Journal Of Neuroendocrinology[JOURNAL]
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200 papers
KNDy kisspeptin is required for metabolic homeostasis in female mice in an ovarian hormone-independent manner.
Nandankar N, Negrón AL, Ganesh H … +5 more , Youssef N, Farooq S, Al-Samerria S, Levine JE, Radovick S
J Neuroendocrinol · 2026 Jun · PMID 42219677 · Publisher ↗
Disorders of gonadotropin pulsatility contribute to reproductive dysfunction in humans and are often associated with metabolic dysfunction. Hypogonadotropic hypogonadism is characterized by chronically insufficient gonad...
Disorders of gonadotropin pulsatility contribute to reproductive dysfunction in humans and are often associated with metabolic dysfunction. Hypogonadotropic hypogonadism is characterized by chronically insufficient gonadotropin hormone production, leading to reproductive and metabolic impairments, such as infertility and obesity. Polycystic ovary syndrome (PCOS) is characterized by accelerated gonadotropin hormone production leading to reproductive and metabolic deficits, including oligomenorrhea, infertility, and an increased risk of type 2 diabetes mellitus. Hypothalamic kisspeptin is a key regulator of gonadotropin secretion, and disruptions in kisspeptin signaling result in abnormal gonadotropin pulsatility. Emerging evidence also implicates kisspeptin in energy metabolism. This study investigates the neuroendocrine mechanisms by which kisspeptin within KNDy neurons influences metabolic homeostasis. Using a Pdyn-Cre/Kiss1 knock-out (Kiss1 KO) mouse model, we combined diet-induced obesity, metabolic testing, and ovarian hormone depletion to assess the role of KNDy neuron kisspeptin in metabolic regulation and the interaction with sex steroids. Peripheral metabolism was more severely impacted in Kiss1 KO females than in KO males, with greater reproductive deficits observed in females. Abnormal glucose metabolism was partly attributable to the lack of ovarian steroids. Our findings indicate that loss of KNDy neuron kisspeptin in females promotes obesity through reduced energy expenditure without altering feeding behavior. Furthermore, this study identifies a female-biased role for KNDy kisspeptin as a central integrator of reproductive and metabolic signals.
Facial mimicry to infant and adult emotions in mothers and non-mothers.
Sinisalo H, Veistola S, Bakermans-Kranenburg MJ … +1 more , Peltola MJ
J Neuroendocrinol · 2026 Jun · PMID 42219260 · Publisher ↗
A key aspect of parent-infant interaction is parental mirroring of infant emotions through facial mimicry, the automatic imitation of observed facial expressions. Facial mimicry can be measured using facial electromyogra...
A key aspect of parent-infant interaction is parental mirroring of infant emotions through facial mimicry, the automatic imitation of observed facial expressions. Facial mimicry can be measured using facial electromyography (EMG) and has been associated with empathic abilities, such as recognizing others' emotions. Currently, there is no research investigating how such empathy-related processes might change during the transition to parenthood. In this study, we compared first-time mothers of young infants and non-mothers in their physiological responses in two facial muscle areas (corrugator supercilii and zygomaticus major) to dynamic emotional infant and adult faces. In addition, we examined whether the EMG responses are associated with salivary testosterone levels. Participants performed an emotion recognition task with dynamic infant and adult emotional expressions changing between happy and distressed expressions while facial mimicry was measured with EMG. Mothers showed a more pronounced zygomaticus response specifically to smiling infant faces, and a greater corrugator response to faces changing to distress, regardless of stimulus age. Non-mothers' zygomaticus response to infant smiles was inversely associated with testosterone level. No other correlations between testosterone and EMG responses were found. These results indicate that new mothers may show heightened affective empathic reactivity especially to infant emotions.
Seasonal profiles of circulating steroids and brain steroid-related gene expression in Gymnotus omarorum, a wild fish with year-round territorial aggression.
Valiño G, Jalabert C, Farías J … +3 more , Sotelo-Silveira JR, Soma KK, Quintana L
J Neuroendocrinol · 2026 Jun · PMID 42219259 · Publisher ↗
Gymnotus omarorum is a teleost fish in which both males and females maintain territorial aggression year-round, despite exhibiting a seasonal reproductive cycle. This provides a unique opportunity to examine seasonal neu...
Gymnotus omarorum is a teleost fish in which both males and females maintain territorial aggression year-round, despite exhibiting a seasonal reproductive cycle. This provides a unique opportunity to examine seasonal neuroendocrine mechanisms across reproductive states. As a teleost, G. omarorum extends our understanding of these neuroendocrine patterns beyond birds and mammals, offering a comparative framework for investigating seasonal neuroendocrine reorganization across the vertebrate reproductive cycle. We quantified eight circulating steroids by LC-MS/MS and measured the expression of steroid-related genes (aromatase, estrogen receptors, and an androgen receptor) by qRT-PCR in three nuclei of the social behavior network in wild breeding and non-breeding males and females. Circulating 11-ketotestosterone in males and estrogens in females showed no marked seasonality. In contrast, androstenedione, a steroid precursor for both androgens and estrogens, was elevated during the non-breeding season in both sexes. This increase was accompanied by upregulation of brain aromatase and estrogen receptor expression, suggesting an enhanced capacity for local estrogen synthesis and signaling outside the breeding period. These results reveal coordinated seasonal shifts in circulating steroid precursors and neural estrogenic pathways that covary with reproductive state, shedding light on the neuroendocrine mechanisms underlying seasonal transitions in vertebrates.
