Mineralocorticoid and renal receptor binding activity of 21-deoxyaldosterone

Hideo Koshida, Isamu Miyamori, Ryuichiro Soma, Takao Matsubara, Masatoshi Ikeda, Ryoyu Takeda, Shinichi Nakamura, Fumiyuki Kiuchi, Yoshisuke Tsuda

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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 3α, 5β-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-deoxyAldo as a potential mineralocorticoid in 21-hydroxylase deficiency, where urinary excretion of this steroid is invariably elevated.

Original languageEnglish
Pages (from-to)1410-1415
Number of pages6
JournalEndocrinology
Volume126
Issue number3
Publication statusPublished - 1990 Mar
Externally publishedYes

Fingerprint

Mineralocorticoid Receptors
Aldosterone
Mineralocorticoids
Kidney
Steroids
Glucocorticoid Receptors
Transcortin
Desoxycorticosterone
Biological Assay
Cytosol
Dexamethasone
Hydrocortisone
21-deoxyaldosterone
Bacteria

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Koshida, H., Miyamori, I., Soma, R., Matsubara, T., Ikeda, M., Takeda, R., ... Tsuda, Y. (1990). Mineralocorticoid and renal receptor binding activity of 21-deoxyaldosterone. Endocrinology, 126(3), 1410-1415.

Mineralocorticoid and renal receptor binding activity of 21-deoxyaldosterone. / Koshida, Hideo; Miyamori, Isamu; Soma, Ryuichiro; Matsubara, Takao; Ikeda, Masatoshi; Takeda, Ryoyu; Nakamura, Shinichi; Kiuchi, Fumiyuki; Tsuda, Yoshisuke.

In: Endocrinology, Vol. 126, No. 3, 03.1990, p. 1410-1415.

Research output: Contribution to journalArticle

Koshida, H, Miyamori, I, Soma, R, Matsubara, T, Ikeda, M, Takeda, R, Nakamura, S, Kiuchi, F & Tsuda, Y 1990, 'Mineralocorticoid and renal receptor binding activity of 21-deoxyaldosterone', Endocrinology, vol. 126, no. 3, pp. 1410-1415.
Koshida H, Miyamori I, Soma R, Matsubara T, Ikeda M, Takeda R et al. Mineralocorticoid and renal receptor binding activity of 21-deoxyaldosterone. Endocrinology. 1990 Mar;126(3):1410-1415.
Koshida, Hideo ; Miyamori, Isamu ; Soma, Ryuichiro ; Matsubara, Takao ; Ikeda, Masatoshi ; Takeda, Ryoyu ; Nakamura, Shinichi ; Kiuchi, Fumiyuki ; Tsuda, Yoshisuke. / Mineralocorticoid and renal receptor binding activity of 21-deoxyaldosterone. In: Endocrinology. 1990 ; Vol. 126, No. 3. pp. 1410-1415.
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abstract = "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 3α, 5β-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-deoxyAldo as a potential mineralocorticoid in 21-hydroxylase deficiency, where urinary excretion of this steroid is invariably elevated.",
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