Endocrine Abstracts

Thyroid hormones (TH) reduce liver steatosis. As steatosis is the initial step of alcoholic liver disease (ALD), we hypothesized that TH treatment could ameliorate ALD. Wildtype (WT) mice were treated with either ethanol (EtOH) or liquid control diet for 10 days followed by a single EtOH or maltose binge on day 11. In both groups, diet was supplemented with either T3 or solvent. Serum triglycerides (TG) were increased by EtOH and, surprisingly, further elevated by T3. Liver we...

Objective: The soluble leptin receptor (sOb-R) is generated by ectodomain shedding of the membrane-associated Ob-R and may modulate leptin action in metabolic dysregulations. The objective of our study was to investigate whether or not sOb-R generation may be induced by indicators of energy availability or metabolic regulators in a cell model.Material and methods: The four human Ob-R isoforms were cloned, characterized by binding experiments with 125-iod...

The systemic function of thyroid hormones (TH) is highly dependent on their local action in distinct cell populations. A major target of TH are immune cells, yet knowledge on the effect of TH on immune responses is still incomplete. Within this study we aimed to determine the impact of TH on T cells, key players of immune responses, in more detail. To this end, we analyzed the activation and function of T cells from mice lacking TRα (TRα0/0) or expressing ...

The thyroid hormone (TH) transporters Mct8 (encoded by Slc16a2) and Oatp1c1 (encoded by Slco1c1) are critically involved in mediating TH passage across mouse brain barrier cells. Mct8/Oatp1c1 deficient mice (= DKO mice) exhibit a strongly reduced brain TH content and consequently, an impaired neuronal development and hypomyelination all of which are also seen in patients with MCT8 deficiency (Allan-Herndon-Dudley Syndrome, AHDS). Our recent studies of mouse mutants lacking bot...

Background: Increasing age is associated with poorer survival in DTC [Oyer SL, 2012]. In the phase 3 COSMIC-311 trial (NCT03690388), cabozantinib, an inhibitor of VEGFR2, MET, AXL and RET, significantly improved the progression-free survival (PFS) vs placebo in previously treated patients with RAI-R DTC (HR 0.22, 96% CI 0.13-0.36; P<0.0001; median follow-up 6.2 months). The impact of age on efficacy and safety was included in the prespecified subgroup analysis.</p...

The mTOR and IGF pathways have been suggested to play a role in the pathogenesis of pheochromocytomas (PCC). mTOR inhibitors, as sirolimus (S) and everolimus (E), as well as IGF1R antagonists could be a potential novel treatment for malignant PPC.The aim of this study was to evaluate the expression of the main components of the IGF/mTOR pathway in human PCC and to investigate the effects of the mTOR inhibitors S and E and of the IGF1R/insulin receptor (I...

Ghrelin, the natural ligand for the GHS-R, modulates proliferation in cell lines derived from malignant breast tissue. It has been suggested that this action is independent of the GHS-R. We have previously demonstrated that MCF7 cells expressed ghrelin but not GHS-R mRNA and MDA-MB231 cells expressed GHS-R but not ghrelin mRNA. To determine whether ghrelin modulates proliferation in MCF7 and MDA-MB231 cells we performed proliferation assays treating with saline, 1 and 10nM ghr...

Introduction: Transcriptional regulation of gene expression by miRNAs is critical for the fine-tuning of adrenal stress response. However, its role in hypercortisolism has not been explored well. The study addresses this gap using adrenal samples of 3 patient groups from the German Cushing’s registry: Cortisol-Producing-Adenoma (CPA), Primary Bilateral Adrenal Hyperplasia (PBMAH) and controls (adrenal samples of patients with pheochromocytoma).Metho...

Introduction: HIV-infected patients often display a moderate to severe GH deficiency (GHD). To investigate the effects of r-hGH on hormonal parameters and body composition in patients with HIV-related lipodystrophy (HIV-r-L) and concomitant GHD, we studied 60 patients with HIV-r-L, 28 male and 32 females aged 18–65 years. According to their response to GHRH+Arginine (GH peak assumed to be normal when >7.5 ng/ml) patients were assigned to the following 3 groups: Group ...

Background: Adult growth hormone (GH) deficiency (AGHD) is related with alterations in body composition, increased abdominal and visceral adiposity, adverse change in lipid and carbohydrate metabolism, and reduction of bone mineral density (BMD).Aim: To compare baseline outcomes concerning body composition and biochemical/hormonal data among adult patients with AGHD referring to a single endocrinological center and grouped according to their history of r...