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New Insights Into Role Of Tumor Necrosis Factor On Sex Hormone Production In Rheumatoid Arthritis

Date:
June 13, 2005
Source:
John Wiley & Sons, Inc.
Summary:
A new study featured in the June 2005 issue of Arthritis & Rheumatism sheds new light on suppression of androgen by TNF in RA patients, as well as on the different nature of inflammation in RA from the most common inflammatory disease: osteoarthritis (OA).

A protein involved in multiple cell functions, tumor necrosis factor (TNF) is perhaps best known for provoking destructive inflammation. Recently, drugs blocking the action of TNF have shown promise in the early treatment of rheumatoid arthritis (RA).

To expand the understanding of TNF's function in chronic inflammatory diseases, researchers at University Hospital Regensburg in Germany and the National Institute of Rheumatic Diseases in the Slovak Republic decided to take a closer look at this cytokine's impact on androgen production. Androgens are thought to play a critical anti-inflammatory role in rheumatic diseases, including various forms of arthritis and lupus, based on extensive clinical trials and animal models. For their study, the team investigated the role of TNF in the conversion of biologically inactive DHEAS--short for dehydroepiandrosterone sulfate--to biologically active DHEA, the steroid hormone parent of androgen, estrogen, and testosterone. Their findings, featured in the June 2005 issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis), shed new light on suppression of androgen by TNF in RA patients, as well as on the different nature of inflammation in RA from the most common inflammatory disease: osteoarthritis (OA).

To get a clear picture of how TNF affects hormone production and regulation, the research team analyzed samples of inflamed synovial tissue--obtained immediately after opening the knee joint capsules of 37 patients who underwent elective joint replacement surgery. 15 of the patients had a longstanding history of RA, with disease duration averaging 15 years. 22 of the patients were OA sufferers. Using tools for biochemical analysis, the team assessed the process of converting DHEAS to DHEA. The results revealed marked differences in the cellular activity of RA and OA patients.

On the evidence of both synovial cell and synovial fluid analysis, levels of DHEA from DHEAS were significantly lower among RA patients than OA patients. In addition, researchers found a negative correlation between converted DHEA and markers of inflammation among RA patients but not in patients with OA. They also found evidence that TNF inhibits the activity of steroid sulfatase, the key enzyme in DHEAS-to-DHEA conversion.

"This is the first study to demonstrate that the conversion of DHEAS to DHEA is decreased in patients with RA as compared with that in patients with OA," notes leading contributor Claudia Weidler. "In the present study, we were fortunate to demonstrate that TNF is also a strong inhibitor of the conversion of DHEAS to DHEA in synovial cells from patients with RA but absolutely not in patients with OA."

Providing the full picture of androgen deficiency in RA, this study affirms the need for further research into early anti-TNF antibody therapy in the treatment of this particular inflammatory disease.

###

Article: "Tumor Necrosis Factor Inhibits Conversion of Dehydroepiandrosterone (DHEAS) TO DHEA in Rheumatoid Arthritis Synovial Cells: A Prerequisite for Local Androgen Deficiency," Claudia Weidler, Sona Struharova, Martin Schmidt, Bernhard Ugele, Jόrgen Schφlmerich, and Rainer H. Straub, Arthritis & Rheumatism, June 2005; 52:6; pp. 1721-1729.


Story Source:

The above story is based on materials provided by John Wiley & Sons, Inc.. Note: Materials may be edited for content and length.


Cite This Page:

John Wiley & Sons, Inc.. "New Insights Into Role Of Tumor Necrosis Factor On Sex Hormone Production In Rheumatoid Arthritis." ScienceDaily. ScienceDaily, 13 June 2005. <www.sciencedaily.com/releases/2005/06/050613063531.htm>.
John Wiley & Sons, Inc.. (2005, June 13). New Insights Into Role Of Tumor Necrosis Factor On Sex Hormone Production In Rheumatoid Arthritis. ScienceDaily. Retrieved October 22, 2014 from www.sciencedaily.com/releases/2005/06/050613063531.htm
John Wiley & Sons, Inc.. "New Insights Into Role Of Tumor Necrosis Factor On Sex Hormone Production In Rheumatoid Arthritis." ScienceDaily. www.sciencedaily.com/releases/2005/06/050613063531.htm (accessed October 22, 2014).

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