Endocrine Abstracts

Neuroendocrine tumors (NETs) are uncommon neoplasms with increasing incidence and limited therapeutic options, wherein identification of new diagnostic/prognostic/therapeutic biomarkers is urgently required. Alterations in somatostatin (SST)/cortistatin (CORT) and ghrelin systems have been associated to development/progression of several cancers. Thus, we evaluated expression levels of SST/CORT/ghrelin system components in gastroenteropancreatic-neuroendocrine tumors (GEP-NETs...

Somatostatin (SST) and cortistatin (CORT) are two highly related neuropeptides involved in the regulation of several endocrine secretions. In particular, SST and CORT are two primary negative regulators of GH secretion. Consequently, SST or CORT knockout (KO) mice exhibit elevated GH levels; however, this does not lead to increased IGF-I levels or somatic growth, which has been suggested that could be due to a compensatory mechanism between both peptides. In order to test this...

The presence of the truncated somatostatin receptor sst5TMD4 has been correlated with poor prognosis in breast cancer tumorsand its overexpression in breast cancer derived cell lines is associated with increased cell malignancy. The objective of this study was to examine the cellular and molecular mechanisms underlying this association in order to identify new molecular targets for diagnosis, prognosis or therapy of these tumors. Accordingly, in this study, a breast cancer der...

ESE Young Investigator AwardIntroduction: GH and IGF1 are thought to promote breast carcinogenesis as circulating levels of GH/IGF1 are positively correlated with breast cancer risk in epidemiologic studies, and mouse models with developmental GH/IGF1 deficiency or resistance are less susceptible to breast cancer development. However, no studies have shown that high levels of circulating GH/IGF1 can promote mammary tumorigenesis. In this...

Somatostatin receptors (sst1–sst5) comprise a family of G-protein-coupled, 7 transmembrane domain (TMD) receptors encoded by five separate, intronless genes widely distributed throughout the organism. Somatostatin (SST) and cortistatin (CORT), two highly-related cyclic neuropeptides, bind to sst1–sst5 with comparable subnanomolar affinity to exert a number of (patho)physiological actions, from inhibition of endocrine secretions (e.g. GH and insulin), to the control o...

Ghrelin has been classically known as a GH- and metabolism-regulating hormone, mainly produced by stomach. However, it also acts as a paracrine or autocrine factor in several tissues, where it can regulate tissue growth and neoplastic cell proliferation. Of note, ghrelin needs to be acylated at Ser3 by the ghrelin-O-acyltransferase (GOAT) enzyme to bind to its receptor GHS-R1a. Interestingly, the ghrelin gene can give rise to distinct additional peptides, generated by alternat...

Ghrelin is a 28-aa peptide originally isolated from stomach but present also in many tissues, including hypothalamus and pituitary, where it stimulates growth hormone (GH) release through the ghrelin/GH secretagogue receptor (GHS-R). Ghrelin also increases food intake and adiposity and could play a key integrative role in the endocrine–metabolic interface. Although its primary pituitary cell target are somatotropes, ghrelin also modulates other pituitary cell types, speci...

The neuropeptide somatostatin (SRIF) exerts a wide variety of actions through five SRIF receptors (sst1-5). However, not all SRIF actions can be explained by activation of the known sst. In this context, our research group has identified two novel isoforms of sst subtype 5 (sst5A) named sst5B and sst5C expressed in human and pig. These isoforms are generated by splicing of cryptic introns within the coding sequence, which alters the open reading frame, and results in new, trun...

Development of type-2 diabetes (T2D) is critically affected by the loss of phenotypic flexibility. There is emerging evidence suggesting that, under adverse metabolic conditions, alternative mRNA splicing is markedly dysregulated at different levels. For this reason, we hypothesized that such dysregulation could contribute to loss of phenotypic flexibility. Consequently, we aimed to explore whether changes in the splicing machinery in peripheral blood mononuclear cells (PBMCs)...

Obesity, a multifactorial chronic endocrine-metabolic disease, represents one of the most serious and complex global health threats, as it is commonly associated with multiple and severe comorbidities (e.g. diabetes type-2). Indeed, as a source of severe metabolic-dysregulation, obesity alters physiological, homeostatic gene expression patters in multiple metabolic-tissues, including the central metabolic hub, i.e. the liver. However, the precise molecular mechanisms underlyin...