Neuroendocrinology最新文献

Introduction: Insulin-like growth factor (IGF)1 and IGF2 have neuroprotective effects, but less is known regarding how other members of the IGF system, including IGF binding proteins (IGFBPs) and the regulatory proteinase pappalysin-1 (PAPP-A) and its endogenous inhibitor stanniocalcin-2 (STC2) participate in this process. Here, we analyzed whether these members of the IGF system are modified in neurons and astrocytes in response to palmitic acid (PA), a fatty acid that induces cell stress when increased centrally.

Methods: Primary hypothalamic astrocyte cultures from male and female PND2 rats and the pro-opiomelanocortin (POMC) neuronal cell line, mHypoA-POMC/GFP-2, were treated with PA, IGF1 or both. To analyze the role of STC2 in astrocytes, siRNA assays were employed.

Results: In astrocytes of both sexes, PA rapidly increased cell stress factors followed by increased Pappa and Stc2 mRNA levels and then a decrease in Igf1, Igf2, and Igfbp2 expression and cell number. Exogenous IGF1 did not revert these effects. In mHypoA-POMC/GFP-2 neurons, PA reduced cell number and Pomc and Igf1 mRNA levels, and increased Igfbp2 and Stc2, again with no effect of exogenous IGF1. PA increased STC2 expression, but no effects of decreasing its levels by interference assays or exogenous STC2 treatment in astrocytes were found.

Conclusions: The response of the IGF system to PA was cell and sex specific, but no protective effects of the IGFs were found. However, the modifications in hypothalamic PAPP-A and STC2 indicate that further studies are required to determine their role in the response to fatty acids and possibly in metabolic control.

Introduction: In 2011, we reported the overall incidence of Cushing's disease (CD) in Iceland from 1955 through 2009 to be 1.5 cases per million per year with highest incidence in the last decade of the study, a higher incidence then earlier reported. We now present a follow-up study reporting the epidemiology of the disease in Iceland during the 10-year period from 2010 to 2019.

Methods: In this nationwide retrospective study, clinical information on patients diagnosed with CD was obtained from electronic medical records, reviewed by consulting endocrinologists.

Results: Seventeen patients were diagnosed with CD, 12 women (71%) and 5 men (29%) giving an overall incidence of 5.2 cases per million per year. The mean age at diagnosis was 46 years (range 13-85 years). Biochemical analysis was recorded for all patients and 12 patients (71%) had visible pituitary adenoma on imaging studies. Sixteen patients (94%) were treated with transsphenoidal surgery of which 4 patients (24%) had gamma knife radiosurgery and three (18%) bilateral adrenalectomy after pituitary surgery. Two patients died during the study period.

Conclusion: The overall incidence of CD of 5.2 cases per million per year is higher than previously reported, indicating the importance of awareness of CD. As all patients with CD are diagnosed and/or treated at the only University Hospital in Iceland, housing the only department of endocrinology as well as neurosurgery, we are confident that all cases diagnosed during the study period were included in the study.

Introduction: To investigate the autoinflammatory effect and biological behaviour of simvastatin (SIM) on adamantinomatous craniopharyngioma (ACP) cells.

Methods: Craniopharyngiomas imaging, intraoperative observations, and tumour histopathology were employed to investigate the correlation between esters and craniopharyngiomas. Filipin III fluorescent probe verified the validity of SIM on the alternations of synthesized cholesterol in craniopharyngioma cells. The cell counting kit-8 (CCK8) assay detected the impacts of SIM on cell proliferation and determined the IC50 value of tumour cells. Reverse transcription polymerase chain reaction (RT-PCR) measured the expression of inflammatory factors. Flow cytometry technique detected the cell cycle and apoptosis, and cell scratch assay judged the cell migration. Meanwhile, Western blot was adopted to determine the expression of proteins related to inflammation, proliferation, and apoptosis signalling pathways.

Results: In the ACP tumour parenchyma, many cholesterol crystalline clefts were observed, and the deposition of esters was closely associated with craniopharyngioma inflammation. After simvastatin intervention, a reduction in cholesterol synthesis within ACP was noted. RT-PCR analysis revealed SIM inhibited the transcription of inflammatory factors in ACP cells. Western blot analysis demonstrated SIM inhibited nuclear factor-kappa B (NF-κB) p65 activation expression while promoted the expressions of Cl-caspase-3 and P38 MAPK. CCK8 assay indicated a decrease in ACP cell activity upon SIM treatment. Scratch assay signified that SIM hindered ACP cell migration. Flow cytometry results suggested that the drug promoted ACP cell apoptosis.