Pulsatile LH release in male and female Sprague Dawley and Wistar rats in different reproductive states.
Nasri N, Prevot V, Fernandois D
J Neuroendocrinol · 2026 Jun · PMID 42215046 · Publisher ↗
This study aims to provide a detailed characterization of luteinizing hormone (LH) pulsatility in male and female Sprague-Dawley and Wistar rats, utilizing a minimally invasive tail-tip blood sampling approach across var...
This study aims to provide a detailed characterization of luteinizing hormone (LH) pulsatility in male and female Sprague-Dawley and Wistar rats, utilizing a minimally invasive tail-tip blood sampling approach across various reproductive states. LH levels were measured in sequential blood samples collected from the tail tip using ultrasensitive ELISA, in both sexes and across different reproductive states. LH pulse frequency, amplitude, pattern and baseline levels were analyzed in intact and gonadectomized rats to assess strain differences and estrous cycle variation. Additionally, we evaluate LH hormonal changes in dams at day 7, 14, and 21 of gestation and lactation. LH pulse frequency and pattern were comparable between the strains in both sexes. In females, LH pulsatility varied across the estrous cycle, peaking during Metestrus and decreasing during Estrus. Gonadectomy elicited a marked increase in LH secretion in both sexes, reflected by higher amplitude and baseline levels at 6- and 10-min interval sampling, while the increase of pulse frequency was only observed at 6-min sampling. The LH surge during Proestrus exhibited substantial temporal variability, with most animals attaining peak levels between late afternoon and early night, aligning with previous observations. During gestation, LH secretion remained pulsatile, with stable frequency but increased amplitude. In lactating females, the restoration of baseline but not pulsatile LH secretion upon the removal of the sucking stimulus was unexpectedly rapid. Collectively, these results demonstrate conserved yet distinct patterns of LH secretion across sex, strain, and reproductive states, strengthening the idea that the rat is a good model for integrative neuroendocrine studies of the hypothalamic-pituitary-gonadal axis, and that the tail-tip sampling method is a reliable, humane, and minimally stressful approach for monitoring LH dynamics in rats.
Prenatal cold-induced sympathetic stress programs long-term cardiac β-adrenergic dysregulation and metabolic impairment in female rat offspring.
Piquer B, Paredes AH, Cruz G … +1 more , Lara HE
J Neuroendocrinol · 2026 Jun · PMID 42210740 · Publisher ↗
Gestational cold-induced sympathetic stress increases maternal norepinephrine (NE) release, thereby altering the fetal environment and enhancing fetal NE exposure. This prenatal insult contributes to developmental progra...
Gestational cold-induced sympathetic stress increases maternal norepinephrine (NE) release, thereby altering the fetal environment and enhancing fetal NE exposure. This prenatal insult contributes to developmental programming, leading to long-term cardiovascular alterations. While most studies have focused on male offspring, we investigated the impact of gestational cold-induced sympathetic stress on cardiovascular and metabolic outcomes in female progeny. Pregnant Sprague-Dawley rats were exposed to intermittent cold stress without hypothermia (4°C for 3 h daily), and their female offspring were evaluated at postnatal days 20 and 60. Hearts were analyzed for β-adrenergic receptor (βAR) mRNA expression, protein abundance, receptor binding affinity, and NE concentration. In addition, in vivo glucose tolerance and cardiovascular responses to isoproterenol (ISO) were assessed. Stressed female offspring showed increased ventricular weight at 20 and 60 days without significant changes in cardiac NE content. βAR mRNA levels were elevated at day 20 in the stressed group, but not at day 60. βAR mRNA expression was also increased at day 20, and the β/β receptor ratio was higher at day 20. Radioligand binding revealed reduced βAR affinity at day 60, despite unaltered receptor density. ISO treatment in vivo led to 40% mortality by the third day in stressed females without mortality in control female offspring. Metabolically, adult female offspring displayed glucose intolerance and compensatory hyperinsulinemia, consistent with insulin resistance. These results indicate that prenatal cold-induced sympathetic stress induces long-lasting alterations in cardiac β-adrenergic signaling and metabolic regulation in female offspring, highlighting a vulnerability to cardiometabolic dysfunction.
Associations of PYY, GLP-1 and LEAP2 with changes in feeding-related cognition, body weight and glucose homeostasis after bariatric surgery in non-diabetic women.
Andreoli MF, De Francesco PN, Zhou W … +6 more , Titova OE, Alsehli A, Fredriksson R, Sundbom M, Perello M, Schiöth HB
J Neuroendocrinol · 2026 Jun · PMID 42210737 · Publisher ↗
Roux-en-Y gastric bypass (RYGB) is an effective surgical intervention for severe obesity, but the role of gastrointestinal hormones in its benefits remains unclear. We examined longitudinal pre-to-post-meal gastrointesti...
