Endocrine Abstracts

Several studies support the existence of multipotent stem/progenitor cells in the adult pituitary, whereas the presence of stem cell in pituitary tumors and their role in pituitary tumorigenesis are still on debate. Aim of this study was to identify and characterize stem-like cells in non-functioning pituitary adenomas (NFPAs). To this purpose primary cell cultures from 25 NFPAs were grown in culture conditions that favored stem cell growth (EGF, bFGF and B27 containing medium...

The term pseudohypoparathyroidism (PHP) defines a heterogeneous group of rare, related and deeply impairing metabolic diseases due to end-organ resistance to the actions of PTH, associated to molecular defects at the GNAS locus. Different subtypes of PHP have been described based on the existence of additional clinical features, such as resistance to other hormones acting via GPCRs and Albright’s hereditary osteodystrophy (AHO). Recently, the detection in a small subset o...

The actin binding protein filamin A (FLNA) is required for somatostatin receptor 2 (SST2) and dopamine receptor 2 (DRD2) expression, intracellular localization and signaling in GH- and PRL-secreting pituitary tumors, respectively, playing a role in tumor responsiveness to somatostatin analogs and dopaminergic drugs. FLNA functions are tightly regulated by several mechanisms, including FLNA phosphorylation. It has recently been shown that in GH-secreting pituitary tumors FLNA p...

cAMP is implicated in the inhibition or stimulation of proliferation depending on cell type. The activation of cAMP–PKA pathway generates proliferative signals in GH-secreting adenomas whereas this effect is not present, or even opposite, in non-functioning pituitary cells (NFPA). Although cAMP effects were initially attributed to PKA activation, recently the discovery of two cAMP-activated guanine nucleotide exchange factors (Epac1,2) was proposed as a novel mechanism fo...

In this study we employed a novel bioluminescence resonance energy transfer (BRET) biosensor to study the coupling specificity of somatostatin receptor 5 (SST5) and its naturally occurring mutant R240W in living cells. Our previous data demonstrated that SST5 carrying the R240W mutation as well as other mutations in the third intracellular loop maintained the ability to inhibit intracellular cAMP levels similarly to the wild-type but failed to mediate the inhibition of intrace...

Pseudohypoparathyroidism (PHP) type I includes two major subtypes, Ia and Ib. About 70% of Ia patients, characterized by Albright hereditary osteodystrophy and multihormone resistance (PTH/TSH/GHRH/gonadotropins), carry point mutations in GNAS exons encoding Gsα. About 60% of Ib patients, with hormone resistance limited to PTH and TSH, have methylation defects within GNAS locus (sporadic or genetic-based). Recently, methylation defects were detected in pts with Ia phenoty...

Introduction: Disorder of water and electrolyte balance may develop after transsphenoidal (TNS) surgery for pituitary adenomas. In particular, delayed hyponatremia (Na<135 mEq/l) due to SIADH is reported in 8–35% of patients and usually resolves with fluid-intake restriction within 6 days. The possible role of vasopressin-2 receptor antagonists in this clinical setting has not been elucidated.Case report: We report a case of a 57-years-old Cauca...

The two main subtypes of pseudohypoparathyroidism (PHP), PHP-Ia and -Ib, are caused by mutations in GNAS exons 1–13 and methylation defects in the imprinted GNAS cluster, respectively. PHP-Ia patients show Albright hereditary osteodystrophy (AHO) and resistance toward multiple hormones (PTH/TSH/GHRH/gonadotropins), whereas PHP-Ib patients classically display hormone resistance limited to PTH and TSH. Incoming data suggest that the two diseases share more genetic and clini...

Dopamine agonists (DA) inhibit prolactin (PRL) secretion and expression on the pituitary lactotrophs by binding dopamine D2 receptor. Prolactinomas are the most common secreting pituitary adenomas, and DA are the first choice for their treatment because they reduce PRL levels and tumor size. However, a subset of patients is resistant to DA. The mechanisms involved in DA resistance are not fully understood, although decreased expression of D2 receptor or altered signal transduc...

Background: Aberrant cAMP signalling is involved in the pathogenesis of somatotropinomas. Recently, variants of phosphodiesterase type 11A (PDE11A) gene have been described in patients with adrenocortical tumors. Aim of the study was to investigate the presence of these variants in patients with somatotropinomas.Subjects and methods: Germ-line DNA of 78 acromegalic patients was screened for known genetic variants of PDE11A by direct sequencing or restric...