Endocrine Abstracts

Non-functioning pituitary tumors (NFPTs), although benign in nature, frequently present local invasiveness that strongly reduces neurosurgery success. Medical therapy is still under debate, although dopamine (DA) receptor 2 (DRD2) agonists may induce tumor shrinkage in some patients. Aims of this study were: 1) to evaluate the effect of DR2D agonist BIM53097 on migration and invasion of NFPT cells, 2) to investigate the molecular mechanisms regulating the motility of these cel...

Introduction: Patients with aryl hydrocarbon receptor-interacting protein (AIP) gene mutations are predisposed to large, invasive, GH- or PRL-secreting pituitary tumours, occurring at a younger age and poorly responsive to treatment. The zebrafish (ZF) model provides anatomical and functional similarities to human neuroendocrine system.Methods: AIP knock down (KD) ZF embryos were generated using antisense morpholino oligonucleotides injected at one-cell ...

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...

Background: Real-time reverse transcription quantitative PCR (RT-qPCR) has become the method of choice for quantification of gene expression changes. Inappropriate data normalization and inconsistent data analyses are some limitations of RT-qPCR. Pituitary adenomas are frequent tumours and the interpretation of increasingly published data within this field is hindered by the lack of a proper selection and validation of stably expressed reference genes.Ai...

Introduction: We have previously reported on the considerable variability in ACTH-secreting pituitary adenomas in terms of responses to major modulators in vitro (Pecori Giraldi et al J. Neuroendocrinol. 2011). Further studies revealed also differences in gene expression profiles in specimens analyzed by microarray analysis. Aim of this study is to correlate transcriptome expression pattern in archival human ACTH-secreting adenomas with clinical features of patients p...

The chemotherapeutic agent temozolomide (TMZ) has been applied for the treatment of pituitary carcinomas, atypical pituitary adenomas and prolactinomas resistant to dopamine agonist treatment with considerable success. Both shrinkage of the tumors and a drop of excessive hormone production were observed in TMZ-responsive patients. In order to clarify whether the TMZ-induced suppression of hormone secretion was a consequence of tumor shrinkage or caused by direct effects on hor...

Heat shock protein 90 (HSP90) plays a pivotal role in maturation and stabilization of proteins in conditions of stress. Many HSP90 client proteins are involved in oncogenic signaling and cancer progression, therefore HSP90 inhibitors have a potential as pharmaceutical agents. We reported a strong HSP90 overexpression in corticotroph adenomas and the treatment with C-terminal HSP90 inhibitors has potent anti-tumorigenic and anti-secretory effects in these tumors in vitro</e...

Somatostatin analogues (SSA) are the mainstay of pituitary-targeted pharmacological treatment in acromegaly, but are characterized by high incidence of resistance in half of cases. The successful management of acromegaly involves in addition to targeting biochemical control the treatment of the metabolic comorbidities and hypopituitarism. In this study we analysed the impact of the concomitant antidiabetic treatment and hormone replacement on the response to SSA. Data were col...

Background: Full-length human prolactin (protein data bank identification P01236), the precursor of vasoinhibins, is structurally classified as a class-I helical cytokine with a four-helix bundle core and only a minimal degree of dark regions. Experimental data on the solution structure of vasoinhibins are not available.Methods: A recombinant, human vasoinhibin with a molecular mass of 16.7 kDa, comprising amino acids 29-176 of prolactin, was expressed i...

Introduction: Silent somatotroph tumours are GH immunoreactive (IR) pituitary tumours without clinical and biological signs of acromegaly. In our series, they represent 16% of all the somatotroph pituitary tumours. The aim of our study was to compare the somatotroph tumours with and without acromegaly to a better characterization of these silent tumours.Materials and methods: Fifty-nine tumours with acromegaly and 21 silent somatotroph tumours were studi...

Introduction: Polychlorinated biphenyls (PCBs) are environmental pollutants that modulate endocrine functions, induce tumorigenesis, and regulate apoptosis in several tissues; however, their effects on the apoptosis of pituitary cells is unknown.The aim of this study was to evaluate the PCBs influence on the apoptosis of normal pituitary cells and elucidate the molecular mechanisms involved.Methods: Primary cell cultures from mouse...

The hypo and hyperthyroidism alter the synthesis/secretion of pituitary hormones, which in normal conditions present fluctuations in serum concentration during the 24h period. An intrinsic pituitary circadian clock might be related to these oscillations; however, the possible interaction between thyroid hormonal conditions and circadian clock gene expression in anterior pituitary is still unknown. The purpose of this study was to investigate the expression of core circadian cl...

Acromegaly results from excess growth hormone (GH) secretion, due to a pituitary adenoma. Surgery is the first option recommended for treatment of GH secreting pituitary adenomas; medical therapy, mostly represented by somatostatin analogues (SSA), is most often used if surgery is not successful. Insulin-like Growth Factor-1 (IGF-1) physiologically reduces GH levels through an endocrine negative feedback loop. IGF-1 exerts its effects also through PI3K/Akt/mTO...

Introduction: We retrospectively evaluated all patients with pituitary tumours treated in our department from 1.1.1997–1.11.2014Patients and methods: 215 patients (124 females: 91 males, mean age 50,9 y.) were treated because of pituitary tumours. All patients underwent basal hormonal analysis and testing in order to check for hormonal activity. Pituitary masses were divided into groups concerning their hormonal status and were further classified ac...

Proper classification of pituitary adenomas (PA) is an important area of research. Thus, developing of new biomarkers is essential to facilitate the early detection of PA, identify the drug response and predict recurrence reliably in all patients. The usual histological markers of tumor aggressiveness and/or invasiveness are often similar between recurring, regrowing, and stable tumors, and therefore are not reliable as prognostic parameters. To quantitate the levels of the HM...

Background: The prolactin/vasoinhibin axis constitutes a novel endocrine axis in which the generation, secretion, and actions of the pituitary hormones prolactin and vasoinhibins are under control of the hypothalamus, the pituitary gland, and of regulators in the target tissue microenvironment. Vasoinhibins are generated in the pituitary gland and in multiple target tissues through proteolytic cleavage of prolactin; it is not known wether they are also produced in the circulat...

Objective: The exogenous somatostatin inhibits insulin secretion in pancreatic cell and could lead to hyperglycemia. But, Glucagon-like peptide-1 (GLP-1) has insulinotropic actions despite stimulating somatostatin secretion in δ cell. So, we examined whether there is a time difference of insulin and somatostatin secretion after GLP-1 stimulation or secretion rate difference of insulin and somatostatin depending on GLP-1 concentration and glucose concentration ins...