Conclusion: SIM suppressed the inflammatory response to craniopharyngiomas by inhibiting craniopharyngioma cholesterol synthesis, inhibited proliferation of ACP cells, and promoted their apoptosis.

Introduction: Cancer stem cells (CSCs) shape the tumor microenvironment via neuroendocrine signaling and orchestrate drug resistance and metastasis. Cytokine antibody array demonstrated the upregulation of neurotrophin-3 (NT-3) in lung CSCs. This study aims to dissect the role of NT-3 in lung CSCs during tumor innervation.

Methods: Western blotting, quantitative reverse transcription-PCR, and flow cytometry were used to determine the expression of the NT-3 axis in lung CSCs. NT-3-knockdown and NT-3-overexpressed cells were derived lung CSCs, followed by examining the stemness gene expression, tumorsphere formation, transwell migration and invasion, drug resistance, soft agar colony formation, and in vivo tumorigenicity. Human lung cancer tissue microarray and bioinformatic databases were used to investigate the clinical relevance of NT-3 in lung cancer.

Results: NT-3 and its receptor tropomyosin receptor kinase C (TrkC) were augmented in lung tumorspheres. NT-3 silencing (shNT-3) suppressed the migration and anchorage-independent growth of lung cancer cells. Further, shNT-3 abolished the sphere-forming capability, chemo-drug resistance, invasion, and in vivo tumorigenicity of lung tumorspheres with a decreased expression of CSC markers. Conversely, NT-3 overexpression promoted migration and anchorage-independent growth and fueled tumorsphere formation by upregulating the expression of CSC markers. Lung cancer tissue microarray analysis revealed that NT-3 increased in patients with advanced-stage, lymphatic metastasis and positively correlated with Sox2 expression. Bioinformatic databases confirmed a co-expression of NT-3/TrkC-axis and demonstrated that NT-3, NT-3/TrkC, NT-3/Sox2, and NT-3/CD133 worsen the survival of lung cancer patients.

Conclusion: NT-3 conferred the stemness features in lung cancer during tumor innervation, which suggests that NT-3-targeting is feasible in eradicating lung CSCs.

Introduction: Immunoglobulins (Ig) reactive with α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide, are present in humans and were previously associated with eating disorders. In this longitudinal study involving patients with anorexia nervosa (AN), we determined whether α-MSH in serum is bound to IgG and analyzed long-term dynamics of both α-MSH peptide and α-MSH-reactive Ig in relation to changes in BMI and gut microbiota composition.

Methods: The study included 64 adolescents with a restrictive form of AN, whose serum samples were collected at hospital admission, discharge, and during a 1-year follow-up visit and 41 healthy controls, all females.

Results: We found that in both study groups, approximately 40% of serum α-MSH was reversibly bound to IgG and that levels of α-MSH-reactive IgG but not of α-MSH peptide in patients with AN were low at hospital admission but recovered 1 year later. Total IgG levels were also low at admission. Moreover, BMI-standard deviation score correlated positively with α-MSH IgG in both groups studied but negatively with α-MSH peptide only in controls. Significant correlations between the abundance of specific bacterial taxa in the gut microbiota and α-MSH peptide and IgG levels were found in both study groups, but they were more frequent in controls.

Conclusion: We conclude that IgG in the blood plays a role as an α-MSH-binding protein, whose characteristics are associated with BMI in both patients with AN and controls. Furthermore, the study suggests that low production of α-MSH-reactive IgG during the starvation phase in patients with AN may be related to altered gut microbiota composition.

Introduction: Protein-enriched diets improve glycemic control in diabetes or emotional behavior in depressive patients. In mice, these benefits depend on intestinal gluconeogenesis activation by di-/tripeptides. Intestinal di-/tripeptides absorption is carried out by the peptide transporter 1, PEPT1. The lack of PEPT1 might thus alter glucose and emotional balance.

Methods: To determine the effects of PEPT1 deficiency under standard dietary conditions or during a dietary challenge known to promote both metabolic and cognitive dysfunction, insulin sensitivity, anxiety, and depressive-like traits, hippocampal serotonin (5-HT) and insulin signaling pathway were measured in wild-type (WT) and Pept1-/- mice fed either a chow or a high-fat high-sucrose (HF-HS) diet.

