Search Results (354)

Zearalenone (ZEA) is a potent estrogenic mycotoxin known to disrupt reproductive functions, but its precise central neuroendocrine mechanisms remain unclear. This study investigated the effects of ZEA on the hypothalamic-pituitary Kiss1/GPR54 signaling pathway in weaned gilts. A total of 32 gilts were randomly assigned to four dietary treatments contained with 0, 0.15, 1.5, or 3.0 mg/kg ZEA for a 32-day feeding trial. Histopathology, immunohistochemistry, and mRNA/protein expression analyses of GPR30, Kiss1, GPR54, GnRH, and GnRHR in the hypothalamus and pituitary gland were conducted. ZEA exposure induced significant histological damage in both tissues. In the hypothalamus, Kiss1, GPR54, GnRH, and GnRHR exhibited a non-linear response, increasing at moderate doses and decreasing at 3.0 mg/kg ZEA, whereas GPR30 expression was continuously upregulated. In the pituitary gland, GnRHR showed a similar non-linear pattern. Furthermore, high-dose ZEA down-regulated pituitary Kiss1 and GPR54 while up-regulating GnRH and GPR30 expressions. In conclusion, ZEA induces reproductive neuroendocrine toxicity through a complex, dose-dependent modulation of the Kiss1/GPR54 signaling axis. The persistent upregulation of GPR30 suggests it acts as a crucial mediator in disrupting this endocrine feedback loop within the hypothalamus and pituitary gland. Full article

Pluripotent stem cells (PSCs) have proven outstanding potential to revolutionize biomedical research. Specifically, their capacity to form 3D multicellular systems that recapitulate organ development and biology, known as organoids, has transformed basic and translational research. The groundbreaking technology is also being applied to the intricate hypothalamus–pituitary (HP) axes, including the target organs (such as gonads, thyroid and adrenal glands). These HP axes govern critical physiological processes, including reproduction, metabolism and stress. Here, we provide an overview of PSC-derived organoid models that are part of the HP axes, both as individual and multi-organ systems, and evaluate their culturing conditions, phenotypic characteristics, advantages, drawbacks and challenges, as well as their potential for disease modeling and therapeutic discovery. By offering this wide perspective, our review will also serve as a key resource for researchers navigating the evolving landscape of PSC-derived organoid technologies in endocrinology. Full article

Background/Objectives: Prognostication in traumatic brain injury (TBI) remains challenging. The urine-to-serum osmolality (U/S) ratio may reflect hypothalamic–pituitary axis integrity, a critical but underexplored prognostic domain. We investigated whether the U/S ratio provides early prognostic value and enhances prediction when combined with conventional severity markers. Methods: This retrospective study included 128 adult TBI patients admitted to a neurosurgical intensive care unit (ICU) with simultaneous osmolality measurements within 6 h of admission. The primary outcome was ICU mortality; the secondary outcome was poor neurological outcomes (Glasgow Outcome Scale 1–3). Results: ICU mortality was 14.1% (18/128), and poor neurological outcome occurred in 41.8% (46/110). Non-survivors had significantly lower U/S ratios than survivors (1.09 ± 0.58 vs. 1.70 ± 0.68, p < 0.001). For ICU mortality, U/S ratios (AUC = 0.803) showed similar discriminative ability to GCS (AUC = 0.806). For poor neurological outcomes, the U/S ratio (AUC = 0.768) significantly outperformed both GCS (AUC = 0.641, p = 0.038) and the Acute Physiology and Chronic Health Evaluation (APACHE) II score (AUC = 0.553, p < 0.001). Combining the U/S ratio with GCS improved mortality prediction (AUC = 0.890), as did combinations with the APACHE II score (AUC = 0.847). The U/S ratio remained independently associated with ICU mortality and poor neurological outcomes after adjusting for GCS or APACHE II scores. Quartile analyses revealed a dose–response relationship, with ICU mortality of 34.4% in Q1 versus 3.1% in Q4 (p for trend < 0.001). Prognostic value was preserved in patients receiving osmotic therapy (n = 86). Conclusions: The U/S ratio is a simple, readily available biomarker that independently predicts mortality and poor neurological outcomes in TBI patients. Particularly for neurological outcome predictions, it outperforms GCS or the APACHE II score alone. Combined with established severity scores, it may serve as a practical bedside tool reflecting hypothalamic–pituitary function in neurocritical care. Full article

