Neuroendocrine Function Research Articles

E-selectin affinity glycoproteomics reveals neuroendocrine proteins and the secretin receptor as a poor-prognosis signature in colorectal cancer.

Colorectal cancer (CRC) cells express sialylated Lewis antigens (sLe), crucial for metastasis via E-selectin binding. However, these glycoepitopes lack cancer specificity, and E-selectin-targeted glycoproteins remain largely unknown. Here, we established a framework for identifying metastasis-linked glycoproteoforms. More than 70% of CRC tumors exhibited overexpression of sLeA/X, yet without discernible associations with metastasis or survival. However, The Cancer Genome Atlas (TCGA) analysis unveiled differing expression patterns of sLeA/X-related glycogenes correlating with disease severity, indicating context-dependent regulation by distinct glycosyltransferases. Deeper exploration of metastatic tumor sialoglycoproteome identified nearly 600 glycoproteins, greatly expanding our understanding of the metastasis-related glycoproteome. These glycoproteins were linked to cell adhesion, oncogenic pathways, and neuroendocrine functions. Using an in-house algorithm, the secretin receptor (SCTR) emerged as a top-ranked targetable glycoprotein. Tumor screening confirmed SCTR's association with poor prognosis and metastasis, with N-glycosylation adding cancer specificity to this glycoprotein. Prognostic links were reinforced by TCGA-based investigations. In summary, SCTR, a relatively unknown CRC glycoprotein, holds potential as a biomarker of poor prognosis and as an E-selectin ligand, suggesting an unforeseen role in disease dissemination. Future investigations should focus on this glycoprotein's biological implications for clinical applications.

Acrylamide-induced hypothalamic-pituitary-gonadal axis disruption in rats: Androgenic protective roles of apigenin by restoring testicular steroidogenesis through upregulation of 17β-HSD, CYP11A1 and CYP17A1

Acrylamide (ARL) exposure induces significant toxicity to the hypothalamic-pituitary-gonadal (HPG) axis, leading to detrimental effects on behavior, neuroendocrine functions, steroidogensis, oxidative stress, inflammation, hormonal balance, sperm quality, and histopathological integrity in rats. This study investigates the protective role of oral apigenin (API; 10 or 20 mg/kg/day for 28 days) against ARL-induced toxicity in the HPG axis of male Wistar rats. Behavioral assessments revealed that ARL exposure impaired motor coordination and balance, as evidenced by increased landing foot splay distance and gait score. ARL-induced toxicity elevated brain Tau protein levels and disrupted hypothalamic GnRH levels, both mitigated by API. ARL triggered oxidative/nitrosative stress, reducing GSH contents and increasing MDA and NO levels in brain and testicular tissues, which were reversed by API. Hormonal imbalance, marked by decreased serum testosterone, FSH, and LH levels, was corrected by API. API enhanced semen quality parameters, with elevation in sperm count concentration and the percentages of both progressive motility and individual motility. It also normalized testicular PS and PC content, enhanced testicular cellular energy and restored seminal amino acid. The repression of testicular steroidogenesis-related enzymes CYP11A1, CYP17A1, and 17β-HSD following ARL exposure was alleviated by API administration. API also mitigated the inflammatory effects of ARL by reducing the expression of p–NF–κB p65 and TNF-α in testicular tissue. Histopathological examinations showed that API reduced neuronal and testicular degeneration, improving spermatogenesis. These findings suggest that API confers significant protective effects against ARL-induced HPG axis toxicity by restoring testicular steroidogenesis through the upregulation of 17β-HSD, CYP11A1, and CYP17A1, potentially due to its antioxidant, anti-inflammatory, and neuroprotective properties.

Inflammation as a shared mechanism of chronic stressrelated disorders with potential novel therapeutic targets.

Stress is a subjective experience that varies across individuals depending on their sensitivity, resilience, and length of exposure to stressors. Stress may be categorised as acute (positive stress) or chronic (negative stress). Acute stress is advantageous for the human body, but chronic stress results in changes in cardiovascular, neuroendocrine, autonomic, and immunological functions, eventually causing different illnesses. The specific process relating stress to chronic stress associated diseases is still a topic of continuing debate. Inflammation has been recognised as a new and fascinating physiological mechanism that connects chronic stress and its associated illnesses. This article explored the relationships between chronic stress, inflammation, and chronic illnesses, including depression, cancer, and cardiovascular disease. This article also emphasises on various possible therapeutic targets for the management of chronic stressrelated illnesses by targeting inflammation, namely lipoxins and alpha7 nicotinic receptors. These therapeutic targets may be useful in developing new and safe therapies for the management of chronic stressrelated dysfunctions.