Results: Pept1-/- mice exhibited slight defects in insulin sensitivity and emotional behavior, which were aggravated by an HF-HS diet. Pept1-/- mice fed a chow diet had lower hippocampal 5-HT levels and exhibited cerebral insulin resistance under HF-HS diet. These defects were independent of intestinal gluconeogenesis but might be linked to increased plasma amino acids levels.

Conclusion: Pept1-/- mice develop prediabetic and depressive-like traits and could thus be used to develop strategies to prevent or cure both diseases.

Background: Multiple factors, including neurobiological, hormonal, psychological, and social/cultural norms, influence the manner in which individuals experience pain. Adipose tissue, once considered solely an energy storage site, has been recognized as a significant endocrine organ that produces and releases a range of hormones and cytokines. In recent years, research has highlighted the role of adipose tissue and its endocrine factors in the pathophysiology of pain.

Summary: This narrative review aimed to provide a comprehensive overview of the current knowledge on the endocrine aspects of pain pathophysiology, with a specific focus on adipose tissue. We examine the role of adipokines released by adipose tissue, such as leptin, adiponectin, resistin, visfatin, asprosin in pain perception and response. We also explore the clinical implications of these findings, including the potential for personalized pain management based on endocrine factors and adipose tissue.

Key messages: Overall, given this background, this review intended to highlight the importance of understanding the endocrine aspects of pain pathophysiology, particularly focusing on the role of adipose tissue, in the development of chronic pain and adipokines. Better understanding the role of adipokines in pain modulation might have therapeutic implications by providing novel targets for addressing underlying mechanism rather than directly focusing on symptoms for chronic pain, particularly in obese individuals.

Introduction: Gender difference may affect lung neuroendocrine tumor (L-NET) onset, progression, and outcomes as emerged in other cancers. This study aimed to analyze gender difference in L-NET to identify potential prognostic factors, to improve patient follow-up and therapeutic strategies.

Methods: Patients with histologically confirmed L-NEN diagnosis referred to the ENETS CoE of the Endocrinology Unit, Federico II University of Naples, from 2013 to 2023, were retrospectively evaluated.

Results: Among 48 patients with L-NEN, 38 (79.2%) with sporadic L-NET were enrolled: 22 typical (57.9%) and 16 atypical (42.1%) carcinoids, 22 (57.9%) female and 16 (42.1%) male, mean age at diagnosis 57.3 years (range 16-84). Median follow-up was 70.5 months (range 12-305). No statistical difference resulted regarding smoking habit, BMI, primary site (left/right and central/peripheral), and histological characteristics, between cohorts. Metastasis at diagnosis was found in 20 patients (52.3%), 10 female (10%) and 10 male (10%) (p: 0.20). Progressive disease (PD) was observed in 14 (36.8%) patients, and male sex developed PD more frequently 9/14 (64.3%) than female 5 (35.7%), p: 0.05. Male sex seemed to show more frequently bone metastasis without reaching statistical difference, 7 male/10 (70%), p: 0.06. Among 9 deaths (23.7%), 7 (77.8%) were men and 7 died for PD, p < 0.03. Male had a poorer prognosis than female regarding progression-free survival (PFS) (p: 0.04) and overall survival (p: 0.001), also when sub-groups of patient metastatic at diagnosis were compared (p: 0.02 and p: 0.02).

Conclusions: This study showed a worse prognosis in male than female with L-NET, despite similar clinical features, tumor type, stage, and treatment, with regard to PFS, OS, and metastatic spread. These findings may suggest a closer follow-up in men, with potential positive impact on outcomes.

Background: "One for all, and all for one", the famous rallying cry of The Three Musketeers, in Alexandre Dumas's popular novel, certainly applies to the 20,000 cells composing the suprachiasmatic nuclei (SCN). These cells work together to form the central clock that coordinates body rhythms in tune with the day-night cycle. Like virtually every body cell, individual SCN cells exhibit autonomous circadian oscillations, but this rhythmicity only reaches a high level of precision and robustness when the cells are coupled with their neighbors. Therefore, understanding the functional network organization of SCN cells beyond their core rhythmicity is an important issue in circadian biology.

Summary: The present review summarizes the main results from our recent study demonstrating the feasibility of recording SCN cells in freely moving mice and the significance of variations in intracellular calcium over several timescales.

Key message: We discuss how in vivo imaging at the cell level will be pivotal to interrogate the mammalian master clock, in an integrated context that preserves the SCN network organization, with intact inputs and outputs.