Pituitary gland and β-catenin signaling: from ontogeny to oncogenesis

Gueorguiev, Maria; Grossman, Ashley

doi:10.1007/s11102-008-0147-x

Cited by 26 publications

(15 citation statements)

References 77 publications

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“…Activation of the Wnt pathway results in cytosolic b-catenin accumulation and its translocation into the nucleus, where it engages in gene activation and the cell cycle (20). Interestingly, recent data have established a major role for the Wnt/ b-catenin signaling pathway in regulating pituitary development and growth (21). These studies demonstrated that b-catenin plays an essential role in transducing the GnRH signal by interacting with multiple DNA-binding proteins in gonadotropes (22)(23)(24).…”

Section: Discussionmentioning

confidence: 99%

“…These studies demonstrated that b-catenin plays an essential role in transducing the GnRH signal by interacting with multiple DNA-binding proteins in gonadotropes (22)(23)(24). In addition, in a mouse model, b-catenin acts as a cofactor for a number of pituitary transcription factors that control pituitary cell specification and exert both stimulatory (prop1 in regulating expression of pit-1) and inhibitory (Hesx1) effects (21,25,26).…”

Section: Discussionmentioning

confidence: 99%

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ANE syndrome caused by mutated RBM28 gene: a novel etiology of combined pituitary hormone deficiency

Spiegel¹,

Shalev²,

Adawi³

et al. 2010

European Journal of Endocrinology

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Objective and design: A homozygous loss-of-function mutation in the gene RBM28 was recently reported to underlie alopecia, neurological defects, and endocrinopathy (ANE) syndrome. The aim of the present study was to characterize the endocrine phenotype of ANE syndrome and to delineate its pathogenesis. Methods: Detailed neuroendocrine assessment was performed in five affected male siblings harboring the homozygous p.L351P mutation in RBM28. Results: All five affected patients, aged 20-39 years, displayed absent puberty, hypogonadism, and variable degrees of short stature. Low IGF1 concentration and a lack of GH response to provocative tests in all siblings were consistent with GH deficiency. Low testosterone and gonadotropin levels with absence or low response to GnRH stimulation indicated hypogonadotropic hypogonadism. ACTH deficiency evolved over time, and glucocorticoid replacement therapy was initiated in four patients. Thyroid analysis showed variable abnormal TSH response to TRH stimulation, suggesting hypothalamic compensated hypothyroidism in four subjects and laboratory hypothyroidism (low free thyroxine) in one patient. Low prolactin levels were shown in one case. Conclusions: The endocrine defects characteristic of ANE syndrome are compatible with variable combined anterior pituitary hormone deficiency (CPHD), which evolves gradually over the years, indicating long-term hormonal monitoring. We propose that defects in the cellular Wnt/b-catenin signaling pathway underlie this endocrinopathy. RBM28 gene defects should be added to the growing list of gene defects associated with syndromic CPHD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

ANE syndrome caused by mutated RBM28 gene: a novel etiology of combined pituitary hormone deficiency

Spiegel¹,

Shalev²,

Adawi³

et al. 2010

European Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…The specific probes and assay IDs are presented in Table S4. These genes were selected by literature reviews and by the KEGG pathway [7], [27], [28]. Reactions were incubated in a 96-well optical plate at 95°C for 10min, followed by 40 cycles of 95°C for 15sec and 60°C for 1 min.…”

Section: Methodsmentioning

confidence: 99%

Components of the Canonical and Non-Canonical Wnt Pathways Are Not Mis-Expressed in Pituitary Tumors