Roux-en-Y gastric bypass (RYGB) is an effective surgical intervention for severe obesity, but the role of gastrointestinal hormones in its benefits remains unclear. We examined longitudinal pre-to-post-meal gastrointestinal hormone changes and their relationships with glucose homeostasis and feeding-related cognitive responses in women undergoing RYGB. Seventeen non-diabetic women were evaluated pre-RYGB (Visit 1, V1), 1-month post-RYGB (Visit 2, V2), and 1-year post-RYGB (Visit 3, V3). Plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), ghrelin, and liver-expressed antimicrobial peptide 2 (LEAP2) were measured before and after a breakfast in all visits. Appetite ratings and feeding-related cognitive performance were evaluated using visual analog scales, Ideal Portion Size, and Food Stroop tasks. At V3, RYGB induced weight loss (30.8%) and improved glucose homeostasis (p = .020), accompanied by reduced hunger (p = .042), smaller self-reported ideal portion size (p < .001), and improved cognitive control toward food-cues (p = .002). Fasting GLP-1 and PYY levels remained stable across visits but showed enhanced post-meal responses at V2 and V3 (GLP-1: p < .001; PYY: p = .013). Ghrelin levels increased post-RYGB (p = .010) without post-meal variation. LEAP2 concentrations remained stable. Fasting LEAP2 correlated positively with BMI at V1 (p < .001). Fasting PYY correlated inversely with BMI at V3 (p = .005), and its post-meal rise inversely correlated with ideal portion size at V1 (p = .022). GLP-1 increments negatively correlated with ideal portion size (p = .007) at all visits and glycemia (p = .017) at V1. In non-diabetic women, RYGB improves feeding-related cognitive processes. BMI is associated with LEAP2 only pre-surgery, and with PYY 1-year post-RYGB. Restoration of GLP-1 and PYY post-meal increments contributes to metabolic and behavioral improvements. Clinical Trial Registry: This study was registered at clinicaltrials.gov as NCT01815216. https://clinicaltrials.gov/study/NCT01815216.
Germline MEN1 testing patterns in patients with neuroendocrine tumors: A 12-year retrospective analysis within NETwerk, an ENETS center of excellence.
Mariën L, Chhajlani S, De Herdt C … +10 more , Ceulemans K, Van Hoegaerden S, Leuridan M, Van Daele N, Abrams P, Demey W, Ulenaers M, Lybaert W, Janssens K, Vandamme T
J Neuroendocrinol · 2026 May · PMID 42140697 · Publisher ↗
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant tumor predisposition syndrome in which neuroendocrine tumors (NET) represent a major driver of morbidity and mortality. Timely recognition of MEN1 after...
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant tumor predisposition syndrome in which neuroendocrine tumors (NET) represent a major driver of morbidity and mortality. Timely recognition of MEN1 after NET diagnosis enables syndrome-specific surveillance and cascade testing, yet real-world evidence on MEN1 testing implementation in oncology pathways remains limited. The aim of this study was to evaluate MEN1 testing practices and assess concordance with guideline-based indications and nomogram-predicted risk. A retrospective cohort study was performed within NETwerk, a Belgian ENETS CoE, with patients <70 years diagnosed between 2012 and 2024 with pancreatic, pulmonary, gastric, or thymic well-differentiated NET. MEN1 testing data were extracted from medical records. In patients without a prior MEN1 diagnosis at NET presentation, guideline-based indications for MEN1 testing were assessed and compared with observed testing. Additionally, nomogram-predicted MEN1 risk was estimated, using a ≥5% threshold for descriptive risk stratification, and overlap between guideline- and nomogram-based indications was described. In 267 patients without prior MEN1 diagnosis, MEN1 testing was performed in 42 (15.7%), mainly in patients ≤50 years. Including 21 patients with MEN1 diagnosis before NET development, overall MEN1 prevalence was 10.4%. In patients without a prior MEN1 diagnosis at NET presentation, guideline-based indications showed moderate agreement with observed testing (κ = 0.50, p <.001) without directional bias toward over- or undertesting, with undertesting most evident in MEN1-suspicious tumor presentations (gastrinoma, early-onset panNET, thymic NET). Among patients tested despite lacking guideline indications (n = 20), none had MEN1. Application of the nomogram yielded an exact risk score for 77 patients and a risk score range for the remaining 190 patients due to incomplete phenotyping. In the patients with complete phenotyping, median predicted MEN1 risk was 3.3% (IQR 2.4-4.3). Testing rate increased with higher predicted risk: 85.7% (12/14) for ≥5% underwent testing vs. 23.8% (15/63) for <5%. Guideline- and nomogram-based stratification overlapped in most patients. In conclusion, this retrospective cohort study shows that MEN1 testing after NET diagnosis showed moderate alignment with guideline-based indications and was constrained by incomplete risk capture and phenotyping. Embedding a standardized MEN1 risk checklist and minimal endocrine phenotyping into NET MDT workflows, supported by quantitative risk estimation in selected cases, may improve guideline-concordant MEN1 detection and downstream benefits for patients and their relatives.
Phosphohistone H3 and Ki-67 as prognostic markers in metastatic small intestinal neuroendocrine tumours: A comparative, retrospective cohort study.
Papantoniou D, Grönberg M, Janson ET
J Neuroendocrinol · 2026 May · PMID 42108725 · Full text
Ki-67 index and mitotic count form the basis of grading of small intestinal neuroendocrine tumours (siNET). We hypothesized that the mitosis-specific marker phosphohistone H3 (PHH3) might better correlate with cancer-spe...
