DNA slows dissociation of progesterone receptor-steroid ligand complexes |
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Authors: | Pokrovskaya E V Levina I S Kamernitsky A V Shevchenko V P Smirnov A N |
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Affiliation: | Laboratory of Endocrinology, School of Biology, Moscow Lomonosov State University, Lenin Hills 1/12, Moscow 119899, Russia. |
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Abstract: | 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 [3H]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 approximately 16alpha,17alpha-cyclopentanoprogesterone>/=16alpha,17alpha-cyclohex-2'-enoprogesterone approximately 6alpha-methyl-16alpha,17alpha-cyclohexanoprogesterone>/=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. |
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Keywords: | Progesterone receptor Progesterone 16α,17α-cycloalkane derivatives Hormone response element Steroid binding kinetics |
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