ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 65 P4 | DOI: 10.1530/endoabs.65.P4

Serum estrogens and the sexual dimorphism in heritable and idiopathic pulmonary arterial hypertension (PAH)

Nina Denver1,2,3, Natalie ZM Homer2, Eric D Austin4, Ruth Andrew2 & Margaret R MacLean3

1University of Glasgow, Glasgow, UK; 2University of Edinburgh, Edinburgh, UK; 3Strathclyde University, Glasgow, UK; 4Vanderbilt University Medical Center, Nashville, Tennessee, USA

Serum was collected with ethical approval from Vanderbilt Medical Center, USA for blinded analysis between clinical phenotypes; heritable and idiopathic PAH patients (hPAH n=13, 14; iPAH n=7, 12) compared to non-PAH control (n =17, 17) (female, males, respectively). Quantification of circulating estrogens in human bio-fluids may reveal insights into disease aetiology but has been hampered through inadequate sensitivity and specificity of immunoassays. Therefore, we developed and applied a liquid chromatography tandem mass spectrometry (LC–MS/MS) method to profile multiple estrogen metabolites in PAH. Results are shown as mean±S.E.M. with P-values following Kruskal–Wallis statistical tests. E2 (23.3 ± 2.5 vs. 15.1 ± 1.5 pg/ml, P=0.02) and 16OHE1 (87.3 ± 20.4 vs. 25.8 ± 1.9 pg/ml, P=0.004) were elevated in male iPAH patient’s vs. controls with a trend also shown toward E1 elevation (41.9 ± 8.0 vs. 24.8 ± 2.4 pg/ml, P=0.08). However, in females, only elevations of 16OHE2 were detected (23.6 ± 4.7 vs. 12.2 ± 2.2 pg/ml, P=0.005). The estrogen profiles of hPAH patients did not differ from those of non-PAH individuals. Therefore, profiling estrogen metabolism by LC–MS/MS reveals increased circulating levels of specific bioactive estrogens in iPAH but not in hPAH. The exact pattern differed between male and female iPAH, in both cases the pathway of 16 hydroxylation was upregulated generating proliferative metabolites that may underpin the pathobiology of disease.

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