Background and Objectives: The pituitary gland plays a central role in endocrine regulation, and chronic illnesses may disrupt pituitary axis function, potentially influencing clinical outcomes. In this study, we aimed to thoroughly investigate the effects of the pituitary axis on all-cause mortality in patients with chronic diseases. Materials and Methods: This prospective observational cohort study included 526 patients with chronic diseases lasting longer than six months who were hospitalized in the Internal Medicine Department of a training and research hospital in Istanbul between 7 May and 30 November 2023. Hormonal parameters were measured within the first 72 h of admission. Demographic characteristics, comorbidities, laboratory findings, intensive care unit (ICU) transfer, and mortality outcomes were recorded. Multivariable binary logistic regression analysis was used to identify independent predictors of mortality. Results: Patients who died were significantly older (75.60 ± 12.6 years, p < 0.001) and had lower free triiodothyronine (FT3) levels (p < 0.001). In hierarchical multivariable logistic regression analysis, increasing age, lower serum albumin levels, immobilization, low FT3 levels, and abnormal luteinizing hormone (LH) levels (defined as values outside sex- and menopausal status-adjusted reference intervals) were independently associated with 6-month mortality. The addition of hormonal parameters significantly improved model performance beyond traditional markers of illness severity. Conclusions: Alterations in pituitary axis hormones, particularly deviations in LH levels and reduced FT3 levels, are independently associated with mortality in hospitalized patients with chronic diseases. These findings suggest that pituitary hormone profiles may contribute to the stratification of mortality risk in this population. Full article

Coronavirus disease 2019 (COVID-19) is increasingly shown to be a multisystem disorder with long-term complications, including endocrine system complications. The thyroid gland is also susceptible, as it contains ACE2 receptors, making it exposed to both direct viral damage and autoimmune-mediated dysfunction. Recent reports document the various thyroid complications that persist well after the acute infection phase. This systematic review investigates the long-term thyroid complications in individuals with a history of SARS-CoV-2 infection. A comprehensive literature search across several databases was conducted. Eligible studies reported new onset long-term thyroid complications occurring post-COVID-19 infection. Abstract and full-text screening as well as data extraction and quality assessment was performed by two independent reviewers. Only 28 studies met our inclusion criteria, reporting 419 patients from 18 countries. These studies included case reports, case series, cohort, and cross-sectional studies. Reported thyroid disorders included subacute thyroiditis, thyrotoxicosis, hyperthyroidism (including Graves’ disease), isolated high T3/T4, hypothyroidism, central hypothyroidism, and non-thyroidal illness syndrome (NTIS). While many of these eventually resolved, a significant portion persisted or recurred, especially autoimmune thyroiditis. COVID-19 is associated with a range of long-term thyroid complications. Although some cases are temporary, others last, especially autoimmune thyroid disorders. Proposed mechanisms include direct viral cytotoxicity, cytokine-mediated Hypothalamic–Pituitary–Thyroid (HPT) axis suppression, post-viral autoimmunity, vascular injury, and neuroendocrine disruption. Routine thyroid function monitoring in COVID-19 survivors, particularly those with severe disease or persistent symptoms is recommended, and larger prospective studies are needed to better understand incidence and outcomes. Full article

Background: Acromegaly is a rare, chronic, systemic, and progressive disease characterized by an excess secretion of growth hormone (GH) and increased circulating insulin-like growth factor 1 (IGF-1) concentrations, typically due to a macroadenoma in the pituitary gland. Both GH and IGF-1 are implicated in cancer promotion based on experimental and epidemiological data, but research findings remain conflicting and population-based data are scarce. Although there is a high mortality rate among acromegalic patients due to cardiovascular diseases, cancer is the third leading cause of death. Aim: The aim of the present study was to assess the risk of different types of cancer in acromegaly and the impact of changes in disease control and patient outcomes over time. Methods: Patients diagnosed with acromegaly at the Ankara University Ibn-i Sina Hospital Endocrinology and Metabolic Diseases Department between 2015 and 2019 were included in this study. Data including demographic data, history of cancer, size of adenoma (micro or macro), serum IGF-1 and GH levels at the time of diagnosis, serum prostate-specific antigen (PSA), thyroid ultrasonography, and, if needed, thyroid fine needle aspiration cytology (TFAC), colonoscopy, and mammography results were collected from patient records retrospectively. Results: We screened 83 patients, and 78 patients with the compensatory data (female/male: 39/39, 50%/50%) were included. The mean age of patients was 49.4 ± 11.9 years and 41.7 ± 12.1 years at the time of diagnosis. The median duration of follow-up was 72 (12–420) months. Periodic thyroid ultrasonography was performed in 65/78 (83.3%) of the patients, and a colonoscopy and mammography were also conducted in 27/78 (34.6%) and 32/39 (82%) of the patients at least once over the course of the disease, respectively. Cancer was detected in 17/78 (21.7%) of the patients; 11/78 (14.1%) of them had well-differentiated thyroid cancer and 2/39 (5.1%) had breast cancer. Prostate cancer, renal cell carcinoma, pancreatic cancer, malignant chordoma, schwannoma, and colon cancer were detected in one patient each. The increased cancer risk in acromegalic patients did not correlate with age, sex, age at diagnosis, time to diagnosing acromegaly, duration of acromegaly, GH and IGF-1 levels at diagnosis, pituitary adenoma size, or Ki-67 levels. Conclusions: Cancer was detected in 21.7% of the acromegaly patients, 14.1% of whom had well-differentiated thyroid cancer. In this study, we demonstrated that thyroid cancer is the most common malignancy in Turkish acromegalic patients, consistent with the results of previous studies. The increased cancer risk in acromegalic patients did not correlate with age, sex, age at diagnosis, time to diagnosing acromegaly, duration of acromegaly, or GH and IGF-1 levels at diagnosis. Full article

