Searchable abstracts of presentations at key conferences in endocrinology

ea0016p660 | Signal transduction | ECE2008

Combined rapamycin-octreotide treatment exerts its superior antiproliferative action by dramatically increasing p27/Kip1 expression

Cerovac Vesna , Stalla Gunter , Theodoropoulou Marily

Combined rapamycin-octreotide treatment has a stronger antiproliferative effect on non-functioning pituitary tumor cells compared with each drug alone. The mechanism of the combined treatment action was studied in AtT-20 pituitary tumor cells. Rapamycin is known to induce cell cycle arrest at the G1/S transition point. The entry of eukaryotic cells into the cell cycle is controlled primarily by the activation of cyclin-dependent kinases (CDK4/CDK6 and CDK2) by their respective...

ea0016p542 | Obesity | ECE2008

The sirtuin activating compound resveratrol decreases GH transcription

Monteserin Jose Luis , Stalla Johanna , Stalla Gunter , Theodoropoulou Marily

Caloric restriction is the best known experimental procedure that extends lifespan and resistance to aging-related diseases. Part of these actions was found to be mediated by the NAD-dependent histone deacetylase Sir2/Sirt1. Resveratrol is a polyphenol found in the skin of grapes, which was identified as a Sirt1 activator and subsequently proposed as a caloric restriction mimetic. The aim of the present study was to determine how resveratrol affects the GH axis, which is centr...

ea0063gp161 | Cushing's | ECE2019

Ubiquitin-specific protease 8 (USP8) potentiates glucocorticoid receptor activity in corticotroph tumour cells

Perez-Rivas Luis , Ciato Denis , Colon-Bolea Paula , Reincke Martin , Theodoropoulou Marily

Cushing’s disease tumours bear activating mutations in the ubiquitin-specific-protease 8 gene (USP8) gene in 40-60% of cases. We have previously observed that patients with USP8 mutant tumours have smaller tumour size and show a better response to high dose (8mg) dexamethasone stimulation test compared to those with wild type USP8 (1). The aim of this study was to define the role of USP8 on glucocorticoid receptor (GR) in corticotroph tumour cells. We did experim...

ea0041gp119 | Neuroendocrinology | ECE2016

Hypoxia-inducible factor 1α triggers growth hormone synthesis in acromegalic tumors

Lucia Kristin , Monteserin-Garcia Jose , Buchfelder Michael , Renner Ulrich , Stalla Gunter , Theodoropoulou Marily

Acromegaly is caused by excessive growth hormone (GH) secretion frequently due to GH-secreting pituitary tumors. Acromegalic tumors (ACRO) display reduced microvascular density versus normal pituitaries, suggesting they are under hypoxic conditions. Under hypoxia, tumors gain a survival advantage by stabilizing the transcription factor known as hypoxia-inducible factor 1 alpha (HIF1a). Western blot screening of ACRO (n=40) revealed significantly higher HIF1a protein l...

ea0041ep860 | Pituitary - Basic | ECE2016

Evidence for better response to somatostatin analogues in acromegalic patients treated with metformin

Winkelmann Moritz , Geraedts Victor , Lucia Kristin , Stormann Sylvere , Buchfelder Michael , Stalla Gunter , Theodoropoulou Marily

Somatostatin analogues (SSA) are the mainstay of pituitary-targeted pharmacological treatment in acromegaly, but are characterized by high incidence of resistance in half of cases. The successful management of acromegaly involves in addition to targeting biochemical control the treatment of the metabolic comorbidities and hypopituitarism. In this study we analysed the impact of the concomitant antidiabetic treatment and hormone replacement on the response to SSA. Data were col...

ea0020p565 | Neuroendocrinology, Pituitary and Behaviour | ECE2009

Expression and regulation of HIF-1α and RSUME in murine and human pituitary tumor cells

Shan Bing , Theodoropoulou Marily , Buchfelder Michael , Rachinger Walter , Losa Marco , Stalla Gunter , Arzt Eduardo , Renner Ulrich

Hypoxia inducible factor-1alpha (HIF-1α) is a transcription factor regulating expression of many genes related to oxygen homeostasis in response to hypoxic stress. RSUME is a sumoylation enhancer, which was recently cloned from a pituitary cell line with an increased tumorigenic and angiogenic potential. It has been shown that RSMUE is induced by hypoxia and enhances the sumoylation of HIF-1α. Although many studies demonstrated that the level of HIF-1α is remark...

ea0056p786 | Pituitary - Basic | ECE2018

Enhanced expression of the transcriptional activators YAP and TAZ in non-secreting pituitary tumours

Xekouki Paraskevi , Lodge Emily , Li Ran , Flitsch Jorg , Bornstein Stefan , Theodoropoulou Marily , Andoniadou Cynthia

The Hippo kinase cascade is a crucial signalling pathway regulating organ growth during development in numerous organs. There is mounting evidence implicating this signalling pathway in tumour formation, where it is emerging as an anti-cancer target due to effective pharmacological inhibition of its transcriptional activators YAP/TAZ. We previously demonstrated activity of the Hippo kinase cascade in the mouse pituitary and nuclear association of YAP/TAZ with SOX2 expressing p...

ea0073pep13.5 | Presented ePosters 13: Pituitary and Neuroendocrinology | ECE2021

Cushing’s syndrome and chronotype

Albani Adriana , Zopp Stephanie , Simon Julia , Vogel Frederick , Reincke Martin , Merrow Martha , Theodoropoulou Marily

Patients with Cushing’s syndrome have a poor quality of sleep. However, little is known about their timing of sleep as regulated by the circadian clock, the so called-chronotype. Considering that patients with Cushing’s syndrome lose their rhythmic circadian cortisol secretion and that corticosteroids act as synchronizer of the circadian clock in cells, aim of the study was to determine whether patients with Cushing’s syndrome alter the timing of their sleep com...

ea0063gp156 | Cushing's | ECE2019

Correlation between responsiveness to CRH stimulation test in Cushing’s disease patients and USP8 mutational status

Albani Adriana , Perez-Rivas Luis , Buchfelder Michael , Honegger Jurgen , Stalla Gunter , Zopp Stefanie , Reincke Martin , Theodoropoulou Marily

Corticotrophin-releasing hormone (CRH) stimulation test is used in the differential diagnosis of Cushing’s syndrome. Cushing’s disease tumours carry somatic driver activating mutations in the ubiquitin-specific-protease 8 (USP8) gene in almost half of the cases. The aim of the present study was to examine whether the USP8 mutational status in Cushing’s disease tumours influences the response to the CRH stimulation test. We did a monocentric, re...

ea0041gp109 | Endocrine Tumours | ECE2016

Expression and mutational status of USP8 in tumours causing ectopic Cushing’s syndrome

Perez-Rivas Luis Gustavo , Theodoropoulou Marily , Oszwald Andrea , Fazel Julia , Komada Masayuki , Kirchner Thomas , Beuschlein Felix , Reincke Martin

Introduction: Mutations activating USP8 have been detected in a high proportion of pituitary adenomas causing Cushing’s disease and have been linked to an increase of ACTH production in corticotroph cells. Whether USP8 mutations are involved in the tumorigenesis of the ectopic Cushing’s syndrome (ECS) caused by neuroendocrine tumors has not been studied.Patients and methods: In this work we evaluate the role of USP8 in a series of 17 t...