Journal of Neuroendocrinology最新文献

Seasonal song production in canaries is influenced by gonadal hormones, but the molecular mechanisms underlying testosterone-induced song development in adult female canaries, which rarely sing naturally, remain poorly understood. We explored testosterone-induced song development in adult female canaries by comparing gene regulatory networks in the song-controlling brain area HVC at multiple time points (1 h to 14 days) post-treatment with those of placebo-treated controls. Females began vocalizing within 4 days of testosterone treatment, with song complexity and HVC volume increasing progressively over 2 weeks. Rapid transcriptional changes involving 2739 genes preceded song initiation. Over 2 weeks, 9913 genes-approximately 64% of the canary's protein-coding genome-were differentially expressed, with 98% being transiently regulated. These genes are linked to various biological functions, with early changes at the cellular level and later changes affecting the nervous system level after prolonged hormone exposure. Our findings suggest that testosterone-induced song development is accompanied by extensive and dynamic transcriptional changes in the HVC, implicating widespread neuronal involvement. These changes underpin the gradual emergence of singing behavior, providing insights into the neural basis of seasonal behavioral patterns.

Postoperative diabetes insipidus (DI) frequently complicates endoscopic transsphenoidal surgery (TSS) in pituitary adenoma (PA) patients, yet reliable predictive methods for DI risk remain lacking. This study aims to identify risk factors associated with DI following endoscopic transsphenoidal resection of PA and to develop a predictive nomogram for assessing postoperative DI risk. This study involved 600 PA patients underwent endoscopic TSS at Shandong Provincial Hospital from 2021 to 2023. Among these patients, 82 developed postoperative DI while 518 did not. The cohort was randomly divided into training (n = 360) and validation (n = 240) groups at 6:4 ratios by R software. Clinical parameters and radiographic features were evaluated using univariable and multivariable logistic regression to construct a predictive nomogram for post-endoscopic TSS DI risk. Model performance was assessed using ROC curves, calibration plots, and decision curve analysis. Subgroup analysis was used to evaluate the model's ability to discriminate between transient and permanent DI. Univariable and multivariable logistic regression analyses on the training group identified several independent risk factors for post-endoscopic TSS DI, including maximum tumor diameter, Knosp grade, Esposito grade, recurrent PA, and pituitary stalk deviation angle. A nomogram was developed based on these factors, demonstrating robust predictive accuracy with ROC areas under curve of 0.840 for the training group and 0.815 for the validation group. Calibration plots indicated excellent agreement between predicted and observed probabilities of postoperative DI. DCA curves highlighted the nomogram's efficacy in guiding clinical decision-making. Subgroup analysis showed that the model was able to discriminate between transient and permanent DI, and the AUC was 0.652 (95% CI 0.525–0.794). This study presents a nomogram designed to predict postoperative DI risk in patients undergoing endoscopic TSS for PA. Internal and external validations underscored the model's high accuracy, calibration, and clinical utility. Simultaneously, the model can also assess the development risk of permanent DI. This predictive tool offers clinicians valuable support in identifying high-risk DI patients, optimizing postoperative care strategies, and tailoring treatment plans to improve patient outcomes.

The arcuate nucleus of the hypothalamus (ARC) is central in the neuronal regulation of fertility and reproduction through translating gonadal steroid hormone cues into the GnRH signaling pathway in the brain. Evidence suggests that circulating gonadal steroids play an important role in modulating female reproduction via kisspeptin and γ-aminobutyric acid (GABA) neurons in the ARC in both development and adulthood. However, the temporal onset of these ARC neurons' sensitivity to gonadal steroids is unknown. Using RNAscope® in situ hybridization, we localized androgen receptor (Ar), estrogen receptor alpha (Esr1), and progesterone receptor (Pgr) expression in ARC kisspeptin or GABA neurons of female mice at postnatal day (P)4, P8, P12, P20, and P60. A probe that binds to kiss1 mRNA or vGat mRNA was used to produce signal in kisspeptin or GABA neurons, respectively. In adult, we identified that the vast majority of kisspeptin neurons coexpressed Esr1 (95%) and Pgr (93%), while a smaller proportion coexpressed Ar (66%). Similar proportions of Ar- or Esr1-positive kisspeptin neurons were seen from P4, suggesting that kisspeptin neurons develop adult-like sensitivity to androgen and estrogen in early postnatal life. In contrast, the proportion of Pgr-positive kisspeptin cells in early life was significantly lower than in adulthood, suggesting that progesterone sensitivity develops over time in the ARC kisspeptin population. ARC GABA neurons also colocalized with Ar (70%), Esr1 (64%), or Pgr (85%) in adulthood. GABA neurons continuously expressed Esr1 or Pgr from the postnatal stages to adulthood, while the proportion of Ar-positive GABA neurons gradually increased from P4 (24%) to P20 (59%). These results suggest that while ARC GABA neurons can respond to circulating estrogen and progesterone from early postnatal ages, this same population may become more sensitive to androgens during later postnatal life. Our findings identified the expression patterns of Ar, Esr1, and Pgr by ARC kisspeptin and GABA neurons during early postnatal life. These data provide the understanding for the hormone sensitivity of these populations during early postnatal life, the critical time for the formation and regulation of female reproductive physiology. [Correction added on 31 January 2025, after first online publication: Abstract has been updated.]

