Endocrine Abstracts

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...

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...

Chronic stress is a pervasive concern in the modern society. A long-term hyper activation of the hypothalamic-pituitary-adrenal (HPA) axis leads to elevated amounts of stress hormones [e.g. ACTH and glucocorticoids (GCs)]. This can incur maladaptation that eventually contributes to mental illness, cardiovascular dysfunctions, diabetes, cancer and autoimmune diseases. Emerging key players for stress adaptation of the HPA axis are stem/progenitor cell populations. In this study,...

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...

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...

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...

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...

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...

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...

Background: Cyclic Cushing’s syndrome (cCS) is a sub-entity of Cushing’s syndrome (CS) associated with diagnostic and therapeutic challenges. It describes a condition, in which phases of clear-cut biochemical hypercortisolism are followed by spontaneous troughs of normal or subnormal cortisol secretion. We conducted the first systematic literature review to identify common features of cCS.Methods: We searched MEDLINE (via PubMed) for eligible s...