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[PMID]: 23667519
[Au] Autor:Haddad NF; Teodoro AJ; Leite de Oliveira F; Soares N; de Mattos RM; Hecht F; Dezonne RS; Vairo L; Goldenberg RC; Gomes FC; de Carvalho DP; Gadelha MR; Nasciutti LE; Miranda-Alves L
[Ad] Address:Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil ; Serviço de Endocrinologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Brazil.
[Ti] Title:Lycopene and Beta-Carotene Induce Growth Inhibition and Proapoptotic Effects on ACTH-Secreting Pituitary Adenoma Cells.
[So] Source:PLoS One;8(5):e62773, 2013.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Pituitary adenomas comprise approximately 10-15% of intracranial tumors and result in morbidity associated with altered hormonal patterns, therapy and compression of adjacent sella turcica structures. The use of functional foods containing carotenoids contributes to reduce the risk of chronic diseases such as cancer and vascular disorders. In this study, we evaluated the influence of different concentrations of beta-carotene and lycopene on cell viability, colony formation, cell cycle, apoptosis, hormone secretion, intercellular communication and expression of connexin 43, Skp2 and p27(kip1) in ACTH-secreting pituitary adenoma cells, the AtT20 cells, incubated for 48 and 96 h with these carotenoids. We observed a decrease in cell viability caused by the lycopene and beta-carotene treatments; in these conditions, the clonogenic ability of the cells was also significantly decreased. Cell cycle analysis revealed that beta-carotene induced an increase of the cells in S and G2/M phases; furthermore, lycopene increased the proportion of these cells in G0/G1 while decreasing the S and G2/M phases. Also, carotenoids induced apoptosis after 96 h. Lycopene and beta-carotene decreased the secretion of ACTH in AtT20 cells in a dose-dependent manner. Carotenoids blocked the gap junction intercellular communication. In addition, the treatments increased the expression of phosphorylated connexin43. Finally, we also demonstrate decreased expression of S-phase kinase-associated protein 2 (Skp2) and increased expression of p27(kip1) in carotenoid-treated cells. These results show that lycopene and beta-carotene were able to negatively modulate events related to the malignant phenotype of AtT-20 cells, through a mechanism that could involve changes in the expression of connexin 43, Skp2 and p27(kip1); and suggest that these compounds might provide a novel pharmacological approach to the treatment of Cushing's disease.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1305
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0062773

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[PMID]: 22851491
[Au] Autor:Pecori Giraldi F; Ambrogio AG; Andrioli M; Sanguin F; Karamouzis I; Karamouzis I; Corsello SM; Scaroni C; Arvat E; Pontecorvi A; Pontercorvi A; Cavagnini F
[Ad] Address:Department of Clinical Sciences and Community Health, University of Milan, Istituto Auxologico Italiano, Piazzale Brescia 40, 20149 Milan, Italy. fpg@auxologico.it
[Ti] Title:Potential role for retinoic acid in patients with Cushing's disease.
[So] Source:J Clin Endocrinol Metab;97(10):3577-83, 2012 Oct.
[Is] ISSN:1945-7197
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:CONTEXT: Cushing's disease, i.e. cortisol excess due to an ACTH-secreting pituitary adenoma, is a rare disorder with considerable morbidity and mortality but no satisfactory medical treatment as yet. Experimental data have recently shown that retinoic acid restrains ACTH secretion by tumoral corticotropes. OBJECTIVE: Our objective was to evaluate the efficacy and safety profile of retinoic acid treatment in patients with Cushing's disease. DESIGN: This is a prospective, multicenter study. Seven patients with Cushing's disease (three men, four postmenopausal women) were started on 10 mg retinoic acid daily and dosage increased up to 80 mg daily for 6-12 months. ACTH, urinary free cortisol (UFC), and serum cortisol as well as clinical features of hypercortisolism and possible side effects of retinoic acid were evaluated at baseline, during retinoic acid administration, and after drug withdrawal. RESULTS: A marked decrease in UFC levels was observed in five patients; mean UFC levels on retinoic acid were 22-73% of baseline values and normalization in UFC was achieved in three patients. Plasma ACTH decreased in the first month of treatment and then returned to pretreatment levels in responsive patients whereas no clear-cut pattern could be detected for serum cortisol. Blood pressure, glycemia, and signs of hypercortisolism, e.g. body weight and facial plethora, were ameliorated to a variable extent on treatment. Patients reported only mild adverse effects, e.g. xerophthalmia and arthralgias. CONCLUSIONS: Long-term treatment with retinoic acid proved beneficial and well tolerated in five of seven patients with Cushing's disease. This represents a novel, promising approach to medical treatment in Cushing's disease.