The prevalence of gastric NEN is estimated worldwide at 8.9% of all gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) and only 0.3%–1% of all gastric neoplasms, but is rising in the last decades. The aim of this project was to map the epidemiology of gastric neuroendocrine neoplasm (gNEN) in Belgium. This is a population-wide retrospective cohort study over 10 years (2010–2019), based on data from the Belgian Cancer Registry. A total of 641 patients were included; 605 patients with gNEN and 36 with MiNEN. The AAIR of gNEN was 0.67 per 100,000 person-years, increasing over the years and with a slight female predominance (55.4%). Neuroendocrine carcinoma (NEC) accounted for 15.7% (N = 95), with an AAIR of 0.11 per 100,000 person-years. The other 510 patients were diagnosed with gNET: G1 NET was most prevalent (54.3%) followed by G2 (32.5%) and G3 NET (3.5%). Concerning the clinical classification (type) of gNET, a diagnosis of type 1 tumors was presumed in 67.6%, type 3 tumors in 17.1% and type 2 tumors in 0.6% of patients. In only 3.8% of patients, the clinical classification was explicitly stated in the pathology report. Stage IV tumors were diagnosed in 13.4% (N = 81). A favorable evolution in pathology reporting is seen. Some variables—for example, clinical classification of gNET—were heavily underreported, stressing the importance of registries integrating clinical and pathological information.

Multiple Endocrine Neoplasia type 1 (MEN1) Clinical Practice Guidelines (2012) are predominantly based on expert opinion due to limited available evidence at the time, leaving room for interpretation and variation in practices. Evidence on the natural course of MEN1-related neuroendocrine tumours (NET) and the value of screening programs has increased and new imaging techniques have emerged. The aim of this study is to provide insight in the current practices of screening and surveillance for MEN1-related NETs in ENETS Centers of Excellence (CoEs). A clinical practice questionnaire was distributed among all 65 ENETS CoEs. Response rate was 91% (59/65). In 14% of CoEs <10 patients, in 50% 10–49, in 31% 50–100 and in 3 centres (5%) >100 patients with MEN1 are seen. Practices with regard to screening and surveillance of NETs were markedly heterogeneous. Differences between countries were noted in the use of gut hormones for biochemical screening and the choice for imaging modality for screening/surveillance of pancreatic NETs (PanNETs). Magnetic resonance imaging (MRI) is the preferred modality for screening and surveillance of PanNETs, whereas this is computed tomography (CT) for thoracic NETs. Practices regarding screening for thoracic NETs were more homogeneous among larger volume CoEs, with longer screening intervals. The majority of CoEs tailored the surveillance of small pancreatic and lung NETs to observed growth rate. 68% of CoEs advise patients with clinical MEN1 with negative genetic testing to undergo periodic screening like mutation-positive patients. In conclusion, there is still marked heterogeneity in practice, although there are also common trends. Differences were sometimes associated with volume or country, but often no association was found. This underscores the need for clear and evidence-based practice recommendations.

There are over 1000 varieties of steroids that have been reported in nature, including the endogenous sex steroid hormones (i.e., progesterone, testosterone, and 17β-estradiol) and corticosteroids which are mainly synthesized by gonads and adrenals, respectively. In addition, an extra-glandular steroidogenesis has been also reported in the brain and in the gastrointestinal tract (GIT). The reason why intestinal steroidogenesis and consequently gut steroids draw our attention is for the communication and interaction with the gut microbiota, which functions like a virtual endocrine organ, and it is also involved in the steroid production. Moreover, both GIT and gut microbiota communicate through neural, endocrine, and humoral ways with the brain, in the so-called gut-microbiota-brain axis. On this basis, in this review, we will discuss several aspects such as (1) intestinal steroidogenesis and its possible regulation, (2) the potential role of gut steroids in physiopathological conditions, and (3) the role of microbiome in steroidogenesis and steroid metabolism. Overall, this review highlights new points of view considering steroid molecules as potential therapeutic approach for gastrointestinal disorders and brain comorbidities.

