Modulation of steroidogenic gene expression and hormone production of H295R cells by pharmaceuticals and other environmentally active compounds

Tannia GRACIA, Klara HILSCHEROVA, Paul D. JONES, John L. NEWSTED, Eric B. HIGLEY, Xiaowei ZHANG, Markus HECKER, Margaret B. MURPHY, Richard M. K. YU, Paul K. S. LAM, Shiu Sun Rudolf WU, John P. GIESY

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Abstract

The H295R cell bioassay was used to evaluate the potential endocrine disrupting effects of 18 of the most commonly used pharmaceuticals in the United States. Exposures for 48 h with single pharmaceuticals and binary mixtures were conducted; the expression of five steroidogenic genes, 3βHSD2, CYP11β1, CYP11β2, CYP17 and CYP19, was quantified by Q-RT-PCR. Production of the steroid hormones estradiol (E2), testosterone (T) and progesterone (P) was also evaluated. Antibiotics were shown to modulate gene expression and hormone production. Amoxicillin up-regulated the expression of CYP11β2 and CYP19 by more than 2-fold and induced estradiol production up to almost 3-fold. Erythromycin significantly increased CYP11β2 expression and the production of P and E2 by 3.5- and 2.4-fold, respectively, while production of T was significantly decreased. The β-blocker salbutamol caused the greatest induction of CYP17, more than 13-fold, and significantly decreased E2 production. The binary mixture of cyproterone and salbutamol significantly down-regulated expression of CYP19, while a mixture of ethynylestradiol and trenbolone, increased E2 production 3.7-fold. Estradiol production was significantly affected by changes in concentrations of trenbolone, cyproterone, and ethynylestradiol. Exposures with individual pharmaceuticals showed the possible secondary effects that drugs may exert on steroid production. Results from binary mixture exposures suggested the possible type of interactions that may occur between drugs and the joint effects product of such interactions. Dose-response results indicated that although two chemicals may share a common mechanism of action the concentration effects observed may be significantly different. Copyright © 2007 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)142-153
JournalToxicology and Applied Pharmacology
Volume225
Issue number2
DOIs
Publication statusPublished - 01 Dec 2007

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Gene expression
Modulation
Aromatase
Hormones
Cyproterone
Gene Expression
Trenbolone Acetate
Steroid 17-alpha-Hydroxylase
Estradiol
Pharmaceutical Preparations
Albuterol
Binary mixtures
Steroids
Amoxicillin
Erythromycin
Biological Assay
Progesterone
Testosterone
Steroid hormones
Anti-Bacterial Agents

Citation

Gracia, T., Hilscherova, K., Jones, P. D., Newsted, J. L., Higley, E. B., Zhang, X., . . . Giesy, J. P. (2007). Modulation of steroidogenic gene expression and hormone production of H295R cells by pharmaceuticals and other environmentally active compounds. Toxicology and Applied Pharmacology, 225(2), 142-153. doi: 10.1016/j.taap.2007.07.013

Keywords

  • Bioassay
  • Steroidogenesis
  • Pharmaceuticals
  • Endocrine disruptors
  • Drug mixtures
  • Dose–response