Endocrine Abstracts

A growing number of studies suggest that extracellular fragments derived from plasma membrane receptors can play relevant functional roles in the development and progression of certain tumoral pathologies which might, therefore, serve as novel tools in the diagnostic and prognostic of such pathologies. In this scenario, the truncated somatostatin receptor sst5TMD4, which is overexpressed in various endocrine-related cancers (i.e. breast, prostate, neuroendocrine, liver and pit...

Metabolic syndrome (MetS) and type-2 diabetes (T2D) development is critically affected by the loss of phenotypic flexibility (i.e. the difficulty to cope with stressors to maintain metabolic homeostasis). Thus, it is essential to identify key modifiers of phenotypic plasticity that define individual susceptibility to develop T2D. Particularly, there is emerging evidence that alternative mRNA splicing is dysregulated under adverse metabolic-conditions, such as T2D, in several t...

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...

Pituitary adenomas (PA) comprise a commonly underestimated pathology in terms of incidence and associated morbimortality. Somatostatin and dopamine analogs constitute the main medical treatment for PA. However, an appreciable subset of patients are resistant or poorly responsive to these drugs, and hence, the search for new therapies to control tumor growth and/or hormone secretion is crucial. Biguanides such as metformin (MF; commonly used to treat type-2 diabetes), phenformi...

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...

It is now widely accepted that the kisspeptins (kps) and their receptor kiss1r play an essential role in the neuroendocrine regulation of the reproductive axis by stimulating hypothalamic GnRH secretion. However, kiss1 and kiss1r expression in tissues distinct from, but related to, the hypothalamus, prompted us to propose that these molecules may exert regulatory functions in additional places of the neuroendocrine system, such as the pituitary and two of its phy...