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Guillemot J.,University of Rouen | Guillemot J.,Clinical Research Institute of Montreal | Thouennon E.,University of Rouen | Guerin M.,University of Rouen | And 9 more authors.
Journal of Molecular Endocrinology | Year: 2012

We have previously demonstrated that measurement of tissue concentrations of the secretogranin II (SgII or SCG2 as listed in the HUGO database)-derived peptide EM66 may help to discriminate between benign and malignant pheochromocytomas and that EM66 represents a sensitive plasma marker of pheochromocytomas. Here, we investigated the gene expression and protein production of SgII in 13 normal adrenal glands, and 35 benign and 16 malignant pheochromocytomas with the goal to examine the molecular mechanisms leading to the marked variations in the expression of EM66 in tumoral chromaffin tissue. EM66 peptide levels were 16-fold higher in benign than in malignant pheochromocytomas and had an area under the receiver-operating characteristic curve of 0.95 for the distinction of benign and malignant tumors. Q-PCR experiments indicated that the SgII gene was significantly underexpressed in malignant tumors compared with benign tumors. Western blot analysis using antisera directed against SgII and SgII-derived fragments revealed lower SgII protein and SgII-processing products in malignant tumors. Western blot also showed that low p-cAMP-responsive element-binding (CREB) concentrations seemed to be associated with the malignant status. In addition, the prohormone convertase PC1 and PC2 genes and proteins were overexpressed in benign pheochromocytomas compared with malignant pheochromocytomas. Low concentrations of EM66 found in malignant tumors are associated with reduced expression and production of SgII and SgII-derived peptides that could be ascribed to a decrease in SgII gene transcription, probably linked to p-CREB down-regulation, and to lower PC levels. These findings highlight the mechanisms leading to lower concentrations of EM66 in malignant pheochromocytoma and strengthen the notion that this peptide is a suitable marker of this neuroendocrine tumor. © 2012 Society for Endocrinology.

The role of GLP-1 receptor agonists (GLP1-RA), known as 'incretin effect', has been proved in type 2 diabetic subjects, not only on the improvement of the glycemic profile but also on a progressive weight loss and it was confirmed in obese non-diabetic patients as well. Increase of insulin secretion and decrease of the postprandial glucagon are found among the already described mechanisms. In addition, GLP-1 induces a decrease of cellular apoptosis, a ß-pancreatic cells' mass protection, an immunomodulation and an antiinflammatory effect in mice. This mechanism could explain the beneficial effect of GLP1-RA in type 1 diabetic patients, as described in the literature, especially the pediatric one. The gastric bypass may improve the glycemic profile of type 2 diabetic subjects, probably through an increase of postprandial GLP-1 secretion over the major effect of a substantial weight loss. We evoke the hypothesis that a perturbation of postprandial glycemia after gastric bypass at a type 1 diabetic patient, might be due to a deficit of GLP-1 in this population. We show the beneficial effect of the association between GLP1-RA and insulin therapy in a type 1 diabetic patient operated for a gastric bypass. Maybe we should talk not only about a defect of insulin but also of incretin secretion in the definition of type 1 diabetes. Extensive studies should explore this association. © 2014 - Elsevier Masson SAS - Tous droits réservés.

Senou M.,Catholic University of Louvain | Khalifa C.,Catholic University of Louvain | Thimmesch M.,Catholic University of Louvain | Jouret F.,Catholic University of Louvain | And 10 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2010

Context: Pendred syndrome is caused by mutations in the gene coding for pendrin, an apical Cl-/I- exchanger. Objective: To analyze intrathyroidal compensatory mechanisms when pendrin is lacking, we investigated the thyroid of a patient with Pendred syndrome. The expression of proteins involved in thyroid hormone synthesis, markers of oxidative stress (OS), cell proliferation, apoptosis, and antioxidant enzymes were analyzed. Results: Three morphological zones were identified: nearly normal follicles with iodine-rich thyroglobulin in the colloid (zone 1.a), small follicles without iodine-rich thyroglobulin in lumina (zone 1.b), and destroyed follicles (zone 2). In zones 1.a, dual oxidase (Duox) and thyroid peroxidase (TPO) were localized at the apical pole, OS and cell apoptosis were absent, but ClC-5 expression was strongly increased. In zones 1.b, Duox and TPOwere aberrantly present and increased in the cytosol and associated with high OS, apoptosis, cell proliferation, and increased expression of peroxiredoxin-5, catalase, and dehalogenase-1 but moderate ClC-5 expression. Conclusion: In conclusion, the absence of pendrin is accompanied by increased ClC-5 expression that may transiently compensate for apical iodide efflux. In more affected follicles, Duox and TPO are relocated in the cytosol, leading to abnormal intracellular thyroid hormone synthesis, which results in cell destruction presumably because intracellular OS cannot be buffered by antioxidant defenses. Copyright © 2010 by The Endocrine Society.

Pienkowski C.,Unite Dendocrinologie | Kalfa N.,Montpellier University Hospital Center
Journal de Gynecologie Obstetrique et Biologie de la Reproduction | Year: 2013

Ovarian tumors in childhood are rare, often organic with 10% of malignant cases. Functional pathology dominates in adolescence and its management is the same as the adult. The clinical symptoms of PBOT (presumed benign ovarian tumor) are non-specific. The main clinical signs are acute pain, associated with peritoneal irritation syndrome, which can suggest an ovarian torsion, a mass or the development of secondary sexual characters. Hyperestrogenemia suggests a McCune-Albright syndrome or a granulosa tumor. Hyperandrogenism evokes a malignant tumor. Pelvic ultrasound is the main examination. Pure liquid cysts are benign but could be organic if persisting beyond 6 months. MRI and tumor markers are needed for heterogeneous cyst diagnosis. The protected extraction of a cyst is recommended during the laparoscopic cystectomy. If case of doubt of malignancy, laparoscopy allows the peritoneal cavity exploration. In case of torsion, ovarian untwisting must be performed. After untwisting, the ovary must be preserved because macroscopic aspect is not predictive of the ovarian function recovery. No medical treatment is effective. After resection, US follow up is required for five years. © 2013 Elsevier Masson SAS. All rights reserved.

Bouvattier C.,University Paris - Sud | Pienkowski C.,Unite Dendocrinologie
Early Puberty: Latest Findings, Diagnosis, Treatment, Long-term Outcome | Year: 2015

This book focuses on the state of the art in fully grasping precocious puberty and its consequences, incorporating advances in the areas of endocrinology, genetics, imaging and therapeutics to offer an indispensable tool for all physicians interested in the latest advances in this field. The authors present the latest findings on early puberty in girls and boys. The dynamic process of maturation is influenced by many signals and reshapes growing children's role within their environment. Readers will benefit from the educational value and level of depth of the individual chapters; written by respected experts and in a self-contained format, they can also be read separately to address specific interests. © Springer International Publishing Switzerland 2016. All rights are reserved.

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