The new world primates as animal models of glucocorticoid resistance.

G. P. Chrousos, Donald (Lynn) Loriaux, M. Tomita, D. D. Brandon, D. Renquist, B. Albertson, M. B. Lipsett

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Many New World primate species have greatly increased plasma cortisol concentrations, decreased plasma cortisol binding globulin capacity and affinity, marked resistance of the hypothalamic-pituitary-adrenal axis to suppression by dexamethasone, and no biological evidence of glucocorticoid excess. These primates also have high levels of circulating progesterone, estrogen, mineralocorticoid, androgen and vitamin D. The glucocorticoid target tissues that have been examined (circulating mononuclear lymphocytes and cultured skin fibroblasts) have normal concentrations of glucocorticoid receptors with decreased affinity for dexamethasone. Transformation of B-lymphocytes with the Epstein-Barr virus leads to glucocorticoid receptor induction that is less than that observed with cells from Old World primates. The receptor in these cells has a low affinity for dexamethasone. The low affinity leads to an increased loss of specific bound ligand during thermal activation. Meroreceptor generation is normal. The molecular weight of the receptor, determined by SDS-PAGE, is similar to that of Old World primates (approximately 92,000) and the activation pattern per se, examined in vitro by heating cytosol and performing phosphocellulose chromatography, appears similar to that of human controls. The ratios of nuclear to cytosolic hormone-receptor-complexes and of cytosolic activated to unactivated receptor complexes in intact cells are similar to Old World primates. Results from mixing studies do not support the hypothesis that a binding inhibitor(s) or a deficient cytosolic positive modifier(s) of binding underlies the findings in these primates. The New World primates, unlike men with the syndrome of primary cortisol resistance, have compensated for their condition with intra-adrenal and mineralocorticoid receptor adaptations. Thus, unlike Old World primates, cortisol in New World primates has only weak sodium-retaining potency because the aldosterone receptor has a low affinity for cortisol. The common element that would explain the apparent resistance to six steroid hormones in New World primates remains unknown.

Original languageEnglish (US)
Pages (from-to)129-144
Number of pages16
JournalAdvances in Experimental Medicine and Biology
Volume196
StatePublished - 1986
Externally publishedYes

Fingerprint

Primates
Glucocorticoids
Animals
Animal Models
Hydrocortisone
Dexamethasone
Mineralocorticoid Receptors
Lymphocytes
Glucocorticoid Receptors
Chemical activation
Steroid hormones
Glucocorticoid Receptor Deficiency
Hormones
Plasmas
Mineralocorticoids
Fibroblasts
Chromatography
Human Herpesvirus 4
Viruses
Vitamin D

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Chrousos, G. P., Loriaux, D. L., Tomita, M., Brandon, D. D., Renquist, D., Albertson, B., & Lipsett, M. B. (1986). The new world primates as animal models of glucocorticoid resistance. Advances in Experimental Medicine and Biology, 196, 129-144.

The new world primates as animal models of glucocorticoid resistance. / Chrousos, G. P.; Loriaux, Donald (Lynn); Tomita, M.; Brandon, D. D.; Renquist, D.; Albertson, B.; Lipsett, M. B.

In: Advances in Experimental Medicine and Biology, Vol. 196, 1986, p. 129-144.

Research output: Contribution to journalArticle

Chrousos, GP, Loriaux, DL, Tomita, M, Brandon, DD, Renquist, D, Albertson, B & Lipsett, MB 1986, 'The new world primates as animal models of glucocorticoid resistance.', Advances in Experimental Medicine and Biology, vol. 196, pp. 129-144.
Chrousos GP, Loriaux DL, Tomita M, Brandon DD, Renquist D, Albertson B et al. The new world primates as animal models of glucocorticoid resistance. Advances in Experimental Medicine and Biology. 1986;196:129-144.
Chrousos, G. P. ; Loriaux, Donald (Lynn) ; Tomita, M. ; Brandon, D. D. ; Renquist, D. ; Albertson, B. ; Lipsett, M. B. / The new world primates as animal models of glucocorticoid resistance. In: Advances in Experimental Medicine and Biology. 1986 ; Vol. 196. pp. 129-144.
@article{143c880b4d4e4a0e9446c6ae0bd43781,
title = "The new world primates as animal models of glucocorticoid resistance.",
abstract = "Many New World primate species have greatly increased plasma cortisol concentrations, decreased plasma cortisol binding globulin capacity and affinity, marked resistance of the hypothalamic-pituitary-adrenal axis to suppression by dexamethasone, and no biological evidence of glucocorticoid excess. These primates also have high levels of circulating progesterone, estrogen, mineralocorticoid, androgen and vitamin D. The glucocorticoid target tissues that have been examined (circulating mononuclear lymphocytes and cultured skin fibroblasts) have normal concentrations of glucocorticoid receptors with decreased affinity for dexamethasone. Transformation of B-lymphocytes with the Epstein-Barr virus leads to glucocorticoid receptor induction that is less than that observed with cells from Old World primates. The receptor in these cells has a low affinity for dexamethasone. The low affinity leads to an increased loss of specific bound ligand during thermal activation. Meroreceptor generation is normal. The molecular weight of the receptor, determined by SDS-PAGE, is similar to that of Old World primates (approximately 92,000) and the activation pattern per se, examined in vitro by heating cytosol and performing phosphocellulose chromatography, appears similar to that of human controls. The ratios of nuclear to cytosolic hormone-receptor-complexes and of cytosolic activated to unactivated receptor complexes in intact cells are similar to Old World primates. Results from mixing studies do not support the hypothesis that a binding inhibitor(s) or a deficient cytosolic positive modifier(s) of binding underlies the findings in these primates. The New World primates, unlike men with the syndrome of primary cortisol resistance, have compensated for their condition with intra-adrenal and mineralocorticoid receptor adaptations. Thus, unlike Old World primates, cortisol in New World primates has only weak sodium-retaining potency because the aldosterone receptor has a low affinity for cortisol. The common element that would explain the apparent resistance to six steroid hormones in New World primates remains unknown.",
author = "Chrousos, {G. P.} and Loriaux, {Donald (Lynn)} and M. Tomita and Brandon, {D. D.} and D. Renquist and B. Albertson and Lipsett, {M. B.}",
year = "1986",
language = "English (US)",
volume = "196",
pages = "129--144",
journal = "Advances in Experimental Medicine and Biology",
issn = "0065-2598",
publisher = "Springer New York",

