11-Deoxycortisol: A glucocorticoid antagonist in vivo

G. B. Cutler, K. M. Barnes, M. A. Sauer, Donald (Lynn) Loriaux

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Previous studies have demonstrated that 11-deoxycortisol competes with glucocorticoids for binding to the glucocorticoid receptor and is a competitive antagonist of glucocorticoid action in vitro. 11-Deoxycortisol, however, has been reported to be ineffective as a glucocorticoid antagonist in vivo. The present study was undertaken to examine this discrepancy between the in vivo and in vitro antiglucocorticoid activities of 11-deoxycortisol. In adrenalectomized rats, 11-deoxycortisol antagonized dexamethasone-induced liver glycogen accumulation and growth suppression at plasma levels comparable to those at which antiglucocorticoid activity has been reported in vitro and was itself devoid of agonist activity. In intact rats, on the other hand, 11-deoxycortisol showed agonist activity in growth suppression and adrenal suppression assays, and failed to antagonize dexamethasone activity. Plasma cortisol, measured by RIA after administration of 11-deoxycortisol, was significantly greater in intact compared to adrenalectomized rats. These observations suggest that adrenal 11-hydroxylation of 11-deoxycortisol may account for its lack of effectiveness as a glucocorticoid antagonist in intact animals. Thus, analogs of 11-deoxycortisol that cannot undergo 11-hydroxylation should be promising compounds to examine in seeking a clinically effective glucocorticoid antagonist.

Original languageEnglish (US)
Pages (from-to)1839-1844
Number of pages6
JournalEndocrinology
Volume104
Issue number6
StatePublished - 1979
Externally publishedYes

Fingerprint

Cortodoxone
Glucocorticoids
Hydroxylation
Dexamethasone
Liver Glycogen
Glucocorticoid Receptors
Growth
Hydrocortisone

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Cutler, G. B., Barnes, K. M., Sauer, M. A., & Loriaux, D. L. (1979). 11-Deoxycortisol: A glucocorticoid antagonist in vivo. Endocrinology, 104(6), 1839-1844.

11-Deoxycortisol : A glucocorticoid antagonist in vivo. / Cutler, G. B.; Barnes, K. M.; Sauer, M. A.; Loriaux, Donald (Lynn).

In: Endocrinology, Vol. 104, No. 6, 1979, p. 1839-1844.

Research output: Contribution to journalArticle

Cutler, GB, Barnes, KM, Sauer, MA & Loriaux, DL 1979, '11-Deoxycortisol: A glucocorticoid antagonist in vivo', Endocrinology, vol. 104, no. 6, pp. 1839-1844.
Cutler GB, Barnes KM, Sauer MA, Loriaux DL. 11-Deoxycortisol: A glucocorticoid antagonist in vivo. Endocrinology. 1979;104(6):1839-1844.
Cutler, G. B. ; Barnes, K. M. ; Sauer, M. A. ; Loriaux, Donald (Lynn). / 11-Deoxycortisol : A glucocorticoid antagonist in vivo. In: Endocrinology. 1979 ; Vol. 104, No. 6. pp. 1839-1844.
@article{9a9284771c914bdf80bb615eda84a8f6,
title = "11-Deoxycortisol: A glucocorticoid antagonist in vivo",
abstract = "Previous studies have demonstrated that 11-deoxycortisol competes with glucocorticoids for binding to the glucocorticoid receptor and is a competitive antagonist of glucocorticoid action in vitro. 11-Deoxycortisol, however, has been reported to be ineffective as a glucocorticoid antagonist in vivo. The present study was undertaken to examine this discrepancy between the in vivo and in vitro antiglucocorticoid activities of 11-deoxycortisol. In adrenalectomized rats, 11-deoxycortisol antagonized dexamethasone-induced liver glycogen accumulation and growth suppression at plasma levels comparable to those at which antiglucocorticoid activity has been reported in vitro and was itself devoid of agonist activity. In intact rats, on the other hand, 11-deoxycortisol showed agonist activity in growth suppression and adrenal suppression assays, and failed to antagonize dexamethasone activity. Plasma cortisol, measured by RIA after administration of 11-deoxycortisol, was significantly greater in intact compared to adrenalectomized rats. These observations suggest that adrenal 11-hydroxylation of 11-deoxycortisol may account for its lack of effectiveness as a glucocorticoid antagonist in intact animals. Thus, analogs of 11-deoxycortisol that cannot undergo 11-hydroxylation should be promising compounds to examine in seeking a clinically effective glucocorticoid antagonist.",
author = "Cutler, {G. B.} and Barnes, {K. M.} and Sauer, {M. A.} and Loriaux, {Donald (Lynn)}",
year = "1979",
language = "English (US)",
volume = "104",
pages = "1839--1844",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "6",