[Mh] MeSH terms primary: ACTH-Secreting Pituitary Adenoma/drug therapy
Adenoma/drug therapy
Antineoplastic Agents/administration & dosage
Pituitary ACTH Hypersecretion/drug therapy
Tretinoin/administration & dosage
[Mh] MeSH terms secundary: Adolescent
Adrenocorticotropic Hormone/blood
Adult
Antineoplastic Agents/adverse effects
Female
Humans
Hydrocortisone/blood
Hydrocortisone/urine
Male
Middle Aged
Prospective Studies
Treatment Outcome
Tretinoin/adverse effects
Young Adult
[Pt] Publication type:CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Antineoplastic Agents); 302-79-4 (Tretinoin); 50-23-7 (Hydrocortisone); 9002-60-2 (Adrenocorticotropic Hormone)
[Em] Entry month:1212
[Cu] Class update date: 130513
[Lr] Last revision date:130513
[Js] Journal subset:AIM; IM
[Da] Date of entry for processing:121008
[St] Status:MEDLINE
[do] DOI:10.1210/jc.2012-2328

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[PMID]: 21556812
[Au] Autor:Shimon I; Manisterski Y; Kanner AA
[Ad] Address:Institute of Endocrinology and Metabolism, Rabin Medical Center, Beilinson Hospital, 49100, Petah Tiqva, Israel. ilanshi@clalit.org.il
[Ti] Title:Acute cortisol release during stereotactic fractionated radiotherapy to an ACTH-secreting pituitary macroadenoma.
[So] Source:Pituitary;15 Suppl 1:S41-5, 2012 Dec.
[Is] ISSN:1573-7403
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:A 33-year old male was diagnosed with Cushing's disease due to a large and invasive ACTH-secreting macroadenoma. After surgical failure ketoconazole therapy was initiated to control cortisol hypersecretion and his symptoms. He was referred to radiotherapy, and fractionated stereotactic radiotherapy in 30 fractions was delivered. After 12 daily fractions of radiotherapy the urinary cortisol release increased abruptly together with clinical deterioration. The daily ketoconazole dose was increased, and 10 days after concluding radiotherapy his urinary cortisol returned to normal values. Hormonal remission was observed less than 1 year following radiotherapy.
[Mh] MeSH terms primary: Adrenocorticotropic Hormone/secretion
Hydrocortisone/metabolism
Pituitary Neoplasms/radiotherapy
Pituitary Neoplasms/secretion
[Mh] MeSH terms secundary: Adult
Humans
Ketoconazole/therapeutic use
Male
Pituitary Neoplasms/drug therapy
[Pt] Publication type:CASE REPORTS; JOURNAL ARTICLE
[Nm] Name of substance:50-23-7 (Hydrocortisone); 65277-42-1 (Ketoconazole); 9002-60-2 (Adrenocorticotropic Hormone)
[Em] Entry month:1305
[Js] Journal subset:IM
[Da] Date of entry for processing:121126
[St] Status:MEDLINE
[do] DOI:10.1007/s11102-011-0315-2

  4 / 552 MEDLINE  
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[PMID]: 20703943
[Au] Autor:Messer CK; Fowkes ME; Gabrilove JL; Post KD; Son H; Levine AC
[Ad] Address:Department of Endocrinology, Mount Kisco Medical Group, 90 South Bedford Road, Mount Kisco, NY 10549, USA. ckmesser@gmail.com
[Ti] Title:ACTH-producing remnants following apoplexy of an ACTH-secreting pituitary macroadenoma.
