Conditional Pten inactivation in pituitary results in sex-specific prolactinoma formation.

Pituitary tumors, including prolactinomas, present significant clinical challenges that require a deeper understanding of their molecular roots for improved diagnostics and therapies. Here, we investigate the role of the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K) pathway in pituitary tumorigenesis using a mouse model. Conditional knockout of Pten in all pituitary cell lineages resulted in prolactinoma formation exclusively in female mice, demonstrating the critical role of PTEN in pituitary homeostasis.

Integrative Clinical, Radiological, and Molecular Analysis for Predicting Remission and Recurrence of Cushing Disease.

Context: Adrenocorticotropin (ACTH)-secreting pituitary tumors (ACTHomas) are associated with severe comorbidities and increased mortality. Current treatments mainly focus on remission and prevention of persistent disease and recurrence. However, there are still no useful biomarkers to accurately predict the clinical outcome after surgery, long-term remission, or disease relapse.

Sex Hormone Receptor Expression in Craniopharyngiomas and Association with Tumor Aggressiveness Characteristics.

Craniopharyngiomas (CPs) are rare tumors of the sellar and suprasellar regions of embryonic origin. The primary treatment for CPs is surgery but it is often unsuccessful. Although CPs are considered benign tumors, they display a relatively high recurrence rate that might compromise quality of life.

GATA4 induces liver fibrosis regression by deactivating hepatic stellate cells.

In response to liver injury, hepatic stellate cells activate and acquire proliferative and contractile features. The regression of liver fibrosis appears to involve the clearance of activated hepatic stellate cells, either by apoptosis or by reversion toward a quiescent-like state, a process called deactivation. Thus, deactivation of active hepatic stellate cells has emerged as a novel and promising therapeutic approach for liver fibrosis.

Quantitative Analysis of Somatostatin and Dopamine Receptors Gene Expression Levels in Non-functioning Pituitary Tumors and Association with Clinical and Molecular Aggressiveness Features.

The primary treatment for non-functioning pituitary tumors (NFPTs) is surgery, but it is often unsuccessful. Previous studies have reported that NFPTs express receptors for somatostatin (SST) and dopamine (DRDs) providing a rationale for the use of dopamine agonists and somatostatin analogues. Here, we systematically assessed SST and DRDs expression by real-time quantitative PCR (RT-qPCR) in a large group of patients with NFPTs ( = 113) and analyzed their potential association with clinical and molecular aggressiveness features.

Loss of GATA4 causes ectopic pancreas in the stomach.

Pancreatic heterotopia is defined as pancreatic tissue outside its normal location in the body and anatomically separated from the pancreas. In this work we have analyzed the stomach glandular epithelium of Gata4 ; Pdx1-Cre mice (Gata4KO mice). We found that Gata4KO glandular epithelium displays an atypical morphology similar to the cornified squamous epithelium and exhibits upregulation of forestomach markers.

A Somatostatin Receptor Subtype-3 (SST) Peptide Agonist Shows Antitumor Effects in Experimental Models of Nonfunctioning Pituitary Tumors.

Purpose: Somatostatin analogues (SSA) are efficacious and safe treatments for a variety of neuroendocrine tumors, especially pituitary neuroendocrine tumors (PitNET). Their therapeutic effects are mainly mediated by somatostatin receptors SST and SST. Most SSAs, such as octreotide/lanreotide/pasireotide, are either nonselective or activate mainly SST.

GATA factors in pancreas development and disease.

There is an urgent need for the development of novel therapeutics options for diabetic patients given the high prevalence of diabetes worldwide and that, currently, there is no cure for this disease. The transplantation of pancreatic islets that contain insulin-producing cells is a promising therapeutic alternative, particularly for type 1 diabetes. However, the shortage of organ donors constitutes a major limitation for this approach; thus, developing alternative sources of insulin-producing cells is of critical importance.

