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Corticotroph Adenomas (corticotroph + adenoma)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Vitamin D and Its Analog EB1089 Induce p27 Accumulation and Diminish Association of p27 with Skp2 Independent of PTEN in Pituitary Corticotroph Cells

BRAIN PATHOLOGY, Issue 4 2002
Wei Liu
Disruption of the gene for the cyclin dependent kinase inhibitor (CDKI) p27/kip1 results in pituitary corticotroph hyperplasia while diminished expression of this protein has been described in aggressive human pituitary tumors. We have previously shown that 1,25-vitamin D3 (VD) hypophosphorylates p27 and interferes with the degradation of this CDKI in thyroid carcinoma cells. In this study we investigated whether VD/EB1089 can induce p27 accumulation and cause growth arrest of pituitary corticotroph cells. VD and EB1089 exhibited a significant reduction in AtT20 corticotroph but not PRL235 Iactotroph cell growth. These changes were accompanied by selective accumulation of p27 in AtT20 but not in PRL235 cells. As p27 levels are highly dependent on protein degradation, we examined the effect of VD/EB1089 on p27 association with factors that target this CDKI to the proteasome. VD/EB1089 significantly restricted the association of p27 with Skp2 as well as with cyclin dependent kinase 2 (CDK2). As the tumor suppressor and phosphatase PTEN has been implicated in p27 regulation, we tested whether the effects of VD/EB1089 on p27 accumulation in corticotrophs could be mediated through this pathway. VD/EB1089 did not appreciably alter PTEN expression. Moreover, transfection of PTEN did not influence the effect of VD on p27 accumulation in corticotrophs. We conclude that VD/EB1089 can selectively arrest pituitary corticotroph growth and induce p27 accumulation. This effect is mediated at least partially through diminished p27 association with Skp2 and with CDK2. In contrast to other cell systems, PTEN does not participate in the regulation of corticotroph p27 and is not involved in mediating the effect of VD on p27 in these cells. Our findings highlight p27 and VD analogs as targets for manipulation and drug development respectively in the treatment of inoperable corticotroph adenomas. [source]

Silent corticotroph adenomas have unique recurrence characteristics compared with other nonfunctioning pituitary adenomas

CLINICAL ENDOCRINOLOGY, Issue 5 2010
Hwa Young Cho
Summary Objective, The prevalence of silent corticotroph adenomas (SCAs) is not rare among nonfunctioning pituitary adenomas (NFPAs); however, it is unknown whether the clinical significance of SCAs differs from that of NFPAs without ACTH immunoreactivity (non-SCAs). Our goal was to compare the clinical characteristics and natural history between patients with SCAs and non-SCAs. Design/patients, We reviewed the medical records of all patients who underwent transsphenoidal surgery for NFPAs from January 1990 to October 2007 at the Seoul National University Hospital. Measurements, We analysed whether clinical manifestations at diagnosis, postoperative recurrence rate and recurrence characteristics differed between SCA and non-SCA patients. Results, In total, 28 patients with SCAs and 134 patients with non-SCAs were analysed. The mean age at the time of diagnosis was 44 years (range, 13,67 years) in the SCA group and 50 years (18,79 years) in the non-SCA group (P = 0·026), with respective follow-up periods of 5·2 (range, 1·0,16·0 years) and 4·2 years (0·5,16·1 years) (P = 0·255). Overall recurrence rates of SCAs and non-SCAs were 25·0% and 26·9% respectively (P = 0·839). More than two recurrences (P = 0·001) and recurrence after more than 5 years (P = 0·040) were associated with SCAs. Multiple recurrences of SCAs were confined to younger patients. Conclusion, The overall recurrence rate was similar between SCAs and non-SCAs. However, young patients with SCAs had a higher frequency of multiple and late recurrences, which showed more aggressive tumour behaviour. Therefore, we suggest that patients with SCAs, especially patients diagnosed at a young age, require careful long-term monitoring. [source]

Of old and new diseases: genetics of pituitary ACTH excess (Cushing) and deficiency

CLINICAL GENETICS, Issue 3 2007
J Drouin
The pituitary gland orchestrates our endocrine environment: it produces hormones in response to hypothalamic factors that integrate neural inputs and its activity is balanced by the feedback action of peripheral hormones. Disruption of this equilibrium has severe consequences that affect multiple systems and may be fatal. Genetic analysis of pituitary function led to discovery of critical transcription factors that cause hormone deficiencies when mis-expressed. This review will summarize recent findings that led to the first complete clinical description of inherited, isolated corticotropin (ACTH) deficiency (IAD) and to the first molecular mechanism for excessive ACTH production in Cushing's disease. Indeed, mutations in TPIT, a positive or negative regulator of cell fates for different pituitary lineages, cause neonatal IAD, a condition considered anecdotic before discovery of this transcription factor. Cushing's disease is caused by corticotroph adenomas that produce excess ACTH as a result of resistance to glucocorticoids (Gc). Molecular investigation of the normal mechanism of Gc feedback led to identification of two essential proteins for pro-opiomelanocortin repression that are often mis-expressed in corticotroph adenomas thus providing a molecular explanation for Gc resistance. These two proteins, Brg1 and histone deacetylase 2 (HDAC2), are involved in chromatin remodeling and may also participate in the tumorigenic process, as Brg1 is a tumor suppressor. These recent advances have provided improved diagnosis and opened new perspectives for patient management and therapies. [source]