Construction of reporter gene assays using
Agonist
Androgen receptor
Antagonist
Estrogen receptor
Inverse agonist
Progesterone receptor
Reporter gene assay
Saccharomyces cerevisiae
Steroid hormone
Journal
Genes and environment : the official journal of the Japanese Environmental Mutagen Society
ISSN: 1880-7046
Titre abrégé: Genes Environ
Pays: England
ID NLM: 101285347
Informations de publication
Date de publication:
2020
2020
Historique:
received:
19
03
2020
accepted:
16
05
2020
entrez:
10
6
2020
pubmed:
10
6
2020
medline:
10
6
2020
Statut:
epublish
Résumé
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. To develop simple reporter gene assays with enhanced sensitivity for the detection of sex steroid hormones, we newly established mutant yeast strains lacking the 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.
Sections du résumé
BACKGROUND
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 32514322
doi: 10.1186/s41021-020-00159-x
pii: 159
pmc: PMC7251871
doi:
Types de publication
Journal Article
Langues
eng
Pagination
20Informations de copyright
© The Author(s) 2020.
Déclaration de conflit d'intérêts
Competing interestsThe authors declare that they have no competing interests.
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