Endocrine Abstracts

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...

Cortisol and cortisone are interconverted by type 1 and type 2 11ßhydroxysteroid dehydrogenase (11ßHSD) isoenzymes. The type 1 isoenzyme is a widely expressed reductase that converts cortisone to cortisol regulating glucocorticoid tissue exposure. Its activity is inhibited by GH and IGF-I, being increased in GH deficiency (GHD) and decreased in acromegaly. In our experience rhGH therapy unmasked a central hypoadrenal state in adults with organic GHD, likely by normal...

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,...

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...

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...

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...

Long-term effects of trans-naso-sphenoidal surgery (TNS) and long-acting somatostatin analogs (SSTa) on hypotalamic-pituitary-adrenal (HPA) function have been poorly investigated. Aim of the study was to evaluate over time the integrity of HPA axis in acromegalic patients with baseline preserved adrenal function and treated with one or both available treatments. We selected 23 patients (15F & 8M, age (±S.D.)=46.8±13.7 yrs) with normal (n=19)...

Dopamine receptor type 2 (DRD2) agonists (DAs) are the first-choice treatment for PRL-secreting pituitary tumors due to their efficacy in reducing tumor size and hormonal secretion. However, DAs are poorly effective in non-functioning pituitary tumors (NFPTs), despite most of them express DRD2. No correlation between DAs clinical responsiveness and DRD2 expression was found, suggesting post-receptor alterations underlying resistance. DRD2 signaling pathways that control cell p...

In human adipocytes the cAMP-dependent pathway mediates signals originating from the activation of beta-adrenergic receptors, thus playing a key role in the regulation of important metabolic processes such as lipolysis and thermogenesis. CyclicAMP effects are mainly mediated by cAMP-dependent protein kinase (PKA), a tetrameric enzyme composed by two catalytic subunits associated with two regulatory (R) subunits. There are four different R subunit genes and proteins (R1A, R1B, ...

A common polymorphic variant of the GH receptor (exon-3 deletion, d3GHR) has been linked with increased response to recombinant human GH (rhGH) in some, but not all, GH deficient (GHD) and non-GHD patients. Aim of this study was to investigate the impact of the GHR genotype on the phenotype of GHD adults and on the metabolic effect of short- and long-term rhGH therapy, with particular focus on glucose homeostasis (1 year: n=100 and 5 years: n=50). Effects of rhGH...