Ki-67 index and mitotic count form the basis of grading of small intestinal neuroendocrine tumours (siNET). We hypothesized that the mitosis-specific marker phosphohistone H3 (PHH3) might better correlate with cancer-specific survival (CSS) and with response to treatment. We evaluated the association between Ki-67 index, PHH3-estimated mitotic count, and survival outcomes in a retrospective cohort of 73 consecutive patients with metastatic siNET. Additionally, we estimated the optimal cut-off for PHH3 and cross-validated the outcome. Both markers adequately distinguished CCS when comparing lower and higher proliferation groups (Ki-67: 128 vs. 95 m; PHH3: 149 vs. 88 m). They were strongly associated with CSS as continuous (HR 1.18 [1.08-1.28] and 1.16 [1.09-1.25]), and dichotomous variables (HR 2.96 [1.31-6.67] and 3.11 [1.50-6.46]). The Cox model based on PHH3 displayed slightly better optimism-corrected Harrell's c-index (0.71 vs. 0.68) and Akaike information criterion (219 vs. 223). Additionally, PHH3 showed significant association with PFS after treatment with somatostatin analogues (HR 1.12 [1.03-1.21]), and borderline significant association with PFS after treatment with peptide receptor radionuclide therapy (HR 1.11 [1.00-1.24]). A cut-off of >2 mitoses per 10 high-power fields estimated by PHH3 seemed to have better discrimination power compared to the standard WHO cut-off (<2). Mitotic count based on PHH3 is associated with CSS and with PFS after treatment with first-line SSA and possibly with PRRT for metastatic siNET. It may be an alternative to Ki-67 for estimation of proliferation and grading. A cut-off of >2 mitoses per 10 HPF might better distinguish G1 and G2 tumours.
Metabolic-endocrine correlates of gut-brain axis mediators in polycystic ovary syndrome: A case-control study.
Bashir R, Asrar M, Kamboj S … +4 more , Yousuf A, Arif T, Jahan N, Ganie MA
J Neuroendocrinol · 2026 May · PMID 42076786 · Publisher ↗
Polycystic ovary syndrome (PCOS) is increasingly recognized as a neuro-metabolic disorder involving disrupted signaling between the brain-gut axis and reproductive system. Peptides such as kisspeptin, ghrelin, serotonin,...
Polycystic ovary syndrome (PCOS) is increasingly recognized as a neuro-metabolic disorder involving disrupted signaling between the brain-gut axis and reproductive system. Peptides such as kisspeptin, ghrelin, serotonin, and peptide tyrosine tyrosine (PYY) are emerging as integrators of metabolic and endocrine function, yet their coordinated alterations in PCOS and relevance to metabolic risk remain underexplored. Therefore, we investigated the combined pattern of serum kisspeptin, ghrelin, serotonin, and PYY in PCOS, and their associations with metabolic and hormonal indices. In this case-control study, a total of 190 women aged 18-40 years were included between June 2023 and June 2024, comprising 96 women diagnosed with PCOS according to 2003 Rotterdam criteria and 94 age-matched healthy controls. Serum levels of kisspeptin, ghrelin, serotonin, and PYY were measured using ELISA. Secondary assessments included clinical, metabolic, hormonal, and inflammatory parameters. Women with PCOS had significantly higher serum kisspeptin levels and lower ghrelin and serotonin levels compared to controls (p < .05), while PYY levels were similar between the groups. Kisspeptin was inversely correlated with ghrelin (r = -.237, p = .003) and serotonin (r = -.303, p < .001). These peptides also showed significant associations with metabolic indices such as fasting insulin, glucose, HOMA-IR, triglyceride-glucose (TyG), and TyG-BMI ratios. In regression models adjusted for BMI, lower ghrelin (OR = 0.661, p = .008) and serotonin (OR = 0.814, p = .016) levels were independently associated with higher odds of PCOS. Exploratory receiver operating characteristic (ROC) analysis showed that kisspeptin demonstrated moderate discriminatory performance for PCOS (AUC = 0.768; 95% CI: 0.696-0.839), with 82.4% sensitivity and 59% specificity, whereas ghrelin, serotonin, and PYY showed lower AUCs, reflecting limited stand-alone discriminatory ability. Elevated kisspeptin with concomitant reductions in ghrelin and serotonin define a reproducible peptide signature in PCOS, linking neuroendocrine perturbations to measurable metabolic risk, independent of obesity. While kisspeptin shows greater biological separation between groups, none of the peptides alone are sufficient for diagnostic classification; instead, they indicate the central role of hypothalamic-gut axis dysfunction, particularly in lean PCOS phenotypes.
Neural variability across the transition to motherhood: Enhanced moment-to-moment neural variability during mentalizing in first-time mothers.
Halmans S, Straathof M, van 't Hof S … +4 more , Denys D, Crone EA, Månsson KNT, Hoekzema E
J Neuroendocrinol · 2026 May · PMID 42062236 · Full text
Pregnancy is known to induce profound structural adaptations in the female brain, especially in regions involved in social cognition. This pre-conception cohort fMRI study examined changes in neural signal variability an...
