Endocrine end-points in rheumatoid arthritis.
Our previous studies are reviewed and at the same time preliminary experimental observation to the topic of endocrine end-points in autoimmune disease is introduced. To this end, we have used rheumatoid arthritis (RA), including synovial fluids and primary cultures of synovial macrophages, as a model system in order to investigate (a) expression and subcellular localization of high-affinity sites of steroid binding in immune effector cells; (b) steroid metabolic profiles in both male and female RA patients, as compared to healthy subjects; and (c) activities of key steroid enzymes that govern intratissue accumulation of sex hormones. In RA tissues and cells, the concurrent evidence for (1) androgen and/or estrogen receptors, (2) high concentrations of biologically active steroids, (3) key enzymes of steroid metabolism, and (4) significant changes of estrogen to androgen ratio, all strongly suggests that individual immune cells, including synovial macrophages, may behave as steroid-sensitive cells, namely, they may represent a target for sex steroids, supporting the hypothesis of a potential endocrine regulation of the immune response also in RA disease. In this respect, definition of several endocrine end-points may have important implications for the treatment of rheumatic disease and other immunological disorders.
Castagnetta
L
L
Institute of Oncology, University Medical School, Palermo, Italy. lucashbl@unipa.it
Cutolo
M
M
Granata
O M
OM
Di Falco
M
M
Bellavia
V
V
Carruba
G
G
D000728:Androgens / Q000378:metabolism; D000818:Animals; D000917:Antibody Formation / Q000502:physiology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D004702:Endocrine Glands / Q000503:physiopathology*; D004967:Estrogens / Q000378:metabolism; D012739:Gonadal Steroid Hormones / Q000502:physiology; D006801:Humans; D011987:Receptors, Steroid / Q000378:metabolism; D013256:Steroids / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism
D000728:Androgens; D004967:Estrogens; D012739:Gonadal Steroid Hormones; D011987:Receptors, Steroid; D013256:Steroids