title: Progesterone-binding site of adult male rat liver microsomes.
abstract: We investigated in greater detail the relationship between steroid structures and their binding affinities to the microsomal progesterone-binding site of the adult male rat liver. Only six steroids of the 100 compounds tested, namely, progesterone, 3 alpha-hydroxy-5 alpha-pregnan-20-one, 3 alpha,11 beta-dihydroxy-5 alpha-pregnan-20-one, 5 alpha-pregnane-3,20-dione, pregnenolone, and pregnenolone-3-sulfate, had high binding affinities to this site. Thus, we were able to draw a conclusion on the steroid structure which should be required for the best interaction with this site. That is, regardless of the whole molecule's lipophilicity, such a steroid should possess not only a planar A-B ring configuration but also the same side chains as progesterone with C-17 beta-acetyl and non-hydroxyl groups. The exception to this are hydrophilic C-3 groups, which may somewhat increase binding affinities in some cases. We compared the steroid specificity of this binding site with those of various other progesterone-binding components. As a result, this site appears to be a novel type of progesterone binder. We, furthermore, examined the relationship between this microsomal progesterone-binding site and the microsomal progesterone-metabolizing activity. The results, although preliminary, suggest that this binding site does not participate universally in the progesterone-metabolizing processes.
authors.affiliation: Department of Pathology, Hyogo College of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yamada
authors.forename: K
authors.initials: K
authors.lastname: Indo
authors.forename: T
authors.initials: T
authors.lastname: Nishigami
authors.forename: K
authors.initials: K
authors.lastname: Nakasho
authors.forename: H
authors.initials: H
authors.lastname: Miyaji
mesh_terms: D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D003022:Clotrimazole / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D008968:Molecular Conformation; D011278:Pregnanes / Q000378:metabolism; D011283:Pregnenes / Q000378:metabolism; D011284:Pregnenolone / Q000031:analogs & derivatives / Q000378:metabolism; D011374:Progesterone / Q000031:analogs & derivatives / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D011278:Pregnanes; D011283:Pregnenes; D011374:Progesterone; D011284:Pregnenolone; D003577:Cytochrome P-450 Enzyme System; D003022:Clotrimazole