Androgen receptors in human synoviocytes and androgen regulation of interleukin 1beta (IL-1beta) induced IL-6 production: a link between hypoandrogenicity and rheumatoid arthritis?
OBJECTIVE
To investigate the hypothesis that synoviocytes possess androgen receptors (AR) that could be modulated by the non-aromatizable androgen, dihydrotestosterone (DHT), resulting in altered levels of inflammatory cytokines.


METHODS
Using molecular analyses of AR in combination with the multiprobe ribonuclease protection assay and ELISA, we investigated the presence of AR and the effect of DHT on interleukin 1beta (IL-1beta) induced expression of the IL-6 superfamily of cytokines in synoviocytes.


RESULTS
Our studies corroborate the presence of AR in synoviocytes. DHT exerts a suppressive effect on IL-1beta induced IL-6, macrophage-colony stimulating factor (CSF), and granulocyte-CSF production by synoviocytes. This modulatory effect is exerted at both the transcriptional and translational level; 17beta-estradiol, at high concentrations, had a stimulatory effect.


CONCLUSIONS
The identification of functional AR in synoviocytes and the modulatory effect of DHT on the inflammatory process in the joint suggest a direct link between hypoandrogenicity and rheumatoid arthritis (RA) disease status. Understanding the complex regulation of inflammatory cytokines by hormones may contribute to the development of new therapeutic targets for clinical intervention in RA.
Khalkhali-Ellis
Zhila
Z
Department of Anatomy and Cell Biology, University of Iowa, Iowa City 52242, USA. zhila-ellis@uiowa.edu
Handa
Robert J
RJ
Price
Richard H
RH
Adams
Brian D
BD
Callaghan
John J
JJ
Hendrix
Mary J C
MJ
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007006:Hypogonadism / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000032:analysis / Q000378:metabolism*; D008875:Middle Aged; D011336:Probability; D011944:Receptors, Androgen / Q000032:analysis / Q000378:metabolism*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism*
D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D011944:Receptors, Androgen; D013196:Dihydrotestosterone