Effects of fluorotelomer alcohol 8:2 FTOH on steroidogenesis in H295R cells: Targeting the cAMP signalling cascade

Journal Article · Wed Sep 15 00:00:00 EDT 2010 · Toxicology and Applied Pharmacology

OSTI ID:21460210

Chunsheng, Liu ^[1]; Hong, Chang; Jones, Paul; Wiseman, Steve; Naile, Jonathan ^[2]; Hecker, Markus ^[2]; Giesy, John P ^[3]

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1. State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China)
2. Department of Veterinary, Biomedical Sciences and Toxicology Centre, University of Saskatchewan, Saskatoon (Canada)
3. State Key Laboratory of Pollution Control and Resource Reuse and School of the Environment, Nanjing University, Nanjing (China)

Previous studies have demonstrated that perfluorinated chemicals (PFCs) can affect reproduction by disruption of steroidogenesis in experimental animals. However, the underlying mechanism(s) of this disruption remain unknown. Here we investigated the effects and mechanisms of action of 1H, 1H, 2H, 2H-perfluoro-decan-1-ol (8:2 FTOH) on steroidogenesis using a human adrenocortical carcinoma cell line (H295R) as a model. H295R cells were exposed to 0, 7.4, 22.2 or 66.6 {mu}M 8:2 FTOH for 24 h and productions of progesterone, 17{alpha}-OH-progesterone, androstenedione, testosterone, deoxycorticosterone, corticosterone and cortisol were quantified by HPLC-MS/MS. With the exception of progesterone, 8:2 FTOH treatment significantly decreased production of all hormones in the high dose group. Exposure to 8:2 FTOH significantly down-regulated cAMP-dependent mRNA expression and protein abundance of several key steroidogenic enzymes, including StAR, CYP11A, CYP11B1, CYP11B2, CYP17 and CYP21. Furthermore, a dose-dependent decrease of cellular cAMP levels was observed in H295R cells exposed to 8:2 FTOH. The observed responses are consistent with reduced cellular cAMP levels. Exposure to 8:2 FTOH resulted in significantly less basal (+ GTP) and isoproterenol-stimulated adenylate cyclase activities, but affected neither total cellular ATP level nor basal (-GTP) or NaF-stimulated adenylate cyclase activities, suggesting that inhibition of steroidogenesis may be due to an alteration in membrane properties. Metabolites of 8:2 FTOH were not detected by HPLC-MS/MS, suggesting that 8:2 FTOH was not metabolized by H295R cells. Overall, the results show that 8:2 FTOH may inhibit steroidogenesis by disrupting the cAMP signalling cascade.

• OSTI ID: 21460210
• Journal Information: Toxicology and Applied Pharmacology, Vol. 247, Issue 3; Other Information: DOI: 10.1016/j.taap.2010.06.016; PII: S0041-008X(10)00226-7; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMP
ANDROSTENEDIONE
CORTICOSTERONE
GENES
HYDROCORTISONE
INHIBITION
PROGESTERONE
TESTOSTERONE
TUMOR CELLS
ADRENAL HORMONES
ANDROGENS
ANDROSTANES
ANIMAL CELLS
CORTICOSTEROIDS
GLUCOCORTICOIDS
HORMONES
HYDROXY COMPOUNDS
KETONES
NUCLEOTIDES
ORGANIC COMPOUNDS
PREGNANES
STEROID HORMONES
STEROIDS