Premium
Steroid Hormone Receptor Gene Expression as a Marker for Phenothiazine Induced Endocrine Disruption and Stress in Mummichog, Fundulus heteroclitus
Author(s) -
Laperche Jacob M,
Chiari John B,
Patel Roshni,
McGinnis Courtney L
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.616.2
Subject(s) - endocrine disruptor , estrogen receptor , endocrinology , medicine , receptor , endocrine system , estrogen receptor alpha , glucocorticoid receptor , biology , chemistry , hormone , cancer , breast cancer
Molecules and contaminants that function as endocrine disruptors from industrial products are known to contaminate ground and surface water through agricultural runoff and industrial dumping. These contaminants are not typically removed during water purification and may have significant effects on biological systems through the disruption of normal endocrine function. This study aims to determine the effects of phenothiazine (PTZ), a potential endocrine disruptor, on markers for endocrine disruption and stress in Fundulus heteroclitus . The following steroid hormone receptors were assessed: glucocorticoid receptor (GR), androgen receptor (AR), progesterone receptor (PR), estrogen related receptor alpha (ERα), estrogen receptor beta A (ERβA), and estrogen receptor beta B (ERβB). Phenothiazine was detected at levels between 1–2ppm via gas chromatography‐mass spectrophotometry (GC‐MS) in river water sampling conducted in southern Connecticut, but the biological impact of the compound is unknown. Phenothiazine has been used previously as an antipsychotic medication, as well as, industrially in plastics to add softness and flexibility. To assess this impact of phenothiazine, fish were exposed to environmentally relevant concentrations of phenothiazine for one week and sacrificed. Brain, liver, and gonad tissues were removed and pooled from each treatment group. Quantitative PCR (qPCR) was conducted on tissues and analysis showed significant changes in gene expression. There was an increase in mRNA expression of ERβB, PR, AR, and GR in gonadal tissue. There was an increase in mRNA expression of AR, PR, and ERβA in liver tissue as well. In brain tissue, AR, PR, ERα, ERβA and ERβB mRNA expression was upregulated. These findings indicate that phenothiazine may alter endocrine function through the steroid hormone receptors. Additionally, there was a downregulation in GR mRNA expression in brain tissue, which has been associated with depression. Collectively, these tissue specific results demonstrate how phenothiazine disrupts normal fish physiology. In addition, to determine the impact of phenothiazine on stress, cortisol levels in the blood were assayed via enzyme linked immunosorbent assay (ELISA). No significant changes in cortisol levels following phenothiazine treatment were observed. Support or Funding Information The Community Foundation for Greater New Haven and Quinnipiac University: College of Arts and Sciences