Abstract
The presence of androgen receptors on synovial macrophages in human normal and rheumatoid synovial tissues has been described previously. It is now reported that primary cultured human macrophages obtained from normal and rheumatoid synovia express functional androgen receptors. We have investigated the capacity of cultured macrophages to metabolize androgens and have found that these cells were capable of metabolizing testosterone to the bioactive metabolite dihydrotestosterone. Therefore, macrophages contain the key enzymes of steroidogenesis, in particular the 5α-treductase. Furthermore, interleukin-1β production by primary cultured rheumatoid macrophages was analysed, following exposure to physiological concentrations of testosterone (10−8 M). A significant decrease of IL-1β levels in conditioned media after 24 h (p < 0.05) was observed. It is concluded that androgens may act directly on human macrophages and may interfere with some of their functions via receptor-dependent mechanisms.
Full Text
The Full Text of this article is available as a PDF (1.1 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arnett F. C., Edworthy S. M., Bloch D. A., McShane D. J., Fries J. F., Cooper N. S., Healey L. A., Kaplan S. R., Liang M. H., Luthra H. S. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. doi: 10.1002/art.1780310302. [DOI] [PubMed] [Google Scholar]
- Bijlsma J. W., Van den Brink H. R. Estrogens and rheumatoid arthritis. Am J Reprod Immunol. 1992 Oct-Dec;28(3-4):231–234. doi: 10.1111/j.1600-0897.1992.tb00800.x. [DOI] [PubMed] [Google Scholar]
- Bizzarro A., Valentini G., Di Martino G., DaPonte A., De Bellis A., Iacono G. Influence of testosterone therapy on clinical and immunological features of autoimmune diseases associated with Klinefelter's syndrome. J Clin Endocrinol Metab. 1987 Jan;64(1):32–36. doi: 10.1210/jcem-64-1-32. [DOI] [PubMed] [Google Scholar]
- Carruba G., Leake R. E., Rinaldi F., Chalmers D., Comito L., Sorci C., Pavone-Macaluso M., Castagnetta L. A. Steroid-growth factor interaction in human prostate cancer. 1. Short-term effects of transforming growth factors on growth of human prostate cancer cells. Steroids. 1994 Jul;59(7):412–420. doi: 10.1016/0039-128x(94)90010-8. [DOI] [PubMed] [Google Scholar]
- Castagnetta L. A., Granata O. M., Lo Casto M., Calabró M., Arcuri F., Carruba G. Simple approach to measure metabolic pathways of steroids in living cells. J Chromatogr. 1991 Dec 6;572(1-2):25–39. doi: 10.1016/0378-4347(91)80470-w. [DOI] [PubMed] [Google Scholar]
- Castagnetta L., Granata O. M., Polito L., Blasi L., Cannella S., Carruba G. Different conversion metabolic rates of testosterone are associated to hormone-sensitive status and -response of human prostate cancer cells. J Steroid Biochem Mol Biol. 1994 Jun;49(4-6):351–357. doi: 10.1016/0960-0760(94)90279-8. [DOI] [PubMed] [Google Scholar]
- Chang C. S., Whelan C. T., Popovich T. C., Kokontis J., Liao S. T. Fusion proteins containing androgen receptor sequences and their use in the production of poly- and monoclonal anti-androgen receptor antibodies. Endocrinology. 1989 Aug;125(2):1097–1099. doi: 10.1210/endo-125-2-1097. [DOI] [PubMed] [Google Scholar]
