Document Detail

Characterization of R5020 and RU486 binding to progesterone receptor from calf uterus.
MedLine Citation:
PMID:  3408715     Owner:  NLM     Status:  MEDLINE    
We have examined and compared the binding characteristics of the progesterone agonist R5020 [promegestone, 17,21-dimethylpregna-4,9(10)-diene-3,20-dione] and the progesterone antagonist RU486 [mifepristone, 17 beta-hydroxy-11 beta-[4-(dimethylamino) phenyl]-17 alpha-(prop-1-ynyl)-estra-4,9-dien-3-one] in calf uterine cytosol. Both steroids bound cytosol macromolecule(s) with high affinity, exhibiting Kd values of 5.6 and 3.6 nM for R5020 and RU486 binding, respectively. The binding of the steroids to the macromolecule(s) was rapid at 4 degrees C, showing saturation of binding sites at 1-2 h for [3H]progesterone and 2-4 h for both [3H]R5020 and [3H]RU486. Addition of molybdate and glycerol to cytosol increased the extent of [3H]R5020 binding. The extent of [3H]RU486 binding remained unchanged in the presence of molybdate, whereas glycerol had an inhibitory effect. Molybdate alone or in combination with glycerol stabilized the [3H]R5020- and [3H]RU486-receptor complexes at 37 degrees C. Although the rate of association of [3H]RU486 with the cytosolic macromolecule was slower than that of [3H]R5020, its dissociation from the ligand-macromolecule complex was significantly slower than [3H]R5020. Competitive steroid binding analysis revealed that [3H]progesterone, [3H]R5020, and [3H]RU486 compete for the same site(s) in the uterine cytosol, suggesting that all three bind to the progesterone receptor (PR). Sedimentation rate analysis showed that both steroids were bound to a molecule that sediments in the 8S region. The 8S [3H]R5020 and [3H]RU486 peaks were abolished by excess radioinert progesterone, RU486, or R5020.(ABSTRACT TRUNCATED AT 250 WORDS)
C Hurd; V K Moudgil
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochemistry     Volume:  27     ISSN:  0006-2960     ISO Abbreviation:  Biochemistry     Publication Date:  1988 May 
Date Detail:
Created Date:  1988-10-11     Completed Date:  1988-10-11     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3618-23     Citation Subset:  IM    
Department of Biological Sciences, Oakland University, Rochester, Michigan 48309-4401.
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MeSH Terms
Cytosol / metabolism
Estrenes / metabolism*
Glycerol / pharmacology
Molybdenum / pharmacology
Norpregnadienes / metabolism*
Progestins / antagonists & inhibitors
Promegestone / metabolism*
Receptors, Progesterone / drug effects,  isolation & purification,  metabolism*
Uterus / metabolism*
Grant Support
Reg. No./Substance:
0/Estrenes; 0/Norpregnadienes; 0/Progestins; 0/Receptors, Progesterone; 14259-85-9/molybdate; 34184-77-5/Promegestone; 56-81-5/Glycerol; 7439-98-7/Molybdenum; 84371-65-3/Mifepristone

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