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Endometriosis is characterized by the presence of endometriotic epithelium and stroma in ectopic locations. It has been proposed that this tissue can synthesize its own growth-supporting steroid hormones by collecting substrate steroids from blood supply or by using cholesterol. In the present work Trilostane, an 3β-hydroxysteroid dehydrogenase inhibitor, was tested.
The analytical part was based on High pressure Liquid Chromatography-tandem Mass Spectrometry analysis with a reverse-phase column coupled to an electrospray source to analyse steroid concentrations. As steroids require the overcome of some difficulties in terms of analysis, oxime derivatization was the key in the analytical method in order to obtain reliable results. To investigate androgen metabolism in endometriosis, endometrial and endometriotic tissues were treated with dehydroepiandrosterone and trilostane, and the steroid concentration in the surrounding medium was measured.
Only three compounds were detected in the samples, Testosterone, Dehydroepiandrosterone and androstenedione, while the others were under the lowest limit of quantitation. Androstenedione concentration results were conclusive, since its accumulation was inhibited by trilostane, whilst for the rest of the compounds it was impossible to take reasonable conclusions, which demonstrates that the enzyme is essential in the androgen production in endometriosis. No accumulation of androstenedione was seen in the endometrium tissue.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2014
Palavras-chave
Endometriosis Steroid hormones Androgens DHEA (Dehydroepiandrosterone) High performance Liquid Chromatography-tandem Mass Spectrometry (HPLC-MS/MS) Oxime derivatization Trilostane Mestrado Integrado - 2014