Chronic Physiological Dysregulation and Changes in Depressive Symptoms: Testing Sex and Race as Vulnerability Factors.

Depression is a growing public health concern that affects approximately 5% of adults in their lifetime (WHO in Depression, 2021). Understanding the biological correlates of depression is imperative for advancing treatment. Of particular interest is allostatic load, a multisystem indicator of chronic physiological dysregulation (McEwen and Seemanin,Ann N Y Acad Sci, 1999). The current longitudinal study examined the association between allostatic load, depressive symptoms, and the moderating roles of sex and race. Participants consisted of 150 young adults (Mage = 18.81) who reported their demographics and depressive symptoms at T1 and T2, a year and a half later. Allostatic load was computed using indicators of metabolic, cardiovascular, and neuroendocrine functioning. Allostatic load was found to predict changes in depressive symptoms. Moreover, interaction effects models revealed that the associations between allostatic load and depressive symptoms at follow-up were further influenced by sex, such that the relationship was significant for males, with pronounced effects for Black males in particular. Black males may be particularly vulnerable to the mental health consequences of biological dysregulation.

8134 Hypothalamic Dlk1 Expression is Not Essential for Preventing Early Maturation of the Reproductive Axis in Female and Male Mice

Abstract Disclosure: D.B. Macedo: None. H. Kim Kyeol: None. A. Abreu: None. A. Latronico: None. R.S. Carroll: None. U.B. Kaiser: None. Background and Objectives: Inactivating mutations in Delta-like homolog 1 (DLK1), a maternally imprinted gene on chromosome 14, have been recognized as a genetic cause of central precocious puberty (CPP) in humans. It is well established that the timing of puberty, especially in females, is highly sensitive to energy stores and metabolic cues, with lower body fat negatively correlated with age at puberty and menarche. Mice lacking Dlk1 have pre- and postnatal growth retardation. Despite their considerably lower body weight (BW), we found that Dlk1 deficient females achieved puberty at the same age as controls (‘relative precocious puberty’). Moreover, Dlk1 deficiency led to activation of the reproductive axis despite lower levels of kisspeptin and leptin, an adipose tissue hormone with a permissive/stimulatory effect on metabolic control of reproduction. Dlk1 is a transmembrane protein that plays an essential role in inhibiting adipocyte differentiation and its biologically active form is soluble. Increased hypothalamic expression postnatally suggests a neuroendocrine function, but the precise mechanism by which DLK1 deficiency leads to CPP is yet to be deciphered. In this study, we aimed to investigate the role of hypothalamic Dlk1 expression on pubertal onset without the interference of diminished BW, using a conditional knockout (cKO) mouse model. Methods and Results: We generated a targeted Dlk1 knockout mouse model by crossing mice expressing Cre recombinase under the control of Nestin gene (Nes Cre), expressed primarily in neuro-epithelial cells, with mice harboring the Dlk1 gene flanked by loxP sites (Dlk1fl). Since Dlk1 is imprinted and expressed only by the paternal allele, we bred heterozygous Dlk1fl/+ male mice with Nes Cre females to obtain Dlk1fl/Cre (Dlk1 cKO), Dlk1+/Cre (Nes Cre) and Dlk1+/+ (wild type - WT). We confirmed by RT-qPCR that Dlk1 mRNA was undetectable in the mediobasal hypothalamus of Dlk1 cKO adult male mice, whereas it was present in Nes Cre and WT mice. We noted a lower BW in Nes Cre compared to WT mice, as previously reported. However, no difference in BW was observed between Dlk1 cKO and Nes Cre mice at the timing of puberty (females: Dlk1 cKO 12.6 ± 0.8 g vs. Nes Cre 13.8 ± 0.2 g, P = 0.18; males: Dlk1 cKO 12.4 ± 0.2 g vs. Nes Cre 13.1 ± 0.5 g, P = 0.26). Puberty onset, assessed by age at vaginal opening (females) and at preputial separation (males), was not affected by hypothalamic Dlk1 deletion (Dlk1 cKO: 35.6 ± 2.7 days vs. Nes Cre 34.6 ± 0.7 days, P = 0.73; Dlk1 cKO 29.0 ± 0.6 vs. Nes Cre: 30.3 ± 0.6 days, P = 0.19). Conclusion: In contrast to global Dlk1 deficiency, targeted deletion of Dlk1 from neuronal and glial cells did not affect body weight or timing of pubertal onset. These findings suggest that Dlk1 originates from peripheral tissues, such as adipocytes, to regulate reproduction and metabolism. Presentation: 6/1/2024