[So] Source:Pituitary;15 Suppl 1:S6-9, 2012 Dec.
[Is] ISSN:1573-7403
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Describe a case of apoplexy of an ACTH-producing pituitary adenoma which resulted not only in an empty sella with concurrent hypothyroidism, hypoprolactinemia, and hypogonadism but persistent hypercortisolemia from two distinct extrasellar remnants of the original adenoma. Review the literature to identify other similar cases. The patient's medical history, physical exam, lab data, imaging exams and histopathological results were analyzed and compiled into a case report, and an extensive review of the literature was performed. Endocrinological data revealed hypercortisolism and an elevated ACTH with an otherwise suppressed pituitary axis. A pituitary MRI showed a macroadenoma in the left cavernous sinus in addition to an empty sella. An octreotide scan revealed lesions in the left sella turcica and the right sphenoid sinus. Tissue samples of both lesions stained positive for ACTH and negative for GH, prolactin, FSH, LH, and TSH. The lesions were surgically removed, and the patient treated with radiation and ketoconazole. This resulted in a significant decrease in ACTH and cortisol as well as a marked improvement in blood glucose control. The review of literature revealed the absence of any similar cases in the past. The patient presented with apoplexy of an ACTH-secreting pituitary macroadenoma with two hormonally active extrasellar remnants. Several cases in the literature describe recurrence of Cushing's disease following infarction of ACTH-secreting adenomas. This is the first documented case of infarction of an ACTH-producing adenoma resulting in two distinct ACTH-producing remnants without recurrence of the original adenoma.
[Mh] MeSH terms primary: ACTH-Secreting Pituitary Adenoma/pathology
Pituitary Gland/pathology
Pituitary Neoplasms/pathology
[Mh] MeSH terms secundary: Adult
Female
Humans
Magnetic Resonance Imaging
[Pt] Publication type:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Em] Entry month:1305
[Js] Journal subset:IM
[Da] Date of entry for processing:121126
[St] Status:MEDLINE
[do] DOI:10.1007/s11102-010-0247-2

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[PMID]: 22918543
[Au] Autor:Shimon I; Rot L; Inbar E
[Ad] Address:Institute of Endocrinology, Rabin Medical Center, Beilinson Hospital, 49100 Petah Tiqva, Israel. ilanshi@clalit.org.il
[Ti] Title:Pituitary-directed medical therapy with pasireotide for a corticotroph macroadenoma: pituitary volume reduction and literature review.
[So] Source:Pituitary;15(4):608-13, 2012 Dec.
[Is] ISSN:1573-7403
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Hypercortisolism due to an ACTH-secreting pituitary adenoma (Cushing's disease) is a chronic condition associated with high morbidity and mortality if inadequately managed. Pasireotide is a multireceptor-targeted somatostatin analogue and is the only approved medical therapy for Cushing's disease that treats the underlying cause of the disorder. This paper reviews the available literature for medical-therapy-induced adenoma volume reduction in patients with Cushing's disease and reports the experience of a 53-year-old surgically, radiologically and medically naïve (de novo) female with a pituitary macroadenoma who declined surgery. This patient was treated with pasireotide as first-line therapy as part of the largest randomized Phase III study evaluating a medical therapy in patients with Cushing's disease (SOM230B2305 trial). Subcutaneous pasireotide significantly decreased tumor volume, suppressed cortisol secretion, and improved clinical signs and symptoms of Cushing's disease in this patient. Based on this experience, first-line pasireotide has the potential to achieve substantial tumor volume reduction in addition to significant improvements in cortisol levels and signs and symptoms in patients with Cushing's disease for whom surgery is not an option.
[Mh] MeSH terms primary: ACTH-Secreting Pituitary Adenoma/drug therapy
Pituitary Gland/pathology
Somatostatin/analogs & derivatives
[Mh] MeSH terms secundary: ACTH-Secreting Pituitary Adenoma/pathology
Humans
Pituitary ACTH Hypersecretion/drug therapy
Pituitary Gland/drug effects
Somatostatin/therapeutic use
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Name of substance:0 (pasireotide); 51110-01-1 (Somatostatin)
[Em] Entry month:1305
[Js] Journal subset:IM
[Da] Date of entry for processing:121109
[St] Status:MEDLINE
[do] DOI:10.1007/s11102-012-0427-3

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[PMID]: 22057967
[Au] Autor:Mathioudakis N; Pendleton C; Quinones-Hinojosa A; Wand GS; Salvatori R
[Ad] Address:Division of Endocrinology, Department of Medicine, The Johns Hopkins University, Baltimore, MD 21287, USA.
