title: 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.
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.
authors: Department of Environmental Health Sciences, School of Public Heath, Seoul National University, Seoul 08826, Republic of Korea.
authors: Juhae
authors: J
authors: Sohn
authors: Department of Environmental Health Sciences, School of Public Heath, Seoul National University, Seoul 08826, Republic of Korea.
authors: Sujin
authors: S
authors: Kim
authors: Federal Environment Agency (Umweltbundesamt), 06813 Dessau-Rosslau, Germany.
authors: Jan
authors: J
authors: Koschorreck
authors: Department of Health, Environment and Safety, Eulji University, Seongnam 13135, Republic of Korea.
authors: Younglim
authors: Y
authors: Kho
authors: Department of Environmental Health Sciences, School of Public Heath, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: kyungho@snu.ac.kr.
authors: Kyungho
authors: K
authors: Choi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003993:Dibutyl Phthalate / Q000031:analogs & derivatives* / Q000633:toxicity; D052244:Endocrine Disruptors / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D008297:Male; D010795:Phthalic Acids / Q000633:toxicity*; D015027:Zebrafish
chemical_list: D052244:Endocrine Disruptors; D012739:Gonadal Steroid Hormones; D010795:Phthalic Acids; D003993:Dibutyl Phthalate; C025605:diisobutyl phthalate; C007379:diethyl phthalate; C027561:butylbenzyl phthalate
keywords: Fish; Hydrolytic metabolites; Low molecular weight phthalates; Sex hormones