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Neuroendocrine regulation is essential for maintaining metabolic homeostasis. However, whether neuroendocrine pathway influence bone metabolism and skeletal senescence is unelucidated. Here, a central neuroendocrine circuit is identified that directly controls osteogenesis. Using virus based tracing, this study is identified that melanin concentrating hormone (MCH) expressing neurons in the lateral hypothalamus (LH) are connected to the bone. Chemogenetic activation of MCH neurons in the LH induces osteogenesis, whereas inhibiting these neurons reduces osteogenesis. Meanwhile, MCH is released into the circulation upon chemogenetic activation of these neurons. Single cell sequencing reveals that blocking MCH neurons in the LH diminishes osteogenic differentiation of bone marrow stromal cells (BMSCs) and induces senescence. Mechanistically, MCH promotes BMSC differentiation by activating MCHR1 via PKA signaling, and activating MCHR1 by MCH agonists attenuate skeletal senescence in mice. By elucidating a brain‐bone connection that autonomously enhances osteogenesis, these findings uncover the neuroendocrinological mechanisms governing bone mass regulation and protect against skeletal senescence. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Here, we reflect on the long career in neuroendocrinology of a single, highly productive scientist ('Bob' Millar), by analysing his oeuvre of published papers through the lens of citation metrics. We use citation network analysis in a novel manner to identify the specific topics to which his papers have made a particular contribution, allowing us to compare the citations of his papers with those of contemporary papers on the same topic, rather than on the same broad field as generally used to normalise citations. It appears that citation rates are highest for topics on which Bob has published a relatively large number of papers that have become core to a tightly‐knit community of authors that cite each other. This analysis shows that an author's impact depends on the existence of a receptive community that is alert to the potential utility of papers from that author, and which uses, amplifies, extends and qualifies the contents of their papers—activities that entail reciprocal citation between authors. The obvious conclusion is that a scientist's impact depends on the use that his or her contemporaries make of his or her contributions, rather than on the contributions in themselves. [ABSTRACT FROM AUTHOR]

Phoenixin (PNX) is a conserved secreted peptide that was identified 10 years ago with numerous studies published on its pleiotropic functions. PNX is associated with estrous cycle length, protection from a high‐fat diet, and reduction of anxiety behavior. However, no study had yet evaluated the impact of deleting PNX in the whole animal. We sought to evaluate a mouse model lacking the PNX parent gene, small integral membrane protein 20 (Smim20), and the resulting effect on reproduction, energy homeostasis, and anxiety. We found that the Smim20 knockout mice had normal fertility and estrous cycle lengths. Consistent with normal fertility, the hypothalamii of the knockout mice showed no changes in the levels of reproduction‐related genes, but the male mice had some changes in energy homeostasis‐related genes, such as melanocortin receptor 4 (Mc4r). When placed on a high‐fat diet, the wildtype and knockout mice responded similarly, but the male heterozygous mice gained slightly less weight. When placed in an open field test box, the female knockout mice traveled less distance in the outer zone, indicating alterations in anxiety or locomotor behavior. In summary, the homozygous knockout of PNX did not alter fertility and modestly alters a few neuroendocrine genes in response to a high‐fat diet, especially in the female mice. However, it altered the behavior of mice in an open field test. PNX therefore may not be crucial for reproductive function or weight, however, we cannot rule out possible compensatory mechanisms in the knockout model. Understanding the role of PNX in physiology may ultimately lead to an enhanced understanding of neuroendocrine mechanisms involving this enigmatic peptide. [ABSTRACT FROM AUTHOR]

Anti-Müllerian hormone (AMH) is a peptide belonging to the transforming growth factor beta superfamily and acts exclusively through its receptor type 2 (AMHR2). From the 8th week of pregnancy, AMH is produced by Sertoli cells, and from the 23rd week of gestation, it is produced by granulosa cells of the ovary. AMH plays a critical role in regulating gonadotropin secretion, ovarian tissue responsiveness to pituitary hormones, and the pathogenesis of polycystic ovarian syndrome. It inhibits the transition from primordial to primary follicles and is considered the best marker of ovarian reserve. Therefore, measuring AMH concentration of the hormone is valuable in managing assisted reproductive technologies. AMH was initially discovered through its role in the degeneration of Müllerian ducts in male fetuses. However, due to its ability to inhibit the cell cycle and induce apoptosis, it has also garnered interest in oncology. For example, antibodies targeting AMHR2 are being investigated for their potential in diagnosing and treating various cancers. Additionally, AMH is present in motor neurons and functions as a protective and growth factor. Consequently, it is involved in learning and memory processes and may support the treatment of Alzheimer's disease. This review aims to provide a comprehensive overview of the biology of AMH and its role in both endocrinology and oncology. [ABSTRACT FROM AUTHOR]