[Ti] Title:ACTH-secreting pituitary adenomas: size does not correlate with hormonal activity.
[So] Source:Pituitary;15(4):526-32, 2012 Dec.
[Is] ISSN:1573-7403
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:ACTH-secreting pituitary adenomas (Cushing's disease, CD) are the most frequent cause of Cushing's syndrome. To test whether the size of ACTH-secreting adenomas correlates with the degree of biochemical and clinical features of hypercortisolism, we retrospectively reviewed all newly diagnosed CD patients seen at our institution by two neuro-endocrinologists over a 10-year time period. We documented the number of clinical manifestations and baseline hormonal measurements. There were 37 microadenomas (µAs) and 16 macroadenomas (MAs). We sought to characterize the relationship between tumor size (µA vs. MA) and number of signs and symptoms of hypercortisolism and biochemical assessment of hypercortisolemia. There were no significant differences in mean age, BMI, or prevalence of hypertension and type 2 diabetes between the µA and MA groups. However, the MAs had fewer clinical manifestations of hypercortisolism (29.4% vs. 36.1%, P = 0.02) compared to µAs. There was a higher prevalence of easy bruisability and proximal muscle weakness in the µAs, but otherwise the prevalence of signs and symptoms were similar between groups. The MAs had a lower random serum cortisol (18.2 ± 2.4 vs. 25.9 ± 1.8 mcg/dl, P = 0.018), lower cortisol:ACTH ratio (0.25 ± 0.03 vs. 0.42 ± 0.05, P < 0.048), and lower cortisol:tumor diameter ratio (14.1 ± 2.2 vs. 56.8 ± 7.2, P < 0.0001) than the µAs. We conclude that tumor size does not directly correlate with the extent of hormonal activity in ACTH-secreting adenomas. Biochemical activity and clinical manifestations may be mild even in larger tumors, and therefore a high index of suspicion may be necessary to recognize hypercortisolism in pituitary MAs.
[Mh] MeSH terms primary: ACTH-Secreting Pituitary Adenoma/blood
Adrenocorticotropic Hormone/blood
[Mh] MeSH terms secundary: Adult
Female
Humans
Hydrocortisone/blood
Pituitary ACTH Hypersecretion/blood
Retrospective Studies
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:50-23-7 (Hydrocortisone); 9002-60-2 (Adrenocorticotropic Hormone)
[Em] Entry month:1305
[Js] Journal subset:IM
[Da] Date of entry for processing:121109
[St] Status:MEDLINE
[do] DOI:10.1007/s11102-011-0362-8

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[PMID]: 22908062
[Au] Autor:Alexandraki KI; Munayem Khan M; Chahal HS; Dalantaeva NS; Trivellin G; Berney DM; Caron P; Popovic V; Pfeifer M; Jordan S; Korbonits M; Grossman AB
[Ad] Address:Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine, London, U.K.
[Ti] Title:Oncogene-induced senescence in pituitary adenomas and carcinomas.
[So] Source:Hormones (Athens);11(3):297-307, 2012 Jul-Sep.
