Endocrine Abstracts

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...

Ghrelin was isolated from stomach by its ability to stimulate growth hormone (GH) release through the GH-secretagogue receptor (GHS-R1a). However, ghrelin/GHS-R expression in multiple tissues and tumor types suggested additional roles for this tandem. Ghrelin, a 28-aminoacid peptide, requires a unique O-acylation at its Ser-3 residue to bind GHS-R1a and release GH. Conversely, unacylated ghrelin (UAG), initially considered inactive, seems to play distinct metabolic role...

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...

Gliomas constitute the most frequent type of brain tumors and are characterized by a rapid growth and high diffusion through the brain. In particular, astrocytomas are a subtype of malignant gliomas that are graded from low to high aggressiveness (i.e. grade I, II, III and IV), being grade IV (glioblastoma multiforme, GBM) the most malignant type, and one of the most common cancers in the brain and CNS. To date, surgery is the first-line therapy combined with chemotherapy or r...

Antidiabetic biguanides, such as metformin (the most commonly prescribed drug to treat type 2 diabetes) and phenformin, are synthetic insulin-sensitizing agents. In addition to their well-known anti-hyperglycemic actions, biguanides are being also studied in other medical disorders due to the beneficial effects that they exert in important pathologies, including cardiovascular disease or different types of cancer. Although some scattered studies have suggested that metformin c...