The metabolism of the four major substances—glucose, lipids, amino acids, and nucleotides—constitutes the most prominent metabolic phenotype of schizophrenia. The pathological axis shared by these substances involves energy pathway imbalances, redox stress, immune-inflammatory activation, and abnormalities in neurotransmitter synthesis/degradation. Existing research confirms that key metabolites within these pathways hold potential as biomarkers for diagnosis or progression monitoring. In recent years, electroconvulsive therapy (ECT) has been shown to improve psychotic symptoms while exerting broad regulatory effects on neurogenesis, immune homeostasis, and the hypothalamic–pituitary–target gland axis, though its precise mechanisms remain unclear. Recent studies indicate that ECT treatment can also regulate changes in brain and peripheral metabolism. We propose an integrated “metabolism-immunity-neuroendocrine” hypothesis to systematically elucidate how metabolic reprogramming during ECT treatment cascades sequentially to the immune, neural, and endocrine systems, thereby revealing the molecular basis of its antipsychotic effects. Furthermore, we conduct a comparative analysis of the effects of antipsychotic drugs on the same metabolic network and explore the universality and specificity of metabolic regulation in other physical therapies (such as rTMS, tDCS) and psychiatric disorders like depression and bipolar disorder. This research aims to provide novel biomarkers and intervention targets for the precision diagnosis and treatment of schizophrenia. Full article

Neuropeptide FF (NPFF) belongs to the RF-amide peptide family and is homologous to gonadotropin-inhibitory hormone (GnIH). The NPFF precursor encodes two mature peptides, NPFF and NPAF (neuropeptide AF). Both peptides share the conserved C-terminal PQRFa motif. However, there is very limited information available on receptor cross-reactivity for NPFF and GnIH peptides in teleosts. As a first step, we cloned two cognate receptor genes for NPFF, designated as NPFFR2-1 and NPFFR2-2, in the flatfish species half-smooth tongue sole. Tissue distribution analysis revealed that npffr2-1 and npffr2-2 transcripts were present at high levels in the brain and pituitary gland, and at lower levels in some peripheral tissues. In vitro functional analysis indicated that NPFF significantly stimulated CRE-luc and SRE-luc activity in COS-7 cells expressing either NPFFR2-1 or NPFFR2-2. However, NPAF increased CRE-luc and SRE-luc activity only via NPFFR2-1. Moreover, NPFF exerted an inhibitory effect on NFAT-RE-luc activity in COS-7 cells transfected with NPFFR2-1, whereas NPAF elicited an evident stimulatory effect via NPFFR2-2. Neither GnIH1 nor GnIH2 altered CRE-luc activity in COS-7 cells transfected with NPFFR2-1 or NPFFR2-2; however, forskolin-induced CRE-luc activity was significantly reduced by these two peptides. Furthermore, neither basal nor forskolin-stimulated CRE-luc activity was modified by NPFF or NPAF in COS-7 cells expressing the GnIH receptor (GnIHR). Both GnIH1 and GnIH2 significantly increased SRE-luc activity in COS-7 cells expressing NPFFR2-1 or NPFFR2-2, and vice versa. Taken together, our findings provide novel evidence that both NPFF and GnIH peptides could exert their functions via three different receptors, and that PKA, PKC, and Ca²⁺ signaling pathways are potential mediators. Full article