[Is] ISSN:1109-3099
[Cp] Country of publication:Greece
[La] Language:eng
[Ab] Abstract:OBJECTIVE: The model of "oncogene-induced senescence" (OIS), resulting in cell-proliferation arrest, has recently been suggested as a possible explanation for the non-progression of pituitary tumours to malignancy. The aim of the study was to compare the expression of ß-galactosidase as a molecular marker of OIS, and p21/p16 as additional markers involved in mediating OIS, in pituitary adenomas, carcinomas and normal pituitary tissue. DESIGN: We performed: a) semi-quantitative immunohistochemistry (ß-galactosidase, p16, p21) in 41 pituitary adenomas [(11 GH-secreting, 9 PRL-secreting, 10 ACTH-secreting, 11 non-functioning (NFPAs)], 6 carcinomas (3 multihormonal: PRL/ACTH/GH, PRL/ACTH, PRL/GH/FSH; 1 non-functioning; 2 ACTH-secreting) and 7 normal pituitary tissues; b) quantitative PCR of mRNA (p16 and p21) in 6 GH-secreting, 6 NFPAs and 6 normal pituitary tissues. RESULTS: ß-galactosidase was significantly increased in GH-secreting tumours (P=0.002), NFPAs (P=0.04), macroadenomas (P=0.03) and carcinomas (P=0.02), as compared to normal pituitary tissue. We found that p16 expression was significantly lower in all tumours (both adenomas and carcinomas) probably secondary to reduced transcription, at least for NFPAs; p21 showed a different biological behaviour, implying that p21 and p16 may play different roles in the senescence of each individual type of adenoma. CONCLUSIONS: ß-galactosidase was significantly over-expressed in GH-secreting and NFPAs, and unexpectedly also in carcinomas. We speculate that the senescence pathway, which may explain the rarity of malignant progression to carcinomas in GH-secreting and NFPAs, might not be universal but cell-type specific.
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Entry month:1208
[Js] Journal subset:IM
[St] Status:In-Process

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[PMID]: 23393167
[Au] Autor:Lambert JK; Goldberg L; Fayngold S; Kostadinov J; Post KD; Geer EB
[Ad] Address:Division of Endocrinology, Mount Sinai Medical Center, New York, New York 10029, USA.
[Ti] Title:Predictors of mortality and long-term outcomes in treated Cushing's disease: a study of 346 patients.
[So] Source:J Clin Endocrinol Metab;98(3):1022-30, 2013 Mar.
[Is] ISSN:1945-7197
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:CONTEXT: Active Cushing's disease (CD) confers a 4-fold increase in mortality and is associated with significant morbidities. Although excess mortality risk may persist even after CD treatment, predictors of risk in treated CD are not well understood. OBJECTIVE: To identify predictors of mortality, cardiovascular (CV) disease, and recurrence after long-term follow-up among patients with treated CD. DESIGN, SETTING, AND PATIENTS: A retrospective chart review was conducted to evaluate patients with CD who underwent transsphenoidal adenectomy with a single surgeon. OUTCOME MEASURES: Patients were categorized based on disease response after initial treatment. Cox proportional hazard models identified predictors of mortality, recurrence, and CV outcomes in the overall cohort and each subgroup. RESULTS: Three hundred forty-six subjects were included. Mean age was 39.9 years, and mean duration of follow-up was 6.3 years (range, 1 mo to 30 y). Duration of exposure to excess glucocorticoids, estimated by duration of symptoms before diagnosis until remission was achieved by any means, was 40.0 months. Multivariate analyses demonstrated that duration of glucocorticoid exposure elevated the risk of death (P = .038), as did older age at diagnosis (P = 0.0001) and preoperative ACTH concentration (P = .007). Among patients who achieved remission, depression increased the hazard of death (P < .01). Male sex, age at diagnosis, diabetes, and depression elevated the risk of CV disease (P < .05). CONCLUSION: Long-term follow-up of a large cohort of treated patients with CD identified several novel predictors of mortality. These data illustrate the importance of early recognition and treatment of CD. Long-term follow-up, with management of persistent comorbidities, is needed even after successful treatment of CD.
