Fiche publication
Date publication
mars 1992
Journal
The Journal of steroid biochemistry and molecular biology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GRONEMEYER Hinrich
,
Dr METZGER Daniel
,
Dr TORA Laszlo
,
Mr LEROUGE Thierry
Tous les auteurs :
Gronemeyer H, Benhamou B, Berry M, Bocquel MT, Gofflo D, Garcia T, Lerouge T, Metzger D, Meyer ME, Tora L
Lien Pubmed
Résumé
The mechanisms of action of two types of anti-hormones is discussed. Type I anti-hormones comprise the antiestrogen hydroxy-tamoxifen and the antiprogestin RU486, both of which promote DNA binding of the cognate receptors and, due to the activity of one of the two transcription activation functions of the estrogen and progesterone receptors, act as mixed agonist/antagonists. Evidence supporting that ICI 164,384 is also a member of the same group is presented. Type II antagonists impair DNA binding of the corresponding receptor in vitro and, in some cases, also in vivo. Ligand-mapping, an approach to identify the site of interaction of a steroid substitution within the hormone-binding domain of the receptor has been used to identify the 11 beta-pocket of the progesterone receptor and revealed that a single amino acid is responsible for the differential antagonistic effect of RU486 in man, chicken and hamster.
Mots clés
Animals, DNA-Binding Proteins, antagonists & inhibitors, Estradiol, analogs & derivatives, Estrogen Antagonists, pharmacology, Humans, Mifepristone, pharmacology, Polyunsaturated Alkamides, Progestins, antagonists & inhibitors, Receptors, Estrogen, drug effects, Receptors, Progesterone, drug effects, Receptors, Steroid, drug effects
Référence
J. Steroid Biochem. Mol. Biol.. 1992 Mar;41(3-8):217-21