- Cohen J. H., Danel L., Cordier G., Saez S., Revillard J. P. Sex steroid receptors in peripheral T cells: absence of androgen receptors and restriction of estrogen receptors to OKT8-positive cells. J Immunol. 1983 Dec;131(6):2767–2771. [PubMed] [Google Scholar]
- Crawford D., Cowan S., Hyder S., McMenamin M., Smith D., Leake R. New storage procedure for human tumor biopsies prior to estrogen receptor measurement. Cancer Res. 1984 Jun;44(6):2348–2351. [PubMed] [Google Scholar]
- Cutolo M., Accardo S. Sex hormones, HLA and rheumatoid arthritis. Clin Exp Rheumatol. 1991 Nov-Dec;9(6):641–646. [PubMed] [Google Scholar]
- Cutolo M., Accardo S., Villaggio B., Clerico P., Bagnasco M., Coviello D. A., Carruba G., lo Casto M., Castagnetta L. Presence of estrogen-binding sites on macrophage-like synoviocytes and CD8+, CD29+, CD45RO+ T lymphocytes in normal and rheumatoid synovium. Arthritis Rheum. 1993 Aug;36(8):1087–1097. doi: 10.1002/art.1780360809. [DOI] [PubMed] [Google Scholar]
- Cutolo M., Accardo S., Villaggio B., Clerico P., Indiveri F., Carruba G., Fecarotta E., Castagnetta L. Evidence for the presence of androgen receptors in the synovial tissue of rheumatoid arthritis patients and healthy controls. Arthritis Rheum. 1992 Sep;35(9):1007–1015. doi: 10.1002/art.1780350905. [DOI] [PubMed] [Google Scholar]
- Cutolo M., Balleari E., Giusti M., Intra E., Accardo S. Androgen replacement therapy in male patients with rheumatoid arthritis. Arthritis Rheum. 1991 Jan;34(1):1–5. doi: 10.1002/art.1780340102. [DOI] [PubMed] [Google Scholar]
- Cutolo M., Balleari E., Giusti M., Monachesi M., Accardo S. Sex hormone status in women suffering from rheumatoid arthritis. J Rheumatol. 1986 Dec;13(6):1019–1023. [PubMed] [Google Scholar]
- Cutolo M., Balleari E., Giusti M., Monachesi M., Accardo S. Sex hormone status of male patients with rheumatoid arthritis: evidence of low serum concentrations of testosterone at baseline and after human chorionic gonadotropin stimulation. Arthritis Rheum. 1988 Oct;31(10):1314–1317. doi: 10.1002/art.1780311015. [DOI] [PubMed] [Google Scholar]
- Ettinger B., Genant H. K., Cann C. E. Long-term estrogen replacement therapy prevents bone loss and fractures. Ann Intern Med. 1985 Mar;102(3):319–324. doi: 10.7326/0003-4819-102-3-319. [DOI] [PubMed] [Google Scholar]
- Goemaere S., Ackerman C., Goethals K., De Keyser F., Van der Straeten C., Verbruggen G., Mielants H., Veys E. M. Onset of symptoms of rheumatoid arthritis in relation to age, sex and menopausal transition. J Rheumatol. 1990 Dec;17(12):1620–1622. [PubMed] [Google Scholar]
- Grossman C. J., Sholiton L. J., Helmsworth J. A. Characteristics of the cytoplasmic and nuclear dihydrotestosterone receptors of human thymic tissue. Steroids. 1983 Jul;42(1):11–22. doi: 10.1016/s0039-128x(83)90048-x. [DOI] [PubMed] [Google Scholar]
- Grossman C. Possible underlying mechanisms of sexual dimorphism in the immune response, fact and hypothesis. J Steroid Biochem. 1989;34(1-6):241–251. doi: 10.1016/0022-4731(89)90088-5. [DOI] [PubMed] [Google Scholar]
- Harris E. D., Jr Rheumatoid arthritis. Pathophysiology and implications for therapy. N Engl J Med. 1990 May 3;322(18):1277–1289. doi: 10.1056/NEJM199005033221805. [DOI] [PubMed] [Google Scholar]