}

TY - JOUR

T1 - The new world primates as animal models of glucocorticoid resistance.

AU - Chrousos, G. P.

AU - Loriaux, Donald (Lynn)

AU - Tomita, M.

AU - Brandon, D. D.

AU - Renquist, D.

AU - Albertson, B.

AU - Lipsett, M. B.

PY - 1986

Y1 - 1986

N2 - Many New World primate species have greatly increased plasma cortisol concentrations, decreased plasma cortisol binding globulin capacity and affinity, marked resistance of the hypothalamic-pituitary-adrenal axis to suppression by dexamethasone, and no biological evidence of glucocorticoid excess. These primates also have high levels of circulating progesterone, estrogen, mineralocorticoid, androgen and vitamin D. The glucocorticoid target tissues that have been examined (circulating mononuclear lymphocytes and cultured skin fibroblasts) have normal concentrations of glucocorticoid receptors with decreased affinity for dexamethasone. Transformation of B-lymphocytes with the Epstein-Barr virus leads to glucocorticoid receptor induction that is less than that observed with cells from Old World primates. The receptor in these cells has a low affinity for dexamethasone. The low affinity leads to an increased loss of specific bound ligand during thermal activation. Meroreceptor generation is normal. The molecular weight of the receptor, determined by SDS-PAGE, is similar to that of Old World primates (approximately 92,000) and the activation pattern per se, examined in vitro by heating cytosol and performing phosphocellulose chromatography, appears similar to that of human controls. The ratios of nuclear to cytosolic hormone-receptor-complexes and of cytosolic activated to unactivated receptor complexes in intact cells are similar to Old World primates. Results from mixing studies do not support the hypothesis that a binding inhibitor(s) or a deficient cytosolic positive modifier(s) of binding underlies the findings in these primates. The New World primates, unlike men with the syndrome of primary cortisol resistance, have compensated for their condition with intra-adrenal and mineralocorticoid receptor adaptations. Thus, unlike Old World primates, cortisol in New World primates has only weak sodium-retaining potency because the aldosterone receptor has a low affinity for cortisol. The common element that would explain the apparent resistance to six steroid hormones in New World primates remains unknown.

AB - Many New World primate species have greatly increased plasma cortisol concentrations, decreased plasma cortisol binding globulin capacity and affinity, marked resistance of the hypothalamic-pituitary-adrenal axis to suppression by dexamethasone, and no biological evidence of glucocorticoid excess. These primates also have high levels of circulating progesterone, estrogen, mineralocorticoid, androgen and vitamin D. The glucocorticoid target tissues that have been examined (circulating mononuclear lymphocytes and cultured skin fibroblasts) have normal concentrations of glucocorticoid receptors with decreased affinity for dexamethasone. Transformation of B-lymphocytes with the Epstein-Barr virus leads to glucocorticoid receptor induction that is less than that observed with cells from Old World primates. The receptor in these cells has a low affinity for dexamethasone. The low affinity leads to an increased loss of specific bound ligand during thermal activation. Meroreceptor generation is normal. The molecular weight of the receptor, determined by SDS-PAGE, is similar to that of Old World primates (approximately 92,000) and the activation pattern per se, examined in vitro by heating cytosol and performing phosphocellulose chromatography, appears similar to that of human controls. The ratios of nuclear to cytosolic hormone-receptor-complexes and of cytosolic activated to unactivated receptor complexes in intact cells are similar to Old World primates. Results from mixing studies do not support the hypothesis that a binding inhibitor(s) or a deficient cytosolic positive modifier(s) of binding underlies the findings in these primates. The New World primates, unlike men with the syndrome of primary cortisol resistance, have compensated for their condition with intra-adrenal and mineralocorticoid receptor adaptations. Thus, unlike Old World primates, cortisol in New World primates has only weak sodium-retaining potency because the aldosterone receptor has a low affinity for cortisol. The common element that would explain the apparent resistance to six steroid hormones in New World primates remains unknown.

UR - http://www.scopus.com/inward/record.url?scp=0022436665&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022436665&partnerID=8YFLogxK

M3 - Article

C2 - 3012975

AN - SCOPUS:0022436665

VL - 196

SP - 129

EP - 144

JO - Advances in Experimental Medicine and Biology

JF - Advances in Experimental Medicine and Biology

SN - 0065-2598

ER -