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Construction of reporter gene assays using CWP and PDR mutant yeasts for enhanced detection of various sex steroids
- Source :
- Genes and Environment, Vol 42, Iss 1, Pp 1-19 (2020), Genes and Environment
- Publication Year :
- 2020
- Publisher :
- BMC, 2020.
-
Abstract
- Background Sex steroid hormone receptors are classified into three classes of receptors: estrogen receptors (ER) α and β, androgen receptor (AR), and progesterone receptor (PR). They belong to the nuclear receptor superfamily and activate their downstream genes in a ligand-dependent manner. Since sex steroid hormones are involved in a wide variety of physiological processes and cancer development, synthetic chemical substances that exhibit sex steroid hormone activities have been applied as pharmaceuticals and consumed in large amounts worldwide. They are potentially hazardous contaminants as endocrine disruptors in the environment because they may induce inappropriate gene expression mediated by sex steroid hormone receptors in vivo. Results To develop simple reporter gene assays with enhanced sensitivity for the detection of sex steroid hormones, we newly established mutant yeast strains lacking the CWP and PDR genes encoding cell wall mannoproteins and plasma membrane drug efflux pumps, respectively, and expressing human ERα, ERβ, AR, and PR. Reporter gene assays with mutant yeast strains responded to endogenous and synthetic ligands more strongly than those with wild-type strains. Sex steroid hormone activities in some pharmaceutical oral tablets and human urine were also detectable in these yeast assays. Conclusions Yeast reporter gene assay systems for all six steroid hormone receptors, including previously established glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) assay yeasts, are now available. Environmental endocrine disrupters with steroid hormone activity will be qualitatively detectable by simple and easy procedures. The yeast-based reporter gene assay will be valuable as a primary screening tool to detect and evaluate steroid hormone activities in various test samples. Our assay system will strongly support the detection of agonists, antagonists, and inverse agonists of steroid hormone receptors in the field of novel drug discovery and assessments of environmental pollutants.
- Subjects :
- 0301 basic medicine
Steroid hormone
Social Psychology
lcsh:QH426-470
medicine.medical_treatment
Agonist
Estrogen receptor
Saccharomyces cerevisiae
Environmental Science (miscellaneous)
Progesterone receptor
03 medical and health sciences
0302 clinical medicine
lcsh:QH540-549.5
Genetics
medicine
Receptor
Reporter gene
Chemistry
Research
Antagonist
Reporter gene assay
Androgen receptor
lcsh:Genetics
030104 developmental biology
Nuclear receptor
Biochemistry
Sex steroid
Hormone receptor
030220 oncology & carcinogenesis
lcsh:Ecology
Inverse agonist
Hormone
Subjects
Details
- Language :
- English
- ISSN :
- 18807062
- Volume :
- 42
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Genes and Environment
- Accession number :
- edsair.doi.dedup.....b268de8e1602cca1af6ca0126ec3a6fe