Surgical Outcome and Treatment of Thyrotropin-Secreting Pituitary Tumors in a Tertiary Referral Center.

Objective: Thyrotropin (TSH)-secreting pituitary tumors are rare and typically present with hyperthyroidism. Here we report the diagnosis, treatment, and surgical outcomes in a series of patients with TSH-secreting pituitary tumors in a tertiary referral center.

Methods: Descriptive retrospective study that included all patients with TSH-secreting pituitary tumors who underwent transsphenoidal surgery in the endocrinology and nutrition unit of the Virgen del Rocío University Hospital (Seville, Spain) between 2004 and 2016.

Surgical Outcomes and Comorbidities in Cushing Disease: 30 Years of Experience in a Referral Center.

Objective: Cushing disease (CD) is a rare, poorly understood entity. Our aim was to add our clinical experience of >30 years in a multidisciplinary specialized unit to the global knowledge of CD.

Methods: This descriptive retrospective study included all patients admitted to the Endocrinology and Nutrition Department of the Virgen del Rocío University Hospital, Seville, Spain, from January 1980 to May 2016.

Chronic adult-onset of growth hormone/IGF-I hypersecretion improves cognitive functions and LTP and promotes neuronal differentiation in adult rats.

Aim: Besides their metabolic and endocrine functions, the growth hormone (GH) and its mediated factor, the insulin-like growth factor I (IGF-I), have been implicated in different brain functions, including neurogenesis. Long-lasting elevated GH and IGF-I levels result in non-reversible somatic, endocrine and metabolic morbidities. However, the subcutaneous implantation of the GH-secreting (GH-S) GC cell line in rats leads to the controllable over-secretion of GH and elevated IGF-I levels, allowing the experimental study of their short-term effects on brain functions.

E-cadherin expression is associated with somatostatin analogue response in acromegaly.

Acromegaly is a rare disease resulting from hypersecretion of growth hormone (GH) and insulin-like growth factor 1 (IGF1) typically caused by pituitary adenomas, which is associated with increased mortality and morbidity. Somatostatin analogues (SSAs) represent the primary medical therapy for acromegaly and are currently used as first-line treatment or as second-line therapy after unsuccessful pituitary surgery. However, a considerable proportion of patients do not adequately respond to SSAs treatment, and therefore, there is an urgent need to identify biomarkers predictors of response to SSAs.

AIP and MEN1 mutations and AIP immunohistochemistry in pituitary adenomas in a tertiary referral center.

Background: Pituitary adenomas have a high disease burden due to tumor growth/invasion and disordered hormonal secretion. Germline mutations in genes such as MEN1 and AIP are associated with early onset of aggressive pituitary adenomas that can be resistant to medical therapy.

Aims: We performed a retrospective screening study using published risk criteria to assess the frequency of AIP and MEN1 mutations in pituitary adenoma patients in a tertiary referral center.

Stabilization of HIF-2α impacts pancreas growth.

Hypoxia inducible factors (HIFs) are critical regulators of the response to oxygen deficiency by activating target genes involved in a variety of biological functions. HIFs have been implicated in the pathophysiology of numerous pathologies including cancer. Patients with mutations in the von Hippel-Lindau (VHL) gene, an essential regulator of HIF activity, develop tumors in several organs including the pancreas.

Association between dopamine and somatostatin receptor expression and pharmacological response to somatostatin analogues in acromegaly.

Acromegaly is a hormonal disorder resulting from excessive growth hormone (GH) secretion frequently produced by pituitary adenomas and consequent increase in insulin-like growth factor 1 (IGF-I). Elevated GH and IGF-I levels result in a wide range of somatic, cardiovascular, endocrine, metabolic and gastrointestinal morbidities. Somatostatin analogues (SSAs) form the basis of medical therapy for acromegaly and are currently used as first-line treatment or as second-line therapy in patients undergoing unsuccessful surgery.

GATA6 Controls Insulin Biosynthesis and Secretion in Adult β-Cells.