Evaluating the potential for psilocybin as a treatment for post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition that develops following exposure to a traumatic event. Individuals with this condition experience numerous physiological and behavioral alterations, including intrusive memories, avoidance of trauma-related stimuli, heightened anxiety, hypervigilance, impaired cognition, elevated resting heart rate and blood pressure, and altered neuroendocrine function, to name a few. In most patients, currently available pharmacological and psychological treatments are insufficient to alleviate the array of symptoms associated with the disorder. Thus, novel treatment options that can more effectively target the core etiology of PTSD are desperately needed. Recent work demonstrating the psychoplastogenic effects of psychedelics has reinvigorated research to examine their therapeutic potential in psychiatric conditions. Psilocybin, one psychedelic found in the Psilocybe genus of mushrooms, has exhibited promising antidepressant and anxiolytic effects in preclinical and clinical studies. The purpose of this review is to summarize the existing research that has examined the behavioral effects of psilocybin and link it to potential efficacy in treating PTSD-related symptoms. The proposed mechanisms for psilocybin's effects are then explored, as are the benefits and drawbacks for the agent's therapeutic use. Finally, the challenges faced by investigators aiming to study psilocybin as a therapeutic aid in future studies are discussed in order to shed light on this budding area of research. Significance Statement Current pharmacotherapy for PTSD is insufficient. Traditional antidepressants and anxiolytics help reduce symptom severity, but nonresponse rates often reach levels greater than 50%, emphasizing the need for more effective treatment options. The goal of this review is to summarize the existing evidence for and the potential mechanisms of the antidepressant and anxiolytic effects of psilocybin, a psychedelic compound found in the Psilocybe genus of mushrooms. We then relate the observed effects to psilocybin's potential use as a treatment for PTSD.

Androgen Inhibition of Reproductive Neuroendocrine Function in Females and Transgender Males.

Ovarian function is controlled by pituitary secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH), which in turn are governed by gonadotropin releasing hormone (GnRH) secreted from the brain. A fundamental principle of reproductive axis regulation is negative feedback signaling by gonadal sex steroids back to the brain to fine-tune GnRH and gonadotropin secretion. Endogenous negative feedback effects can be mimicked by exogenous steroid treatments, including androgens, in both sexes. Indeed, a growing number of clinical and animal studies indicate that high levels of exogenous androgens, in the typically male physiological range, can inhibit LH secretion in females, as occurs in males. However, the mechanisms by which male-level androgens inhibit GnRH and LH secretion still remain poorly understood, and this knowledge gap is particularly pronounced in transgender men (individuals designated female at birth but identifying as male). Indeed, many transgender men take long-term gender-affirming hormone therapy that mimics male-level testosterone levels. The impact of such gender-affirming testosterone on the reproductive axis, both at the ovarian and neuroendocrine level, is a long-understudied area that still requires further investigation. Importantly, the few concepts of androgen actions in females mostly come from studies of polycystic ovary syndrome, which does not recapitulate a similar androgen milieu or a pathophysiology of inhibited LH secretion as occurs in testosterone-treated transgender men. This review summarizes clinical evidence indicating that exogenous androgens can impair neuroendocrine reproductive function in both female individuals and transgender men and highlights emerging experimental data supporting this in recently developed transgender rodent models.

Maternal immune activation by toll-like receptor 7 agonist during mid-gestation increases susceptibility to blood-brain barrier leakage after puberty

