Intraarticular progesterone inhibits 3H-dexamethasone binding to synovial cells from patients with rheumatoid arthritis. A study by dry radioautographic technique.
Glucocorticoids are known to exert their antiinflammatory effects through an interaction with specific hormone receptors. Progesterone is able to bind to these glucocorticoid receptors exerting either agonistic or antagonistic actions. We have reported that a single intraarticular injection of progesterone exerts a local antiinflammatory action in patients with rheumatoid arthritis (RA), suggesting an agonistic effect of progesterone on local glucocorticoid receptors. To corroborate this possible mechanism of action, we investigated the binding of 3H-dexamethasone to local glucocorticoid receptors in synovial tissue from 3 patients with active RA, before and 14 days after a single intraarticular injection of progesterone. Both cytoplasmic and nuclear 3H-dexamethasone binding sites were observed within synoviocytes, macrophages, fibroblasts, lymphocytes and endothelial cells. Dry radioautograms of biopsied synovial tissue demonstrated a marked decrease of 3H-dexamethasone binding following progesterone treatment in all patients (p less than 0.001 for each comparison). Although the number of cases is not large enough to draw definitive conclusions, our data confirm the marked anti-inflammatory effect of intraarticular progesterone and support the hypothesis of an agonistic effect of progesterone (or its metabolites) on glucocorticoid receptors.
Department of Medicine, Clinical Hospital, J.J. Aguirre, University of Chile, Santiago.
M
M
Cuchacovich
R
R
Wurgaft
M A
MA
Mena
C
C
Valenzuela
H
H
Gatica
A N
AN
Tchernitchin
D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D001345:Autoradiography / Q000379:methods; D001706:Biopsy; D003907:Dexamethasone / Q000378:metabolism*; D006801:Humans; D007270:Injections, Intra-Articular; D011374:Progesterone / Q000494:pharmacology*; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology; D014316:Tritium
D014316:Tritium; D011374:Progesterone; D003907:Dexamethasone