Pregnancy is known to induce profound structural adaptations in the female brain, especially in regions involved in social cognition. This pre-conception cohort fMRI study examined changes in neural signal variability and functional connectivity during mentalizing tasks among 110 women (M = 30.5 years, SD = 3.5, range = 25-41), including 40 first-time mothers, 30 s-time mothers, and 40 nulliparous control women. Participants completed a mentalizing task before and after pregnancy, and, for a subset, 1 year postpartum. First-time mothers exhibited increased neural variability in response to child-related stimuli in the early postpartum period relative to their pre-conception baseline, whereas control women and second-time mothers showed decreases consistent with typical age-related changes. In controls, decreased neural variability correlated with declines in mentalizing task performance, suggesting that neural variability supports flexible and effective cognitive processing. Effects were stimulus- and parity-specific, with first-time mothers showing selective increases to child-related cues and second-time mothers showing distinct changes in adult-related processing. These findings suggest that pregnancy, particularly in first-time mothers, selectively preserves or enhances neural flexibility for processing infant social cues and that neural variability is a key marker of these adaptations.
Correction to "Capillary connections between sensory circumventricular organs and adjacent parenchyma enable local volume transmission".
J Neuroendocrinol · 2026 May · PMID 42046479 · Publisher ↗
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Retinal ganglion cell degeneration in glaucoma disrupts HPA axis temporal organization and dampens corticosterone production.
Barsanele PS, da Silva JJ, Cortes BFDS … +5 more , de Oliveira Furtado EM, Cipolla-Neto J, de Assis LVM, Poletini MO, Moraes MN
J Neuroendocrinol · 2026 Apr · PMID 42029480 · Full text
Glaucoma is a chronic optic neuropathy characterized by progressive vision loss. A previous study from our group showed that glaucoma-induced retinal degeneration disrupts photic signaling to the suprachiasmatic nucleus...
Glaucoma is a chronic optic neuropathy characterized by progressive vision loss. A previous study from our group showed that glaucoma-induced retinal degeneration disrupts photic signaling to the suprachiasmatic nucleus (SCN), altering the molecular components of the central circadian clock. Through its hypothalamic projections, the SCN entrains the hypothalamic-pituitary-adrenal (HPA) axis and drives the rhythmic secretion of corticosterone. In this study, we investigated whether central circadian clock disruption in glaucoma impacts the HPA axis and its downstream physiological rhythms. We analyzed the temporal profiles of key genes controlling the HPA axis in mice with glaucoma. The Crh gene expression was reduced in the paraventricular nucleus, while Crh-r1 exhibited a 10-h phase delay in the pituitary in response to glaucoma. Additionally, Pomc in the pituitary and Mc2r in the adrenal lost rhythmicity. The modulation of the daily rhythms of these key genes was associated with alterations in the diurnal rhythms of clock genes in the PVN, pituitary and adrenal gland. Glaucoma-induced phase shifts and amplitude alterations in the rhythmic expression of Per1, Per2, Nr1d1, and Bmal1 in the pituitary and adrenal gland, resulted in a temporal misalignment between the pituitary and adrenal rhythms. These molecular changes were associated with reduced corticosterone amplitude, suggesting impaired communication between central and peripheral clocks. Together, these findings demonstrate that glaucoma alters the temporal coordination of the HPA axis, highlighting how retinal dysfunction can propagate beyond the visual system to disturb systemic circadian and neuroendocrine regulation.
Type III CD38 is present in the membrane of neurosecretory vesicles and has a cytosol-facing catalytic domain in primate oxytocin neurons.
Miyamoto T, Matsushima A, Otubo A … +4 more , Song C, Murata K, Oti T, Sakamoto H
J Neuroendocrinol · 2026 Apr · PMID 42001898 · Full text
CD38, an ADP-ribosyl cyclase that generates cyclic ADP-ribose (cADPR), is essential for Ca-dependent oxytocin release. However, its subcellular localisation and membrane topology within oxytocin neurones have remained un...
CD38, an ADP-ribosyl cyclase that generates cyclic ADP-ribose (cADPR), is essential for Ca-dependent oxytocin release. However, its subcellular localisation and membrane topology within oxytocin neurones have remained unclear. We investigated the distribution and orientation of CD38 in oxytocin-producing neurones of Japanese macaques (Macaca fuscata) using immunoelectron microscopy combined with biochemical isolation of neurosecretory vesicles (NSVs). CD38 immunoreactivity was selectively detected on oxytocin-containing NSVs in axon terminals in the posterior pituitary and dendrites of the supraoptic nucleus, whereas vasopressin vesicles and the plasma membrane lacked detectable labelling. Cryo-electron microscopy confirmed the structural integrity of purified NSV fractions, and Western blotting verified the presence of CD38 protein within these fractions. Permeabilisation-dependent immunogold labelling further demonstrated that the NSV membrane localisation of CD38 and that the N-terminal region of CD38 is oriented toward the vesicle lumen, consistent with a type III membrane topology in which the catalytic domain faces the cytosol. This arrangement positions the active site near cytosolic NAD, enabling localised cADPR production adjacent to Ca-mobilising channels that support regulated exocytosis. These findings identify, in primate oxytocin neurones, a previously unrecognised, vesicle-associated pool of CD38 with a cytosol-facing catalytic domain and provide a structural framework for understanding how intracellular type III CD38 contributes to neuropeptide release.