Maternal immune activation (MIA), a maternal stressor, increases risk for neuropsychiatric diseases, such as Major Depressive Disorder in offspring. MIA of toll-like receptor 7 (TLR7) initiates an immune response in mother and fetuses in a sex-selective manner. The paraventricular nucleus of the hypothalamus (PVN), a brain region that is sexually dimorphic and regulates hypothalamic-pituitary-adrenal (HPA) stress responses, have been tied to stress-related behaviors (i.e., depression, anxiety, social impairments). The current study characterized the sex-selective impact of mid-gestational TLR7 activation on PVN vasculature of adult offspring based on a prior study of excess prenatal glucocorticoid stress. The PVN of offspring were evaluated to determine if fetal MIA impacted vascular leakage in the brains of adult mice with or without restraint stress. Timed-pregnant female mice were administered the TLR7 agonist Resiquimod (RQ) or saline vehicle on embryonic day (E) 12.5. Basal and restraint stress-induced corticosterone was measured to examine changes in stress response. Mice were perfused transcardially with fluorescein isothiocyanate (FITC) to assess blood vessel integrity. Sections with FITC-labeled blood vessels through the PVN of offspring were immunolabeled for Glial Fibrillary Acidic Protein (GFAP; astrocytic end feet) and IBA-1 (microglia). MIA with RQ led to elevated levels of plasma corticosterone 60-minutes after restraint in offspring, suggesting prenatal RQ impairs glucocorticoid negative feedback. Blood-brain barrier integrity was assessed. Adult offspring of RQ injected dams showed greater leakage in the PVN (greater in males than females). GFAP+ colocalization with FITC-labeled vessels was lower in the PVN of offspring from RQ treated dams, potentially contributing to the observed increased FITC leakage. Microglia were examined in relation to the vasculature as an indicator of a neuroimmune response. Data show IBA-1+ cells greater in size and number in the PVN with closer proximity to blood vessels after maternal injection of RQ in a male-selective manner. Microglia were unchanged in females from RQ-treated dams but were smaller in size after restraint. This study provides support for sex-selective influences of fetal immune antecedents for altered brain vascular and blood brain barrier development and adult neuroendocrine function that could indicate a PVN locus for increased susceptibility for adult disorders.

Obesity and the gut microbiota: implications of neuroendocrine and immune signaling.

Obesity is a major health challenge due to its high prevalence and associated comorbidities. The excessive intake of a diet rich in fat and sugars leads to a persistent imbalance between energy intake and energy expenditure, which increases adiposity. Here, we provide an update on relevant diet-microbe-host interactions contributing to or protecting from obesity. In particular, we focus on how unhealthy diets shape the gut microbiota and thus impact crucial intestinal neuroendocrine and immune system functions. We describe how these interactions promote dysfunction in gut-to-brain neuroendocrine pathways involved in food intake control and postprandial metabolism and elevate the intestinal proinflammatory tone, promoting obesity and metabolic complications. In addition, we provide examples of how this knowledge may inspire microbiome-based interventions, such as fecal microbiota transplants, probiotics, and biotherapeutics, to effectively combat obesity-related disorders. We also discuss the current limitations and gaps in knowledge of gut microbiota research in obesity.

Mineralocorticoid Receptor Signaling in Peripheral Blood Cells in Patients with Multiple Sclerosis.

Multiple sclerosis (MS) is associated with alterations in neuroendocrine function, primarily the hypothalamic-pituitary-adrenal axis, including lower expression of the glucocorticoid receptor (GR) and its target genes in peripheral blood mononuclear cells (PBMC) or full blood. We previously found reduced mineralocorticoid receptor (MR) expression in MS patients' peripheral blood. MS is being treated with a widening variety of disease-modifying treatments (DMT), some of which have similar efficacy but different mechanisms of action; body-fluid biomarkers to support the choice of the optimal initial DMT and/or to indicate an unsatisfactory response before clinical activity are unavailable. Using cell culture of volunteers' PBMCs and subsequent gene expression analysis (microarray and qPCR validation), we identified the mRNA expression of OTUD1 to represent MR signaling. The MR and MR target gene expression levels were then measured in full blood samples. In 119 MS (or CIS) patients, the expression of both MR and OTUD1 was lower than in 42 controls. The expression pattern was related to treatment, with the MR expression being particularly low in patients treated with fingolimod. While MR signaling may be involved in the therapeutic effects of some disease-modifying treatments, MR and OTUD1 expression can complement the neuroendocrine assessment of MS disease course. If confirmed, such assessment may support clinical decision-making.