- Kay C. R., Wingrave S. J. Oral contraceptives and rheumatoid arthritis. Lancet. 1983 Jun 25;1(8339):1437–1437. doi: 10.1016/s0140-6736(83)92378-4. [DOI] [PubMed] [Google Scholar]
- Koch A. E., Kunkel S. L., Harlow L. A., Mazarakis D. D., Haines G. K., Burdick M. D., Pope R. M., Strieter R. M. Macrophage inflammatory protein-1 alpha. A novel chemotactic cytokine for macrophages in rheumatoid arthritis. J Clin Invest. 1994 Mar;93(3):921–928. doi: 10.1172/JCI117097. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lahita R. G. Sex steroids and the rheumatic diseases. Arthritis Rheum. 1985 Feb;28(2):121–126. doi: 10.1002/art.1780280202. [DOI] [PubMed] [Google Scholar]
- Li Z. G., Danis V. A., Brooks P. M. Effect of gonadal steroids on the production of IL-1 and IL-6 by blood mononuclear cells in vitro. Clin Exp Rheumatol. 1993 Mar-Apr;11(2):157–162. [PubMed] [Google Scholar]
- Lindblad S., Wredmark T. Traumatic synovitis analysed by arthroscopy and immunohistopathology. Br J Rheumatol. 1990 Dec;29(6):422–425. doi: 10.1093/rheumatology/29.6.422. [DOI] [PubMed] [Google Scholar]
- Masi A. T. Incidence of rheumatoid arthritis: do the observed age-sex interaction patterns support a role of androgenic-anabolic steroid deficiency in its pathogenesis? Br J Rheumatol. 1994 Aug;33(8):697–699. doi: 10.1093/rheumatology/33.8.697. [DOI] [PubMed] [Google Scholar]
- Ollier W., Spector T., Silman A., Perry L., Ord J., Thomson W., Festenstein H. Are certain HLA haplotypes responsible for low testosterone levels in males? Dis Markers. 1989 Jul-Sep;7(3):139–143. [PubMed] [Google Scholar]
- Polan M. L., Loukides J., Nelson P., Carding S., Diamond M., Walsh A., Bottomly K. Progesterone and estradiol modulate interleukin-1 beta messenger ribonucleic acid levels in cultured human peripheral monocytes. J Clin Endocrinol Metab. 1989 Dec;69(6):1200–1206. doi: 10.1210/jcem-69-6-1200. [DOI] [PubMed] [Google Scholar]
- Schuurs A. H., Verheul H. A. Effects of gender and sex steroids on the immune response. J Steroid Biochem. 1990 Feb;35(2):157–172. doi: 10.1016/0022-4731(90)90270-3. [DOI] [PubMed] [Google Scholar]
- Sthoeger Z. M., Chiorazzi N., Lahita R. G. Regulation of the immune response by sex hormones. I. In vitro effects of estradiol and testosterone on pokeweed mitogen-induced human B cell differentiation. J Immunol. 1988 Jul 1;141(1):91–98. [PubMed] [Google Scholar]
- Talal N. Autoimmunity and sex revisited. Clin Immunol Immunopathol. 1989 Dec;53(3):355–357. doi: 10.1016/0090-1229(89)90001-9. [DOI] [PubMed] [Google Scholar]
- Tsoukas C. D., Provvedini D. M., Manolagas S. C. 1,25-dihydroxyvitamin D3: a novel immunoregulatory hormone. Science. 1984 Jun 29;224(4656):1438–1440. doi: 10.1126/science.6427926. [DOI] [PubMed] [Google Scholar]
- Zava D. T., McGuire W. L. Androgen action through estrogen receptor in a human breast cancer cell line. Endocrinology. 1978 Aug;103(2):624–631. doi: 10.1210/endo-103-2-624. [DOI] [PubMed] [Google Scholar]
- van Vollenhoven R. F., Engleman E. G., McGuire J. L. An open study of dehydroepiandrosterone in systemic lupus erythematosus. Arthritis Rheum. 1994 Sep;37(9):1305–1310. doi: 10.1002/art.1780370906. [DOI] [PubMed] [Google Scholar]