Neuroendocrinology最新文献

In the article "Sex Differences in Brain and Plasma β-Endorphin Content following Testosterone, Dihydrotestosterone and Estradiol Administration to Gonadectomized Rats" [Neuroendocrinology. 2009;89(4):411-423; https://doi.org/10.1159/000209506] by Pluchino et al., the following should be noted.Following publication, it was brought to the journal's attention that the data presented in Table 1 of this article had been previously published by the authors [1], which was not referenced in the article.When asked to comment, the authors stated that in order to limit the number of animals used in the experiments, the same cohort of rats was employed for the different analyses and that the data is repeated solely for descriptive purposes, to document well-expected hormonal changes of animals undergoing gonadectomy or hormonal replacement therapy.Discrepancies between the articles in the following reported values are noted:1.Testosterone, ng/mL for OVX + T (10 μg/kg/day) group2.Estradiol, pg/mL for OVX + Estradiol group3.Testosterone, ng/mL for Gonad intact male group4.Testosterone, ng/mL for OCX + T (1 mg/kg/day) groupThe authors state these are due to typographical errors and the data in the Neuroendocrinology article should be considered the correct version.This notice is to inform readers of the known data republication and discrepancies in the reported values.

Background: A number of factors contribute to the development of diabetes mellitus, but until recently, the role of hypothalamic dysfunction in the development of this disorder has not received sufficient attention. Hypothalamic neurons that project to the autonomic nervous system control overall glucose metabolism and insulin sensitivity. These neurons, in turn, are controlled by specialized astrocytes possessing proteins that enable them to function as nutrient sensors for glucose and fatty acids. An aging-related pathological process (that of mitochondrial degeneration) is present in these specific hypothalamic astrocytes. This mitochondrial degeneration can be accelerated by access to a high-fat diet, which also induces hypothalamic resistance to leptin, generalized insulin resistance, and an abnormal glucose homeostasis. An impaired astrocyte-neuron signaling, caused by this pathological mitochondrial degeneration, may underlie an abnormal hypothalamic function that leads to the development of type II diabetes. Pharmacological agents that protect astrocytes from mitochondrial degeneration may have a place in the treatment of type II diabetes.

Summary: This article reviews evidence that hypothalamic pathology may make an important contribution to the etiology of type II diabetes mellitus.

Key messages: abnormalities in hypothalamic astrocytes provokes a disturbed hypothalamic function that contributes to the development of diabetes mellitus.

Metabolic dysfunction and the associated diseases (e.g. diabetes) are globally on the rise and a sedentary lifestyle directly contributes to this issue. In fact, post-menopausal women are at increased risk for obesity and metabolic disease due to the loss of metabolically protective estrogen (E2). Exercise is vital for overall health, greatly reducing disease risk, but the central brain regions involved in drive for physical activity remain unclear. Female Sprague-Dawley (SD) rats were ovariectomized (OVX) and concurrently bilaterally implanted with cannulae targeting the nucleus accumbens (NAc) brain region, traditionally associated with reward and addiction. Daily voluntary wheel running (VWR) was tracked before and after OVX. One month after surgery, rats were treated with intra-accumbens microinjections (0.5ul total volume) of one of three doses of E2: 0.6ug/ul (Low), 1.5ug/ul (Moderate), or 10ug/ul (High). Daily VWR was significantly increased by intra-accumbens E2 microinjections in a non-rapid manner that persisted 48 hrs. following microinjections. Findings demonstrate for the first time that intra-accumbens E2 partially rescues OVX-induced decreases in daily wheel running.

Background: Neuroendocrine tumor G3 (NET G3) is a new category introduced in the WHO 2017 classification. Accordingly, evidence regarding chemotherapy for NET G3 is limited. A multicenter, retrospective analysis was performed to evaluate the outcomes of systemic therapy for NET G3 and to identify the optimal regimens.

Methods: Patient demographic and treatment outcome data were retrospectively collected for 73 patients with pathologically diagnosed NET G3 who started chemotherapy at participating institutions between January 2011 and December 2019, excluding those who were ineligible by central pathological review. The chemotherapy regimens used and their efficacies were evaluated.

Results: Of the 73 patients, 47 had pancreatic NETs, 10 had gastrointestinal NETs, and 16 had NETs at other sites. Central pathological review was performed for 44 patients, with a concordance rate of 95%. Initial treatment regimens included NET-based treatment (somatostatin analog, molecular-targeted agent, cytotoxic chemotherapy such as streptozocin and temozolomide) for 37 patients, neuroendocrine carcinoma (NEC)-based treatment (platinum-containing chemotherapy) for 32 patients, and other regimens for 2 patients. There were no significant differences in progression-free survival (PFS) or overall survival (OS) between patients receiving NET-based and NEC-based treatment or among the individual treatment regimens. However, the response rate (RR) was higher for NET-based cytotoxic chemotherapy (50%) compared with NEC-based treatment (16%), suggesting greater efficacy of NET-based cytotoxic chemotherapy.