The associations of spirituality and Hispanic ethnicity with neuroendocrine biomarkers among patients with colorectal cancer

ObjectiveDealing with cancer evokes not only physical and emotional distress, but may also promote resilience through spirituality. Patients with cancer are vulnerable to neuroendocrine dysregulation. This longitudinal observational study examined the degree to which spirituality was associated with neuroendocrine biomarkers and the moderating role of Hispanic ethnicity. MethodsParticipants were adults who were recently diagnosed with colorectal cancer (n = 81, 55 years old, 66% male, 63% Hispanic, 72% advanced cancer, 7 months post-diagnosis). The domains of spirituality (faith, meaning, and peace) and ethnicity (Hispanic vs. non-Hispanic) were self-reported. Cortisol and alpha amylase (sAA) were assayed from saliva samples collected at waking and bedtime on seven consecutive days. Mean levels at waking and bedtime, and diurnal slopes over seven days were calculated. Age and cancer stage were covariates. Results: Overall, patients reported moderate to high levels of spirituality. General linear modeling revealed that greater faith was associated with higher levels of sAA at waking and bedtime as well as more blunted diurnal pattern of sAA only among Hispanic patients (p ≤ .045). Greater peace was associated with steeper diurnal pattern of sAA, regardless of ethnicity (B = 0.021, p = .005). Meaning and cortisol were not significantly associated with study variables. ConclusionsFindings indicate that presence of peace facing a cancer diagnosis associated with neuroendocrine regulation, whereas drawing on one's faith, particularly among Hispanic patients, associated with neuroendocrine dysregulation during the first months after the diagnosis. Further investigations of psychobiobehavioral moderators and mediators for healthy neuroendocrine functioning among patients with cancer are warranted.

Viscerosensory signalling to the nucleus accumbens via the solitary tract nucleus.

The nucleus of the solitary tract (NTS) receives direct viscerosensory vagal afferent input that drives autonomic reflexes, neuroendocrine function and modulates behaviour. A subpopulation of NTS neurons project to the nucleus accumbens (NAc); however, the function of this NTS-NAc pathway remains unknown. A combination of neuroanatomical tracing, slice electrophysiology and fibre photometry was used in mice and/or rats to determine how NTS-NAc neurons fit within the viscerosensory network. NTS-NAc projection neurons are predominantly located in the medial and caudal portions of the NTS with 54 ± 7% (mice) and 65 ± 3% (rat) being TH-positive, representing the A2 NTS cell group. In horizontal brainstem slices, solitary tract (ST) stimulation evoked excitatory post-synaptic currents (EPSCs) in NTS-NAc projection neurons. The majority (75%) received low-jitter, zero-failure EPSCs characteristic of monosynaptic ST afferent input that identifies them as second order to primary sensory neurons. We then examined whether NTS-NAc neurons respond to cholecystokinin (CCK, 20 μg/kg ip) invivo in both mice and rats. Surprisingly, there was no difference in the number of activated NTS-NAc cells between CCK and saline-treated mice. In rats, just 6% of NTS-NAc cells were recruited by CCK. As NTS TH neurons are the primary source for NAc noradrenaline, we measured noradrenaline release in the NAc and showed that NAc noradrenaline levels declined in response to cue-induced reward retrieval but not foot shock. Combined, these findings suggest that high-fidelity afferent information from viscerosensory afferents reaches the NAc. These signals are likely unrelated to CCK-sensitive vagal afferents but could interact with other sensory and higher order inputs to modulate learned appetitive behaviours.

Research Progress in the Pathogenesis of Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is one of the most common gynecological endocrine disorders. Most pathophysiological changes of PCOS begin in the peripubertal phase, and these pathophysiological changes will continuously affect women's health in the later stages of their lives. The pathogenic mechanisms of PCOS remain unclear, involving key aspects such as the regulation of hypothalamic-pituitary function, ovarian cellular functions, androgen levels, and insulin resistance. Herein, we summarized the latest findings on the pathogenesis of PCOS from the perspectives of the genetic background, intrauterine development, neuroendocrine function, inflammatory factors, gut microbiome, and environmental factors. This review will help provide new ideas for a deeper understanding of the disease, as well as its clinical diagnosis and treatment.