Somatostatin receptor (SST) positron emission tomography with computed tomography (PET/CT) is the gold standard for functional imaging of neuroendocrine tumors (NETs), but FDG PET/CT is increasingly recognized for its prognostic value, particularly for higher-grade NETs and to detect disease heterogeneity. Despite the established role of pathological grading, clinical heterogeneity within the tumor burden often complicates accurate prognostication. Evidence suggests FDG PET/CT can outperform WHO grading in predicting outcomes by identifying aggressive, undifferentiated tumor clones that influence long-term prognosis and treatment decisions. Several grading systems integrating both SST and FDG PET/CT have been proposed to better capture tumor heterogeneity and guide clinical management. Studies demonstrate that FDG PET/CT can influence management in a significant subset of patients, although variably reported. Its use remains variable across centers, also affected by different reimbursement policies and local clinical practices. This review explores the indications to FDG PET/CT in NET and the clinical impact of combined SST and FDG PET/CT imaging.

The First International Symposium on Avian Endocrinology (ISAE) was held 47 years ago at the Grand Hotel in Kolkata (Calcutta), India. Professor Asok Ghosh organized and convened the symposium, and Professor Donald S. Farner was President. The 1977 ISAE was convened at a time when neuroendocrine cascades were emerging as major pathways by which environmental events are perceived and transduced resulting in endocrine secretions that then orchestrate life history stages. Methods to measure hormone concentrations in blood and other tissues were relatively recent allowing the advance of laboratory and field investigations to explore ecological bases of endocrine control systems. The rise of evolutionary endocrinology and theory in ecological contexts followed-topics that are flourishing today. Studies on poultry continue to play central roles at ISAE meetings. In recent decades, the incorporation of genomics, transcriptomics, proteomics, epigenetics and other technologies provide us with an unprecedented array of tools to explore endocrinological processes at mechanistic levels we could never have dreamed of in 1977. The future looks to be an era of major advances in neuroendocrinology. What technologies will arise and transform our knowledge further? Artificial intelligence (AI) is emerging as a tool in avian endocrinology in at least research on endocrine disrupting chemicals. Will AI facilitate new advances and research directions across the field? The future of basic research has never been brighter than it is now. As in the past, ISAEs in the next decades will integrate new discoveries across environmental and applied biology. New challenges will doubtless appear.

To evaluate a radiomic strategy for predicting progression in advanced gastroenteropancreatic neuroendocrine tumor (GEP-NET) patients treated with somatostatin analogs (SSAs). Fifty-eight patients with GEP-NETs and liver metastases, with baseline computerized tomography (CT) scans from June 2013 to November 2020, were studied retrospectively. Data collected included progression-free survival (PFS), overall survival (OS), tumor grading, death, and Ki67 index. Patients were categorized into progressive and non-progressive groups. Two radiologists performed 3D liver segmentation on baseline CT scans using 3DSlicer v4.10.2. One hundred six radiomic features were extracted and analyzed (T-test or Mann–Whitney). Radiomic feature efficacy was evaluated via receiver operating characteristic curves, and both univariate and multivariate logistic regression were used to develop predictive models. A significance level of p < .05 was maintained. Of 55 patients, 38 were progressive (median PFS and OS: 14 and 34 months, respectively), and 17 were non-progressive (median PFS and OS: 58 months each). Six radiomic features significantly differed between groups (p < .05), with an area under the curve (AUC) range of 0.64–0.74. Ki67 was the only clinical parameter significantly associated with progression risk (odds ratio (OR) = 1.14, p < .05). The combined radiomic features and Ki67 model proved most effective, showing an AUC of 0.814 (p = .008). The radiomic model alone did not reach statistical significance (p = .07). A combined model incorporating radiomic features and the Ki67 index effectively predicts disease progression in GEP-NET patients eligible for SSA treatment.

Peptide receptor radionuclide therapy (PRRT) using [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate (¹⁷⁷Lu-DOTATATE) represents an established treatment modality for somatostatin receptor-positive, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumours (GEP NET) of grade 1 or 2. The studies have demonstrated that four cycles of PRRT with ¹⁷⁷Lu-DOTATATE prolongs progression-free survival and preserves quality of life, in patients with grade 1 and 2 advanced GEP NET. Notably, first-line PRRT using ¹⁷⁷Lu-DOTATATE in grade 2 and 3 GEP NET patients has also shown efficacy and safety. Furthermore, PRRT can ameliorate symptoms in patients with NET-associated functioning syndromes. Although various studies have explored alternative radionuclides for PRRT, none currently meet the criteria for routine clinical implementation. Ongoing research aims to further enhance PRRT, and the results from large clinical trials comparing PRRT with other NET treatments are anticipated, potentially leading to significant modifications in NET treatment strategies and PRRT protocols. The results of these studies are likely to help address existing knowledge gaps in the coming years. This review describes the clinical practice, recent developments and future treatment options of PRRT in patients with grade 1 and 2 GEP NET.