Endocrine Abstracts

The primary treatment of adrenocortical carcinoma (ACC) is surgery and the adrenolytic mitotane. In order to test the effect of everolimus, nilotinib, imatinib and zoledronic Acid/ZOL in combination with mitotane were used ACC cell line NCI-H295R, in monolayer (2D) and spheroid (3D) cell cultures. The cytotoxicity promoted by treatments was analyzed by MTS and Cell Death assays. These assays were also performed intending of use them to test drugs in tumor cell cultures from pa...

Our previous data showed that histological markers of the X-zone in mice adrenal (fetal zone in human adrenal) were still present in adult males and postpartum SF1/SOCS3 KO females. This change led to a distinct distribution of lipid droplets along the adrenal cortex and a blunted ACTH-induced corticosterone secretion in SF1/SOCS3 KO mice. Here we have examined the morphological and functional adrenals of SF1/SOCS3KO male mice adrenals at 3, 8 and 15 weeks through histochemica...

Changes in the composition of the extracellular matrix (ECM) induce different cell signaling in normal tissues and in pathological conditions. ECM alteration in the adrenal microenvironment may contribute to both the development and function of adrenal gland. The adrenal gland consists of a cortex, with three concentric zones, glomerulosa (ZG), fasciculata (ZF) and reticularis (ZR), and the medulla (M), surrounded by a capsule. Here, we describe the differences among the ECM s...

Background: Germline mutations of ARMC5 (Armadillo repeat containing 5 gene) were identified as a frequent cause of primary bilateral macronodular adrenal hyperplasia (PBMAH). ARMC5 is considered as a tumor suppressor gene regulating apoptosis and steroidogenesis by unknown mechanisms. The ARMC5 protein contains a N-terminal domain made of Armadillo (ARM) repeats and a C-terminal ‘Bric-a-Brac, Tramtrack, Broad-complex/Pox virus and Zinc finger (BTB/POZ)&...

Background: The mechanisms causing hypercortisolism in primary macronodular adrenocortical hyperplasia (PMAH) are not fully clarified. The participation of ectopic receptors and autocrine/paracrine regulation of intra-adrenal ACTH in hyperplastic tissue have been considered. Additionally, germline ARMC5 mutations have been described as main cause of PMAH. So far, the functional study that analyzed the role of ARMC5 used the adrenocortical carcinoma cell line, H295R. T...

Background: ARMC5 (armadillo repeat containing 5) has been identified as the gene responsible for PBMAH (Primary Bilateral Macronodular Adrenal Hyperplasia). ARMC5 inactivating mutations are reported in 20 to 25% of PBMAH patients. ARMC5, is considered as a tumor suppressor gene controlling apoptosis and regulating steroidogenesis. The mechanisms of action of ARMC5 are unknown. The structure of the ARMC5 protein contains ARM repeats and a BT...