Binding of steroids to the progestin and glucocorticoid receptors analyzed by correspondence analysis

Abstract

The relative binding affinities of over 30 steroids have been measured for the cytosol glucocorticoid receptor (GR) of thymus, liver, and hepatoma tissue culture cells and for progestin, androgen, and mineralocorticoid receptors. The data have been analyzed by correspondence analysis to reveal the singularities among the receptors of different hormonal classes, the similarities in GR of different origins, and the different specificities of the ligands. Additional data on new steroids have been injected into the system as well as results on a further parameter, namely the induction of tyrosine aminotransferase (TAT) activity, to illustrate the power and flexibility of the methodology. The analysis has confirmed previous correlations between GR binding and TAT response but also highlighted the antiglucocorticoid activity of progestins. This method should prove to be a substantial aid to the interpretation of increasingly complex data, in particular with regard to the action of existing and newly synthesized steroids on glucocorticoid systems of differential sensitivity.

Differences in the glucocorticoid to progesterone receptor selectivity of inhaled glucocorticoids

“…The present study investigated a wide range of clinically employed glucocorticoids for their binding to the GR and PR and assessed their selectivity. GR affinities determined in the current study were in agreement with previously published work for the human and rat GR [1,5,[13][14][15][16][17].…”

“…RAYNAUD and coworkers [1,14] showed that synthetic glucocorticoids, such as TAA and fluocinolone acetonide, have the ability to bind to the PR indicating low GR selectivity. Recently, cellbased functional assays conducted by AUSTIN et al [4] have shown that MF interacts with the PR as an agonist, with much higher activity than FP.…”

Genetic Recombination as a Reporter for Screening Steroid Receptor Agonists and Antagonists

“…4A). These results are consistent with the relative binding affinities of these steroids for GR (17) and show that the Cre system can accurately rank the relative binding affinities of receptor ligands, regardless of their agonist or antagonist effects.…”

PA1 Protein, a New Competitive Decelerator Acting at More than One Step to Impede Glucocorticoid Receptor-mediated Transactivation

“…However, abundant evidence over the last decade indicates that neither the EC 50 nor the A max of gene expression regulated by GRs (and other members of the steroid receptor superfamily) is constant, and both can be tuned like a rheostat by various transcriptional coactivators, corepressors, and comodulators without changing the identity of the bound steroid (6,8,9). In addition, the sub-maximal activity of antiglucocorticoids is not invariant as was originally proposed (10). Most antisteroids display some residual or partial agonist activity (PAA), and most of the cofactors that alter the A max and EC 50 also modulate the PAA of antisteroids (6,8,9,11).…”