et al. 2013

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IntroductionCanonical and non-canonical Wnt pathways are involved in the genesis of multiple tumors; however, their role in pituitary tumorigenesis is mostly unknown.ObjectiveThis study evaluated gene and protein expression of Wnt pathways in pituitary tumors and whether these expression correlate to clinical outcome.Materials and MethodsGenes of the Wnt canonical pathway: activating ligands (WNT11, WNT4, WNT5A), binding inhibitors (DKK3, sFRP1), β-catenin (CTNNB1), β-catenin degradation complex (APC, AXIN1, GSK3β), inhibitor of β-catenin degradation complex (AKT1), sequester of β-catenin (CDH1), pathway effectors (TCF7, MAPK8, NFAT5), pathway mediators (DVL-1, DVL-2, DVL-3, PRICKLE, VANGL1), target genes (MYB, MYC, WISP2, SPRY1, TP53, CCND1); calcium dependent pathway (PLCB1, CAMK2A, PRKCA, CHP); and planar cell polarity pathway (PTK7, DAAM1, RHOA) were evaluated by QPCR, in 19 GH-, 18 ACTH-secreting, 21 non-secreting (NS) pituitary tumors, and 5 normal pituitaries. Also, the main effectors of canonical (β-catenin), planar cell polarity (JNK), and calcium dependent (NFAT5) Wnt pathways were evaluated by immunohistochemistry.ResultsThere are no differences in gene expression of canonical and non-canonical Wnt pathways between all studied subtypes of pituitary tumors and normal pituitaries, except for WISP2, which was over-expressed in ACTH-secreting tumors compared to normal pituitaries (4.8x; p = 0.02), NS pituitary tumors (7.7x; p = 0.004) and GH-secreting tumors (5.0x; p = 0.05). β-catenin, NFAT5 and JNK proteins showed no expression in normal pituitaries and in any of the pituitary tumor subtypes. Furthermore, no association of the studied gene or protein expression was observed with tumor size, recurrence, and progressive disease. The hierarchical clustering showed a regular pattern of genes of the canonical and non-canonical Wnt pathways randomly distributed throughout the dendrogram.ConclusionsOur data reinforce previous reports suggesting no activation of canonical Wnt pathway in pituitary tumorigenesis. Moreover, we describe, for the first time, evidence that non-canonical Wnt pathways are also not mis-expressed in the pituitary tumors.

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“…(P)RR expressed in the anterior pituitary may be related to the survival of anterior pituitary cells, and the processing and secretion of anterior pituitary hormones, via the association with V-ATPase. Furthermore, (P)RR is involved in the Wnt/β-catenin pathway, which is essential for adult and embryonic stem cell biology, embryonic development and tumorigenesis, including pituitary adenomas [3, 8, 15]. …”

Section: Resultsmentioning

confidence: 99%

<i>In Situ</i> Hybridization Method Reveals (Pro)renin Receptor Expressing Cells in the Pituitary Gland of Rats: Correlation with Anterior Pituitary Hormones

Takahashi

Yatabe

Fujiwara

et al. 2013

Acta Histochem. Cytochem

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Expression of (pro)renin receptor ((P)RR), a specific receptor for renin and prorenin, was studied in rat pituitary gland. In situ hybridization showed that cells expressing (P)RR mRNA were widely distributed in the anterior lobe and intermediate lobe of the pituitary gland. Double-staining using in situ hybridization for (P)RR mRNA and immunohistochemistry for the pituitary hormones showed that (P)RR mRNA was expressed in most of the GH cells and ACTH cells in the anterior lobe. (P)RR mRNA was also expressed in a few prolactin cells and TSH cells, but not in LH cells. The present study has shown for the first time the distribution of (P)RR mRNA expressing cells in the rat pituitary gland. These findings suggest that (P)RR plays physiological roles in the pituitary gland, such as the modulation of the pituitary hormone secretion.

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Pituitary gland and β-catenin signaling: from ontogeny to oncogenesis

Cited by 26 publications

References 77 publications

ANE syndrome caused by mutated RBM28 gene: a novel etiology of combined pituitary hormone deficiency

ANE syndrome caused by mutated RBM28 gene: a novel etiology of combined pituitary hormone deficiency

Components of the Canonical and Non-Canonical Wnt Pathways Are Not Mis-Expressed in Pituitary Tumors

<i>In Situ</i> Hybridization Method Reveals (Pro)renin Receptor Expressing Cells in the Pituitary Gland of Rats: Correlation with Anterior Pituitary Hormones

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