Background: Sheehan syndrome is the infarction of a pituitary gland that has been physiologically enlarged as a result of postpartum bleeding. A galactorrhea and amenorrhea are classic symptoms, but a constellation ofmanifestations occurs in both the acute and chronic forms. These manifestations can remain largely non emergent unless Sheehan syndrome is complicated by severe adrenal dysfunction secondary to an inciting event such as dengue. We present a case of Sheehan syndrome that was uncovered in a patient with a dengue infection presenting as adrenal crisis. Case Report: A 45-year-old female presented with symptoms of acute gastroenteritis and severe dehydration. Her medical history was significant for secondary amenorrhea for 14 years after her last delivery followed by symptoms of endocrine dysfunction. At presentation, the patient was in adrenal crisis with hypotension, hypoglycemia, and hyperthermia. Dengue nonstructural protein 1 antigen was positive, along with signs of plasma leakage. Blood work showed bicytopenia with abnormal liver enzymes. Ultra-sonography and computed tomography of the abdomen were suggestive of serositis with a calculous cholecystitis. Magnetic resonance imaging of the brain revealed an empty sella. Anterior pituitary hormone levels were significantly decreased with low serum cortisol, and the patient's thyroid profile analysis suggested secondary hypothyroidism. The inal diagnosis was Sheehan syndrome presenting as adrenal crisis precipitated by severe dengue fever. The patient was managed conservatively and discharged on hormone supplement therapy. Conclusion: Sheehan syndrome is an important cause of panhypopituitarism in the developing world. Knowledge of Sheehan syndrome is important to help prevent its occurrence and reduce its resultant multifactorial effects. [ABSTRACT FROM AUTHOR]

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 ERa and ERb. The aim of this review is to summarize the genetic studies that have been undertaken to comprehend the specific contribution of ERa and ERb in the neural circuits underlying the regulation of the hypothalamicpituitary-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. [ABSTRACT FROM AUTHOR]

Introduction: Owing to their privileged anatomical location, neurons of the arcuate nucleus of the hypothalamus (ARC) play critical roles in sensing and responding to metabolic signals such as leptin and glucagon-like peptide 1 (GLP-1). In addition to the well-known proopiomelanocortin (POMC)- and agouti-related peptide (AgRP)-expressing neurons, subpopulations of GABAergic neurons are emerging as key regulators of energy balance. However, the precise identity of these metabolic neurons is still elusive. Here, we identified and characterized the molecular signature of a novel population of GABAergic neurons of the ARC expressing Cellular retinoic acid binding protein 1 (Crabp1). Methods: Using a combination of immunohistochemistry and in situ hybridization techniques, we investigated the expression of Crabp1 across the mouse brain and characterized the molecular identity of Crabp1ARC neurons. We also determined whether Crabp1ARC neurons are sensitive to fasting, leptin, and GLP1R agonism by assessing cFOS immunoreactivity as a marker of neuronal activity. Results:Crabp1ARC neurons represent a novel GABAergic neuronal population robustly enriched in the ARC and are distinct from the prototypical melanocortin neurons. Crabp1ARC neurons overlap with three subpopulations of yet uncharacterized ARC neurons expressing Htr3b, Tbx19, and Tmem215. Notably, Crabp1ARC neurons express receptors for metabolic hormones and their activity is modulated by the nutritional state and GLP1R agonism. Conclusion:Crabp1ARC neurons represent a novel heterogeneous population of GABAergic neurons sensitive to metabolic status. [ABSTRACT FROM AUTHOR]

GH acts in numerous organs expressing the GH receptor (GHR), including the brain. However, the mechanisms behind the brain's permeability to GH and how this hormone accesses different brain regions remain unclear. It is well-known that an acute GH administration induces phosphorylation of the signal transducer and activator of transcription 5 (pSTAT5) in the mouse brain. Thus, the pattern of pSTAT5 immunoreactive cells was analyzed at different time points after IP or intracerebroventricular GH injections. After a systemic GH injection, the first cells expressing pSTAT5 were those near circumventricular organs, such as arcuate nucleus neurons adjacent to the median eminence. Both systemic and central GH injections induced a medial-to-lateral pattern of pSTAT5 immunoreactivity over time because GH-responsive cells were initially observed in periventricular areas and were progressively detected in lateral brain structures. Very few choroid plexus cells exhibited GH-induced pSTAT5. Additionally, Ghr mRNA was poorly expressed in the mouse choroid plexus. In contrast, some tanycytes lining the floor of the third ventricle expressed Ghr mRNA and exhibited GH-induced pSTAT5. The transport of radiolabeled GH into the hypothalamus did not differ between wild-type and dwarf Ghr knockout mice, indicating that GH transport into the mouse brain is GHR independent. Also, single-photon emission computed tomography confirmed that radiolabeled GH rapidly reaches the ventral part of the tuberal hypothalamus. In conclusion, our study provides novel and valuable information about the pattern and mechanisms behind GH transport into the mouse brain. [ABSTRACT FROM AUTHOR]

Abstract Neuroendocrine regulation is essential for maintaining metabolic homeostasis. However, whether neuroendocrine pathway influence bone metabolism and skeletal senescence is unelucidated. Here, a central neuroendocrine circuit is identified that directly controls osteogenesis. Using virus based tracing, this study is identified that melanin concentrating hormone (MCH) expressing neurons in the lateral hypothalamus (LH) are connected to the bone. Chemogenetic activation of MCH neurons in the LH induces osteogenesis, whereas inhibiting these neurons reduces osteogenesis. Meanwhile, MCH is released into the circulation upon chemogenetic activation of these neurons. Single cell sequencing reveals that blocking MCH neurons in the LH diminishes osteogenic differentiation of bone marrow stromal cells (BMSCs) and induces senescence. Mechanistically, MCH promotes BMSC differentiation by activating MCHR1 via PKA signaling, and activating MCHR1 by MCH agonists attenuate skeletal senescence in mice. By elucidating a brain‐bone connection that autonomously enhances osteogenesis, these findings uncover the neuroendocrinological mechanisms governing bone mass regulation and protect against skeletal senescence.

