The Complex Biology of the Aryl Hydrocarbon Receptor and Its Role in the Pituitary Gland.

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor best known for its ability to mediate the effects of environmental toxins such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin), polycyclic aromatic hydrocarbons (PAHs), benzene, and polychlorinated biphenyls (PCBs) through the initiation of transcription of a number of metabolically active enzymes. Therefore, the AHR has been studied mostly in the context of xenobiotic signaling. However, several studies have shown that the AHR is constitutively active and plays an important role in general cell physiology, independently of its activity as a xenobiotic receptor and in the absence of exogenous ligands.

Expression of cell cycle regulators and biomarkers of proliferation and regrowth in human pituitary adenomas.

Purpose: The pathogenesis of pituitary adenomas (PA) is complex. Ki-67, pituitary tumour transforming gene (PTTG), vascular endothelial growth factor (VEGF), cyclin D1, c-MYC and pituitary adenylate cyclase-activating peptide (PACAP) protein expression were analysed and correlated with tumour and patient characteristics.

Methods: 74 pituitary tumour samples (48 non-functional PA, 26 functional PAs); Immunohistochemical analysis of protein expression, retrospective analysis of MR images and in vitro analysis of octreotide treatment was carried out on GH3 cells.

Aryl Hydrocarbon Receptor-Interacting Protein (AIP) N-Terminus Gene Mutations Identified in Pituitary Adenoma Patients Alter Protein Stability and Function.

Mutations spanning the entire aryl hydrocarbon receptor-interacting protein (AIP) gene have been found in isolated familial cases of pituitary adenomas (PA). Missense mutations located in the N-terminus of the gene have been identified in several patients. However, the functional significance of these mutations remains a matter of controversy.

Expression and clinical significance of Wnt players and survivin in pituitary tumours.

Deregulation of the Wnt pathway has been implicated in oncogenesis of numerous tissues including the pituitary gland. Immunohistochemical localization and quantification of β-catenin, Cyclin D1, c-MYC and Survivin expression in 47 pituitary adenomas (35 non-functioning, seven GH-secreting, three prolactinomas, two ACTH-secreting tumour) and six normal controls was undertaken in this study and correlation of protein expression to patient and tumour characteristics analysed. β-catenin was strictly membrane-bound with no difference observed between normal and tumour tissue.

Functional polymorphisms within the TNFRSF11B (osteoprotegerin) gene increase the risk for low bone mineral density.

Polymorphisms within the TNFRSF11B gene have been studied and associated with osteoporosis and fracture risk. Osteoprotegerin (OPG), the product of this gene, is a key negative regulator of osteoclastogenesis and is secreted by osteoblasts/stromal cells. A previous study in Maltese postmenopausal women showed positive association of low bone mineral density (BMD) with a polymorphism found within the promoter region of this gene (C950T).