Low levels of female sex hormones called estrogens might drive disease processes leading to skin fibrosis in scleroderma, according to a recent study evaluating the effect of estrogen on fibrosis in mice. The findings indicate that estrogen therapy might be used to harness fibrotic processes in women — an idea that the research group behind the study now plans to explore.
The findings were presented at the European League Against Rheumatism Annual Congress (EULAR 2016) June 8-11 in London, and raised the question of whether hormonal differences can explain the fact that postmenopausal women constitute the majority of scleroderma patients.
“Because of the clear sex bias in systemic sclerosis, we decided to assess whether blocking the action of estrogens (female hormones that decrease in menopause), plays a role in the development or vulnerability to this disease,” explained the lead author of the study, Dr. Jerome Avouac from Paris Descartes University in France, in a press release provided to Scleroderma News.
Researchers induced skin fibrosis in mice by exposing them to the drug bleomycin, or studied a genetically engineered mouse referred to as Tsk-1, a strain that is prone to developing skin fibrosis. In the study, “Estrogens Inhibit the Profibrotic Effects Of TGF-Beta and Protect From the Development Of Experimental Dermal Fibrosis,” researchers then explored how blocking estrogen signaling in two different ways affected skin fibrosis in the animals.
First, researchers removed the gene encoding the estrogen receptor. To make sure it was an estrogen-specific effect they were looking at, the team also treated mice with the estrogen blocker tamoxifen.
Blocking estrogen signaling in either way increased TGF-β levels and worsened skin fibrosis in both mouse types. The bleomycin-treated mice also had higher numbers of fibrosis-causing myofibroblasts, so the research team went on to study fibroblasts isolated from patients’ skin.
Cultured fibroblasts were treated with TGF-β to induce fibrosis — a process that could be verified by the specialization of fibroblasts to myofibroblasts and increased production of collagen. The team then added estrogen at different concentrations, which reduced the fibrotic processes. If, on the other hand, they added the estrogen blocker tamoxifen along with estrogen, the cells again showed increased fibrotic changes.
“Having confirmed that estrogens indeed play a role in protecting against skin fibrosis in experimental models representative of SSC [systemic sclerosis], the next step will be to begin investigating the potential role of hormone therapies as a treatment of SSc skin disease,” Avouac concluded.