Endocrine Abstracts

Background: Familial isolated pituitary adenoma (FIPA) is recently identified autosomal dominant condition with incomplete penetrance. Heterozygote mutations have been identified in the aryl-hydrocarbon receptor interacting protein (AIP) gene in 20–30% of FIPA families. AIP mutation positive patients have distinct phenotype: the disease is occurring at a younger age and have more aggressive tumours.Aims: The aim of this study was to perform comparat...

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...

Introduction: Loss-of-function mutations in AIP are associated with familial isolated pituitary adenoma, often leading to gigantism due to invasive GH-secreting pituitary adenomas. One challenging problem in the management of patients carrying a missense AIP variant is to determine whether the missense variant is a disease-causing mutation or not. As most of the molecular mechanisms involved in the control of growth and the cell cycle are well-conserved, we p...

The transcription factor and proto-oncogene GLI1 is the terminal mediator of the Hedgehog signalling pathway which is involved in developmental processes, stem cell maintenance and cell proliferation. Although the pathway is mainly active during embryogenesis and tissue repair, it is frequently reactivated in several cancer types.Based on these findings we investigated the potential role of GLI1 in the pathogenesis of pituitary adenomas. GLI1 expression ...

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...

Background: Medical treatment of pituitary adenomas with somatostatin analogs depends on tumor type and somatostatin receptor expression. Using polyclonal antibodies, their immunohistochemical (IHC) detection gave conflicting results. Therefore, we studied the IHC expression of SSTR2A and SSTR5 using two specific MABs in five types of pituitary adenomas.Methods: SSTR2A and SSTR5 expression was studied using two...

IGF1 represents an important growth factor in pituitary physiology and pathology, also mediating the negative feed-back mechanisms on somatotroph axis. It has been previously demonstrated that IGF1 promotes cell viability in primary cultures of human non functioning pituitary adenomas, by a mechanisms involving, at least in part, mTOR signaling, which is involved in many pathways controlling proliferation. We aimed at investigating whether mTOR may mediate IGF1 effects also in...

Introduction: Anophthalmia/microphthalmia is a rare developmental craniofacial defect often associated to congenital hypopituitarism with GH deficiency and hypogonadism. SOX2 gene plays a key role in embryonic development regulation and heterozygous mutations of this gene, reported only in 14 patients to date, have been associated to anophthalmia/microphthalmia and congenital hypopituitarism in uo to 10% of cases. Therefore, the study of the SOX2 gene can be clinically useful ...

Introduction: Somatostatin analogs (SSAs) are the first-line clinical treatment for patients with pituitary adenomas (PAs) but their efficacy is highly variable among patients. This could be due to a differential expression of somatostatin receptor subtypes (Ssts) among tumors, but this issue is still unresolved. Nonfunctioning pituitary adenomas (NFPAs), which mostly derive from gonadotroph cells, are among the tumors that poorly respond to SSAs. Rats carrying a germline loss...

Introduction: The aim of our study was to investigate clinical and morphological features of dopamine agonist-resistant prolactinomas.Methods/design: The study included 51 patients (38 women, 13 men) with prolactin-secreting pituitary adenoma that is resistant to treatment with dopamine agonists, age 15–82 years.Results: Median of the serum PRL level distribution at the onset of the disease was 4500 mIU/l (3480, 140 300). The ...

Connexins are a proteins critically involved in the formation of gap junction, which connect cells with each other and enable the exchange of small compounds and, besides having a role independently of gap junction formation. At least, in the anterior pituitary two cellular networks have already been identified, one of them is composed of the endocrine inactive folliculo-stellate cells and the second one is the GH-producing somatotroph cell network. It is supposed that gap jun...

Objective: The aim of this study was to quantitatively estimate SSTR2 in clinically non-functioning pituitary adenomas (CNFAs) with use of RNA in-situ hybridization (ISH) and quantitative real-time RT-PCR and correlate the results of both methods.Methods: A standard histological and immunohistochemical examination was performed on the resected pituitary tumour. Afterwards in-situ hybridization for somatostatine 2 receptor (SSTR2) RNA wa...

Ghrelin, the endogenous ligand of GH secretagogue receptor type 1a, has emerged as pleiotropic modulator of diverse biological functions, including energy homeostasis and recently, reproduction. The effects of i.c.v. administered ghrelin on morphological characteristics of pituitary FSH- and LH-cells were examined in adult male Wistar rats. The animals were randomized in two groups: control and experimental group, each consisted of seven animals, and implanted with an i.c.v. c...

Introduction: During clinical observation the behaviour of pituitary tumours is often unpredictable. The work was aimed at evaluating Ki-67 and pituitary tumour transforming gene (PTTG) indices in pituitary adenomas.Material and methods: The Ki-67 and PTTG indices were determined by immunochemistry in specimens excised from neurosurgically removed pituitary tumours. In fifty two examined patients (30 females and 22 males, mean age 50.5±15.4 years) w...

Introduction: Medical therapy of acromegaly is indicated in patients who failed to achieve remission after surgery, with contraindication or refusal for surgical therapy or following radiotherapy in order to bridge the interval until complete remission.Objective: Evaluate the medical therapy – somatostatin analogs (SSA), dopamine agonist (DAs) and GH receptor-antagonist (Pegvisomant) – in acromegalic patients followed from 1988–2011.<p...

Daidzein, one of the main phytoestrogens of soy, is able to act as estrogen-like compounds due to its structural similarity with 17β-estradiol, which gives them the capacity to bind estrogen receptors and to induce hormone-like effects. Considering, that somatotropic system is sensitive to sex steroids, the aim of this study was to investigate the effects of daidzein on stereological and biochemical parameters of pituitary somatotropic (GH) cells in orchidectomized adult ...

Objective: 8-Prenylnaringenin (8-PN) is a phytoestrogen discovered in hops. GH3 pituitary adenoma cells of the rat show a variety of responses to phytoestrogens in vitro. This in vitro study aims to analyze changes in hormone expression in GH3 cells treated with 8-PN.Methods: GH3 cells were incubated with 0.5–50 μM 8-PN for 4 h. Medium and ethanol served as controls. Changes in expression of growth hormone (GH) and prolactin (...