This study summarizes new data on induced spawning of Steindachneridion parahybae, focusing on the aggressive behavior of females. This study characterizes the vasotocinergic system using immunohistochemistry, highlighting the potential influence of arginine-vasotocin (AVT) on reproductive physiology. Two experimental groups were proposed: (A) control, with one female in the aquarium, and (B) experimental, with two females in the same aquarium. Dominant (D) females presented a more aggressive behavior and did not show any injury. They apparently had a length and body mass higher than injured nondominant (ND) females. The analysis identified positive AVT immunoreactive (ir) neurons exclusively within the preoptic area, including parvocellular, magnocellular, and gigantocellular subpopulations, containing fibers-ir extending into the pituitary gland. Cellular and nuclear areas were greater in D compared to ND in the magnocellular subpopulation. There were no differences between parvocellular and gigantocellular subpopulations. There was a difference on the steroid plasma profile of cortisol (more in ND than in D) and 17α,20β-dihydroxy-4-pregnen-3-one (more in D than in ND). Furthermore, control and D females presented higher optical densities for AVT-ir, gonadotropin-releasing hormone-ir, and luteinizing hormone-ir than ND. In general, there were no differences in the results of female (control group) with D females. The AVT system is highly complex, possibly counting multiple sites of action during artificial reproduction and acting directly and/or indirectly associated with behavioral and physiological changes in S. parahybae females when induced to spawning. [ABSTRACT FROM AUTHOR]

Hypopituitarism in the elderly is an underestimated condition mainly due to the non-specific presentation that can be attributed to the effects of aging and the presence of comorbidities. Diagnosis and treatment of hypopituitarism often represent a challenging task and this is even more significant in the elderly. Diagnosis can be insidious due to the physiological changes occurring with aging that complicate the interpretation of hormonal investigations, and the need to avoid some provocative tests that carry higher risks of side effects in this population. Treatment of hypopituitarism has generally the goal to replace the hormonal deficiencies to restore a physiological balance as close as possible to that of healthy individuals but in the elderly this must be balanced with the risks of over-replacement and worsening of comorbidities. Moreover, the benefit of some hormonal replacement therapies in the elderly, including sex hormones and growth hormone, remains controversial. [ABSTRACT FROM AUTHOR]

Treatment response is hard to predict and detailed mechanisms unknown. Lower levels of the dehydroepiandrosterone sulphate (DHEA(S)) – a precursor to testosterone and estrogen – have been associated to depression and to response to antidepressant treatment. Previous studies however may have been ridden by confounding and reverse causation. The aim of this study is to evaluate whether higher levels of DHEA(S) are causally linked to response to antidepressants using mendelian randomization (MR). We performed a Two-sample MR analysis using data the largest publicly available GWAS of DHEA(S) levels (n = 14,846) using eight common genetic variants associated to DHEA(S) (seven single nucleotide polymorphisms and one variant rs2497306) and the largest GWAS of antidepressant response (n = 5218) using various MR methods (IVW, MR Egger, Weighted mean, weighted mode, MR-PRESSO) and single SNP analysis. We further investigated for pleiotropy conducting a look up on PhenoScanner and GWAS Catalog. Results show no evidence for DHEA(S) gene risk score from any of MR methods, however, we found a significant association on individual variant analysis for rs11761538, rs17277546, and rs2497306. There was some evidence for heterogeneity and pleiotropy. This is the first paper to show some evidence for a causal association of genetically-predicted DHEA and improvement of depressive symptoms. The effect is not a simple linear effect, and we were unable to dissect whether the effect was direct effect of DHEA(S), mediated by DHEA(S) or on the pathway is not yet clear. Further studies using more refined instrumental variables will help clarify this association. [ABSTRACT FROM AUTHOR]

Anti-Müllerian hormone (AMH) is a peptide belonging to the transforming growth factor beta superfamily and acts exclusively through its receptor type 2 (AMHR2). From the 8th week of pregnancy, AMH is produced by Sertoli cells, and from the 23rd week of gestation, it is produced by granulosa cells of the ovary. AMH plays a critical role in regulating gonadotropin secretion, ovarian tissue responsiveness to pituitary hormones, and the pathogenesis of polycystic ovarian syndrome. It inhibits the transition from primordial to primary follicles and is considered the best marker of ovarian reserve. Therefore, measuring AMH concentration of the hormone is valuable in managing assisted reproductive technologies. AMH was initially discovered through its role in the degeneration of Müllerian ducts in male fetuses. However, due to its ability to inhibit the cell cycle and induce apoptosis, it has also garnered interest in oncology. For example, antibodies targeting AMHR2 are being investigated for their potential in diagnosing and treating various cancers. Additionally, AMH is present in motor neurons and functions as a protective and growth factor. Consequently, it is involved in learning and memory processes and may support the treatment of Alzheimer’s disease. This review aims to provide a comprehensive overview of the biology of AMH and its role in both endocrinology and oncology.

