title: Analytical methodology for the profiling and characterization of androgen receptor active compounds in human placenta.
abstract: The exposure to endocrine disrupting chemicals during foetal development has been proposed to cause reproductive dysfunctions in the neonate or later life. In order to support such studies, an analytical method was developed to profile the receptor mediated (anti)androgenic activities present in extracts of placenta samples. Placenta samples from women giving birth to healthy male neonates were extracted and fractionated by HPLC. Fractions containing androgen receptor (AR) activity were detected using an in vitro yeast-based human androgen receptor transcription screen. GC-MS analyses of receptor active fractions resulted in detection of chemical contaminants including antimicrobial and cosmetic compounds which exhibited AR antagonist activity in the yeast screen, and endogenously derived steroids which contributed to both the agonist and antagonistic activity in the samples. The bioassay-directed fractionation methodology developed in this study revealed the potential to identify mixtures of chemical contaminants that should be investigated for potential effects on the reproductive system.
authors: School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QJ, UK.
authors: Paolo
authors: P
authors: Indiveri
authors: School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QJ, UK.
authors: Julia
authors: J
authors: Horwood
authors: School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QJ, UK.
authors: Alaa
authors: A
authors: Abdul-Sada
authors: Laboratory of Medical Investigations, San Cecilio Hospital, University of Granada, Granada 18071, Spain.
authors: Juan P
authors: JP
authors: Arrebola
authors: Laboratory of Medical Investigations, San Cecilio Hospital, University of Granada, Granada 18071, Spain.
authors: Nicolas
authors: N
authors: Olea
authors: School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QJ, UK. Electronic address: e.m.hill@sussex.ac.uk.
authors: Elizabeth M
authors: EM
authors: Hill
mesh_terms: D000726:Androgen Antagonists / Q000378:metabolism*; D000728:Androgens / Q000378:metabolism*; D001681:Biological Assay; D002851:Chromatography, High Pressure Liquid; D052244:Endocrine Disruptors / Q000378:metabolism; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D015003:Yeasts / Q000235:genetics; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: C410798:AR protein, human; D000726:Androgen Antagonists; D000728:Androgens; D052244:Endocrine Disruptors; D011944:Receptors, Androgen; D001616:beta-Galactosidase
keywords: Androgen receptor assay; Endocrine disruptor chemical; GC–MS; HPLC; LC–MS; Sex steroid