Pregna-D'-pentarane structure influences progesterone receptor affinity for DNA.
Electrophoretic mobility shift assay was used to determine whether pregna-D'-pentaranes allow progesterone receptor (PR) from rat uterine cytosol to bind hormone response element (HRE)-containing oligonucleotide duplexes and to measure the affinity of this interaction. The formation of DNA-protein complexes in low salt medium was progesterone-related ligand-, temperature-, and PR-dependent, and specific for HRE. The highest affinity of PR to DNA (equilibrium K(a) = 0.420 +/- 0.185 nM(-1)) was found in the presence of the partial agonist/antagonist RU486, while the lowest affinity (K(a) = 0.074 +/- 0.013 nM(-1)) was demonstrated with the full agonist 6alpha-methyl-16alpha,17alpha-cyclohexanoprogesterone. With the exception of the strong full agonist R5020, there was a tendency toward correlation between the induced lower affinity of PR for DNA in the context of tyrosine aminotransferase HRE and the full agonistic activity of tested compounds.
Shchelkunova
T A
TA
Lab. of Endocrinology, School of Biology, Moscow Lomonosov State University, Lenin Hills 1/12, 119899 Moscow, Russia.
Rubtsov
P M
PM
Levina
I S
IS
Kamerntsky
A V
AV
Smirnov
A N
AN
D000818:Animals; D001665:Binding Sites; D003600:Cytosol; D004247:DNA / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D007700:Kinetics; D015394:Molecular Structure; D011374:Progesterone / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D017208:Rats, Wistar; D011980:Receptors, Progesterone / Q000378:metabolism*; D020218:Response Elements; D015533:Transcriptional Activation; D014444:Tyrosine Transaminase / Q000235:genetics / Q000378:metabolism; D014599:Uterus / Q000378:metabolism
D017931:DNA Primers; D011980:Receptors, Progesterone; D011374:Progesterone; D004247:DNA; D014444:Tyrosine Transaminase