Evaluating routine blood and cerebrospinal fluid samples in narcolepsy patients

Cerebrospinal fluid hypocretin-1 is proven to be a precise diagnostic marker of narcolepsy Type 1 (NT1). However other characteristics of cerebrospinal fluid and blood parameters have not yet been described. The objective of this study was to evaluate the differences in routine blood and cerebrospinal fluid analyses between NT1 patients and patients suspected of hypersomnia. We collected retrospectively all measures of cerebrospinal fluid hypocretin-1 between 2019 and 2022. This yielded 612 patients out of which 146 were diagnosed with NT1 and the rest (466 patients) were used as a control group. We selected the most relevant routine samples from both blood, plasma and cerebrospinal fluid and compared the two groups. The only significantly different analytes were plasma lactate dehydrogenase and cerebrospinal fluid hypocretin-1. No other differences were found between the groups including thyroid markers, markers of neuroendocrine function, inflammatory markers in blood or cerebrospinal fluid, markers of permeability of the blood brain barrier or metabolic markers in blood samples. We found no significant differences in routine blood or cerebrospinal fluid components, neuroendocrine function, neuroinflammation and metabolic markers. The results reflect that the hypocretin system does not seem to play a chronic major role in regulation of these markers. None of the parameters routinely measured in blood in these patients could differentiate between NT1 and non-NT1 disorders besides CSF-hcrt-1.

Reproductive function and behaviors: an update on the role of neural estrogen receptors alpha and beta.

Infertility is becoming a major public health problem, with increasing frequency due to medical, environmental and societal causes. The increasingly late age of childbearing, growing exposure to endocrine disruptors and other reprotoxic products, and increasing number of medical reproductive dysfunctions (endometriosis, polycystic ovary syndrome, etc.) are among the most common causes. Fertility relies on fine-tuned control of both neuroendocrine function and reproductive behaviors, those are critically regulated by sex steroid hormones. Testosterone and estradiol exert organizational and activational effects throughout life to establish and activate the neural circuits underlying reproductive function. This regulation is mediated through estrogen receptors (ERs) and androgen receptor (AR). Estradiol acts mainly via nuclear estrogen receptors ERα and ERβ. The aim of this review is to summarize the genetic studies that have been undertaken to comprehend the specific contribution of ERα and ERβ in the neural circuits underlying the regulation of the hypothalamic-pituitary-gonadal axis and the expression of reproductive behaviors, including sexual and parental behavior. Particular emphasis will be placed on the neural role of these receptors and the underlying sex differences.

Proteomic Blueprint of Atlantic Cod (Gadus morhua) Otoliths Revealing Environmental Stress Insights through Label-Free Quantitative Shotgun Proteomics

Otoliths of the fish’s inner ear serve as a natural chronological recorder because of their continuous formation marked by daily, monthly, and annual increments. Despite their importance, the comprehensive protein content of otoliths remains not fully identified. Using the label-free shotgun proteomics method with one-dimensional liquid chromatography coupled to electrospray ionization-orbitrap tandem mass spectrometry, we quantified a broad range of proteins, with individual otoliths containing between 1341 and 1839 proteins. The identified proteins could potentially serve as a blueprint for fish growth from embryo to adult. We quantified eleven heat-shock proteins (HSPs) in both sexes and several proteins impacted by endocrine disruptors, indicating the otolith’s capacity to reflect environmental stress, potentially linked to climate change effects and altering of hormonal and neuroendocrine functions. Our bioinformatic ontology analysis confirmed the presence of proteins critical for various biological processes, including structural and enzymatic proteins. Protein–protein interaction (PPI) mapping also identified key interactions between the identified proteins. These findings significantly advance our understanding of otolith proteomics, offering a solid foundation for future work. Most of the identified proteins deposited daily and influenced by the environment were not implicated in the biomineralization of otolith, raising the potential for the otolith proteome to recreate details of fish life history at previously unrealized levels.

Effect of delayed diagnosis on neuroendocrine function in individuals with suprasellar germ cell tumors.

The impact of delayed diagnosis on tumor-related prognosis appears to be minimal in individuals with intracranial germ cell tumors (iGCTs). However, its effect on neuroendocrine functions remains unclear. We aimed to assess the effects of delayed diagnosis on neuroendocrine function in individuals with suprasellar GCTs. We conducted a retrospective cohort study of 459 individuals with suprasellar GCTs and categorized them into two groups based on disease duration: delayed diagnosis (> 6 months) and non-delayed diagnosis (≤ 6 months). We compared endocrinological symptoms, neuroendocrine dysfunction and its grading (categorized into 0-3 grades based on severity), and recovery from neuroendocrine dysfunction in both groups. Patients with delayed diagnosis exhibited higher incidences of amenorrhea, slow growth, fatigue, and polyuria/polydipsia. Neuroendocrine dysfunction, including central adrenal insufficiency (CAI), central hypothyroidism (CHT), arginine vasopressin deficiency (AVP-D), growth hormone deficiency, hypogonadism, and hyperprolactinemia, was more pronounced in the delayed diagnosis group at diagnosis, the end of treatment, and the last follow-up. Furthermore, individuals with delayed diagnosis showed higher grades of neuroendocrine dysfunction at diagnosis (OR=3.005, 95% CI 1.929-4.845, p<0.001), end of oncologic treatment (OR=4.802, 95% CI 2.878-8.004, p<0.001), and last follow-up(OR=2.335, 95% CI 1.307-4.170, p=0.005) after adjusting for confounders. Finally, less recovery, particularly in CAI, CHT, and AVP-D, was seen among the group with delayed diagnosis after treatment. Among individuals with suprasellar GCTs, delayed diagnosis is associated with increased, more severe, and less recovered neuroendocrine dysfunction, emphasizing the importance of early diagnosis and treatment to reduce neuroendocrine dysfunction.