GATA4 and GATA6 play essential, but redundant, roles in pancreas formation in mice, and mutations cause pancreatic agenesis in humans. mutations have also recently been linked to adult-onset diabetes, with subclinical or no exocrine insufficiency, suggesting an important role for GATA6 in human β-cell physiology. To investigate the role of GATA6 in the adult endocrine pancreas, we generated mice in which is specifically inactivated in the pancreas.

Mitochondrial Dynamics Mediated by Mitofusin 1 Is Required for POMC Neuron Glucose-Sensing and Insulin Release Control.

Proopiomelanocortin (POMC) neurons are critical sensors of nutrient availability implicated in energy balance and glucose metabolism control. However, the precise mechanisms underlying nutrient sensing in POMC neurons remain incompletely understood. We show that mitochondrial dynamics mediated by Mitofusin 1 (MFN1) in POMC neurons couple nutrient sensing with systemic glucose metabolism.

Loss of Pancreas upon Activated Wnt Signaling Is Concomitant with Emergence of Gastrointestinal Identity.

Organ formation is achieved through the complex interplay between signaling pathways and transcriptional cascades. The canonical Wnt signaling pathway plays multiple roles during embryonic development including patterning, proliferation and differentiation in distinct tissues. Previous studies have established the importance of this pathway at multiple stages of pancreas formation as well as in postnatal organ function and homeostasis.

A Probabilistic Model for Cushing's Syndrome Screening in At-Risk Populations: A Prospective Multicenter Study.

Context: Cushing's syndrome (CS) is challenging to diagnose. Increased prevalence of CS in specific patient populations has been reported, but routine screening for CS remains questionable. To decrease the diagnostic delay and improve disease outcomes, simple new screening methods for CS in at-risk populations are needed.

The Effects of Bariatric Surgery-Induced Weight Loss on Adipose Tissue in Morbidly Obese Women Depends on the Initial Metabolic Status.

Background: Adipose tissue (AT) dysfunction in obesity is commonly linked to insulin resistance and promotes the development of metabolic disease. Bariatric surgery (BS) represents an effective strategy to reduce weight and to improve metabolic health in morbidly obese subjects. However, the mechanisms and pathways that are modified in AT in response to BS are not fully understood, and few information is still available as to whether these may vary depending on the metabolic status of obese subjects.

Molecular Characterization of Growth Hormone-producing Tumors in the GC Rat Model of Acromegaly.

Acromegaly is a disorder resulting from excessive production of growth hormone (GH) and consequent increase of insulin-like growth factor 1 (IGF-I), most frequently caused by pituitary adenomas. Elevated GH and IGF-I levels results in wide range of somatic, cardiovascular, endocrine, metabolic, and gastrointestinal morbidities. Subcutaneous implantation of the GH-secreting GC cell line in rats leads to the formation of tumors.

The effect of maternal diabetes on the Wnt-PCP pathway during embryogenesis as reflected in the developing mouse eye.

Embryopathies that develop as a consequence of maternal diabetes have been studied intensely in both experimental and clinical scenarios. Accordingly, hyperglycaemia has been shown to downregulate the expression of elements in the non-canonical Wnt-PCP pathway, such as the Dishevelled-associated activator of morphogenesis 1 (Daam1) and Vangl2. Daam1 is a formin that is essential for actin polymerization and for cytoskeletal reorganization, and it is expressed strongly in certain organs during mouse development, including the eye, neural tube and heart.

Genetically engineered mouse models of pituitary tumors.

Animal models constitute valuable tools for investigating the pathogenesis of cancer as well as for preclinical testing of novel therapeutics approaches. However, the pathogenic mechanisms of pituitary-tumor formation remain poorly understood, particularly in sporadic adenomas, thus, making it a challenge to model pituitary tumors in mice. Nevertheless, genetically engineered mouse models (GEMMs) of pituitary tumors have provided important insight into pituitary tumor biology.