Conclusions: Although no significant difference in PFS or OS was found among the chemotherapy regimens for NET G3, RR was notably higher for NET-based cytotoxic chemotherapy than for NEC-based treatment.

Introduction: Neuroendocrine neoplasms (NENs) classification and diagnosis have substantially advanced, prompting specialization of pathologists and clinicians in NEN fields and fostering close interdisciplinary collaboration. In these rare diseases, misdiagnosis may undermine therapeutic strategies, highlighting the importance of a strong clinician-pathologist partnership. While the NEN-dedicated pathologist's role is well acknowledged, in clinical practice, accurate histological review depends on the clinician's ability to pose focused diagnostic questions within a well-defined clinical context.

Methods: We retrospectively analyzed all NEN histological second opinions performed by a dedicated pathologist at our ENETS Center of Excellence in 01/2023-12/2024. Second opinions were requested by referring clinicians in cases of diagnostic uncertainty or clinical-pathological discordance. Discrepancies between initial and final diagnoses were categorized as "major" (with a substantial impact on patients' management) or "minor."

Results: Of 63 reviewed cases, we identified 36 not concordant cases. Among them, we reported 29/36 (81%) cases with significant discrepancies between the initial and the final diagnosis, with a following change in therapeutic strategy in 28 (e.g., shift from surveillance to surgery or modification of systemic therapy). Clinical requests for a histological review were prompted by inconsistency between clinical history and pathological diagnosis, incomplete or incoherent initial pathology report, or need for diagnostic confirmation to support specific clinical indications (e.g., surgery or chemotherapy).

Conclusion: Our findings underscore the critical role of clinician's expertise in the multidisciplinary management of NEN patients. Underestimating clinician's role in coordinating the diagnostic process can lead to suboptimal care. Additionally, there is an urgent need to redesign the NEN care pathway, ensuring early access to specialized evaluation since the early diagnostic phase.

Background: N-methyl-D-aspartate receptors (NMDARs) are widely distributed in the brain and pancreas. Preliminary evidence indicates that aberrant NMDAR-mediated glutamatergic signaling may disrupt pancreatic islet function and glucose-insulin homeostasis. The frequent comorbidity of depression and diabetes underscores the potential role of NMDAR signaling in pancreatic function as a shared pathophysiological mechanism. Herein, this systematic review aims to evaluate the effects of NMDAR antagonism on pancreatic cells (i.e., alpha, beta, delta) viability and function (i.e., activation, hormone production, and release).

Methods: We performed a systematic search on PubMed and Ovid databases from inception to September 11, 2024. A manual search was also conducted on Google Scholar and Scopus databases. Eligible studies were primary, controlled in vitro or in vivo studies investigating the effects of NMDAR antagonism on pancreatic islet function and viability. Results were synthesized and presented descriptively. Risk of bias was assessed independently by two reviewers using a modified SYRCLE risk of bias tool.

Results: We reviewed 14 studies evaluating NMDA receptor antagonism in whole islets, beta and alpha cells; however, no studies evaluated delta cells. Within beta cells, NMDAR antagonism improved glucose-stimulated insulin secretion and increased cell proliferation and viability. Similarly, alpha cells were protected against stress-induced apoptosis.

Conclusion: Our results suggest that NMDAR antagonism improves alpha and beta cell function and viability, which may have translational relevance to comorbid metabolic dysfunction in depression. These mechanisms may subserve the antidepressant effects of select NMDA antagonists (e.g., ketamine/esketamine, dextromethorphan). Further research should aim to investigate the effects of subanesthetic doses of ketamine/esketamine on pancreatic function and on delta cells.

Introduction: Congenital hypogonadotropic hypogonadism (CHH) arises from defects in the synthesis, secretion, or action of gonadotropin-releasing hormone (GnRH), resulting in incomplete or absent pubertal development and various nonreproductive features. CHH is genetically heterogeneous, with over 50 genes implicated in its pathogenesis. This study aimed to elucidate the genetic variants of CHH in a cohort of patients from a single-center endocrinology unit.

Methods: We used a targeted next-generation sequencing panel to analyze 52 CHH-related genes in 35 patients. Functional studies validated two of the identified variants.

Results: Molecular etiology was identified in 20 of 35 (57%) patients. Among these, 12 (39%) had variants in multiple CHH-related genes, with oligogenic inheritance confirmed in two cases. Novel pathogenic variants (both single nucleotide variants and copy number variants) were identified, including ANOS1 p.Gln238* and c.318+2T>C, CHD7 p.Ser734Ilefs5 and p.Gln592Serfs16, FGFR1 p.Ala36Profs67, c.1663+5G>A, and p.Tyr210*, DMXL2 deletion (83.1 Kb), and SOX2 deletion (1.1 Mb). In total, 21 pathogenic or likely pathogenic variants across 15 CHH-related genes were detected, including ANOS1, CHD7, FGFR1, PROKR2, and others. A functional study confirmed the loss of function in the KISS1R p.Ala203Asp variant.

