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Title: Aryl‐hydrocarbon receptor activity modulates prolactin expression in the pituitary

Abstract

Pituitary tumors account for 15% of intracranial neoplasms, however the extent to which environmental toxicants contribute to the proliferation and hormone expression of pituitary cells is unknown. Aryl-hydrocarbon receptor (AhR) interacting protein (AIP) loss of function mutations cause somatotrope and lactotrope adenomas in humans. AIP sequesters AhR and inhibits its transcriptional function. Because of the link between AIP and pituitary tumors, we hypothesize that exposure to dioxins, potent exogenous ligands for AhR that are persistent in the environment, may predispose to pituitary dysfunction through activation of AhR. In the present study, we examined the effect of AhR activation on proliferation and endogenous pituitary hormone expression in the GH3 rat somatolactotrope tumor cell line and the effect of loss of AhR action in knockout mice. GH3 cells respond to nM doses of the reversible AhR agonist β-naphthoflavone with a robust induction of Cyp1a1. Although mRNA levels of the anti-proliferative signaling cytokine TGFbeta1 are suppressed upon β-naphthoflavone treatment, we did not observe an alteration in cell proliferation. AhR activation with β-naphthoflavone suppresses Ahr expression and impairs expression of prolactin (PRL), but not growth hormone (GH) mRNA in GH3 cells. In mice, loss of Ahr similarly leads to a reduction in Prl mRNAmore » at P3, while Gh is unaffected. Additionally, there is a significant reduction in pituitary hormones Lhb and Fshb in the absence of Ahr. Overall, these results demonstrate that AhR is important for pituitary hormone expression and suggest that environmental dioxins can exert endocrine disrupting effects at the pituitary. -- Highlights: ► AhR signaling suppresses Prl mRNA expression. ► AhR signaling does not influence pituitary proliferation in culture. ► AhR is necessary for Prl, Lhb and Fshb expression at postnatal day 3.« less

Authors:
; ;
Publication Date:
OSTI Identifier:
22215983
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 265; Journal Issue: 1; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADENOMAS; CELL PROLIFERATION; DIOXIN; HYDROCARBONS; KNOCK-OUT REACTIONS; LIGANDS; LTH; MESSENGER-RNA; MICE; MUTATIONS; RATS; RECEPTORS; STH; TUMOR CELLS

Citation Formats

Moran, Tyler B., Brannick, Katherine E., and Raetzman, Lori T., E-mail: raetzman@life.illinois.edu. Aryl‐hydrocarbon receptor activity modulates prolactin expression in the pituitary. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2012.08.026.
Moran, Tyler B., Brannick, Katherine E., & Raetzman, Lori T., E-mail: raetzman@life.illinois.edu. Aryl‐hydrocarbon receptor activity modulates prolactin expression in the pituitary. United States. doi:10.1016/J.TAAP.2012.08.026.
Moran, Tyler B., Brannick, Katherine E., and Raetzman, Lori T., E-mail: raetzman@life.illinois.edu. Thu . "Aryl‐hydrocarbon receptor activity modulates prolactin expression in the pituitary". United States. doi:10.1016/J.TAAP.2012.08.026.
@article{osti_22215983,
title = {Aryl‐hydrocarbon receptor activity modulates prolactin expression in the pituitary},
author = {Moran, Tyler B. and Brannick, Katherine E. and Raetzman, Lori T., E-mail: raetzman@life.illinois.edu},
abstractNote = {Pituitary tumors account for 15% of intracranial neoplasms, however the extent to which environmental toxicants contribute to the proliferation and hormone expression of pituitary cells is unknown. Aryl-hydrocarbon receptor (AhR) interacting protein (AIP) loss of function mutations cause somatotrope and lactotrope adenomas in humans. AIP sequesters AhR and inhibits its transcriptional function. Because of the link between AIP and pituitary tumors, we hypothesize that exposure to dioxins, potent exogenous ligands for AhR that are persistent in the environment, may predispose to pituitary dysfunction through activation of AhR. In the present study, we examined the effect of AhR activation on proliferation and endogenous pituitary hormone expression in the GH3 rat somatolactotrope tumor cell line and the effect of loss of AhR action in knockout mice. GH3 cells respond to nM doses of the reversible AhR agonist β-naphthoflavone with a robust induction of Cyp1a1. Although mRNA levels of the anti-proliferative signaling cytokine TGFbeta1 are suppressed upon β-naphthoflavone treatment, we did not observe an alteration in cell proliferation. AhR activation with β-naphthoflavone suppresses Ahr expression and impairs expression of prolactin (PRL), but not growth hormone (GH) mRNA in GH3 cells. In mice, loss of Ahr similarly leads to a reduction in Prl mRNA at P3, while Gh is unaffected. Additionally, there is a significant reduction in pituitary hormones Lhb and Fshb in the absence of Ahr. Overall, these results demonstrate that AhR is important for pituitary hormone expression and suggest that environmental dioxins can exert endocrine disrupting effects at the pituitary. -- Highlights: ► AhR signaling suppresses Prl mRNA expression. ► AhR signaling does not influence pituitary proliferation in culture. ► AhR is necessary for Prl, Lhb and Fshb expression at postnatal day 3.},
doi = {10.1016/J.TAAP.2012.08.026},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 265,
place = {United States},
year = {2012},
month = {11}
}