DNA slows dissociation of progesterone receptor-steroid ligand complexes

Steroid ligands are known to affect the interactions of their respective receptors with DNA. In the present study, the possibility of DNA interference in progesterone receptor-ligand interactions was investigated. An oligonucleotide containing a hormone response element (HRE) was shown to decrease the dissociation rate of complexes of [H-3]progesterone or [3H]16alpha,17alpha-cycloalkanoprogesterones with PRs from rabbit and rat uterine cytosol. The extent to which the oligonucleotide affected the dissociation constant varied from about 4- to 1.5-fold depending on the ligand structure and was ranked in the following order: progesterone > 16alpha,17alpha-cyclopropanoprogesterone similar to 16alpha,17alpha-cyclopentanoprogesterone greater than or equal to 16alpha,17alpha-cyclohex-2'-enoprogesterone similar to 6alpha-methyl-16alpha,17alpha-cyclohexanoprogesterone greater than or equal to 16alpha, 17alpha-cyclohexanoprogesterone. The control oligonucleotide lacking HRE had a weak effect, if any, on the dissociation kinetics. No influence of the HRE-containing oligonucleotide on the equilibrium binding of ligands to PR was observed. The results suggest that the DNA partner affects binding of PR to its ligand. (C) 2003 Elsevier Science Inc. All rights reserved.