Androgen and Progesterone Receptors Are Targets for Bisphenol A (BPA), 4-Methyl-2,4-bis-(P-Hydroxyphenyl)Pent-1-Ene—A Potent Metabolite of BPA, and 4-Tert-Octylphenol: A Computational Insight

• DOI: 10.1371/journal.pone.0138438
• Publication Date: 2015-09-17T18:24:32Z
• Authors: Mohd Rehan; Ejaz Ahmad; Ishfaq A. Sheikh; Adel M. Abuzenadah; Ghazi A. Damanhouri; Osama S. Bajouh; Samera F. AlBasri; Mansour M. Assiri; Mohd A. Beg
• Keywords: Endocrine disruptor

Exposure to toxic industrial chemicals that have capacity disrupt the endocrine system, also known as disrupting (EDCs), has been increasingly associated with reproductive problems in human population. Bisphenol A (BPA; 4,4'-(propane-2,2-diyl)diphenol) and 4-tert-octylphenol (OP; 4-(1,1,3,3-tetramethylbutyl)phenol) are among most common environmental contaminants possessing disruption properties present plastics, epoxy resins, detergents other commercial products of personal use. metabolite BPA, 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) is about 1000 times more biologically active compared BPA. Epidemiological, clinical, experimental studies shown association BPA OP adverse effects on male female system animals. The activity can occur through multiple pathways including binding steroid receptors. Androgen receptor (AR) progesterone (PR) critical for tract growth function. Structural characterization MBP, AR PR using molecular docking simulation approaches revealed novel interactions PR, MBP PR. For OP, five interacting residues Leu-701, Leu-704, Asn-705, Met-742, Phe-764 overlapped those native ligand testosterone, four Leu-715, Leu-718, Met-756, Met-759 co-complex ligand, norethindrone. both receptors strength was maximum three compounds. Thus, these compounds potential block or interfere endogenous ligands and, hence, resulting dysfunction. knowledge key important amino-acid allows better prediction xenobiotic molecules AR- PR-mediated pathways, thus, helping design less potent alternatives