Background: The sphenoid sinus is essential for transsphenoidal surgical accesses to the sellar and parasellar regions because of its anatomic proximity to vital vascular and neurologic structures such as the internal carotid artery, optic nerve, and cavernous sinus. The high degree of morphological variability of the sphenoid sinus has a significant impact on surgical technique and the risk of intraoperative complications. Detailed knowledge of individual anatomy is therefore crucial for the safety and efficacy of transsphenoidal approaches. Objectives: This review aims to conduct a systematic analysis of the current scientific literature on anatomical variations in the sphenoid sinus and their clinical relevance in surgical interventions to the skull base. Special attention is paid to the influence of morphological features on surgical strategies to pathological processes in this area and postoperative outcomes. Materials and Methods: A systematic review of the literature was conducted according to PRISMA 2020 guidelines. The PubMed, Scopus, Web of Science, and Google Scholar databases were searched for the period March 2010 to March 2025. Keywords such as “sphenoid sinus”, “anatomical variations”, “transsphenoidal surgery” and “skull base” were used. Original studies, systematic reviews, and meta-analyses focused on the anatomy, pneumatization, and surgical significance of sphenoid sinus variations are included. Quality and relevance criteria for published material were considered in the selection of articles. Results: The most commonly identified anatomic variations included sellar and lateral pneumaticity, the presence of Onodi cells, multiple and deviated septa, and dehiscence of the posterior wall of the sphenoid sinus and prolapse into its cavity of the internal carotid artery. These variations are associated with an increased risk of intraoperative vascular injury, visual deficit, and postoperative liquorrhea. Accurate preoperative assessment by high-resolution computed axial tomography and magnetic resonance imaging, as well as the use of intraoperative neuronavigation, are critical to reduce surgical risk. Conclusions: Anatomic variations in the sphenoid sinus are an essential factor to consider when planning and performing transsphenoidal surgical accesses. An individualized approach based on detailed diagnostic imaging analysis and neuronavigation technologies contributes to a higher safety of the performed surgical interventions, a better radicality of tumor resection and more favorable postoperative outcomes. Full article

Neuropeptide Y (NPY) is a small signalling molecule produced by neurons through the cleavage of a precursor protein. It generally binds to and activates G protein-coupled receptors to modulate complex homeostatic processes and behaviours in animals. Mammals provide definitive proof of the role of NPY in the thyroid axis, but in reptiles, this link is unclear. We demonstrate that the thyroid axis responds to NPY administration in a dose-dependent manner, with a reduction in plasma TRH and TSH concentrations, and an increase in plasma T₃ and T₄ levels 2 and 24 h after administration, suggesting that NPY may activate the thyroid axis. This increase in thyroid hormones is supported by morphological findings in the thyroid gland, which show clear signs of stimulation demonstrated by a dose-dependent increase in the height of the follicular epithelium and the presence of numerous resorption vacuoles. Moreover, we investigated the 5-T₄ ORD (type II) Monodeiodinase activity at the hepatic level, showing that NPY increased hepatic T₃ levels and decreased hepatic T₄ levels, and suggesting an alternative mode of signalling by NPY on peripheral biosynthesis of thyroid hormones. Our study helps to address the current lack of research in the field of endocrinology concerning the effects of NPY on metabolism and thyroid function. Full article

Chronic stress alters hypothalamic–pituitary–adrenal (HPA) axis function, affecting corticosterone regulation and adaptive responses. Understanding individual variability in stress adaptation requires identifying distinct HPA axis response patterns. Here, we assessed HPA axis sensitivity in male C57BL6 mice exposed to 30 days of chronic social defeat stress (CSDS). Negative feedback integrity was evaluated using the dexamethasone suppression test (DST), with corticosterone measured after saline or low-dose dexamethasone administration at days 10 and 30. Behavioral testing (open field, elevated plus maze, social interaction test, partition, social defeat, forced swimming test, sucrose preference test) and qPCR analysis of HPA-axis-related genes in the hypothalamus (Crh, Crhr1, Crhbp, Fkbp5, Nr3c1), pituitary (Pomc, Crhr1, Nr3c1, Nr3c2), and adrenal glands (Cyp11a1, Cyp11b1, Hsd11b1, Mc2r, Star, Fkbp5, Nr3c1) were performed. K-means cluster analysis identified three distinct response profiles differing in baseline and dexamethasone-suppressed corticosterone levels. Clusters also exhibited differences in behavioral phenotypes and HPA axis gene expression. Cluster 1 showed low basal corticosterone and an abnormal dexamethasone suppression response, without significant Crh or Crhbp dysregulation in the hypothalamus. Cluster 2 exhibited elevated basal corticosterone, a blunted dexamethasone response, anhedonia, and reduced immobility in the forced swim test; increased Crh and reduced Fkbp5 suggested enhanced glucocorticoid receptor sensitivity and sustained hypercortisolemia. Cluster 3, characterized by normal basal corticosterone and normal dexamethasone response, displayed upregulation of Crh and Crhbp, consistent with balanced and potentially adaptive HPA axis regulation under chronic stress. These results demonstrate that corticosterone response heterogeneity reflects distinct adaptive trajectories under chronic stress. Identifying behavioral and molecular markers of these strategies may advance understanding of stress vulnerability and resilience mechanisms, with implications for stress-related disorders. Full article