Micromanaging the neuroendocrine system - A review on miR-7 and the other physiologically relevant miRNAs in the hypothalamic-pituitary axis.

The hypothalamic-pituitary axis is central to the functioning of the neuroendocrine system and essential for regulating physiological and behavioral homeostasis and coordinating fundamental body functions. The expanding line of evidence shows the indispensable role of the microRNA pathway in regulating the gene expression profile in the developing and adult hypothalamus and pituitary gland. Experiments provoking a depletion of miRNA maturation in the context of the hypothalamic-pituitary axis brought into focus a prominent involvement of miRNAs in neuroendocrine functions. There are also a few individual miRNAs and miRNA families that have been studied in depth revealing their crucial role in mediating the regulation of fundamental processes such as temporal precision of puberty timing, hormone production, fertility and reproduction capacity, and energy balance. Among these miRNAs, miR-7 was shown to be hypothalamus-enriched and the top one highly expressed in the pituitary gland, where it has a profound impact on gene expression regulation. Here, we review miRNA profiles, knockout phenotypes, and miRNA interaction (targets) in the hypothalamic-pituitary axis that advance our understanding of the roles of miRNAs in mammalian neurosecretion and related physiology.

Association of gut dysbiosis with first‑episode psychosis (Review).

The gut‑microbiota‑brain axis is a complex bidirectional communication system linking the gastrointestinal tract to the brain. Changes in the balance, composition and diversity of the gut‑microbiota (gut dysbiosis) have been found to be associated with the development of psychosis. Early‑life stress, along with various stressors encountered in different developmental phases, have been shown to be associated with the abnormal composition of the gut microbiota, leading to irregular immunological and neuroendocrine functions, which are potentially responsible for the occurrence of first‑episode psychosis (FEP). The aim of the present narrative review was to summarize the significant differences of the altered microbiome composition in patients suffering from FEP vs. healthy controls, and to discuss its effects on the occurrence and intensity of symptoms in FEP.

Co-exposure to Aluminium and Cadmium Mediates Postpartum Maternal Variation in Brain Architecture and Behaviour of Mice; Involvement of Oxido-nitrergic and Cholinergic Mechanisms : Postpartum effects of Aluminium and Cadmium co-exposure in pregnancy.

Most research has not been done on the possible relationship between pregnant women's cross-metal exposures and postpartum neuroendocrine functions. The purpose of this study was to look into how co-exposure to aluminium chloride (AlCl3) and cadmium chloride (CdCl2) affected the neuroendocrine and neurometabolic changes in postpartum mice. A total of 24 adult pregnant female mice were used for the study. Group 1 served as control and received neither AlCl3nor CdCl2 (n=6), group 2 comprised pregnant mice treated with AlCl3 (10mg/kg), group 3 with CdCl2 (1.5mg/kg), group 4 with a combination of AlCl3(10 mg/kg) and CdCl2 (1.5 mg/kg).Oral treatment of animals was done daily from gestation day 7 to gestation day 20. Upon delivery and weaning on postnatal day 21 (PND 21), behavioural assessment was done on the postpartum mice and immediately followed by sacrifice for assessment of histological and neuroendocrine markers. Our findings revealed that the brain-to-body weight ratio was affected and brain oxidative stress was elevated in mice exposed to AlCl3 and CdCl2 during pregnancy. Given the strong association between postpartum hyperactivity, social interaction index, brain catalase and acetylcholinesterase activity, and the brain/body weight ratio, it is plausible that these effects have played a role in the adverse behavioural abnormalities observed in the postpartum maternal mice. Moreover, it was noted that in certain situations, co-exposures to the metals tended to have opposite effects to single metal exposures.