Testosterone, cortisol, and fNIRS-based cortical activation associated with competitive task persistence and difficulty.
Casto KV, Cohen DJ, Hicks C … +1 more , Bowser A
J Neuroendocrinol · 2026 Apr · PMID 42001854 · Full text
Motivation for social or resource-related rewards is regulated by areas of the brain that control executive functioning and regulate attention, including the prefrontal cortex (PFC) and temporoparietal junction (TPJ). Te...
Motivation for social or resource-related rewards is regulated by areas of the brain that control executive functioning and regulate attention, including the prefrontal cortex (PFC) and temporoparietal junction (TPJ). Testosterone and cortisol are two steroid hormones that influence behaviors related to motivation in social competition and are thought to do so via their independent and interactive effects on these same brain networks. Yet there remains relatively limited evidence for functional hormone-brain correspondence during status contests in humans. In ~120-130 participants, we measured frontal-temporal cortical patterns of neural activity via functional near-infrared spectroscopy (fNIRS), salivary testosterone and cortisol, and task performance in a competitive key-pressing contest for rewards in which the cognitive difficulty of the task was varied. Participants completed the task under one of three conditions for incentivizing performance: a cash prize, positive social judgement, or negative social judgement. The competitive task was associated with increased neural activity bilaterally across the PFC and decreased TPJ activity, especially as task difficulty increased. Individuals who performed better showed greater frontal cortical activation overall and were more likely to have increasing testosterone across the task, but only if cortisol levels simultaneously declined. While hormone change across the task had limited direct ties to brain activity, basal testosterone predicted right vlPFC activation, while the interaction of basal testosterone and cortisol predicted activity in the right TPJ depending on task difficulty. Incentive condition had no clear effects on patterns of brain activity or hormone-brain relationships. These findings support an emerging model of testosterone and cortisol's influence on implicit brain processes underlying attention and goal salience when pursuing social goals. More broadly, this research raises new directions for understanding the neuroendocrine mechanisms behind social and reward-seeking behavior.
The pituitary adenylate cyclase-activating polypeptide receptor and its splice variants: Unique roles in affective and motivated behavior.
Carpenter BA, Barson JR
J Neuroendocrinol · 2026 Apr · PMID 41980614 · Full text
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide with established roles in stress, affective behavior, and motivated behavior. Its primary receptor in the brain, the PACAP type I r...
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide with established roles in stress, affective behavior, and motivated behavior. Its primary receptor in the brain, the PACAP type I receptor (PAC1), has multiple variants due to alternative splicing of the gene, and these variants have been found to have different relationships with the stress response. In the field of motivated behavior, however, there has been much more limited research on these variants. This review focuses on the PAC1 and its splice variants, to propose that they should be thoroughly characterized in the context of motivated behavior. It develops the hypothesis that, for the motivated behavior of drug use, upregulation of a specific receptor variant during repeated episodes of drug use and withdrawal serves to reverse the early relationship between PACAP and drug use, switching from negative feedback in a non-dependent state to positive feedback in a dependent state. The review will first examine the known brain distribution and receptor dynamics of the PAC1 variants. Next, it will examine the known roles of PACAP and its receptor variants in stress, anxiety, and depression. Then, it will describe the known role of the PACAP system in alcohol use, as an example of drug use. Finally, the review will consider these known relationships in order to advance the proposal about how the PAC1 receptor variants may interact with drug use and dependence. Further research on this relationship could allow for the development of novel and effective medications for the treatment of drug use disorders.
Disruption of circadian rhythms is associated with cognitive impairment during gestation.
Li S, Xu J, Yue H … +8 more , Yin J, Yuan Y, Ni S, Wang H, Zhang Y, Liao X, Tao J, Yang Y
J Neuroendocrinol · 2026 Apr · PMID 41980611 · Publisher ↗
Disruption of circadian rhythms is increasingly recognized as a contributor to cognitive dysfunction, but its role in gestation-associated cognitive changes remains unexplored. Here we combine human cognitive screening w...
Disruption of circadian rhythms is increasingly recognized as a contributor to cognitive dysfunction, but its role in gestation-associated cognitive changes remains unexplored. Here we combine human cognitive screening with a comprehensive longitudinal mouse model to investigate whether gestational cognitive impairment and postpartum recovery are coupled with disruption and restoration of hippocampal circadian rhythms. Cognitive function was assessed in pregnant and postpartum women using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). In mice, four reproductive stages were compared: control, gestation, 1 month postpartum, and 3 months postpartum. Serum gonadotropins and sex hormones levels were quantified using ELISA. Home-cage locomotor activity was recorded over 48 h under a 12 h:12 h light-dark cycle. Hippocampal-dependent memory was evaluated using the novel object recognition test and Barnes maze at Zeitgeber times ZT6 (day) and ZT18 (night). Hippocampal amyloid β (Aβ) deposition was visualized via immunofluorescence; protein expression of amyloid precursor protein (APP), β-site amyloid precursor protein cleaving enzyme-1 (BACE1), and phosphorylated tau was measured by Western blots. Hippocampal clock gene expression was quantified by RT-qPCR at six time points; circadian parameters (mesor, amplitude, acrophase) were derived by cosinor analysis and compared between groups. Human cognitive screening confirmed modest gestational decline with postpartum recovery. In mice, gestation disrupted daily locomotor activity rhythms and reduced nocturnal preference; both partially recovered by 1 month and fully by 3 months postpartum. Behaviourally, pregnancy impaired the normal day-night difference and performance in novel object exploration and Barnes maze, which recovered progressively. At the molecular level, gestation increased hippocampal APP and BACE1 expression, elevated Aβ42 deposition, and induced tau hyperphosphorylation at multiple sites-hallmarks of Alzheimer's disease-related pathology. These alterations partially reversed by 1 month postpartum and normalized by 3 months. Hippocampal clock genes maintained 24 h rhythmicity, but gestation induced gene-specific phase shifts, amplitude reductions, and mesor alterations. These parameters showed gradual, gene-dependent normalization postpartum. Gestational cognitive impairment and postpartum recovery are associated with reversible disruption and restoration of both hippocampal circadian rhythms and Alzheimer's disease-related molecular pathology. These findings are correlational in nature and provide a foundation for future causal investigations.
