Endocrine Abstracts

Although generally benign, pituitary tumors frequently present local invasiveness that strongly reduces neurosurgery success. We recently demonstrated a role for the actin binding protein cofilin in promoting non functioning pituitary tumors invasiveness and an inhibitory effect of dopamine receptor type 2. Somatostatin (SS) receptor type 2 (SSTR2) is the main target of pharmacological therapy of GH-secreting pituitary tumors, reducing both GH secretion and cell proliferation,...

Pulmonary neuroendocrine tumors (PNTs) comprise a spectrum of neoplasms, ranging from low grade carcinoids to the highly malignant small cell lung cancers. Several studies identified cytoskeleton protein Filamin A (FLNA) as determinant in cancer progression and metastasis. To date, the role of FLNA in PNTs aggressiveness and progression is still unknown.To address this question, we decided: i) to evaluate FLNA expression in PNTs ranging from typical carc...

SSTR2 is one of the main pharmacological target for GH-secreting pituitary adenomas treatment and the cytoskeletal protein FLNA plays an important role in tumor responsiveness by regulating SSTR2 expression and signaling. Single-Molecule Imaging was used to investigate the spatial distribution of FLNA-SSTR2 at the plasma membrane level and the involvement of FLNA in SSTR2 mobility, receptor clustering organization/internalization. This method is based on labeling SNAP/CLIP-tag...

Somatostatin receptor type 2 (SST2) is the main pharmacological target of long-acting somatostatin analogues (SSA) widely used in patients with pancreatic neuroendocrine tumours (P-NETs). A subset of patients is resistant to SSA, although the molecular mechanisms responsible for resistance are poorly understood. Several studies identified cytoskeleton protein interactions as determinant in receptor anchoring, expression and signalling. Since SST2 was recently demonstrated to a...

cAMP is an ubiquitous second messenger that is implicated in the regulation of a wide variety of cell functions, including cell proliferation that is differently affected depending on the cell type. Although the effects exerted by cAMP were initially attributed to PKA activation, two exchange proteins directly activated by cAMP (Epac1/2) have been identified as cAMP targets able to mediate several cAMP effects. Aim of this study was to investigate the effect of cAMP on neuroen...

Somatostatin (SS) binds to different SS receptors (SSTR1–5) and SS analogues are the first choice medical treatment of GH-secreting pituitary adenomas (GH-omas). A subset of patients is resistant to SS, although the mechanisms involved in SS resistance are not fully understood. Recent studies identified specific protein–protein interactions as determinant in the regulation of receptor anchoring and signalling. Filamin A (FLNA) is a widely expressed cytoskeleton prote...

PKA regulatory subunit 2B (R2B) is the most expressed in mouse adipose tissue, where it plays an important role in regulating energy balance. We previously demonstrated that R2B is the most abundant R subunit in human adult subcutaneous and visceral adipose tissues. We further showed that R2B expression and PKA activation are reduced in adipose tissues from obese as compared to non-obese subjects. Normal adipose tissue development and increases in fat mass associated with obes...

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 PTH and additional hormones, while PHP-Ib patients do not have AHO and hormone resistance is limited to PTH and TSH. Recently, methylation defects have been detected in 5 patients with PHP-Ia, indicating a m...

Pseudohypoparathyroidism (PHP) is a disorder characterized by hypocalcemia and hyperphosphatemia due to end-organ resistance to the action of PTH. The two main subtypes of PHP, PHP type Ia and Ib are caused by heterozygous loss-of-function mutations in GNAS exons 1–13, which encode Gsα, and by methylation defects in the imprinted GNAS cluster, respectively. Individuals affected with PHP-Ia typically show clinical abnormalities referred to as Albright hereditary osteo...

Somatostatin (SS) is a widely distributed polypeptide that exerts inhibitory effects on hormone secretion and cell proliferation by interacting with five different receptors (SST1-SST5), that display important differences in tissue distribution, coupling to second messengers, affinity for SS and intracellular trafficking. SS analogues currently used in the treatment of acromegaly inhibit hormone secretion and cell proliferation by binding to SST2 and 5. Beta-arrestins have bee...