Conclusion: Our findings demonstrate the utility of a next-generation sequencing panel in diagnosing genetically complex conditions like CHH and underscore the role of oligogenic inheritance in its phenotypic diversity. The inclusion of genes previously associated with syndromic CHH forms such as CHARGE in the exome panel may highlight possible shared mechanisms with neurodevelopmental disorders, aiding early diagnosis, genetic counseling, and treatment.

Background: Pituitary adenomas are benign brain tumors that develop from hormone-producing cells in the anterior pituitary gland and account for 10-20% of all intracranial tumors. However, pituitary adenomas can have significant morbidity due to local invasion and changes to hormonal secretion. Though radiotherapy can result in side effects ranging from hypopituitarism to visual changes, radiation therapy remains an important tool due to its long-term benefits and high tumor control rates. Summary: Standard treatment for pituitary adenomas often includes surgical resection followed by radiation therapy. Recent developments in radiation delivery methods and techniques include external beam radiotherapy, stereotactic radiosurgery, proton therapy, and peptide receptor radionuclide therapy, which have improved precision while minimizing damage to healthy tissues. These advancements have continued to improve patient safety and long-term outcomes in cases of both functioning and nonfunctioning pituitary adenomas. Key Messages: Pituitary adenomas, while benign, can have significant clinical consequences. Advances in radiation therapy have expanded the therapeutic landscape to offer safer, more effective and more precise treatment options. Modern radiotherapy techniques have enhanced long-term outcomes and quality of life for patients with pituitary adenomas.

Introduction: Obstructive sleep apnea (OSA) may influence the hypothalamic-pituitary-adrenal (HPA) axis and result in subsequent physiological dysregulation. Given the inconsistent findings of the current literature and the lack of investigations on stress hormones, this study explored the potential impact of OSA on stress markers of adrenocroticotrophic hormone (ACTH), cortisol, and dehydroepiandrosterone (DHEA)/DHEA-S in male overweight OSA patients.

Methods: This prospective, single-blind, cross-sectional study enrolled male overweight (body mass index >25 kg/m2) OSA patients. The patients were grouped into mild/moderate and severe OSA groups based on the apnea/hypopnea index to investigate the differences in stress hormones. The inter-relationships among ACTH, cortisol, and DHEA in both groups were further analyzed in detail with Pearson's correlations to determine the potential impact of OSA severity.

Results: Overall, 144 subjects were recruited. DHEA in saliva and serum DHEA-S were found significantly lower in the severe OSA group compared to the mild/moderate OSA group. Pearson's correlations demonstrated that in both groups, ACTH and cortisol concentrations (morning and night) showed significant positive correlations. Significant relationships between night ACTH and DHEA-S in saliva (r = 0.368, p = 0.023) and blood (r = 0.361, p = 0.017) were also found in mild/moderate OSA group, but neither was noted in the severe group.

Conclusion: Severe OSA may impact the HPA axis by reducing concentrations of DHEA and DHEA-S without affecting cortisol and ACTH concentrations in male overweight OSA patients. This could possibly imply the dysregulation of DHEA/DHEA-S production in a much severe sleep disturbance situation.

Objective: Early-onset puberty is a major reason for pediatric endocrinology clinics, particularly among girls. Obesity is linked to disruptions in the hypothalamic-pituitary-gonadal (HPG) axis, thereby leading to early-onset puberty. This study was designed to investigate the regulatory effects of soyasaponin Aa in an animal model of obesity-associated precocious puberty.

Study design: A rat model of obesity-induced precocious puberty was established through high-fat diet (HFD) feeding, which closely mimics the condition in children caused by excessive caloric intake. Obesity was assessed through body weight, serum lipid levels, and gonadal fat mass. Western blotting was performed to assess key adipogenesis regulators (PPARγ and C/EBPα) in gonadal white adipose tissues. ELISA was used to analyze serum levels of hormones (LH, FSH, and GnRH). The mRNA expression of HPG axis-related genes in the hypothalamus, pituitary gland, and ovary were detected by RT-qPCR. Histopathological changes in ovarian and uterine tissues were examined using hematoxylin and eosin staining.

Results: Soyasaponin Aa significantly reduced body weight gain in HFD-fed rats and suppressed increases in serum lipid levels and gonadal white adipose tissue mass. It inhibited HFD-induced lipogenesis, as indicated by reduced expression of PPARγ and C/EBPα. Soyasaponin Aa effectively delayed puberty onset in female rats, as evidenced by prolonged vaginal opening and first estrous cycle, reduced endometrium thickness, and lower uterine and ovarian weights, along with suppressed follicular maturation. The HFD group showed elevated serum LH and FSH levels and increased hypothalamic GnRH secretion, all of which were significantly counteracted by soyasaponin Aa. Moreover, soyasaponin Aa downregulated HPG axis-related gene expression.

Conclusion: Soyasaponin Aa protects against obesity-induced precocious puberty by suppressing the activation of HPG axis.