Hemicolectomy or appendectomy for appendiceal neuroendocrine tumours sized 1-2 cm? A retrospective population-based study of 1514 patients.
Tan KS, Abdelhameed A, Mortagy M … +3 more , White BE, Burns D, Ramage J
J Neuroendocrinol · 2026 Apr · PMID 41980606 · Publisher ↗
Management of appendiceal neuroendocrine tumours (aNET) with a size of 1-2 cm is a topic of debate, with the conflict centred on the potential oncological benefits of right hemicolectomy (RHC) versus appendectomy and the...
Management of appendiceal neuroendocrine tumours (aNET) with a size of 1-2 cm is a topic of debate, with the conflict centred on the potential oncological benefits of right hemicolectomy (RHC) versus appendectomy and the impact of RHC on quality of life. A recent study suggested that RHC may not be needed for certain aNET 1-2 cm in size. A total of 1244 adult patients with aNET 1-2 cm (diagnosed 2012-2022) who underwent appendectomy or RHC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Similarly, a total of 270 patients (diagnosed 2012-2021) were extracted from the National Cancer Registration and Analysis Service (NCRAS) database. Kaplan-Meier (KM) plots for overall survival (OS) were generated with log-rank tests (LR). Univariable and multivariable Cox regression for all-cause mortality were performed. In the NCRAS cohort, 159 and 111 patients underwent appendectomy and RHC, respectively. The median age was 41 and 51 years for appendectomy and RHC, respectively. Most patients were female (63.7%) and of white race (86.3%). Patients who underwent RHC had a higher proportion of node-positive disease. In the SEER cohort, 957 and 287 patients underwent appendectomy and RHC, respectively. Median age was 39 and 47 years for appendectomy and RHC, respectively. Most patients were females (65.3%) and of white race (67.7%). Patients who underwent RHC had a higher proportion of node-positive disease and M1 stage. Sex and race distribution were similar for the two procedures in both NCRAS and SEER. The KM plot for OS in NCRAS (p = .061) and SEER (p = .14) showed no statistical difference between appendectomy and RHC. Cox regression for all-cause mortality showed that there is no statistical difference between appendectomy and RHC in both cohorts after adjusting for other factors, including age and N stage. Cox regression for all-cause mortality for both cohorts combined showed the same result. Survival of appendectomy is non-inferior to RHC in the management of aNET 1-2 cm, even in patients with node-positive disease. These study findings address the gap in current clinical practice guidelines.
The effect of LysaKare infusion on serum potassium levels in patients with gastroenteropancreatic neuroendocrine tumours eligible for treatment with [Lu]Lu-DOTA-TATE: A post-authorisation safety study.
Hofland J, Grana CM, Weickert MO … +10 more , Moore AR, Shah T, Prakash V, Kolasińska-Ćwikła A, de Herder WW, Spada F, Xu L, Fite R, Wu Y, Ćwikła JB
J Neuroendocrinol · 2026 Apr · PMID 41978231 · Full text
A post-authorisation safety study (PASS) was conducted to assess the impact of LysaKare (2.5% Lysine-Arginine solution) on serum potassium concentrations and its safety/tolerability profile in patients with gastroenterop...
A post-authorisation safety study (PASS) was conducted to assess the impact of LysaKare (2.5% Lysine-Arginine solution) on serum potassium concentrations and its safety/tolerability profile in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NET) eligible for Lu-DOTATATE treatment. In a phase IV, multicentre, single-arm, open-label PASS, adults with somatostatin receptor-positive GEP-NET who were eligible for Lu-DOTATATE treatment received 1000 mL of LysaKare (monotherapy) intravenously over 4 h. The primary endpoint was the change in serum potassium levels over the course of 24 h. Secondary endpoints included the incidence of LysaKare-related adverse events (AEs) and changes in laboratory parameters. Forty-one patients were treated (median age, 57 years; 92.7% White and 7.3% Black; 53.7% male) and 40 completed post-treatment follow-up. Mean (standard deviation [SD]) serum potassium was 4.33 (0.397) mmol/L pre-dose, increasing by 0.60 (0.666) mmol/L after 4 h (time to maximum change, range, 2-24 h) before decreasing to around the pre-dose level: the mean (SD) increase after 24 h was 0.07 (0.396) mmol/L. Other electrolytes and blood gas components mostly showed transient changes that lasted ~24 h. A general trend of transient metabolic acidosis was also observed based on laboratory values. Serum potassium grade increased from baseline in 41.5% of patients. By comparison, five patients (12.2%) had a treatment-related AE of hyperkalaemia (grade 3, n = 1); all resolved within 24 h, either without treatment (n = 3) or following intravenous furosemide (n = 2). There were no serious AEs and no AEs leading to treatment discontinuation/interruption. This PASS identified no new safety signals attributable to LysaKare. Trial registration: EudraCT, 2019-004073-76. Registered 20/08/2020.
