Modulators of the glucocorticoid receptor also regulate mineralocorticoid receptor function

Journal Article · Mon Feb 17 23:00:00 EST 1992 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00121a022· OSTI ID:5559667

Schulman, G ^[1]; Bodine, P V; Litwack, G ^[2]

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1. Temple Univ., Philadelphia, PA (United States)
2. Fels Inst. for Cancer Research and Molecular Biology, Philadelphia, PA (United States)

Modulators are proposed to be novel ether aminophosphoglycerides that stabilize unoccupied and occupied glucocorticoid receptor steroid binding and inhibit glucocorticoid receptor complex activation. Two isoforms, modulator 1 and modulator 2, have been purified from rat liver cytosol. Since the mineralocorticoid receptor is relatively resistant to activation, modulator's effect on rat distal colon mineralocorticoid receptor is relatively resistant to activation, modulator's effect on rat distal colon mineralocorticoid receptor function was examined. Double-reciprocal analysis showed linear kinetics, and mixing modulator isoforms together had additive effects on unoccupied and occupied receptor steroid binding stabilization and activation inhibition. Colon cytosol contained a low molecular weight, heat-stable factor(s) which inhibited receptor activation and stabilized occupied receptor steroid binding. Molybdate completely stabilized unoccupied mineralocorticoid receptor steroid binding and inhibited activation with half-maximal effects at 3-4 mM but only stabilized occupied receptor binding by {approximately}40%. These data indicate that (1) apparent physiologic concentrations of modulator stabilize mineralocorticoid receptor steroid binding and inhibit receptor activation, (2) an aldosterone-responsive tissue contains a modulator-like activity, and (3) molybdate mimics the effects of modulator.

• OSTI ID: 5559667
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Journal Issue: 6 Vol. 31:6; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADRENAL HORMONES
ALDEHYDES
ALDOSTERONE
BIOCHEMICAL REACTION KINETICS
CORTICOSTEROIDS
DOSE-RESPONSE RELATIONSHIPS
GLUCOCORTICOIDS
HORMONES
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KETONES
KINETICS
MEMBRANE PROTEINS
MINERALOCORTICOIDS
NUCLEOPROTEINS
ORGANIC COMPOUNDS
PREGNANES
PROTEINS
RADIORECEPTOR ASSAY
REACTION KINETICS
RECEPTORS
STEROID HORMONES
STEROIDS
TRACER TECHNIQUES
TRANSCRIPTION FACTORS