Endocrine Abstracts

Recently, mutations in the PRKACA (catalytic subunit α of the PKA) gene have been identified as causative in 35% of adrenocortical adenomas (ACA) with overt Cushing’s syndrome (Beuschlein et al. 2014). These mutations lead to constitutive activation of PKA signaling and subsequently to an excessive production of cortisol. Protein kinase A is a heterotetramer consisting of two catalytic and two regulatory subunits with several isoforms (Cα, β, &#947...

The vault complex, consisting of a major vault protein (MVP), two minor vault proteins (VPARP and TEP1) and small untranslated RNA molecules (vault RNAs 1–4), is considered the largest intracellular ribonucleoprotein particle. Although in recent years, vaults were believed to be involved in multidrug resistance, the exact function of this complex has remained unclear. Recently, we investigated the therapeutic applicability of a Tumour-Vascular-Disrupting Agent (ASA) in pr...

Introduction: Acromegaly is a rare chronic disorder caused by growth hormone hypersecretion due to GH-producing pituitary adenoma. Surgery is the first-line treatment modality. However, patients with severe cardiac involvement are high-risk candidates for pituitary surgery. These patients may benefit from rapid preoperative biochemical control of acromegaly. There is emerging evidence of efficacy of pegvisomant, a GH-receptor antagonist, (either alone or in combination with so...

A genome-wide association study indicated a correlation between a locus at 5q32 and high aldosterone to renin ratio in subjects from KORA F4 survey. As we considered the genes in this locus for their potential relevance for the etiology of primary aldosteronism, we observed significantly higher expression of one of them, SLC26A2, in mouse adrenal glands, even though the gene’s function in the adrenal was not reported in the literature. Using the human adrenocortical cell ...

Fabry Disease (FD) is a rare X–linked metabolic storage disease characterized by a–galactosidase A deficiency and deficient lysosomal function. The patients suffer from diffuse organ manifestations due to the accumulation of the substrate globotriaosylceramide (Gb3), which are only partially reversed by the available enzyme replacement (ERT) therapies. Previous endocrinological studies in patients with FD included small patient numbers or focused on a certain organ...

In an attempt, to overcome the lack of preclinical models for adrenocortical carcinoma (ACC), we recently aimed at the development of patient-individual tumor models for ACC. During these studies one xenograft (MUC-1), derived from a neck metastasis of an ACC, showed extraordinary engraftment properties and sustained tumor growth over several passages in the murine host. During ongoing studies we investigated and compared all currently available xenograft models for ACC (NCI-H...

Medical treatment of adrenocortical carcinoma (ACC) is limited to common cytotoxic agents, which are usually given in combination with mitotane (M). Recently, we investigated together with M the effects of i) the classical EDP protocol (etoposide, doxorubicin, and cisplatin) and ii) a novel paclitaxel containing scheme PDP (paclitaxel, doxorubicin, and cisplatin) on human NCIh295 cells indicating anti-tumoral superiority of PDP-M over EDP-M regarding cell viability (P...

Urocortin 2 (Ucn2) is a recently identified neuropeptide of the CRF-Family, involved in homeostatic mechanisms for stress response and control of anxiety. To further elucidate Ucn2 effects on steroidogenesis, we developed a mouse model with Ucn2 overexpression in the adrenals, gonads and parts of the hypothalamus, by crossbreeding SF1-Cre+/− mice with R26stop UCN2/stop UCN2 mice. Following genotypes were obtained: SF1-Cre&...

MicroRNAs (miRs) are a subset of small RNA molecules that regulate gene expression post-transcriptionally. Little is known about the expression and the role of miRs in the adrenal gland. Thus, we determined the miRs expression pattern under baseline conditions and 10, 30 and 60 min after ACTH stimulation test in mice adrenal glands using miRs microarray. The miRs expression profile of adrenals obtained from the array was bioinformatically analyzed to indentify miRs that putati...

Medical treatment of adrenocortical carcinoma (ACC) is limited to common cytotoxic agents, which are usually given in combination with mitotane. Recently we have developed a novel therapeutic approach by coupling a monoclonal IGF1 receptor blocking antibody (1H7) to sterically stabilized liposomal doxorubicin (SSLD). 1H7 coupled liposomes showed in vitro high and significant cellular association and furthermore internalization in various human tumor cell lines as well a...