Alterations in specificity of the glucocorticoid receptor with temperature in rat splenic lymphocytes

Richard G. MacDonald, John A. Cidlowski

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Rat splenic lymphocytes contain specific, saturable glucocorticoid receptors. When suspensions of these cells are incubated at 0°C in the presence of [3H]-triamcinolone acetonide ([3H]-TA). 80% of receptor-bound steroid is found associated with the cytoplasm, whereas at 37°C, 80% of [3H]-TA binding is associated with the nucleus. The equilibrium dissociation constant for interaction of [3H]-TA with the cytoplasmic receptor at 0°C is 5.6 nM while that for nuclear binding at 37°C is 0.85 nM, suggesting an increase in receptor affinity for [3H]-TA at physiological temperatures. Specificity studies show a high degree of glucocorticoid specificity at 37°C both in cytoplasm and nucleus, with little competition observed for either progesterone (P) or cortexolone (S). At 0°C, however, P and S compete with [3H]-TA for receptor binding as effectively as dexamethasone. Estradiol-17β, testosterone, 5α-dihydrotestosterone and cortisone do not compete under any of these conditions. When cells are incubated at 0°C in the presence of 0.02 μM [3H]-TA and concentrations of P and S ranging from 0.04 to 2.56 μM, [3H]-TA binding is inhibited at steroid concentrations as low as 0.1 μM. If these same cells are then warmed to 37°C [3H]-TA binding in cytoplasm and nucleus is inhibited only at P and S concentrations ≥ 1 μM. Thus, there is, concomitant with increasing temperature, an increase in affinity and specificity of the receptor for active glucocorticoids. This specificity change is regarded as evidence for a conformational change in the hormone-receptor complex coincident with activation.

Original languageEnglish (US)
Pages (from-to)21-29
Number of pages9
JournalJournal of Steroid Biochemistry
Volume10
Issue number1
DOIs
StatePublished - Jan 1979
Externally publishedYes

Fingerprint

Lymphocytes
Glucocorticoid Receptors
Glucocorticoids
Rats
Cytoplasm
Steroids
Cortodoxone
Triamcinolone Acetonide
Temperature
Dihydrotestosterone
Cortisone
Cytoplasmic and Nuclear Receptors
Dexamethasone
Progesterone
Testosterone
Estradiol
Suspensions
Steroid Receptors
Chemical activation
Hormones

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

Alterations in specificity of the glucocorticoid receptor with temperature in rat splenic lymphocytes. / MacDonald, Richard G.; Cidlowski, John A.

In: Journal of Steroid Biochemistry, Vol. 10, No. 1, 01.1979, p. 21-29.

Research output: Contribution to journalArticle

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