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16th European Congress of Endocrinology

Oral Communications

IGF-1 and Thyroid Basic

ea0035oc7.1 | IGF-1 and Thyroid Basic | ECE2014

GH induces chemoresistance in human endometrial cancer cell lines involving ERK 1/2 and PKCdelta

Zuolo Giulia , Minoia Mariella , Gentilin Erica , Gagliano Teresa , Tagliati Federico , Zatelli Maria Chiara , Uberti Ettore degli

Background: Surgery is the main therapeutic option for advanced endometrial cancer; however, when disease relapses, chemotherapy is the only option. Chemoresistance is a very common phenomenon in these tumors. We previously demonstrated that GH protects breast cancer cells towards the cytotoxic effects of doxorubicin, inducing chemoresistance. Recent evidences show that endometrial cancer cells secrete GH, stimulating their own growth in an autocrine fashion.<p class="abst...

ea0035oc7.2 | IGF-1 and Thyroid Basic | ECE2014

The proposed molecular mechanism underlying isolated growth hormone deficiency (IGHD) caused by C53S mutation

Sander Max , Wu Zida , Strasburger Christian J.

Background: Besson A et al. described a patient with homozygous for C53S-hGH suffering from IGHD (JCEM2005 90:2493-9). They observed reduced ability of the mutant to bind and activate GHR in vitro. C53A-hGH lacks the disulfide bond between C53 and C165, which is conserved in GH/prolactin family.Methods: Mouse pituitary AtT-20 cells, HEK-293 and CHO-K1 cells were transfected with plasmids containing C53S, C53A or C53S/C165A cDNA. hGH from cell supernatant...

ea0035oc7.3 | IGF-1 and Thyroid Basic | ECE2014

Targeting the insulin-like growth factor 1 (IGF1R) and insulin (IR) receptor with a dual IGF1R/IR inhibitor, OSI-906, to potentiate mTOR inhibitor effects in experimental models of hepatocellular carcinoma (HCC)

Pivonello Claudia , Negri Mariarosaria , De Martino Maria Cristina , de Angelis Cristina , Napolitano Maria , Izzo Francesco , Colao Annamaria , Hofland Leo J. , Pivonello Rosario

The mTOR and IGF/insulin pathways are frequently dysregulated in HCC. Antitumoral activity of mTOR inhibitors (mTORi) has been demonstrated in experimental models but in early clinical studies mTORi alone have shown modest antitumoral activity. IGF/insulin-dependent Akt activation, via IGF1R and IR, has been suggested as potential mechanism for mTORi resistance. This study aimed at evaluating the expression of mTOR and IGF/insulin pathway components and the effects of mTORi al...

ea0035oc7.4 | IGF-1 and Thyroid Basic | ECE2014

Training MCT10 to transport thyroxine: Structure based targeted mutations in MCT10

Schweizer Ulrich , Braun Doreen , Johannes Jorg

With the identification of mutations in the monocarboxylate transporter 8 (MCT8) gene in patients afflicted with the Allan–Herndon–Dudley syndrome (AHDS), the concept of transporter-mediated transmembrane transport of thyroid hormones was finally accepted. Impaired thyroid hormone transport into neurons and pituitary cells is believed to cause severe psychomotor retardation and altered thyroid hormone function tests. MCT8 is a specific thyroid hormone transporter abl...

ea0035oc7.5 | IGF-1 and Thyroid Basic | ECE2014

Direct triiodothyronine effects in brown adipocytes

Schroder Erich , Perwitz Nina , Resch Julia , Klein Johannes , Lehnert Hendrik , Weitzel Joachim M. , Alexander Iwen K. , Brabant Georg

Introduction: Thyroid hormones (TH) are essential regulators of metabolism and increase energy expenditure (EE). Mitochondria-rich brown adipose tissue (BAT) is specialised in thermogenesis and significantly contributes to EE. BAT contains essential components of TH action but TH transporters like MCT8 have not been characterised so far. As direct effects on O2 consumption and mitochondrial action have not been investigated before we tested MCT8 expression and direct effects o...