Wnt signaling pathways are important regulators of normal embryological development including that of the pituitary gland. Altered Wnt pathway expression is common in many human tumors however until recently the role of these pathways in human pituitary tumorigenesis has received little attention. The advent of microarray analysis has identified several Wnt pathway inhibitors that are frequently perturbed in pituitary tumors. In this review we summarize the role of these inhibitors in other human tumor types and review the current state of knowledge of Wnt inhibitor expression in pituitary tumors.
"Giles et al. showed that Wnt4 is expressed in the adult pituitary gland and that its expression is increased by estrogen exposure, suggesting that adult tissue plasticity is likely to involve í µí»½-catenin-independent signaling pathways, and conclusively showed Wnt signaling in estrogen-induced lactotroph proliferation . A review of 13 whole genome approaches in pituitary tumors with the goal of identifying Wnt family inhibitors showed that expression of WF1, SFRP2, FRZB, SFRP4, DKK2, and SOSTDC1 genes is decreased in pituitary adenomas compared to normal pituitary tissue, while that of SFRP1 and SFRP4 is increased . "
[Show abstract][Hide abstract] ABSTRACT: Gremlin is an antagonist of bone morphogenetic protein (BMP) and a major driving force in skeletal modeling in the fetal stage. Several recent reports have shown that Gremlin is also involved in angiogenesis of lung cancer and diabetic retinopathy. The purpose of this study was to investigate the role of Gremlin in tumor angiogenesis in pituitary adenoma. Double fluorescence immunohistochemistry of Gremlin and CD34 was performed in pituitary adenoma tissues obtained during transsphenoidal surgery in 45 cases (7 PRLoma, 17 GHoma, 2 ACTHoma, and 2 TSHoma). Gremlin and microvascular density (MVD) were detected by double-immunofluorescence microscopy in CD34-positive vessels from tissue microarray analysis of 60 cases of pituitary adenomas (6 PRLoma, 23 GHoma, 22 NFoma, 5 ACTHoma, and 4 TSHoma). In tissue microarray analysis, MVD was significantly correlated with an increased Gremlin level (linear regression: P < 0.005, r (2) = 0.4958). In contrast, Gremlin expression showed no correlation with tumor subtype or Knosp score. The high level of expression of Gremlin in pituitary adenoma tissue with many CD34-positive vessels and the strong coherence of these regions indicate that Gremlin is associated with angiogenesis in pituitary adenoma cells.
International Journal of Endocrinology 04/2015; 2015:834137. DOI:10.1155/2015/834137 · 1.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The present study investigated the influence of anti-estrogen treatment (fulvestrant) on pituitary adenoma cell line GH3 biological activity, the estrogen receptor α pathway, the WnT pathway, and mechanisms of decreased Wnt inhibitory factor-1 expression in GH3 cells. Results showed that fulvestrant suppressed GH3 cell proliferation and reduced hormone secretion in a dose-dependent manner. Estrogen receptor α and Wnt4 expression decreased, but Wnt inhibitory factor-1 expression increased in a dose-dependent manner following fulvestrant treatment, and β-catenin expression remained unchanged. Inhibitors of DNA methylation and histone modification upregulated Wnt inhibitory factor-1 expression. Results suggested that fulvestrant suppressed biological activity of GH3 cells via the estrogen receptor α and Wnt pathways. These results suggested that decreased Wnt inhibitory factor-1 expression in GH3 cells played a role in epigenetic mechanisms. Anti-estrogen therapies could provide novel treatments for growth hormone adenomas.
Neural Regeneration Research 02/2012; 7(4):283-9. DOI:10.3969/j.issn.1673-5374.2012.04.008 · 0.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We reported that weight loss induces bone loss which is prevented by exercise training; however, the mechanism for this observation remains unclear. Sclerostin, an inhibitor of bone formation, has been found to increase in states of unloading and may mediate the changes in bone metabolism associated with weight loss and exercise. The objective of the study was to determine the effect of lifestyle intervention in obese older adults on sclerostin levels, and on hip geometry parameters. A total of 107 obese (body mass index [BMI] ≥ 30 kg/m(2)) older (≥65 years) adults were randomly assigned to control, diet, exercise, and combined diet-exercise for 1 year. Sclerostin levels were measured by ELISA at baseline, 6 months, and 12 months, while hip geometry parameters were obtained from bone mineral density (BMD) images done by dual-energy X-ray absorptiometry using hip structure analysis at baseline and 12 months. Both the diet and diet-exercise groups had significant decreases in body weight (-9.6% and -9.4%, respectively), whereas weight was stable in the exercise and control groups. Sclerostin levels increased significantly and progressively in the diet group (6.6% ± 1.7% and 10.5% ± 1.9% at 6 and 12 months, respectively, all p < 0.05), whereas they were unchanged in the other groups; in particular, they were stable in the diet-exercise group (0.7% ± 1.6% and 0.4% ± 1.7% at 6 and 12 months, respectively, all p = 0.05). Hip geometry parameters showed significant decreases in cross-sectional area, cortical thickness, and BMD; and increases in buckling ratio at the narrow neck, intertrochanter, and femoral shaft. These negative changes on bone geometry were not observed in the diet-exercise group. Significant correlations between changes in sclerostin and changes in certain hip geometry parameters were also observed (p < 0.05). In conclusion, the increase in sclerostin levels with weight loss that was prevented by exercise may partly mediate the negative effects of weight loss on bone metabolism and the osteoprotective effect of exercise training.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 05/2012; 27(5):1215-21. DOI:10.1002/jbmr.1560 · 6.83 Impact Factor
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