Arcuate nucleus-specific progesterone receptor knockdown in female mice is sufficient to induce PCOS-like hyperactivity in the reproductive axis.
Glendining KA, Prescott M, Potapov K … +2 more , Kip E, Campbell RE
J Neuroendocrinol · 2026 Apr · PMID 41968288 · Full text
Mammalian reproductive function is dependent upon gonadal steroid hormone feedback within the hypothalamic-pituitary-gonadal (HPG) axis. In polycystic ovary syndrome (PCOS), impaired progesterone (P4) negative feedback l...
Mammalian reproductive function is dependent upon gonadal steroid hormone feedback within the hypothalamic-pituitary-gonadal (HPG) axis. In polycystic ovary syndrome (PCOS), impaired progesterone (P4) negative feedback leads to hyperactive pulsatile secretion of luteinising hormone (LH) and impaired reproductive function. Although the precise upstream neuronal network modulating P4 negative feedback remains undefined, gamma-aminobutyric acid (GABA)ergic neurons in the arcuate nucleus (ARC) have been implicated. To identify the critical location of P4 negative feedback, we knocked out progesterone receptors (PR) specifically from GABA neurons by genetic cross (VGAT-Cre; PR) or specifically from the arcuate nucleus by stereotaxic AAV-Cre delivery to PR mice and assessed HPG axis function. Females with GABA-specific PR knockout (GABAPRKO) exhibited delayed vaginal opening and fewer estrous cycles compared to controls, but LH pulse frequency and P4 negative feedback were unaffected. In contrast, females with AAV-Cre-mediated knockdown of PR specifically in the ARC exhibited increased LH pulse frequency in comparison to control and AAV-Cre off-target animals. ARC-specific PR knockdown also resulted in significantly decreased estrous cycle frequency, increased cycle length, reduced time spent in proestrus, and impaired P4 negative feedback, but no change in testosterone levels. These data show that reduced PR signalling in the ARC of adult female mice is sufficient to drive hyperactivity within the HPG axis and mimic some but not all reproductive features of PCOS. The subtle reproductive deficits in GABAPRKO may reflect compensatory mechanisms or the involvement of multiple neuronal phenotypes in P4 negative feedback. Together, this work supports the ARC as a critical site for P4 negative feedback regulation of the reproductive axis.
Optimizing the diagnosis of primary aldosteronism: The role of adrenal vein sampling and the need for high-expertise reference centers.
Herrera-Martínez AD, Rebollo-Román Á, Remón-Ruiz P … +12 more , Picón-César MJ, Guirado-Peláez P, Tenorio-Jiménez C, López-Pereira C, Aguilar-Diosdado M, Iturregui-Guevara M, Doulatram-Gamgaram VK, Pérez-Montilla ME, Espejo-Herrero JJ, Galvez-Moreno MÁ, Soto-Moreno A, Neuroendocrine Group of the Andalusian Society of Endocrinology, Diabetes and Nutrition
J Neuroendocrinol · 2026 Apr · PMID 41968277 · Full text
Adrenal vein sampling (AVS) is the cornerstone diagnostic procedure for subtype differentiation in primary hyperaldosteronism, guiding therapeutic decision-making and offering the possibility of curative surgery to a sub...
Adrenal vein sampling (AVS) is the cornerstone diagnostic procedure for subtype differentiation in primary hyperaldosteronism, guiding therapeutic decision-making and offering the possibility of curative surgery to a subset of patients. However, technical challenges limit its use, and success rates vary substantially across centers, restricting equitable access for all patients with primary hyperaldosteronism. To evaluate AVS success rates in major hospitals across Andalucía and to assess the clinical evolution of patients who underwent surgery, with the goal of identifying referral centers and optimizing patient care. A retrospective observational study was conducted across six centers in Andalucía. A total of 151 procedures were performed in 140 patients, with an overall success rate of 55.62%. Intercenter analysis revealed successful catheterization rates ranging from 25% to 75.5%. Among patients without a computed tomography-detected adenoma, 27.4% demonstrated unilateral or bilateral aldosterone secretion. In patients with a single adenoma, discordant lateralization was observed in 9.80%, and bilateral secretion in 11.76%. Half of the patients with bilateral adenomas exhibited unilateral secretion. In total, discordant results reached 21.57%. Following surgery, all patients with successful AVS discontinued potassium supplementation, accompanied by a significant reduction in antihypertensive medication requirements (p < .001). There were no significant differences among patients that underwent unilateral adrenalectomy based on imaging or AVS. Surgical management of primary hyperaldosteronism leads to significant clinical improvement, which is most accurately achieved when guided by successful AVS. Identifying and supporting expert centers is essential to improve access to AVS and enhance clinical outcomes for patients with primary hyperaldosteronism.
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