Steroid hormones bind to specific receptors that act as transcription factors to modify gene expression in the brain to regulate physiological and behavioural processes. The specific genes controlled by steroid hormones in the brain are not fully known. Identifying these genes is integral to establishing a comprehensive understanding of how hormones impact physiology and behaviour. A popular organism for answering this question is the cichlid fish Astatotilapia burtoni. Recently, CRISPR/Cas9 was used to engineer A. burtoni that lack functional androgen receptor (AR) genes encoding ARα. ARα mutant male A. burtoni produced fewer aggressive displays and possessed reduced expression of the gene encoding brain-specific aromatase, cyp19a1, in the ventromedial hypothalamus (VMH), an aggression locus. As a follow-up, we investigated whether ARα deficiency affected cyp19a1 expression in female A. burtoni using the same genetic line. We find that female A. burtoni possessing one or two non-functional ARα alleles had much higher expression of cyp19a1 in the preoptic area (POA), while females with one non-functional ARα allele possessed lower expression of cyp19a1 in the putative fish homologue of the bed nucleus of the stria terminalis (BNST). Thus, ARα may have a sex-specific role in modifying cyp19a1 expression in the teleost POA and BNST, regions that underlie sex differences across vertebrates.

The vase tunicate, Ciona intestinalis (Linnaeus, 1767), is a social hut non-colonial ascidian that is implicated in biofouling of aquatic structures and destruction of the shellfish industry through competition for planktonic nutrients and substrate settling habitats. The sequencing of the C. intestinalis genome has provided insight into the phylogenetic origins of this species, indicating that this lineage and its allies represent a sister taxon to the chordates. Although the practical use of this genomic information at controlling this invasive species is equivocal, a number of new studies on the neurological and neuroendocrine aspects of C. intestinalis have suggested new molecular targets that may be exploited for practical applications on the control of C. intestinalis to protect and enhance the shellfish industry from this invasive species. As a result, we have developed a novel behavioural assay for C. intestinalis, which can be employed to investigate novel agents that inhibit growth and development in this species. Key words: ascidian, protochordate, GnRH, CRF, behaviour, urochordates, genome, tunicate, Ciona intestinalis, Ciona robusta, 1. Introduction The vase tunicate, Ciona intestinalis (Linnaeus, 1767), is a sessile saltwater ascidian positioned in a unique branch of chordate phylogeny. Ascidians belong to the subphylum Urochordata, and are [...]

This document is an editorial published in the journal Frontiers in Endocrinology. It discusses the role of environmental and internal factors in the neuroendocrine regulation of fish. The editorial highlights the importance of the brain-pituitary axis in controlling various physiological processes in fish, such as growth, reproduction, metabolism, and stress responses. It also mentions recent research findings on new components and mechanisms involved in endocrine regulation and plasticity in fish. The editorial introduces a research topic on neuroendocrine regulations in fish, which includes five original research articles covering different aspects of neuroendocrine regulation in fish. The articles explore the measurement of signaling molecules in fish tissues, the role of aromatases in zebrafish reproduction, the hormonal regulation of oocyte hydration in marine teleosts, the effects of cysteamine on growth and the GH/IGF axis in gilthead sea bream, and the role of somatostatin in regulating growth hormone secretion and reproductive hormone levels in tilapia. The editorial concludes by stating that the research topic provides valuable insights into the complex neuroendocrine mechanisms that regulate growth and reproduction in fish and hopes that it will contribute to the development of more effective strategies for promoting growth and reproductive success in fish populations. [Extracted from the article]

Introduction: Hypophysitis is a rare condition, and as such, each case may exhibit a unique clinical course. Majority of literature identifies labor and immunotherapy as the two most common causes of hypophysitis, neither is applicable in this case. While there is currently no universal cure for hypophysitis, symptomatic management aimed at correcting dysfunctional pituitary axes can significantly improve patients' quality of life. Case Report: The 61-year-old male patient was admitted to the Endocrinology Clinic in February 2023 with complaints including fatigue, dizziness, flushing, hyperhidrosis, polyuria, nocturia, anorexia with a 5-kilogram weight loss, dry mouth, and dry skin persisting for 4 months. Laboratory results from January of that year indicated secondary hypothyroidism and secondary hypocorticoidism. Further endocrine diagnostics was inconclusive, showing an uncommon ho rmonal landscape. Conclusion: We present a case of an uncommon clinical and hormonal picture of hypophysitis in a course of pituitary stalk thickening. This case appoints the uniqueness of every case of this rare condition, underlining the role of hormonal and imaging tests. [ABSTRACT FROM AUTHOR]

Importance A paradoxical increase of growth hormone (GH) following oral glucose load has been described in ∼30% of patients with acromegaly and has been related to the ectopic expression of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) in somatotropinomas. Recently, we identified germline pathogenic variants and somatic loss of heterozygosity of lysine demethylase 1A (KDM1A) in patients with GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing's syndrome. The ectopic expression of GIPR in both adrenal and pituitary lesions suggests a common molecular mechanism. Objective We aimed to analyze KDM1A gene sequence and KDM1A and GIPR expressions in somatotroph pituitary adenomas. Settings We conducted a cohort study at university hospitals in France and in Italy. We collected pituitary adenoma specimens from acromegalic patients who had undergone pituitary surgery. We performed targeted exome sequencing (gene panel analysis) and array-comparative genomic hybridization on somatic DNA derived from adenomas and performed droplet digital PCR on adenoma samples to quantify KDM1A and GIPR expressions. Results One hundred and forty-six patients with sporadic acromegaly were studied; 72.6% presented unsuppressed classical GH response, whereas 27.4% displayed a paradoxical rise in GH after oral glucose load. We did not identify any pathogenic variant in the KDM1A gene in the adenomas of these patients. However, we identified a recurrent 1p deletion encompassing the KDM1A locus in 29 adenomas and observed a higher prevalence of paradoxical GH rise (P =.0166), lower KDM1A expression (4.47 ± 2.49 vs 8.56 ± 5.62, P <.0001), and higher GIPR expression (1.09 ± 0.92 vs 0.43 ± 0.51, P =.0012) in adenomas from patients with KDM1A haploinsufficiency compared with those with 2 KDM1A copies. Conclusions and relevance Unlike in GIP-dependent primary bilateral macronodular adrenal hyperplasia, KDM1A genetic variations are not the cause of GIPR expression in somatotroph pituitary adenomas. Recurrent KDM1A haploinsufficiency, more frequently observed in GIPR-expressing adenomas, could be responsible for decreased KDM1A function resulting in transcriptional derepression on the GIPR locus. [ABSTRACT FROM AUTHOR]

Social behaviors are regulated by sex steroid hormones, such as androgens and estrogens. However, the specific molecular and neural processes modulated by steroid hormones to generate social behaviors remain to be elucidated. We investigated whether some actions of androgen signaling in the control of social behavior may occur through the regulation of estradiol synthesis in the highly social cichlid fish, Astatotilapia burtoni. Specifically, we examined the expression of cyp19a1, a brain‐specific aromatase, in the brains of male A. burtoni lacking a functional ARα gene (ar1), which was recently found to be necessary for aggression in this species. We found that cyp19a1 expression is higher in wild‐type males compared to ar1 mutant males in the anterior tuberal nucleus (ATn), the putative fish homolog of the mammalian ventromedial hypothalamus, a brain region that is critical for aggression across taxa. Using in situ hybridization chain reaction, we determined that cyp19a1+ cells coexpress ar1 throughout the brain, including in the ATn. We speculate that ARα may modulate cyp19a1 expression in the ATn to govern aggression in A. burtoni. These studies provide novel insights into the hormonal mechanisms of social behavior in teleosts and lay a foundation for future functional studies. [ABSTRACT FROM AUTHOR]

Purpose: Pediatric pituitary adenomas (PPA) are rare. Although PPAs are mostly benign, they can be challenging to manage. Most studies evaluating PPA are based on surgical series. We aimed to present the clinical features, hormonal status and treatment outcomes of children with PPA managed in a joint neuroendocrine setting. Methods: In this single-center study, demographic, clinical and endocrinological data of patients under 19 years old who were followed up with the diagnosis of PPA between 2002-2022 were retrospectively reviewed. A total of 21 studies published in the past 20 years were also systematically reviewed. Results: There were 79 patients (52 girls, 27 boys) with a median age of 15.8 years. Median follow-up time was 30 months. The most common adenoma subtype was non-functioning adenoma (NFA) (35.5%), followed by prolactinoma (29.1%), corticotropinoma (21.5%), and somatotropinoma (13.9%), respectively. The frequency of micro and macroadenomas was almost equal while 38% of all adenomas were invasive. Headache, visual impairment and menstrual irregularity were the most common complaints, while the most common hormonal deficiency at diagnosis was central hypothyroidism (31.6%), followed by hypogonadotropic hypogonadism (22.7%), growth hormone deficiency (15.2%) and central adrenal insufficiency (11.4%), respectively. Fifty patients (63.2%) underwent endoscopic endonasal transsphenoidal surgery (EETS). Following the surgery, impaired endocrine functions recovered at a rate of 62% while permanent central diabetes insipidus was observed in 6%, and new onset hypopituitarism developed in 4%. Conclusion: NFA was more common in this cohort than in previous reports, which is one of the largest PPA series in the literature. Hormonal disorders, which were common at the time of diagnosis, were largely resolved with appropriate endocrinological and surgical approaches, while the rate of pituitary hormonal deficiencies after EETS was relatively low. Therefore, we recommend that children with PPA be managed in the setting of a high-volume pituitary center to provide long-term low morbidity. [ABSTRACT FROM AUTHOR]

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.

Objectives: Vitamin D is involved in brain health and function. Our objective was to determine whether vitamin D deficiency was associated with behavioral disorders in geriatric patients. Design: The observational cross-sectional CLIP (Cognition and LIPophilic vitamins) study. The report followed the STROBE statement. Setting: Geriatric acute care unit in a tertiary university hospital in France for 3 months at the end of winter and beginning of spring. Participants: 272 patients ≥65 years consecutively hospitalized or seen in consultation. Measurements: Participants were separated into two groups according to vitamin D deficiency (i.e., serum 25-hydroxyvitamin D ≤25 nmol/L). Behavior was assessed using the reduced version of the Neuropsychiatric Inventory Scale (NPI-R) score and subscores. Age, sex, BMI, education level, comorbidities, MMSE and GDS scores, use psychoactive drugs and vitamin D supplements, and serum concentrations of calcium, parathyroid hormone, TSH and estimated glomerular filtration rate (eGFR) were used as potential confounders. Results: Participants with vitamin D deficiency (n = 78) had similar NPI-R score (17.4 ± 20.3 versus 17.2 ± 16.1, p = 0.92) but higher (i.e., worse) subscore of agitation and aggressiveness (2.0 ± 3.3 versus 1.2 ± 2.4, p = 0.02) and higher (i.e., worse) subscore of disinhibition (0.99 ± 2.98 versus 0.38 ± 1.42, p = 0.02) than those without vitamin D deficiency (n = 194). In multiple linear regressions, vitamin D deficiency was inversely associated with the subscore of agitation and aggressiveness (β = 1.37, p = 0.005) and with the subscore of disinhibition (β = 0.96, p = 0.008). Conclusion: Vitamin D deficiency was associated with more severe subscores of agitation and aggressiveness and of disinhibition among older adults. This provides a scientific basis to test the efficacy of vitamin D supplementation on behavioral disorders in older patients with vitamin D deficiency.

Objective: Sex steroids exert important biological functions within the CNS, but the underlying mechanisms are poorly understood. The contribution of circulating sex steroids to the levels in CNS tissue and cerebrospinal fluid (CSF) has been sparsely investigated in human and with inconclusive results. This could partly be due to lack of sensitive validated assays. To address this, we validated a gas chromatography–tandem mass spectrometry (GC-MS/MS) assay for quantification of sex steroid hormones/precursors in CSF. Methods: GC-MS/MS quantification of dihydrotestosterone (DHT, CSF lower limit of quantification, 1.5 pg/mL), testosterone (4.9), estrone (E1, 0.88), estradiol (E2, 0.25), dehydroepiandrosterone (DHEA, 38.4), androstenedione (4D, 22.3), and progesterone (P, 4.2) in CSF, and corresponding serum samples from 47 men. Results: Analyses of CSF revealed that DHEA was the major sex steroid (73.5 ± 31.7 pg/mL) followed by 4D (61.4 ± 29.6 pg/mL) and testosterone (49.5 ± 18.9 pg/mL). The CSF levels of DHT, E2, and E1 were substantially lower, and P was in general not detectable in CSF. For all sex steroids except E2, strong associations between corresponding CSF and serum levels were observed. We propose that testosterone in CSF is derived from circulating testosterone, DHT in CSF is from local conversion from testosterone, while E2 in CSF is from local conversion from 4D in CNS. Conclusions: We describe the first thoroughly validated highly sensitive mass spectrometric assay for a broad sex steroid hormone panel suitable for human CSF. This assay constitutes a new tool for investigation of the role of sex steroid hormones in the human CNS. Significance statement In this study, a fully validated highly sensitive mass spectrometric assay for sex steroids was applied to human CSF. The results were used to describe the relative contribution of peripheral circulating sex steroids together with locally transformation of sex steroids to the levels in CSF. The results are of importance to understand the biological processes of the human brain.

Abstract Oxytocin is a neuropeptide produced mainly in the hypothalamus and secreted in the CNS and blood. In the brain, it plays a major role in promoting social interactions. Here we show that in human plasma about 60% of oxytocin is naturally bound to IgG which modulates oxytocin receptor signaling. Further, we found that IgG of violent aggressive inmates were characterized by lower affinity for oxytocin, causing decreased oxytocin carrier capacity and reduced receptor activation as compared to men from the general population. Moreover, peripheral administration of oxytocin together with human oxytocin-reactive IgG to resident mice in a resident-intruder test, reduced c-fos activation in several brain regions involved in the regulation of aggressive/defensive behavior correlating with the attack number and duration. We conclude that IgG is a natural oxytocin carrier protein modulating oxytocin receptor signaling which can be relevant to the biological mechanisms of aggressive behavior.

This document is an editorial published in the journal Frontiers in Neuroscience. It discusses the relationship between physical exercise and brain health, specifically focusing on the role of neuroendocrinology. The editorial highlights the potential benefits of exercise in addressing neuropsychiatric and metabolic disorders, such as diabetes and obesity. It also emphasizes the impact of exercise on neural signaling molecules, hormone regulation, and peripheral mechanisms. The editorial concludes by calling for further research and interdisciplinary collaborations to better understand the effects of exercise on brain function and its potential therapeutic applications. [Extracted from the article]

Hypothalamic kisspeptin neurons are master regulators of mammalian reproduction via direct stimulation of gonadotropin-releasing hormone and consequent gonadotropin release. Here, we generated novel Kiss1 (kisspeptin gene)-Cre rats and investigated the developmental changes and sex differences in visualized Kiss1 neurons of Kiss1-Cre-activated tdTomato reporter rats. First, we validated Kiss1-Cre rats by generating Kiss1-expressing cell-specific Kiss1 knockout (Kiss1-KpKO) rats, which were obtained by crossing the current Kiss1-Cre rats with Kiss1-floxed rats. The resulting male Kiss1-KpKO rats lacked Kiss1 expression in the brain and exhibited hypogonadotropic hypogonadism, similar to the hypogonadal phenotype of global Kiss1 KO rats. Histological analysis of Kiss1 neurons in Kiss1-Cre-activated tdTomato reporter rats revealed that tdTomato signals in the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC) were not affected by estrogen, and that tdTomato signals in the ARC, AVPV, and medial amygdala (MeA) were sexually dimorphic. Notably, neonatal AVPV tdTomato signals were detected only in males, but a larger number of tdTomato-expressing cells were detected in the AVPV and ARC, and a smaller number of cells in the MeA was detected in females than in males at postpuberty. These findings suggest that Kiss1-visualized rats can be used to examine the effect of estrogen feedback mechanisms on Kiss1 expression in the AVPV and ARC. Moreover, the Kiss1-Cre and Kiss1-visualized rats could be valuable tools for further detailed analyses of sexual differentiation in the brain and the physiological role of kisspeptin neurons across the brain in rats.

Purpose: Intracranial germ cell tumors frequently arise from the midline of the brain, occasionally presenting as bifocal diseases. The predominant le sion might affect clinical characteristics and neuroendocrine outcomes. Method: A retrospective cohort study involving 38 patients with intracranial bifocal germ cell tumors was performed. Result: Twenty-one patients were assigned to the sellar-predominant group, while the other 17 patients were assigned to the non-sellar-predominant g roup. Differences in gender ratio, age, manifestation, the incidence of metastasis, the incidence of elevated tumor markers, human chorionic gonadotropin levels in serum and in cerebrospinal fluid, diagnostic method, and tumor type were not significant bet ween the sellar-predominant group and the non-sellar-predominant group. Before treatment, the sellar-predominant group had a higher incidence of adenohypophysis hor mone deficiencies and central diabetes insipidus than those of the non-sellar-predominant group, without significant differences. After multidisciplinary therapy, the sellar-predominant group also had a higher incidence of adenohypophysis hormone deficienc ies and central diabetes insipidus than those of the non-sellar-predominant gro up. The differences in the hypothalamic–pituitary–adrenal (HPA) axis impairment (P = 0.008), hypothalamic– pituitary–thyroid (HPT) axis impairment (P = 0.048), and hypothalamic–pituitary–gonad (HPG) axis impairment (P = 0.029) were significant between sellar-predominant group and non-sellar-predominant group, while the others were not. At median 6 (3, 43) months of follow-up visit, sellar-predominant group had a higher incidence of adenohypophysis hormone deficiencies than those of non-sellar-predominant group. The differences in the HPA impairment (P = 0.002), HPT impairment (P = 0.024), and HPG impairment (P < 0.000) were significant, while the others were not. Further c omparison of the neuroendocrine function between different subtypes of sel lar-predominant patients indicated that the differences in adenohypophysis hormo ne deficiencies and central diabetes insipidus were not significant between the two subtype groups. Conclusion: Bifocal patients with different predominant lesions present simi lar manifestations and neuroendocrine disorders before treatment. Non-sellar-predominant patients would have better neuroendocrine outcomes after tumor treatment. The distinction of the predominant lesion in patients with bifocal intracranial germ cell tumor plays a valuable role in predicting neuroendocrine outcomes, as well as in optimizing long-term neuroendocrine management during survival time.

Emotional episodic memory is an important cognitive mechanism that has been extensively studied, however, auditory emotional memory in particular has yet to be thoroughly understood. In addition, sex hormones have been found to affect brain structure and regulate regions of the brain that support higher order cognitive functions. Considering the global usage of oral hormonal contraceptive pills, it is vitally important to investigate the effects of oral contraceptives on executive function, including memory. The aim of the present study was to investigate the extent to which oral contraceptives influence recall for an emotional auditory episodic memory compared to a neutral memory. Participants (N = 90; 45 on an oral contraceptive, 45 naturally cycling) performed a free recall task for an emotional and a neutral auditory story, and their recalls were categorized into gist and detail elements and rated for accuracy. Recall accuracy for an emotional or neutral auditory story was not different between women on oral hormonal contraceptives and women who were naturally cycling, however, both groups of women recalled more information regarding the neutral story compared to the emotional story. These findings inform how the use of hormonal contraceptive pills, combined with high emotional valence, may impact the content and accuracy of recalled episodic events. [ABSTRACT FROM AUTHOR]

Oxytocin is a neuropeptide produced mainly in the hypothalamus and secreted in the CNS and blood. In the brain, it plays a major role in promoting social interactions. Here we show that in human plasma about 60% of oxytocin is naturally bound to IgG which modulates oxytocin receptor signaling. Further, we found that IgG of violent aggressive inmates were characterized by lower affinity for oxytocin, causing decreased oxytocin carrier capacity and reduced receptor activation as compared to men from the general population. Moreover, peripheral administration of oxytocin together with human oxytocin-reactive IgG to resident mice in a resident-intruder test, reduced c-fos activation in several brain regions involved in the regulation of aggressive/defensive behavior correlating with the attack number and duration. We conclude that IgG is a natural oxytocin carrier protein modulating oxytocin receptor signaling which can be relevant to the biological mechanisms of aggressive behavior. [ABSTRACT FROM AUTHOR]

According to classic neuroendocrinology, hypothalamic oxytocin cells can be categorized into parvo‐ and magnocellular neurons. However, research in the last decade provided ample evidence that this black‐and‐white model of oxytocin neurons is most likely oversimplified. Novel genetic, functional and morphological studies indicate that oxytocin neurons might be organized in functional modules and suggest the existence of five or more distinct oxytocinergic subpopulations. However, many of these novel, automated high‐throughput techniques might be inherently biased and interpretation of acquired data needs to be approached with caution to enable drawing sound and reliable conclusions. In addition, the recent finding that astrocytes in various brain regions express functional oxytocin receptors represents a paradigm shift and challenges the view that oxytocin primarily acts as a direct peptidergic neurotransmitter. This review highlights the latest technical advances in oxytocinergic research, puts recent studies on the oxytocin system into context and formulates various provocative ideas based on novel findings that challenges various prevailing hypotheses and dogmas about oxytocinergic modulation. [ABSTRACT FROM AUTHOR]

Cushing disease (CD) is the main cause of endogenous Cushing syndrome (CS) and is produced by an adrenocorticotropic hormone (ACTH)-producing pituitary adenoma. Its relevance in pediatrics is due to the retardation of both growth and developmental processes because of hypercortisolism. In childhood, the main features of CS are facial changes, rapid or exaggerated weight gain, hirsutism, virilization, and acne. Endogenous hypercortisolism should be established after exogenous CS has been ruled out based on 24-hour urinary free cortisol, midnight serum or salivary cortisol, and dexamethasone suppression test; after that, ACTH dependence should be established. The diagnosis should be confirmed by pathology. The goal of treatment is to normalize cortisol level and reverse the signs and symptoms. Treatment options include surgery, medication, radiotherapy, or combined therapy. CD represents a challenge for physicians owing to its multiple associated conditions involving growth and pubertal development; thus, it is important to achieve an early diagnosis and treatment in order to control hypercortisolism and improve the prognosis. Its rarity in pediatric patients has led physicians to have limited experience in its management. The objective of this narrative review is to summarize the current knowledge about the pathophysiology, diagnosis, and treatment of CD in the pediatric population.

Carcinoid syndrome is the most frequent hormonal complication associated with neuroendocrine neoplasms. It was first reported in 1954, and the classical symptoms are diarrhoea, flushing and abdominal pain. It is caused by the secr etion of several vasoactive substances, the most prominent being serotonin, which play a pathophysiological role in the clinical symptoms which characterise carcinoid syndrome. Therefore, the focus of carcinoid syndrome treatment is to reduce serotonin production and hence improve the patient’s quality of life. There are a variety of managemen t options for carcinoid syndrome including medical, surgical and loco-regional interventional radiological procedures. The most widely used are somatostatin analogues with three clinically approved drugs: lanreotide and octreotide (first-generation) and pasireotide (second-generation). Both everolimus and interferon used in combination with octreotide have shown significant reduction in urinary 5-hydroxyindoleacetic acid compared to octreotide alone. Telotristat ethyl has been increasingly utilised for patients with symptoms despite taking somatostatin analogues. It has also been shown to have a significant improvement in bowel movement frequency which was associated with a significant improvement in quality of life. Peptide receptor radionuclide therapy has proven symptomatic improvement in patients with uncontrolled symptoms. Chemotherapy is primarily reserved for patients with high proliferation tumours, with limited research on the efficacy in reducing symptoms. Surgical resection remains the optimal treatment due to being the only one that can achieve a cure. Liver-directed t herapies are considered in patients where curative resection is not possible. There are therefore numerous different therapies. This paper describes the pathophysiology and therapy of carcinoid syndrome.

The document titled "Acknowledgement to Reviewers" from the journal Neuroendocrinology lists the names of reviewers who have supported the journal by reviewing manuscripts. The list includes reviewers from various countries such as the USA, UK, Italy, Spain, Brazil, and many others. The document expresses gratitude to these reviewers for their ongoing support in reviewing manuscripts for Neuroendocrinology. [Extracted from the article]

This study summarizes new data on induced spawning of Steindachneridion parahybae, focusing on the aggressive behavior of females. This study characterizes the vasotocinergic system using immunohistochemistry, highlighting the potential influence of arginine-vasotocin (AVT) on reproductive physiology. Two experimental groups were proposed: (A) control, with one female in the aquarium, and (B) experimental, with two females in the same aquarium. Dominant (D) females presented a more aggressive behavior and did not show any injury. They apparently had a length and body mass higher than injured nondominant (ND) females. The analysis identified positive AVT immunoreactive (ir) neurons exclusively within the preoptic area, including parvocellular, magnocellular, and gigantocellular subpopulations, containing fibers-ir extending into the pituitary gland. Cellular and nuclear areas were greater in D compared to ND in the magnocellular subpopulation. There were no differences between parvocellular and gigantocellular subpopulations. There was a difference on the steroid plasma profile of cortisol (more in ND than in D) and 17α,20β-dihydroxy-4-pregnen-3-one (more in D than in ND). Furthermore, control and D females presented higher optical densities for AVT-ir, gonadotropin-releasing hormone-ir, and luteinizing hormone-ir than ND. In general, there were no differences in the results of female (control group) with D females. The AVT system is highly complex, possibly counting multiple sites of action during artificial reproduction and acting directly and/or indirectly associated with behavioral and physiological changes in S. parahybae females when induced to spawning.

Background Studies have shown a relationship between oestrogen and Alzheimer's disease. However, there is neither clear nor strong evidence on the use of oestrogen-only therapy in reducing the risk of Alzheimer's disease. Aims To assess the effects of oestrogen-only therapy on reducing the risk of Alzheimer's disease. Method Inclusion criteria was determined with the PICO framework. Outcome was cognitive function measured by neuropsychological tests and strict protocols. Exclusion criteria included non-Alzheimer's dementia, progesterone-only therapy and pre-menopausal women. Searches were conducted in nine electronic healthcare databases, last searched in July 2022. Quality assessments conducted on randomised controlled trials (RCTs) were performed with the GRADE assessment, and cohort studies and case–control studies were assessed with the Newcastle–Ottawa Scale. Extracted data were used to analyse participants, interventions and outcomes. Results Twenty-four studies satisfied the search criteria (four RCTs, nine cohort studies, 11 case–control studies). Fifteen studies showed positive associations for oestrogen-only therapy reducing the risk of Alzheimer's disease, and the remaining nine found no evidence of association. Conclusions Fifteen studies showed that oestrogen-only therapy effectively reduced the risk of Alzheimer's disease, whereas nine showed no correlation. Studies also investigated oestrogen-related variables such as length of oestrogen exposure, being an apolipoprotein E ε4 carrier and concomitant use of non-steroidal anti-inflammatory drugs, and their role in neuroprotection. This review was limited by the limited ranges of duration of oestrogen treatment and type of oestrogen-only therapy used. In conclusion, oestrogen-only therapy has potential for use in preventing Alzheimer's disease, although current evidence is inconclusive and requires further study.