To explore the induction of low temperature the Tiger Puffer (Takifugu rubripes) In this study, the influence of temperature on the pituitary gland during masculinization was investigated through chronic hypothermia stress experiments. Metabolomics was used to analyze the metabolic regulatory network of the pituitary gland under hypothermia stress. ELISA technology was employed to determine the activity content of oxidative stress-related enzymes in the pituitary gland. Further, TUNEL fluorescence labeling and qPCR were used to detect the apoptosis level of pituitary cells. Finally, to assess the impact of low-temperature stress on muscle tissue, HE staining and qPCR techniques were employed. The results showed that after 45 days of low-temperature stress, the differential metabolites of the pituitary gland were mainly enriched in the amino acid metabolic signaling pathway, and the contents of amino acids such as GSH and its synthetic precursors in the pituitary tissue changed significantly. The contents of oxidative stress indicators such as ROS and MDA all showed a trend of first increasing and then decreasing. The qPCR results of TUNEL fluorescence labeling and apoptosis-related genes were consistent, indicating that the apoptotic level of pituitary cells first increased and then decreased with the stress process. Histological analysis revealed that low temperature led to muscle cell atrophy and increased interstitial space in muscle tissue. The expression changes in genes related to muscle development further confirmed that low temperature significantly inhibited muscle growth and development. Therefore, this study speculates that after being subjected to chronic low-temperature stress, the pituitary gland of the red-finned Oriental pufferfish can alleviate the oxidative stress response of the body by strengthening the amino acid metabolic pathway, and the fish body has shown a physiological trend of gradually adapting to low-temperature stress, but the growth and development of muscles are still significantly inhibited. The results of this study can provide theoretical support for understanding the physiological adaptation mechanism of the red-finned Oriental pufferfish to low-temperature stress and lay a foundation for subsequent in-depth exploration of the pituitary response mechanism to low temperatures. Full article

Sulfoxaflor, an insecticide, acts on nicotinic acetylcholine receptors. It has a functional group similar to that of neonicotinoid insecticides, which are testicular toxicants. Recently, the adverse effects of sulfoxaflor on the testes have been reported in rats. This study aimed to address the lack of reports on sulfoxaflor administration in mice and its effects on the testes. ICR mice (3- and 10-week-old) were treated ad libitum with two different concentrations (10 and 100 mg/kg) of sulfoxaflor for 4 and 8 weeks. Histological analysis and real-time reverse transcription polymerase chain reaction were performed. Testis weights relative to body weights in the sulfoxaflor groups showed no significant difference compared to the control group. Testicular tissue in the sulfoxaflor groups was unchanged compared to that in the control group. The sulfoxaflor-treated group showed no significant differences in the mRNA expression of luteinizing hormone and follicle-stimulating hormone in the pituitary gland compared to the control group. Furthermore, no significant differences were noted in the mRNA expression levels of various gene markers in the testes between the sulfoxaflor-treated and control groups. These markers include those related to Leydig cells, testosterone synthesis, Sertoli cells, proliferating cells, meiotic cells, pachytene spermatocytes, round spermatids, apoptotic cells, antioxidant enzymes, oxidative stress factors, and mitochondrial function. In contrast to findings in rats, which showed testicular toxicity, sulfoxaflor administration at low concentrations did not adversely affect intratesticular cells in either mature or immature mice at the doses and time points examined. In the future, we would like to conduct research on high concentrations of sulfoxaflor by changing the administration method. Full article