Endocrine Abstracts

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...

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...

Vascular disrupting agents (VDAs) differ from angiogenesis inhibitors by attacking established tumor blood vessels rather than preventing growth of new ones. We investigated effects of the tumor-VDA ASA404 against neuroendocrine tumors of the gastroenteropancreatic system (GEP-NETs) and adrenocortical carcinoma (ACC) 24 h after treatment of BON and NCIh295 tumor bearing mice with ASA404 (A), paclitaxel (P) or the combined administration (A+P). A significant decrease in cell pr...

Bone morphogenetic proteins (BMPs) have been demonstrated to impact tumorigenesis in a variety of tumors. As for the adrenal cortex, quantitative real time PCR analyses revealed down-regulation of various BMPs (e.g. BMP2, BMP5) in tissue samples from adrenocortical carcinoma and adrenocortical tumor cell lines in comparison to normal adrenal glands. Other members, by contrast, as seen for BMP6 remained unaltered. Integrity of BMP dependent pathways in the investigated cell lin...

Aldosterone is synthesized acutely upon stimulation of the renin-angiotensin-aldosterone system from the cells of the zona glomerulosa. Several enzymes are involved in this steroidogenic process including the steroidogenic acute regulatory protein (StAR), P450 side chain cleavage enzyme (Cyp11a1) and aldosterone synthase, the product of the gene Cyp11b2.We investigated the short time transcriptional regulation of these genes in wild type mi...

Objective: To evaluate reduced fertility rates and their possible causes in a cohort of well controlled male adult patients with congenital adrenal hyperplasia.Methods: We clinically assessed 22 male patients with congenital adrenal hyperplasia (15 salt wasting form, 7 simple virilising, age 18–49) according to their hormonal control. Further, we performed testicular ultrasound, MRI of the testis and a sperm count of each. As laboratory markers 17-O...

Bone morphogenic proteins (BMPs) have been demonstrated to impact tumorigenesis in a variety of tumors. As for the adrenal cortex, BMP6 has been implicated as an important modulator of aldosterone secretion. To screen for alterations of BMP dependent pathways in adrenal tumorigenesis we performed gene profiling experiments. By comparing human adrenal carcinoma (ACC) against normal adrenal glands (Co) we detected a down-regulation of various BMPs (e.g. BMP2, BMP5) which was fur...