| First Author | Moran TB | Year | 2012 |
| Journal | Toxicol Appl Pharmacol | Volume | 265 |
| Issue | 1 | Pages | 139-45 |
| PubMed ID | 22975028 | Mgi Jnum | J:189015 |
| Mgi Id | MGI:5444065 | Doi | 10.1016/j.taap.2012.08.026 |
| Citation | Moran TB, et al. (2012) Aryl-hydrocarbon receptor activity modulates prolactin expression in the pituitary. Toxicol Appl Pharmacol 265(1):139-45 |
| abstractText | 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 beta-naphthoflavone with a robust induction of Cyp1a1. Although mRNA levels of the anti-proliferative signaling cytokine TGFbeta1 are suppressed upon beta-naphthoflavone treatment, we did not observe an alteration in cell proliferation. AhR activation with beta-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. |
