Endocrine Abstracts

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...

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...

Complete androgen insensitivity syndrome (CAIS) is a rare X-linked disorder caused by androgen receptor gene (AR) mutations that result in complete impairment of genital virilisation. Usually CAIS patients, who have normal production of AMH by Sertoli Cells, do not show Mullerian derivatives, although the persistence of Mullerian duct derivatives up to now have been described in nine cases.Here, we report the case of a fetus aborted at 20 weeks for genit...

Somatostatin exerts inhibitory effects on hormone secretion and cell proliferation by interacting with five different receptors (SST1–SST5) linked to effector systems via G proteins. The receptor structural domains mediating these effects have not been identified. Since SS is the hypothalamic peptide that physiologically inhibits GH secretion, aim of this study was to investigate the molecular determinants mediating the interaction of the human SST5 with G proteins and su...

Tools that are highly effective in the treatment of differentiated thyroid cancer (DTC) loose their therapeutic potentials in poorly differentiated tumors. The synthetic analog 8-Cl-cAMP has been known to have an antiproliferative effect in a variety of cancer cells and is tested as antineoplastic agent in clinical trials. The signaling mechanisms that govern the 8-Cl-cAMP-induced growth inhibition are still uncertain and data in thyroid neoplasia are lacking. Therefore, we te...

Primary hyperparathyroidism (PHPT) may occur sporadically or within MEN syndromes. It is classically thought that PHPT in MEN occurs at earlier ages than sporadic PHPT without significant differences in clinical and biochemical presentation. The aim of the study was to compare clinical and biochemical parameters between sporadic PHPT and MEN1 patients. The study included 41 genetically diagnosed MEN1 patients (14M, 27F) and 88 sporadic PHPT patients (24M, 64F) matched for age ...

Dopamine agonist cabergoline (CB) is the first-choice treatment in prolactin-secreting adenomas (PRL-omas). It is effective in reducing PRL secretion and tumour size in about 90% of patients by binding dopamine D2 receptor (DRD2). Although no mutations in DRD2 were found, it has been reported that several polymorphisms of this locus associate with alcoholism and schizophrenia, diseases in which dopaminergic system plays an important role. To assess the possible asso...

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...