for rat renal glucocorticoid receptors was 23%, less than 0.01%, and less than 0.01% that of dexamethasone, and for corticosteroid-binding globulin 17%, less than 0.01%, and less than 0.01% that of cortisol. These results show that the naturally occurring steroid, 21-deoxy-Aldo, possesses mineralocorticoid agonist activity which is equivalent to that of 11-deoxycorticosterone, and has substantial affinity for rat renal mineralocorticoid and glucocorticoid receptors. The results also implicate the pathophysiological role of 21-deoxy-Aldo as a potential mineralocorticoid in 21-hydroxylase deficiency, where urinary excretion of this steroid is invariably elevated.
Koshida
H
H
Second Department of Internal Medicine, School of Medicine, Kanazawa University, Japan.
Miyamori
I
I
Soma
R
R
Matsubara
T
T
Ikeda
M
M
Takeda
R
R
Nakamura
S
S
Kiuchi
F
F
Tsuda
Y
Y
D000315:Adrenalectomy; D000450:Aldosterone / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D003600:Cytosol / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008901:Mineralocorticoids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid / Q000378:metabolism*
D008901:Mineralocorticoids; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; C032486:21-deoxyaldosterone; D000450:Aldosterone; D003907:Dexamethasone