The progesterone receptor. Biological effects of progestins and antiprogestins.
The progesterone receptor displays the typical three-domains structure of the steroid-thyroid receptor family. The central domain contains two 'zinc finger' structures responsible for the specific recognition of the cognate DNA sequences. The carboxy-terminal domain contains the hormone and anti-hormone binding site. Progesterone and synthetic progestins (R5020, Org 2058) activate the receptor, provoke its phosphorylation and DNA-binding ability and induce its regulatory activities. The antagonist RU38486 elicits the same sequence of events but leads to an abortive conclusion without specific gene transactivation. The progesterone receptor is down-regulated by its own ligand at the transcriptional level through inhibition of oestrogen receptor-mediated induction through protein-protein interactions. This mechanism is also inhibited by RU38486.
Savouret
J F
JF
Institut National de la Santé et de la Recherche Médicale, Unité 135, Hôpital de Bicêtre, France.
Chauchereau
A
A
Misrahi
M
M
Lescop
P
P
Mantel
A
A
Bailly
A
A
Milgrom
E
E
D000818:Animals; D001665:Binding Sites; D004247:DNA / Q000378:metabolism; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D010766:Phosphorylation; D011372:Progestins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011817:Rabbits; D011980:Receptors, Progesterone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000187:drug effects*; D015533:Transcriptional Activation; D016335:Zinc Fingers
D011372:Progestins; D011980:Receptors, Progesterone; D004247:DNA