Characterization of R5020 (Promegestone) and RU486 (Mifepristone) binding to calf uterine progesterone receptor

Conference · Fri May 01 04:00:00 EDT 1987 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6156868

Hurd, C; Moudgil, V

The authors have examined and compared the binding characteristics of progesterone (P)-agonist R5020 (R5) and P antagonist RU486 (RU) in calf uterine cytosol. Both steroids bound to cytosol macromolecule(s) with high affinity and exhibited maximum specific binding when incubated at a 10-20 nM concentration. The binding of the steroids to the macromolecule(s) was rapid at 4C, showing saturation between 1-2 h for (TH)P and 2-4 h for (TH)R5 and (TH)RU. Although it took longer for (TH) -RU to occupy all the available sites in the cytosol than (TH)R5, once bound, dissociation of (TH)RU from its receptor was significantly slower. Competitive steroid binding analyses revealed that (TH)P, (TH)R5, and (TH)RU, competed for the same site(s) in the uterine cytosol, suggesting that all three steroids bind to the progesterone receptor (PR). Photoaffinity labeling in the presence of these steroids showed that (TH)R5 was associated specifically with a 116,000 Da peptide and to a lesser extent with a 97,000 Da peptide. (TH)RU was covalently linked mainly to a 97,000 Da peptide. In addition, both (TH)R5 and (TH)RU bind to a molecule that sediments in the 8S region in 8-30% glycerol gradients. The results of this study suggest that although there are some differences in the nature of their interaction with the PR, both R5 and RU bind to the same 8S PR in calf uterine cytosol.

• Research Organization: Oakland Univ., Rochester, MI
• OSTI ID: 6156868
• Report Number(s): CONF-870644-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 46:6
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
ALCOHOLS
ANIMALS
BIOCHEMICAL REACTION KINETICS
BODY
CALVES
CATTLE
DOMESTIC ANIMALS
FEMALE GENITALS
GLYCEROL
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LABELLING
MAMMALS
ORGANIC COMPOUNDS
ORGANS
REACTION KINETICS
RECEPTORS
RUMINANTS
STEROIDS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
UTERUS
VERTEBRATES