Cytoplasmic glucocorticoid binding proteins in bone cells

David Feldman*, Rosemary Dziak, Ronald Koehler, Paula Stern

*Corresponding author for this work

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

The binding of 3H-dexamethasone (3H-DM) was studied in the cytoplasmic fraction of bone cells isolated from fetal rat calvaria by enzymatic digestion. An high-affinity glucocorticoid binding protein resembling those described in other target tissues was demonstrated. Scatchard analysis revealed a single class of binding sites with an apparent dissociationconstant for 3H-DM (0 C) of 7 × 10−9M and a concentration of binding sites of 0.11 pmoles/mg cytosol protein. The number of cytoplasmic binding sites per cell was calculated at 6,000 which is probably an underestimate due to occupancy of some sites by endogenous steroids. The binding sites appeared protein in nature since incubation with pronase destroyed 100% of the binding. Nuclear transfer was demonstrated in a reconstituted system utilizing bone cytosol as donor and liver nuclei as the acceptor. Competitive binding analysis revealed corticosterone to be equivalent to DM in binding affinity; progesterone was 75% as potent as DM. Aldosterone and SC-26304 (a spirolactone analogue) had, respectively, ¼ and 1/10the potency of DM while testosterone and estradiol exhibited minimal competitive ability. Vitamin A, vitamin D3 and 25-OH vitamin D3 failed to compete at a concentration ratio of 100:1 while cortexolone competed for 80% of the binding sites under these conditions. The findingof presumed glucocorticoid receptors suggests a direct action by this class of hormones on bone. Although the physiological functions mediated by these receptors remain to be elucidated, the general catabolic effect of glucocorticoids on connective tissue suggests a possible role for these receptors in glucocorticoid-induced osteoporosis.

Original languageEnglish (US)
Pages (from-to)29-36
Number of pages8
JournalEndocrinology
Volume96
Issue number1
DOIs
StatePublished - Jan 1975

ASJC Scopus subject areas

  • Endocrinology

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