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 [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.
Pokrovskaya
E V
EV
Laboratory of Endocrinology, School of Biology, Moscow Lomonosov State University, Lenin Hills 1/12, Moscow 119899, Russia.
Levina
I S
IS
Kamernitsky
A V
AV
Shevchenko
V P
VP
Smirnov
A N
AN
D000818:Animals; D001483:Base Sequence; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D008024:Ligands; D009841:Oligonucleotides / Q000235:genetics / Q000494:pharmacology; D011374:Progesterone / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism; D011372:Progestins / Q000737:chemistry / Q000378:metabolism; D011817:Rabbits; D011869:Radioligand Assay; D051381:Rats; D011980:Receptors, Progesterone / Q000737:chemistry* / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D014316:Tritium; D014599:Uterus / Q000378:metabolism
D008024:Ligands; D009841:Oligonucleotides; D011372:Progestins; D011980:Receptors, Progesterone; D014316:Tritium; D011374:Progesterone; D004247:DNA