}

TY - JOUR

T1 - 11-Deoxycortisol

T2 - A glucocorticoid antagonist in vivo

AU - Cutler, G. B.

AU - Barnes, K. M.

AU - Sauer, M. A.

AU - Loriaux, Donald (Lynn)

PY - 1979

Y1 - 1979

N2 - Previous studies have demonstrated that 11-deoxycortisol competes with glucocorticoids for binding to the glucocorticoid receptor and is a competitive antagonist of glucocorticoid action in vitro. 11-Deoxycortisol, however, has been reported to be ineffective as a glucocorticoid antagonist in vivo. The present study was undertaken to examine this discrepancy between the in vivo and in vitro antiglucocorticoid activities of 11-deoxycortisol. In adrenalectomized rats, 11-deoxycortisol antagonized dexamethasone-induced liver glycogen accumulation and growth suppression at plasma levels comparable to those at which antiglucocorticoid activity has been reported in vitro and was itself devoid of agonist activity. In intact rats, on the other hand, 11-deoxycortisol showed agonist activity in growth suppression and adrenal suppression assays, and failed to antagonize dexamethasone activity. Plasma cortisol, measured by RIA after administration of 11-deoxycortisol, was significantly greater in intact compared to adrenalectomized rats. These observations suggest that adrenal 11-hydroxylation of 11-deoxycortisol may account for its lack of effectiveness as a glucocorticoid antagonist in intact animals. Thus, analogs of 11-deoxycortisol that cannot undergo 11-hydroxylation should be promising compounds to examine in seeking a clinically effective glucocorticoid antagonist.

AB - Previous studies have demonstrated that 11-deoxycortisol competes with glucocorticoids for binding to the glucocorticoid receptor and is a competitive antagonist of glucocorticoid action in vitro. 11-Deoxycortisol, however, has been reported to be ineffective as a glucocorticoid antagonist in vivo. The present study was undertaken to examine this discrepancy between the in vivo and in vitro antiglucocorticoid activities of 11-deoxycortisol. In adrenalectomized rats, 11-deoxycortisol antagonized dexamethasone-induced liver glycogen accumulation and growth suppression at plasma levels comparable to those at which antiglucocorticoid activity has been reported in vitro and was itself devoid of agonist activity. In intact rats, on the other hand, 11-deoxycortisol showed agonist activity in growth suppression and adrenal suppression assays, and failed to antagonize dexamethasone activity. Plasma cortisol, measured by RIA after administration of 11-deoxycortisol, was significantly greater in intact compared to adrenalectomized rats. These observations suggest that adrenal 11-hydroxylation of 11-deoxycortisol may account for its lack of effectiveness as a glucocorticoid antagonist in intact animals. Thus, analogs of 11-deoxycortisol that cannot undergo 11-hydroxylation should be promising compounds to examine in seeking a clinically effective glucocorticoid antagonist.

UR - http://www.scopus.com/inward/record.url?scp=0018759167&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0018759167&partnerID=8YFLogxK

M3 - Article

C2 - 446401

AN - SCOPUS:0018759167

VL - 104

SP - 1839

EP - 1844

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 6

ER -