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Role of glucocorticoid receptor in acclimation of killifish (Fundulus heteroclitus) to seawater and effects of arsenic.
Am J Physiol Regul Integr Comp Physiol. 2007 Feb; 292(2):R1052-60.AJ

Abstract

Killifish are euryhaline teleosts that adapt to rapid changes in the salinity of the seawater. It is generally accepted that acclimation to seawater is mediated by cortisol activation of the glucocorticoid receptor (GR), which stimulates CFTR mRNA expression and CFTR-mediated Cl- secretion by the gill. Because there is no direct evidence in killifish that the GR stimulates CFTR gene expression, quantitative PCR studies were conducted to test the hypothesis that cortisol activation of GR upregulates CFTR mRNA expression and that this response is required for acclimation to seawater. Inhibition of the GR by RU-486 prevented killifish from acclimating to increased salinity and blocked the increase in CFTR mRNA. In contrast, inhibition of the mineralocorticoid receptor by spironolactone had no effect on acclimation to seawater. Thus acclimation to increased salinity in killifish requires signaling via the GR and includes an increase in CFTR gene expression. Because arsenic, a toxic metalloid that naturally occurs in the aquatic environment, has been shown to disrupt GR transcriptional regulation in avian and mammalian systems, studies were also conducted to determine whether arsenic disrupts cortisol-mediated activation of CFTR gene expression in this in vivo fish model and thereby blocks the ability of killifish to acclimate to increased salinity. Arsenic prevented acclimation to seawater and decreased CFTR protein abundance. However, arsenic did not disrupt the GR-induced increase in CFTR mRNA. Thus arsenic blocks acclimation to seawater in killifish by a mechanism that does not disrupt GR-mediated induction of CFTR gene expression.

Authors+Show Affiliations

Department of Physiology, Dartmouth College, Dartmouth Medical School, N. College St., Hanover, NH 03755, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

17038445

Citation

Shaw, Joseph R., et al. "Role of Glucocorticoid Receptor in Acclimation of Killifish (Fundulus Heteroclitus) to Seawater and Effects of Arsenic." American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, vol. 292, no. 2, 2007, pp. R1052-60.
Shaw JR, Gabor K, Hand E, et al. Role of glucocorticoid receptor in acclimation of killifish (Fundulus heteroclitus) to seawater and effects of arsenic. Am J Physiol Regul Integr Comp Physiol. 2007;292(2):R1052-60.
Shaw, J. R., Gabor, K., Hand, E., Lankowski, A., Durant, L., Thibodeau, R., Stanton, C. R., Barnaby, R., Coutermarsh, B., Karlson, K. H., Sato, J. D., Hamilton, J. W., & Stanton, B. A. (2007). Role of glucocorticoid receptor in acclimation of killifish (Fundulus heteroclitus) to seawater and effects of arsenic. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 292(2), R1052-60.
Shaw JR, et al. Role of Glucocorticoid Receptor in Acclimation of Killifish (Fundulus Heteroclitus) to Seawater and Effects of Arsenic. Am J Physiol Regul Integr Comp Physiol. 2007;292(2):R1052-60. PubMed PMID: 17038445.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of glucocorticoid receptor in acclimation of killifish (Fundulus heteroclitus) to seawater and effects of arsenic. AU - Shaw,Joseph R, AU - Gabor,Kristen, AU - Hand,Emily, AU - Lankowski,Alexander, AU - Durant,Lydia, AU - Thibodeau,Renee, AU - Stanton,Caitlin R, AU - Barnaby,Roxanna, AU - Coutermarsh,Bonita, AU - Karlson,Katherine H, AU - Sato,J Denry, AU - Hamilton,Joshua W, AU - Stanton,Bruce A, Y1 - 2006/10/12/ PY - 2006/10/14/pubmed PY - 2007/3/9/medline PY - 2006/10/14/entrez SP - R1052 EP - 60 JF - American journal of physiology. Regulatory, integrative and comparative physiology JO - Am. J. Physiol. Regul. Integr. Comp. Physiol. VL - 292 IS - 2 N2 - Killifish are euryhaline teleosts that adapt to rapid changes in the salinity of the seawater. It is generally accepted that acclimation to seawater is mediated by cortisol activation of the glucocorticoid receptor (GR), which stimulates CFTR mRNA expression and CFTR-mediated Cl- secretion by the gill. Because there is no direct evidence in killifish that the GR stimulates CFTR gene expression, quantitative PCR studies were conducted to test the hypothesis that cortisol activation of GR upregulates CFTR mRNA expression and that this response is required for acclimation to seawater. Inhibition of the GR by RU-486 prevented killifish from acclimating to increased salinity and blocked the increase in CFTR mRNA. In contrast, inhibition of the mineralocorticoid receptor by spironolactone had no effect on acclimation to seawater. Thus acclimation to increased salinity in killifish requires signaling via the GR and includes an increase in CFTR gene expression. Because arsenic, a toxic metalloid that naturally occurs in the aquatic environment, has been shown to disrupt GR transcriptional regulation in avian and mammalian systems, studies were also conducted to determine whether arsenic disrupts cortisol-mediated activation of CFTR gene expression in this in vivo fish model and thereby blocks the ability of killifish to acclimate to increased salinity. Arsenic prevented acclimation to seawater and decreased CFTR protein abundance. However, arsenic did not disrupt the GR-induced increase in CFTR mRNA. Thus arsenic blocks acclimation to seawater in killifish by a mechanism that does not disrupt GR-mediated induction of CFTR gene expression. SN - 0363-6119 UR - https://www.unboundmedicine.com/medline/citation/17038445/Role_of_glucocorticoid_receptor_in_acclimation_of_killifish__Fundulus_heteroclitus__to_seawater_and_effects_of_arsenic_ L2 - http://www.physiology.org/doi/full/10.1152/ajpregu.00328.2006?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -