Frontiers in Neuroendocrinology最新文献

{"title":"Depression and bone loss: associations, skeletal features and mechanisms from clinical and preclinical studies.","authors":"Hong Xu, Xu Tang","doi":"10.1016/j.yfrne.2026.101291","DOIUrl":"https://doi.org/10.1016/j.yfrne.2026.101291","url":null,"abstract":"<p><p>Depression has been associated with negative skeletal outcomes, but the specific characteristics and underlying mechanisms remain incompletely understood. This narrative review summarizes clinical and preclinical studies in this field. Current findings suggest that depression may be associated with lower bone mineral density, altered bone remodeling and microarchitecture, and increased risks of falls and fractures. The magnitude and pattern of these associations may vary according to depression severity and chronicity, skeletal site, sex, and life stage. Experimental studies indicate that skeletal changes may involve impaired bone formation, increased bone resorption, or both. Candidate mechanisms include dysregulation of the hypothalamic-pituitary-adrenal axis, sympathetic activation, inflammation, alterations in calcium, vitamin D metabolism, and behavioral and treatment-related factors. Better longitudinal and mechanistic studies are needed to identify patients at greatest skeletal risk.</p>","PeriodicalId":12469,"journal":{"name":"Frontiers in Neuroendocrinology","volume":" ","pages":"101291"},"PeriodicalIF":7.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in responses to neurosteroid therapy after preterm birth.","authors":"Jonathan J Hirst, Hannah K Palliser, Rebecca Glover, Carlton L Pavy, Julia C Shaw, Roisin A Moloney","doi":"10.1016/j.yfrne.2026.101289","DOIUrl":"https://doi.org/10.1016/j.yfrne.2026.101289","url":null,"abstract":"<p><p>Progesterone production by the placenta leads to elevated levels of neurosteroids in both the maternal and fetal circulations during late gestation. Allopregnanolone levels are crucial because they provide both neuroprotective and trophic support in the fetal brain. These include protecting against excessive excitation and supporting oligodendrocyte development and myelination. Pregnancy compromises and particularly premature birth reduce or totally deprive the newborn brain of this neurosteroid mediated protection and support. The premature fall in allopregnanolone levels may increase susceptibility to damage from hypoxic episodes and excitotoxicity. Reduced neurosteroid support is also associated with alterations in oligodendrocyte maturation and myelination, which may contribute to subsequent neurodevelopmental and behavioural abnormalities. This in turn contributes to the onset of behavioural disorders including attention deficit hyperactivity disorder (ADHD). Importantly male offspring have been shown to do more poorly after preterm birth as well as after other compromises. Increasing allopregnanolone action using the synthetic analogue, zuranolone, markedly improved myelination after premature delivery in an animal model. Treatment with the mitochondrial translocator protein (TSPO) ligand etifoxine, which promotes endogenous allopregnanolone production, provided protective effects in primary cell cultures following oxygen-glucose deprivation in vitro. Prematurely delivered male offspring showed markedly increased hyperactive behaviour which was also reversed by zuranolone therapy. Female offspring exhibited reduced myelination following preterm birth, without evidence of oligodendrocyte maturational arrest, and this hypomyelination was restored by zuranolone therapy. In contrast, males showed oligodendrocyte maturational arrest and a hyperactive behavioural phenotype. Together, these findings suggest that the effects of preterm birth on white matter development may differ between males and females. These findings support further investigation of allopregnanolone replacement therapy after preterm birth, including pharmacokinetic, safety, toxicology and efficacy studies in neonatal populations.</p>","PeriodicalId":12469,"journal":{"name":"Frontiers in Neuroendocrinology","volume":" ","pages":"101289"},"PeriodicalIF":7.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors determining the time-course of the response of the hypothalamus-pituitary-adrenal axis to stress: Much more than negative glucocorticoid feedback","authors":"Antonio Armario","doi":"10.1016/j.yfrne.2026.101287","DOIUrl":"10.1016/j.yfrne.2026.101287","url":null,"abstract":"<div><div>The consequences of hypothalamic-pituitary-adrenal (HPA) axis activation depend on the area under the curve of the response, including the post-stress period. However, scarce attention has been paid to factors other than negative glucocorticoid feedback (nGF) that can affect its time course. Here, I analyze the influence of stressor characteristics, aging, prior early life and adult stress experiences. Although nGF contributes to shape the initial response, the decline during prolonged emotional stress may largely stem from a safety signal triggered when stress exposure lacks real damage, alongside an inability to sustain a high response to severe stressors. This safety signal appears to be the primary factor reducing the response after repeated experience with the same stressor, particularly during post-stress recovery. The brain origin and processes determining this safety signal remain to be characterized.</div></div>","PeriodicalId":12469,"journal":{"name":"Frontiers in Neuroendocrinology","volume":"83 ","pages":"Article 101287"},"PeriodicalIF":7.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thyroid hormones and neurovascular development: An integrated framework","authors":"Isabel Ochando,&nbsp;Daniela Navarro","doi":"10.1016/j.yfrne.2026.101288","DOIUrl":"10.1016/j.yfrne.2026.101288","url":null,"abstract":"<div><div>Thyroid hormones (THs) are essential regulators of brain development known for their roles in neuronal proliferation, migration, differentiation, and maturation. However, brain development relies on coordinated interactions among neural, glial, vascular, and extracellular matrix components, supporting a broader role for TH beyond neuronal effects.</div><div>Here, we examine how spatial regulation of TH availability contributes to neurovascular development by integrating findings from developmental animal models, human fetal tissue, cerebral organoids, and TH transport disorders. We discuss the molecular mechanisms controlling TH availability and examine how TH signaling influences angiogenesis, astrocyte maturation, extracellular matrix remodeling, and blood-brain barrier formation.</div><div>Together, these findings support a conceptual framework in which local regulation of TH action may coordinate signaling among vascular, glial, and neural compartments during neurovascular unit assembly. This perspective provides a hypothesis-generating framework for understanding how impaired TH signaling may affect multiple developmental processes simultaneously, including maternal thyroid dysfunction and transport disorders.</div></div>","PeriodicalId":12469,"journal":{"name":"Frontiers in Neuroendocrinology","volume":"83 ","pages":"Article 101288"},"PeriodicalIF":7.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Light, melanin, and the microbial clock: Rewiring the gut–brain–skin axis","authors":"Allison Clark,&nbsp;Núria Mach","doi":"10.1016/j.yfrne.2026.101271","DOIUrl":"10.1016/j.yfrne.2026.101271","url":null,"abstract":"<div><div>Sunlight exposure has shaped the evolutionary biology of most life forms through circadian entrainment. Full-spectrum sunlight regulates circadian rhythms, modulates gut and skin microbiomes, influences the gut-brain-skin axis, and drives dermal melanin and vitamin D synthesis. The skin acts as the body’s largest photoreceptive organ and neuroendocrine hub. Melanocytes, keratinocytes, and immune cells in the skin translate photons into hormonal, metabolic, and neuronal signals. Melanin, present across vertebrate tissues, bacteria, and fungi, is a unifying photoreceptive molecule whose redox properties and signaling within the melanocortin pathway bridge host and microbial photic cues.</div><div>Light signals the suprachiasmatic nucleus, triggering hypothalamic-pituitary-adrenal glucocorticoid release and peripheral clock expression throughout the gut-brain-skin axis, influencing rhythmic gastrointestinal functions, short-chain fatty acid production, and vagal feedback to the brain. Microbial photoreceptors, including melanin, flavins, and cryptochromes, extend the photoneuroendocrinology into the holobiont, revealing a shared molecular pathway through which light calibrates the host-microbe interactions.</div><div>Shift work, nocturnal blue light, sun avoidance, abnormal feeding times, and circadian desynchrony disrupt the gut-brain-skin axis, resulting in dysbiosis, intestinal and skin epithelial barrier dysfunction, shifts in immune signaling, and metabolic disorders. Vitamin D intersects with these pathways, yet its possible circadian regulation remains unknown.</div><div>This review synthesizes evidence positioning host and microbial melanin as the key signaling molecule of the melanocortin pathway, which is inherently circadian-regulated, governing metabolic and immune homeostasis across the gut-brain-skin axis. We outline mechanistic models and research gaps, and propose that reframing melanin as a holobiont photoreceptor opens therapeutic opportunities across dermatology, gastroenterology, and neuroendocrinology.</div></div>","PeriodicalId":12469,"journal":{"name":"Frontiers in Neuroendocrinology","volume":"82 ","pages":"Article 101271"},"PeriodicalIF":7.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aging-related autonomic nervous system imbalance and adrenergic regulation of immunity: Implications for inflammaging, autoimmunity, and long COVID","authors":"Sergio Giunta,&nbsp;Jacopo Sabbatinelli,&nbsp;Fabiola Olivieri,&nbsp;Angelica Giuliani","doi":"10.1016/j.yfrne.2026.101269","DOIUrl":"10.1016/j.yfrne.2026.101269","url":null,"abstract":"<div><div>The autonomic nervous system (ANS) plays a central role in immune homeostasis by integrating sympathetic and parasympathetic signals that regulate inflammation, immune cell trafficking, and tolerance. Aging is associated with a progressive autonomic imbalance characterized by sympathetic overactivation, reduced parasympathetic tone, and impaired β-adrenergic signaling in immune cells, which together contribute to inflammaging and immune dysregulation. In this review, we discuss how aging-related alterations in adrenergic pathways affect immune cell differentiation and cytokine networks, with particular emphasis on β₂-adrenergic control of the Th17/regulatory T cell balance through cAMP-dependent mechanisms interacting with cytokine-driven STAT signaling. Chronic sympathetic stimulation and β-adrenergic desensitization weaken these regulatory constraints, favoring pro-inflammatory immune trajectories and loss of immune tolerance. Finally, we propose Long COVID as a paradigmatic condition in which pre-existing inflammaging and autonomic vulnerability are amplified by viral infection, leading to persistent inflammation, impaired immune regulation, and increased susceptibility to autoimmune manifestations.</div></div>","PeriodicalId":12469,"journal":{"name":"Frontiers in Neuroendocrinology","volume":"82 ","pages":"Article 101269"},"PeriodicalIF":7.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148316624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroactive steroids as targets of micro- and nano-plastics: Putative impact on brain function and disease","authors":"Patrizia Porcu ,&nbsp;Mariangela Serra ,&nbsp;Augusta Pisanu ,&nbsp;Maria Giuseppina Pisu ,&nbsp;Liana Fattore","doi":"10.1016/j.yfrne.2026.101266","DOIUrl":"10.1016/j.yfrne.2026.101266","url":null,"abstract":"<div><div>Among environmental pollutants, microplastics (MPs) and nanoplastics (NPs) represent a major threat to marine and terrestrial ecosystems because of their widespread distribution, environmental persistence, accumulation in animal and human organs, and toxicity. MPs and NPs target the major endocrine components, including the hypothalamic-pituitary-adrenal (HPA) and gonadal (HPG) axes, thus affecting steroid milieu with repercussions for peripheral endocrine glands and brain functions. Steroid hormones, either locally synthesized by neurons and glial cells, or reaching the brain from peripheral glands, exert neuroactive actions regulating neuronal excitability, neurogenesis, mood, and behavior. Despite numerous studies investigating the endocrine-disrupting effects of MPs/NPs and their potential reproductive toxicity, the implications of such effects on brain neuroactive steroids are poorly investigated. Here, we first illustrate how neuroactive steroids affect brain functions, then we review clinical and preclinical studies assessing the effects of MPs/NPs on neuroactive steroid levels, with the aim to understand putative implications for mental health.</div></div>","PeriodicalId":12469,"journal":{"name":"Frontiers in Neuroendocrinology","volume":"82 ","pages":"Article 101266"},"PeriodicalIF":7.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of photoperiodic polyphenism in vertebrates","authors":"Tyler J. Stevenson,&nbsp;Irem Senman,&nbsp;Anna Przybylska-Piech","doi":"10.1016/j.yfrne.2026.101265","DOIUrl":"10.1016/j.yfrne.2026.101265","url":null,"abstract":"<div><div>Variation is a fundamental principle of natural and artificial selection. Annual cycles in daylength or photoperiod are an environmental cue that most species in the plant and animal kingdoms use to determine the time of year and the direction of annual changes. Despite phylogenetic variation in mechanisms of light detection, the neural and molecular substrates that transduce photoperiod information are common across vertebrates. However, there is considerable conditional plasticity in the neuroendocrine mechanism that govern seasonal physiology leading to a spectrum of phenotypes within a single species. Here, we cover the phylogenetic history and conditional plasticity that contribute to photoperiodic polyphenisms. This Review presents the current understanding of how light is detected and represented in the vertebrate central nervous system and highlights phenotypic variation in photoperiod responses in amniotes. The Review provides future directions for addressing gaps in understanding how photoperiodic polyphenisms are involved in adaptations to changing environments.</div></div>","PeriodicalId":12469,"journal":{"name":"Frontiers in Neuroendocrinology","volume":"82 ","pages":"Article 101265"},"PeriodicalIF":7.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systems neuroendocrinology in ME/CFS and long COVID: a chronobiological framework for hormone-based research","authors":"Natalie Thomas,&nbsp;Katherine Huang,&nbsp;Elena K. Schneider-Futschik,&nbsp;Beth Pollack,&nbsp;Michal Caspi Tal,&nbsp;David Fineberg,&nbsp;Xiaoyun Wang,&nbsp;Caroline Gurvich,&nbsp;Resia Pretorius,&nbsp;Jonas Bergquist,&nbsp;Christopher W. Armstrong","doi":"10.1016/j.yfrne.2026.101268","DOIUrl":"10.1016/j.yfrne.2026.101268","url":null,"abstract":"<div><div>Hormonal dysregulation is increasingly reported in ME/CFS and Long COVID, yet the broader role of neuroendocrine disruption in these conditions remains underexplored. While changes in steroid, peptide, and neuropeptide hormones have been identified, these findings are often considered in isolation and without attention to their timing or integration within broader physiological systems. The hypothalamic-pituitary axes regulate endocrine, immune, autonomic, nervous, and metabolic functions, systems commonly affected in both conditions, yet their circadian and menstrual dynamics are rarely investigated.</div><div>In this review, we examine the evidence for neuroendocrine dysfunction in ME/CFS and Long COVID, focusing on hormone output, functional assays, receptor expression, and the coordination of endocrine biorhythms. Sex hormone signalling emerges as a key area of vulnerability, particularly given the female predominance in both conditions and the complexity of reproductive hormone regulation.</div><div>We argue that accurate hormone measurement and time-structured sampling, including circadian and menstrual rhythms, are essential for detecting meaningful biological differences. By embedding chronobiology-aware, dense-sampling strategies and integrating multi-omic analyses into multi-system study designs, we outline a framework for investigating dynamic endocrine mechanisms underlying symptom variability and multisystem dysfunction, which may ultimately support the development of more targeted, personalised interventions.</div></div>","PeriodicalId":12469,"journal":{"name":"Frontiers in Neuroendocrinology","volume":"82 ","pages":"Article 101268"},"PeriodicalIF":7.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroendocrine mechanisms of stress-induced KNDy–GnRH pulse generator suppression: Linking HPA-axis activation to female reproductive dysfunction","authors":"Wenjie Bo,&nbsp;Yujing Li,&nbsp;Ruiying Wang,&nbsp;Xinyu Qiao,&nbsp;Yuchan Zhong,&nbsp;Tingting Liu,&nbsp;Jiagui Liang,&nbsp;Huiqiao Lai,&nbsp;Wei Huang","doi":"10.1016/j.yfrne.2026.101270","DOIUrl":"10.1016/j.yfrne.2026.101270","url":null,"abstract":"<div><div>Chronic stress disrupts female reproductive function, but the central mechanisms linking stress exposure to altered gonadotropin-releasing hormone (GnRH) pulsatility remain incompletely defined. The arcuate kisspeptin/neurokinin B/dynorphin (KNDy) network is a core component of the GnRH pulse generator, yet it functions within an expanded regulatory system involving fast amino-acid neurotransmission, steroid feedback, nitric oxide signaling, glial communication, metabolic cues, and stress-responsive neuropeptides. This review synthesizes evidence showing how hypothalamic–pituitary–adrenal (HPA)-axis activation may suppress KNDy–GnRH output. Corticotropin-releasing hormone, glucocorticoids, gonadotropin-inhibitory hormone/RFamide-related peptide-3, glial inflammatory mediators, serotonergic input, and energy-sensitive neuropeptides may converge to impair GnRH pulse-generator function. We further discuss the relevance of these mechanisms to functional hypothalamic amenorrhea, stress-sensitive polycystic ovary syndrome (PCOS) phenotypes, and developmental versus adult stress exposure. Overall, stress-induced reproductive dysfunction is best understood as disrupted network-level neuroendocrine rhythm regulation.</div></div>","PeriodicalId":12469,"journal":{"name":"Frontiers in Neuroendocrinology","volume":"82 ","pages":"Article 101270"},"PeriodicalIF":7.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}