Increased levels of enzymes involved in local estradiol synthesis in chronic obstructive pulmonary disease

- ERα, ERβ and GPER are expressed in normal and COPD lung tissue.
- All main enzymes involved in the local generation and degradation of estrogens are expressed in lung tissue.
- The balance of reducing and oxidizing 17β-HSDs is shifted towards the reducing 17β-HSD 1 in COPD patients.
- The ratio of 17β-HSD 1 / 17β-HSD 2 is increased in COPD patients.
- The expression of aromatase is associated with disease state.

IntroductionSteroid hormones are involved in lung development, pulmonary inflammation, and lung cancer. Estrogen signaling and exposure may play a role in pulmonary disorders, including COPD. In both genders, estrogens can be generated locally in the lungs and this contributes importantly to the tissue exposure to these steroids.ObjectiveTo characterize and assess differences in localization of estrogen receptors and enzymes involved in the local generation of estrogens in COPD.MethodsEstrogen Receptor alpha (ERα/ESR1), Estrogen Receptor beta (ERβ/ESR2) and G-protein-coupled estrogen receptor 1 (GPER) were explored by real-time (RT)-PCR analysis (mRNA expression), immunohistochemistry and western blotting in controls and COPD patients.mRNA expression of the enzymes involved in the local estrogen generation - i.e. aromatase (CYP19A1), 17beta-hydroxysteroid dehydrogenases (17β-HSDs) 1, 2, 4, 5, 7 and 12, steroid sulfatase (STS) and sulfotransferase (SULT1E1) - were analyzed by RT-PCR.ResultsERα, ERβ and GPER were expressed in lung tissue, but no differences were observed between patients and controls. The main enzymes involved in local estrogen generation were also present in both normal and COPD lung tissue. In lungs of COPD patients compared with controls, we observed increased expression of the enzymes 17β-HSD type 1 and aromatase (positive association), both involved in the local synthesis of active estrogens.ConclusionAll ER subtypes are present in the lung. The shift in local mRNA level of estrogen metabolic enzymes suggests that exposure to estrogens is involved in the pathogenesis of COPD.