[Mh] MeSH terms primary: ACTH-Secreting Pituitary Adenoma/mortality
ACTH-Secreting Pituitary Adenoma/surgery
Adenoma/mortality
Adenoma/surgery
Pituitary ACTH Hypersecretion/mortality
Pituitary ACTH Hypersecretion/surgery
[Mh] MeSH terms secundary: Adolescent
Adult
Aged
Child
Comorbidity
Female
Follow-Up Studies
Humans
Incidence
Kaplan-Meier Estimate
Male
Middle Aged
Multivariate Analysis
Predictive Value of Tests
Remission Induction
Retrospective Studies
Risk Factors
Treatment Outcome
Young Adult
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Em] Entry month:1304
[Js] Journal subset:AIM; IM
[Da] Date of entry for processing:130308
[St] Status:MEDLINE
[do] DOI:10.1210/jc.2012-2893

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[PMID]: 23299948
[Au] Autor:Veit JA; Boehm B; Luster M; Scheuerle A; Rotter N; Rettinger G; Scheithauer M
[Ad] Address:Department of ENT Surgery, University Hospital Ulm, Ulm, Germany.
[Ti] Title:Detection of paranasal ectopic adrenocorticotropic hormone-secreting pituitary adenoma by Ga-68-DOTANOC positron-emission tomography-computed tomography.
[So] Source:Laryngoscope;123(5):1132-5, 2013 May.
[Is] ISSN:1531-4995
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Ectopic adrenocorticotropic hormone (ACTH)-secreting tumors account for approximately 10% of Cushing's syndrome (CS). We present an extremely rare case of a patient with CS caused by an ectopic ACTH-secreting pituitary adenoma (EAPA) of the ethmoid sinus. The tumor was identified by positron-emission tomography-computed tomography (PET/CT) using the somatostatin receptor analogue Ga-68-DOTANOC. Transnasal endoscopic resection was performed and the patient showed significant clinical improvement with normalization of the endocrine pituitary axis. Immunostaining showed a somatostatin receptor 2 and 5-positive ACTH-producing adenoma. In patients with ectopic ACTH secretion, Ga-68-DOTANOC-PET/CT may play an important role in the localization of EAPA. Transnasal endoscopic resection is the therapy of choice.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1304
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1002/lary.23867

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[PMID]: 23525216
[Au] Autor:Gentilin E; Tagliati F; Filieri C; Molè D; Minoia M; Rosaria Ambrosio M; Degli Uberti EC; Zatelli MC
[Ad] Address:MD, PhD, Section of Endocrinology, Department of Medical Sciences, University of Ferrara, Via Savonarola 9, 44100 Ferrara, Italy. ztlmch@unife.it.
[Ti] Title:miR-26a Plays an Important Role in Cell Cycle Regulation in ACTH-Secreting Pituitary Adenomas by Modulating Protein Kinase Cδ.
[So] Source:Endocrinology;154(5):1690-700, 2013 May.
[Is] ISSN:1945-7170
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The functional aftermath of microRNA (miRNA) dysregulation in ACTH-secreting pituitary adenomas has not been demonstrated. miRNAs represent diagnostic and prognostic biomarkers as well as putative therapeutic targets; their investigation may shed light on the mechanisms that underpin pituitary adenoma development and progression. Drugs interacting with such pathways may help in achieving disease control also in the settings of ACTH-secreting pituitary adenomas. We investigated the expression of 10 miRNAs among those that were found as most dysregulated in human pituitary adenoma tissues in the settings of a murine ACTH-secreting pituitary adenoma cell line, AtT20/D16v-F2. The selected miRNAs to be submitted to further investigation in AtT20/D16v-F2 cells represent an expression panel including 5 up-regulated and 5 down-regulated miRNAs. Among these, we selected the most dysregulated mouse miRNA and searched for miRNA targets and their biological function. We found that AtT20/D16v-F2 cells have a specific miRNA expression profile and that miR-26a is the most dysregulated miRNA. The latter is overexpressed in human pituitary adenomas and can control viable cell number in the in vitro model without involving caspase 3/7-mediated apoptosis. We demonstrated that protein kinase Cδ (PRKCD) is a direct target of miR-26a and that miR26a inhibition delays the cell cycle in G1 phase. This effect involves down-regulation of cyclin E and cyclin A expression via PRKCD modulation. miR-26a and related pathways, such as PRKCD, play an important role in cell cycle control of ACTH pituitary cells, opening new therapeutic possibilities for the treatment of persistent/recurrent Cushing's disease.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1304
[Js] Journal subset:AIM; IM
[St] Status:In-Data-Review
[do] DOI:10.1210/en.2012-2070


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