[Antagonist and agonist effects of the antiprogesterone RU 486].
The mechanism of action of the antihormone substances, and more particularly of RU 486 antiprogesterone, is still poorly understood. The antagonist effect may take place at the receptor site while the latter is in its 8S inactive form. The antihormone blocks the heat shock protein 90 (HSP 90) and prevents the receptor from changing into its 4S active form, solely capable of binding the DNA-specific hormone responding element (HRE). However, if the antihormone does not impede receptor 4S activation, the antagonist effect may be explained by insufficient HRE affinity. Another possibility would be that the antihormone-4S receptor complex becomes chromatin-bound, although no bond is formed at the HRE-specific site. A certain affinity for HRE would explain the agonist effect of the antihormones. An affinity for DNA, outside HRE, would explain some specific activities peculiar to the antihormone. RU 486, which is both an antiprogesterone and an antiglucocorticoid substance, exhibits some powerful antagonistic characteristics. When neither progesterone nor cortisol is available, RU 486 displays weak agonistic effects. It can, therefore, serve as a good experimental model from which to study the mode of action of the antihormones.
Schaison
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Service d'Endocrinologie et des maladies de la reproduction, Hôpital de Bicêtre, Le Kremlin Bicêtre.
D000818:Animals; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology*; D011374:Progesterone / Q000037:antagonists & inhibitors; D011372:Progestins / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D011980:Receptors, Progesterone / Q000378:metabolism
D006360:Heat-Shock Proteins; D011372:Progestins; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D015735:Mifepristone; D011374:Progesterone
Effets antagonistes et agonistes de l'antiprogestérone RU 486.