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. 2000 Sep;59(9):657–661. doi: 10.1136/ard.59.9.657

Recent aspects of gonadal hormone and neurotransmitter interactions with synovial and immune cells: implications in rheumatoid arthritis

M CUTOLO 1, R STRAUB 1
PMCID: PMC1753272  PMID: 10976076

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Figure 1  .

Figure 1  

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Major stimulatory (+) or inhibitory (−) effects (direct and indirect) of androgens (A) and oestrogens (O) on cytokine/immunoglobulin production by synovial/immune cells at the level of the synovial rheumatoid tissue.

Figure 2  .

Figure 2  

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Locally produced inflammatory cytokines (that is, tumour necrosis factor α (TNFα), interleukin 1 (IL1), IL6) can markedly stimulate the aromatase activity (P450Arom) in peripheral tissues (that is, synovial tissue) with subsequent increased conversion of androgens (testosterone and androstenedione) to oestrogens (oestrone and oestradiol, respectively). In addition, IL6 has been found to mediate an increase in reductive 17β-hydroxysteroid dehydrogenase (17β-HSD) activity that converts oestrone to the biologically more active 17β-oestradiol. These effects might explain the altered balance with lower androgens and higher oestrogens found in the synovial RA fluids, as well as their resulting effects on synovial cells.

Figure 3  .

Figure 3  

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Impact of sensory and sympathetic nerve fibres on inflammation in the synovial tissue. The diagram shows the balance of proinflammatory and anti-inflammatory mechanisms. Substance P of sensory nerve fibres and norepinephrine/adenosine at low concentrations seem to be proinflammatory, whereas norepinephrine/adenosine at high concentrations seem to be anti-inflammatory. α2 = alpha 2 adrenergic; β = beta adrenergic; A1 = adenosine receptor 1; A2 = adenosine receptor 2. 

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