Expression of estrogen receptors and estrogen metabolism genes in lungs of COPD patients

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Background: Steroid hormones are involved in the biology of organs outside the reproductive system. As females are biologically more susceptible to smoke, estrogen receptors (ER) may play a role in COPD. In addition, lung cells are able to synthesize estrogen. This study aims to investigate ER and major genes involved in estrogen metabolism in lung tissue of non-smokers (NS), asymptomatic smokers (AS) and COPD patients. Methods: A total of 50 patients were included: 9 NS (61±10yr, FEV1 98%pred), 17 AS (61±10yr, FEV1 106%pred), 24 COPD (67±8yr, FEV1 67%pred). Non-tumor lung tissue samples were analyzed for expression of estrogen receptor 1 ( ERS1 ), estrogen receptor 2 ( ERS2 ), G-protein-coupled estrogen receptor 1 ( GPER ), aromatase ( CYP19A1 ), 17beta-hydroxysteroid dehydrogenases 1 and 2 ( HSD17B1, HSD17B2 ) by RT-PCR. Presence of full-length ERS1, ERS2 and GPER was analyzed by western blotting (WB). Results: ERS1, ERS2 and the novel ER GPER were highly expressed in lung tissue. In addition, full-length ERS1, ERS2 and GPER protein was confirmed by WB. Gene expression of all three ER was not different between NS, AS and COPD subjects. However, expression of CYP19A1 and HSD17B1 was significantly increased in COPD patients compared to NS and AS. Regression analysis showed CYP19A1 (R=0.862; p=0.001) , HSD17B1 (R=0.837; p=0.012) and ratio HSD17B1/ HSD17B2 (R=0.849; p=0.003) to be associated with disease state. In addition, CYP19A1 (R=0.590; p=0.005) was also associated with lung function impairment. Conclusion: Expression of ER and estrogen metabolism genes in lung tissue suggests a role for endogenous estrogen in the pathogenesis of COPD. Grant: Lung Foundation Netherlands (3.2.10.076).