PUBLICATION
Alteration of sex hormone levels and steroidogenic pathway by several low molecular weight phthalates and their metabolites in male zebrafish (Danio rerio) and/or human adrenal cell (H295R) line
- Authors
- Sohn, J., Kim, S., Koschorreck, J., Kho, Y., Choi, K.
- ID
- ZDB-PUB-160812-2
- Date
- 2016
- Source
- Journal of hazardous materials 320: 45-54 (Journal)
- Registered Authors
- Choi, Kyungho
- Keywords
- Fish, Hydrolytic metabolites, Low molecular weight phthalates, Sex hormones
- MeSH Terms
-
- Animals
- Cell Line, Tumor
- Dibutyl Phthalate/analogs & derivatives*
- Dibutyl Phthalate/toxicity
- Endocrine Disruptors/toxicity*
- Gene Expression/drug effects
- Gonadal Steroid Hormones/blood*
- Humans
- Male
- Phthalic Acids/toxicity*
- Zebrafish
- PubMed
- 27513369 Full text @ J. Hazard. Mater.
Citation
Sohn, J., Kim, S., Koschorreck, J., Kho, Y., Choi, K. (2016) Alteration of sex hormone levels and steroidogenic pathway by several low molecular weight phthalates and their metabolites in male zebrafish (Danio rerio) and/or human adrenal cell (H295R) line. Journal of hazardous materials. 320:45-54.
Abstract
Low molecular weight phthalates, such as diethyl phthalate (DEP), benzyl butyl phthalate (BBzP), or diisobutyl phthalate (DiBP), are suspected to disrupt endocrine system. However, their adverse effects on sex steroid hormones and underlying mechanisms are not well-documented. The aim of this study is to investigate the effects of major low molecular weight phthalates (LMWPs), i.e., DEP, BBzP, and DiBP, and their hydrolytic metabolites, on sex steroid hormone system, employing male zebrafish and/or a human adrenocortical carcinoma (H295R) cell. In male zebrafish, 14-day exposure to DEP, BBzP, or DiBP significantly decreased testosterone (T) concentrations. All test compounds significantly up-regulated cyp19a gene expression, and down-regulated star and 3β hsd genes in the male fish. In H295R cell, all test compounds except monoisobutyl phthalate (MiBP) reduced T concentrations and increased E2/T ratio. Gene expression changes in H295R cell, e.g., significant down-regulation of StAR gene and up-regulation of CYP19A gene, supported depressed synthesis of sex hormones in the adrenal cell. Our results show that not only DEP, BBzP, and DiBP, but also their hydrolytic metabolites disrupt sex hormone balances through modulating key steroidogenic genes in the human adrenal cells and in zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping