Journal Of Neuroendocrinology[JOURNAL]
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200 papers
The intermediate conductance calcium-dependent K channel does not contribute to the slow after hyperpolarization in oxytocin and vasopressin hypothalamic magnocellular neurons.
Shook L, Kirchner MK, Campos-Lira E … +1 more , Stern JE
J Neuroendocrinol · 2026 · PMID 41634942 · Publisher ↗
Vasopressin (VP) magnocellular neurosecretory neurons of the hypothalamic supraoptic nucleus (SON) are critical regulators of renal water retention and vascular tone. VP neurons undergo detrimental plastic changes in car...
Vasopressin (VP) magnocellular neurosecretory neurons of the hypothalamic supraoptic nucleus (SON) are critical regulators of renal water retention and vascular tone. VP neurons undergo detrimental plastic changes in cardiovascular diseases such as heart failure (HF), resulting in hyperexcitability and thus altered fluid/electrolyte balance. A major intrinsic mechanism that regulates the firing activity of VP neurons is the slow afterhyperpolarization (sAHP), a phenomenon underlain by a calcium-dependent K current (I). The sAHP is activated by Ca and results in an efflux of K from the cell, hyperpolarizing it and throttling firing. Importantly, we previously reported that a blunted sAHP contributes to hyperexcitability of VP neurons in heart failure rats. While the features of the sAHP are well characterized, the identity of the channel underlying the I remains unknown. Combining patch clamp electrophysiology, pharmacology and immunohistochemistry in Wistar rats, we investigated Intermediate conductance Ca-dependent K (IK) channels as a potential candidate responsible for carrying the I. We generated and measured the I in voltage clamp via 20 Hz trains of 20 square voltage pulses (from -50 to +10) once per minute. After 4 min of baseline recording, we bath applied TRAM-34 (1 μM), a specific IK channel blocker. Blocking IK with TRAM-34 failed to inhibit I peak amplitude, amplitude at 1 s after stimulus end, or area. Post hoc immunohistochemistry was performed to identify the phenotype of the recorded cell. We observed no inhibitory effect of TRAM-34 on the I in either VP or OT neurons. We also saw no inhibition of I (voltage clamp) or sAHP (current clamp) in slices preincubated in TRAM-34 for at least 1 h prior to recording. Conversely, we found that TRAM-34 inhibited isolated whole cell K currents, supporting the presence of functional, TRAM-34-sensitive IK channels in SON neurons. Taken together, our results indicate that despite the expression of IK in SON neurons and astrocytes, we observed no evidence of a significant contribution to the sAHP in either OT or VP SON neurons. Future studies will be needed to determine other potential K channel candidates contributing to the sAHP in SON neurons.
Blunted arginine vasopressin secretion in individuals experiencing a major depressive episode with comorbid post-traumatic stress disorder: Results from an exploratory study using copeptin as a surrogate marker.
Hu H, Lee Y, Tillman AN … +8 more , Ballard ED, Waldman L, Yuan P, Johnston JN, Peng S, Kvarta MD, Verbalis JG, Zarate CA
J Neuroendocrinol · 2026 Jan · PMID 41555748 · Publisher ↗
Arginine vasopressin (AVP) modulates stress responsivity and social-affective behaviors, but its role in mood and trauma-related disorders remains poorly defined due to challenges in peripheral measurement. This study us...
Arginine vasopressin (AVP) modulates stress responsivity and social-affective behaviors, but its role in mood and trauma-related disorders remains poorly defined due to challenges in peripheral measurement. This study used copeptin, a stable, reliable, and well-validated surrogate marker of AVP secretion, to assess vasopressinergic function in a transdiagnostic sample of individuals experiencing a major depressive episode (MDE) with and without post-traumatic stress disorder (PTSD), as well as healthy volunteers (HVs). Baseline levels of copeptin, corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and urine cortisol were compared across groups and examined in relation to clinical symptoms and behavioral traits. Acute changes in copeptin and other hypothalamic-pituitary-adrenal axis markers following a single subanesthetic-dose ketamine infusion were also investigated in a subset of patients. Participants with MDE + PTSD exhibited significantly lower baseline copeptin levels and a blunted reduction in copeptin levels post-ketamine compared to MDE-only participants. Copeptin was unrelated to primary mood diagnosis and to symptom severity of depression, anxiety, post-traumatic stress, anhedonia, suicidal ideation, childhood trauma history, or behavioral traits other than aggression. Higher baseline copeptin levels were associated with verbal aggression, and PTSD comorbidity attenuated these associations. Collectively, these findings suggest a possible biological subtype of attenuated AVP secretion in the dual diagnostic subgroup of co-occurring MDE and PTSD that is independent of symptom burden. Plasma copeptin might therefore serve not only as a peripheral biomarker but also as a proxy for central neuromodulatory changes relevant to AVP-driven circuits in the study of neuropsychiatric disorders. Future studies integrating the temporal dynamics of copeptin with neuroimaging, genetic, and stress-challenge paradigms are needed to delineate the potential neural pathways through which AVP contributes to the pathophysiology and treatment responsiveness of mood and trauma-related disorders. Clinical Trial Registration: www.clinicaltrials.gov (NCT02543983).
Sexual receptivity increases in synchrony with the ovulatory cycle in female medaka.
Tomihara S, Shimomai R, Nakajo M … +2 more , Oka Y, Umatani C
J Neuroendocrinol · 2026 Jan · PMID 41506729 · Publisher ↗
BACKGROUND: Successful reproduction requires coordinated regulation of gonadal function and sexual behavior. Nonetheless, the mechanisms underlying this coordination in teleosts remain elusive. Here, we aimed to find out...
BACKGROUND: Successful reproduction requires coordinated regulation of gonadal function and sexual behavior. Nonetheless, the mechanisms underlying this coordination in teleosts remain elusive. Here, we aimed to find out the possible involvement of ovulation in the control of female sexual behavior using medaka. METHODS: We analyzed the sexual behavior of medaka with targeted knockouts of genes involved in ovulation. We also examined the actual timing of ovulation and sexual behavior. Furthermore, we investigated the possible contribution of a progesterone derivative through pharmacological treatment and analyzed the localization of the progesterone receptor in the brain using in situ hybridization. RESULTS AND CONCLUSION: Genetically anovulatory female medaka did not show female receptivity, although they were normally courted by males. Consistently, intact females exhibited sexual behavior only after ovulation. Additionally, the administration of progesterone, which is released during ovulation, partially reinstated the sexual receptivity of anovulatory knockout females. Taken together with our result that progesterone receptor is expressed in brain regions that are considered strong candidates for regulation of sexual behavior, we propose that female sexual receptivity is facilitated in synchrony with the ovulatory cycle via progesterone receptor signaling in specific brain regions around the time of ovulation.
Sex differences in PRA and PRB expression in the neonatal mouse brain.
Lalitsasivimol D, Acharya KD, Graney PL … +3 more , Nettles SA, Tetel MJ, Wagner CK
J Neuroendocrinol · 2026 Jan · PMID 41499283 · Publisher ↗
During development, there is a significant sex difference in the expression of progestin receptor (PR) in the medial preoptic nucleus (MPN) of rodents. Males express high levels of PR immunoreactivity (PR-ir) in the MPN...
During development, there is a significant sex difference in the expression of progestin receptor (PR) in the medial preoptic nucleus (MPN) of rodents. Males express high levels of PR immunoreactivity (PR-ir) in the MPN beginning at embryonic day 19, whereas PR is virtually absent in females until the second postnatal week. This sex difference indicates a developmental window during which the male MPN is more sensitive to progestins than the female MPN. The two PR isoforms, full-length PRB and the truncated PRA, can differentially regulate the expression of specific genes. Yet, it is unknown how these isoforms contribute to the sex difference in PR expression. In the present study, we investigated the relative contributions of PRA and PRB expression in the MPN during development. PR-ir in neonatal male and female PRA knockout (PRAKO) or PRBKO mice were compared with their wildtype (WT) counterparts. In the MPN, levels of PR-ir were higher in WT males than in WT females consistent with previous results from our lab. Moreover, this sex difference was also detected in both PRAKO and PRBKO mice, suggesting that both isoforms contribute to PR expression in males. We also investigated the expression of PRA and PRB in the ventrolateral subdivision of the ventromedial nucleus of the hypothalamus (VMN) and arcuate nucleus (ARC), two additional brain regions implicated in progestin function in reproduction in which males expressed PR at higher levels than females. Interestingly, in the VMN and the ARC, PRA was the predominant isoform. These findings suggest that the differential expressions of PRA and PRB result in sex differences in PR in the brain regions associated with sexually dimorphic behaviors and neuroendocrine functions.
Genetic inactivation of the CRF receptor eliminates age-linked elevation of hippocampal 11β-hydroxysteroid dehydrogenase type 1 activity in female mice.
Brossaud J, Piccin A, Contarino A … +1 more , Moisan MP
J Neuroendocrinol · 2026 Jan · PMID 41499274 · Publisher ↗
Glucocorticoids are produced through activation of the hypothalamic-pituitary-adrenal (HPA) axis, initiated by the release of corticotropin-releasing factor (CRF) from the hypothalamus. CRF acts through two receptor subt...
Glucocorticoids are produced through activation of the hypothalamic-pituitary-adrenal (HPA) axis, initiated by the release of corticotropin-releasing factor (CRF) from the hypothalamus. CRF acts through two receptor subtypes, CRF1 and CRF2. However, the specific contributions of CRF and CRF receptors to age-related changes in brain glucocorticoid activity remain largely unexplored. In certain tissues, including the hippocampus, glucocorticoid signaling is further amplified by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which regenerates inactive glucocorticoid metabolites into their active form. Notably, prior research investigating the role of hippocampal 11β-HSD1 in aging has focused exclusively on male subjects. In this study, we used genetic mouse models lacking functional CRF or CRF receptors to investigate their respective roles in regulating hippocampal 11β-HSD1 activity and glucocorticoid levels across age and sex. Mice of both sexes at 6 and 18 months of age were analyzed. Hippocampal 11β-HSD1 activity was assessed by measuring the ratio of corticosterone to dehydrocorticosterone using mass spectrometry in tissue extracts from CRF and CRF wild-type (WT), heterozygous (HET), and knockout (KO) mice. Our results demonstrate that hippocampal 11β-HSD1 activity increases with age in female CRF WT and HET mice but not in CRF KO females. In contrast, aged males exhibit elevated 11β-HSD1 activity regardless of CRF genotype. In CRF males, the age-related increase in hippocampal 11β-HSD1 activity is associated with higher hippocampal corticosterone levels, whereas in CRF females, it corresponds with a decrease in hippocampal dehydrocorticosterone. CRF deficiency leads to reduced hippocampal levels of both corticosterone and dehydrocorticosterone in males and females at both ages. CRF deficiency is also associated with decreased plasma corticosterone levels in both male and female mice. Male, but not female, CRF mice show an age-dependent increase in hippocampal 11β-HSD1 activity, which is not altered by CRF deficiency. Moreover, CRF deficiency results in increased plasma corticosterone in female, but not in male, mice. Overall, our findings reveal that hippocampal 11β-HSD1 activity increases with age in both sexes. In females, this increase is dependent on the presence of functional CRF receptors. In contrast, males exhibit age-related increases in 11β-HSD1 activity independent of CRF function. These findings underscore the importance of considering sex as a biological variable when developing therapeutic strategies targeting 11β-HSD1 to mitigate age-related memory decline.
Development of the neurohypophysis: A major neuroendocrine interface.
Ramesh AR, Nedunchezhian N, Ali MH … +3 more , Pęcherz S, Kowalewska N, Anbalagan S
J Neuroendocrinol · 2026 Jan · PMID 41466085 · Full text
The neurohypophysis is a major central neuroendocrine interface regulating reproductive functions and water homeostasis. Distinct neurovascular cell types interact via evolutionarily conserved signaling molecules in the...
The neurohypophysis is a major central neuroendocrine interface regulating reproductive functions and water homeostasis. Distinct neurovascular cell types interact via evolutionarily conserved signaling molecules in the developing neurohypophysis, providing a model system for studying principles in neuroendocrine interface morphogenesis. This review provides an overview of neurohypophysis development with a focus on paracrine signaling and the intrinsic mechanisms that regulate the major cell types and neurovascular interface development.
The transition to human fatherhood involves increased brain activation to infant stimuli in regions involved with reward and motivation.
Rilling JK, Lee M, Zhou C … +6 more , Jung E, Arrant E, Wu S, Cooper JA, Davenport-Nicholson A, Treadway MT
J Neuroendocrinol · 2026 Jan · PMID 41429437 · Publisher ↗
In species where males provide parental care, the transition to fatherhood involves a shift in life history strategy in the direction of increased parenting and decreased mating effort. In non-human mammals, the transiti...
In species where males provide parental care, the transition to fatherhood involves a shift in life history strategy in the direction of increased parenting and decreased mating effort. In non-human mammals, the transition to parenthood involves an increase in the motivation to approach and care for offspring, which is mediated by changes in a neural system that includes the medial preoptic area and the mesolimbic dopamine system. Whether humans experience increased activity in this parental brain system with the transition to parenthood has not been established. Here, we use an effort-based decision-making task to longitudinally track changes in parenting and mating motivation, and functional MRI to track accompanying changes in brain function across the transition to first-time fatherhood in men and compare these changes with those found in a sample of non-father control males. Fathers were generally less willing than non-fathers to exert effort to view female stimuli; however, there were no apparent changes in motivation to engage with either infant or female stimuli across the transition to fatherhood. On the other hand, changes in brain activation were evident. In response to cues predicting infant pictures, new fathers showed a pre- to post-natal increase in activation of brain regions that are part of the mesolimbic dopamine system, and this change was not found in non-father male controls. Fathers, but not non-fathers, also showed increases in activation to infant stimuli in brain regions implicated in empathy, such as the anterior insula. While univariate analyses showed no significant change in the neural response to pictures of adult females among fathers, a multivariate brain signature that was previously found to classify pleasure responses to a wide range of stimuli revealed that fathers showed an increase in pleasure-related activity to infant stimuli, as well as a decrease in pleasure-related activity to female stimuli. Our findings suggest that human fathers experience neurofunctional changes that may adapt them to their new parental role.
KNDy neurons as an indirect target of insulin-like growth factor-1.
Silva JDN, de Sousa LMM, de Sousa ME … +6 more , Vieira HR, Alves GA, Neifert NT, Moore AM, Donato J, Frazao R
J Neuroendocrinol · 2026 Jan · PMID 41423875 · Full text
Neurons in the arcuate nucleus of the hypothalamus (ARH) that coexpress kisspeptin, neurokinin B, and dynorphin (KNDy neurons) are considered the gonadotropin-releasing hormone (GnRH) pulse generator necessary for fertil...
Neurons in the arcuate nucleus of the hypothalamus (ARH) that coexpress kisspeptin, neurokinin B, and dynorphin (KNDy neurons) are considered the gonadotropin-releasing hormone (GnRH) pulse generator necessary for fertility. KNDy neurons are also metabolic sensors controlling the hypothalamic-pituitary-gonadal (HPG) axis. Insulin-like growth factor-1 (IGF-1) secretion is influenced by nutritional status and may serve as a cue detected by neurons to regulate various physiological processes, including reproduction. However, whether IGF-1 modulates KNDy neuron activity remains unclear. RNAscope was used to assess the number of kisspeptin neurons expressing the IGF-1 receptor (IGF1R). Additionally, the effects of IGF-1 on LH secretion, Kiss1 mRNA levels, intracellular calcium concentration ([Ca]i) in KNDy neurons, and resting membrane potential of kisspeptin neurons were investigated. Kisspeptin cells located at the ARH and anteroventral periventricular and rostral periventricular nuclei (here designated as AVPV) expressed the Igf1r in male and female mice. Intracerebroventricular IGF-1 administration acutely increased LH secretion without altering hypothalamic Kiss1 mRNA in male mice. In brain slices, IGF-1 administration elevated [Ca]i in KNDy cells of male mice and depolarized KNDy neurons in both sexes. IGF-1-induced depolarization was abolished by TTX and amino acid receptor antagonists, indicating an indirect mechanism. In contrast, IGF-1 has no effect on the RMP of AVPV kisspeptin neurons in female mice. IGF-1 acutely stimulates KNDy neuron activity via indirect effects despite Igf1r expression in these cells. These findings identify IGF-1 as a metabolic signal that modulates KNDy neuron excitability and, consequently, influences the reproductive axis.
The role of hypothalamic kisspeptin neurons in coordinating reproduction and metabolism.
Rønnekleiv OK, Qiu J, Kelly MJ
J Neuroendocrinol · 2026 Jan · PMID 41407546 · Publisher ↗
The hypothalamic control of fertility is a quintessential homeostatic function. Given that reproduction is metabolically demanding, coordination between energy status and reproductive function is essential. Since GnRH ne...
The hypothalamic control of fertility is a quintessential homeostatic function. Given that reproduction is metabolically demanding, coordination between energy status and reproductive function is essential. Since GnRH neurons lack receptors for key metabolic hormones, nutrient sensing must occur via presynaptic neurons. Among the candidates are anorexigenic POMC and orexigenic NPY/AgRP neurons, both of which are in close apposition to the median eminence, a circumventricular organ permissive to circulating signals. These neurons are inversely regulated by glucose and metabolic hormones, with POMC neurons generally excited by insulin and leptin, and NPY/AgRP neurons inhibited by them. However, their synaptic input to GnRH neurons is sparse, and GnRH neurons may lack the necessary postsynaptic receptors. The discovery of kisspeptin neurons in the early part of this century revolutionized our understanding of reproductive regulation. These neurons project to and control GnRH neuronal excitability. More recently, arcuate kisspeptin neurons (KNDy) have been identified as the command neurons driving pulsatile release of GnRH and are essential for the GnRH/LH surge. Notably, these neurons express both steroid hormone receptors and metabolic hormone receptors and, like POMC neurons, are excited by insulin and leptin. Therefore, arcuate kisspeptin neurons likely serve as a central hub in linking metabolic signals with reproduction. This review will examine how these vital neurons control pulsatile GnRH release, their reciprocal synaptic connections with POMC and NPY/AgRP neurons, and how E2 can regulate their excitability. Through integration of metabolic and hormonal cues, these neurons help align reproductive capacity with the organism's energy status.
Chronic hyperprolactinemia is associated with enhanced high-fat diet binge eating in female mice.
Cornejo MP, Lopez-Vicchi F, de Winne C … +5 more , Pascual F, Ornstein AM, Reynaldo M, Perello M, Becu-Villalobos D
J Neuroendocrinol · 2026 Jan · PMID 41404884 · Publisher ↗
Prolactin is fundamental for pregnancy and lactation, and also has numerous metabolic roles including the stimulation of appetite. Mice with chronic hyperprolactinemia display increased food intake, enhanced expression o...
Prolactin is fundamental for pregnancy and lactation, and also has numerous metabolic roles including the stimulation of appetite. Mice with chronic hyperprolactinemia display increased food intake, enhanced expression of orexigenic genes in hypothalamic brain centers, and also develop obesity. Here, we tested whether the consumption of a rewarding high-fat diet (HFD) is altered in a mouse model of chronic hyperprolactinemia: LacDrd2KO mice, which lack dopamine Drd2 receptors in lactotrophs, preventing dopamine inhibition of prolactin secretion. We exposed control and LacDrd2KO mice to a binge-like eating protocol in which satiated mice have access to a HFD pellet for 2-h on four consecutive days. We found that both control and LacDrd2KO animals displayed binge-like eating of HFD, and that hyperprolactinemic mice nearly doubled their HFD intake compared to controls. Subsequently, we analyzed the activation of mesocorticolimbic brain nuclei involved in reward processing. We observed that, in response to HFD consumption, c-Fos levels were higher in dopaminergic neurons of the parabrachial pigmented area within the ventral tegmental area (VTA), a key brain center involved in reward regulation, and also in the core subdivision of the nucleus accumbens (Acb), the main target of dopaminergic VTA neurons. Furthermore, hyperprolactinemic mice had greater c-Fos activation in dopaminergic neurons of the VTA in response to HFD consumption, compared to control animals. Finally, c-Fos levels in the hypothalamic arcuate nucleus, mainly involved in the control of homeostatic food intake, were lower in LacDrd2KO mice and unaffected by HFD exposure. Current results suggest that chronic hyperprolactinemia is associated with increased consumption of a rewarding stimulus, engaging the activation of dopaminergic neurons in the VTA.
Conventional ambient temperature housing impacts central oxytocin levels in mice.
Kenkel WM, Partie ME, Rogers KF … +1 more , Watanasriyakul WT
J Neuroendocrinol · 2026 Jan · PMID 41404881 · Full text
Neuroscience depends heavily on research done in mice (Mus musculus), yet the field has done little to address the chronic cold stress mice perpetually face during conventional "room temperature" housing (20°C-22°C). Con...
Neuroscience depends heavily on research done in mice (Mus musculus), yet the field has done little to address the chronic cold stress mice perpetually face during conventional "room temperature" housing (20°C-22°C). Contributions from other biomedical fields, such as immunology, oncology, and metabolic physiology, have shown that housing mice at room temperature substantially impacts broad and fundamental aspects of murine biology in ways that negatively affect the translational value of the research derived from these animals. Prairie voles (Microtus ochragaster) are an alternative small rodent model for neuroscience that are adapted for cold weather and better tolerate the ambient temperature of conventional housing. Here, we examined the effect of 3 days of housing at one of three ambient temperature conditions: 20°C, 25°C, or 30°C on oxytocin and vasopressin immunoreactivity within the paraventricular nucleus of the hypothalamus in both mice and voles. We found that increases in ambient temperature above 20°C led to a 32% reduction in oxytocin immunoreactivity in mice, while having no effect in voles. Vasopressin was unaffected in either species. Since oxytocin is a pleiotropic neuropeptide, responsible for regulating a number of homeostatic, emotional, and social circuits, this work calls into question whether findings from mice housed at 20°C can be reliably translated to humans living in thermoneutral conditions. This finding should spur further neuroscience research to reconcile how the assumptions of conventional housing have shaped murine neurobiology.
Characterization of tyrosine hydroxylase- and non-tyrosine hydroxylase-immunoreactive sexually dimorphic oxytocin receptor-expressing neurons in the anteroventral periventricular nucleus of female mice.
Govar AA, Ghimire B, Nishimori K … +1 more , Teruyama R
J Neuroendocrinol · 2026 Jan · PMID 41404880 · Publisher ↗
Oxytocin is involved in the regulation of maternal behavior by binding to the oxytocin receptor (OXTR) in various parts of the brain. Our previous studies demonstrated that OXTRs are specifically expressed in the anterov...
Oxytocin is involved in the regulation of maternal behavior by binding to the oxytocin receptor (OXTR) in various parts of the brain. Our previous studies demonstrated that OXTRs are specifically expressed in the anteroventral periventricular nucleus (AVPV) of female mice, but not in male mice. Furthermore, the activity of the OXTR neurons is essential for proper expression of maternal behavior. The present study aimed to characterize two different populations of OXTR neurons found in the AVPV in the previous study: tyrosine hydroxylase immunoreactive (TH) and non-TH immunoreactive (TH) neurons. Whole-cell patch clamp recordings were used to observe the intrinsic electrophysiological properties of the OXTR neurons. TH neurons displayed a pacemaker-like intrinsic rhythmic short bursting activity, whereas TH neurons displayed either no firing at all, irregular firing, or phasic firing. Some TH OXTR neurons could switch back and forth among these firing patterns. The differences in the firing patterns between these two populations were likely derived from the difference in their expression of afterpotentials. TH OXTR neurons showed more depolarizing afterpotential (DAP) than after-hyperpolarization (AHP), while TH OXTR neurons exhibited more AHP than DAP. Activation of OXTR by a specific agonist caused a steady state depolarization and increase in Ca transient resulting in changes in the firing activity in both TH and TH neurons. Lastly, biocytin was injected into the OXTR neurons during the whole-cell recordings to visualize the recorded neurons for immuno-identification of neuron type and morphological analysis. TH neurons displayed significantly more dendritic arborization than TH neurons. Therefore, TH and TH neurons are electrophysiologically and morphologically distinct. Moreover, because activation of OXTR caused a change in the firing activity of these neurons, oxytocin likely modulates the firing activity of both TH and TH OXTR neurons to influence maternal behavior.
Human growth hormone-induced mitotic maladaptation in podocytes and implications in diabetic kidney disease.
Banoth B, Raviraj S, Pasupulati AK
J Neuroendocrinol · 2026 Feb · PMID 41387190 · Publisher ↗
Diabetes is a significant risk factor for the development of diabetic kidney disease, and about 30% of people with type I diabetes mellitus will eventually develop end-stage kidney disease. Growth hormone (GH) and its me...
Diabetes is a significant risk factor for the development of diabetic kidney disease, and about 30% of people with type I diabetes mellitus will eventually develop end-stage kidney disease. Growth hormone (GH) and its mediator insulin-like growth factor (IGF-I) are crucial for kidney development and function in healthy conditions. However, elevated circulatory levels of GH in type I diabetes mellitus disrupt homeostasis and cause changes in the kidney's structure and function, such as hypertrophy, glomerulosclerosis, and proteinuria. Glomerular podocytes are specialized cells in the nephron, and they practically represent the kidney's filtration function. Podocytes are terminally differentiated cells, and podocyte injury or loss causes significant damage to the glomerulus manifested by varying degrees of proteinuria. Recent studies have identified that podocytes express GH receptors and are key targets of GH action, particularly in settings with type I diabetes mellitus. GH could negatively affect podocyte biology, thus potentially contributing to glomerular manifestations, kidney damage, and thereby contribute to diabetic kidney disease. GH evokes the reactivation of the embryologically active Notch signaling in adult podocytes. As a consequence, terminally differentiated podocytes undergo cell-cycle reentry. This manuscript overviews the aberrant activation of embryologically active pathways in quiescent adult podocytes, complications of cell-cycle reentry, aberrations in cytokinesis, and consequent mitosis-associated cell death.
C-Hydroxyephedrine PET/CT for preoperative surgical planning in large pheochromocytoma and paraganglioma.
Vyakaranam AR, Norlén O, Akural A … +6 more , Crona J, Annebäck M, Klimàcek B, Stålberg P, Sundin A, Åkerström T
J Neuroendocrinol · 2026 Jan · PMID 41319260 · Full text
Early detection of metastases and timely surgical intervention play a crucial role in the management of neuroendocrine tumors. In large-sized pheochromocytomas and sympathetic paragangliomas (PPGL), functional imaging wi...
Early detection of metastases and timely surgical intervention play a crucial role in the management of neuroendocrine tumors. In large-sized pheochromocytomas and sympathetic paragangliomas (PPGL), functional imaging with positron emission tomography (PET) is recommended, as it improves the detection of metastases, which may go undetected on conventional radiologic imaging. C-hydroxyephedrine binds to the norepinephrine transporter receptor and is detected by PET/CT (HED-PET/CT). It has previously demonstrated high accuracy in detecting primary and metastatic PPGL; however, its impact on preoperative staging is unclear. In this study, we retrospectively analyzed a selected cohort of 44 patients with large PPGL to evaluate whether HED-PET/CT influences preoperative clinical decision-making. All patients who underwent HED-PET/CT at Uppsala University Hospital between 2004 and 2024 were screened for inclusion. In total, 44 patients with pheochromocytomas >5 cm and paragangliomas >4 cm were included. HED-PET/CT results were compared with CT/MR findings, and a final consensus was reached on whether preoperative HED-PET/CT would have altered clinical decision-making. HED-PET/CT identified previously undetected metastatic disease in three patients (6.8%), which had not been visualized on CT/MR. Additionally, two patients had discordant findings, where HED-PET/CT revealed additional metastases. In one case, a liver metastasis was identified postoperatively with HED-PET/CT, leading to a metastasectomy that could have potentially been avoided. These findings suggest that HED-PET/CT is highly accurate in detecting metastases; however, its routine preoperative use may be limited and appears to provide significant clinical benefit only in selected patients.
Kisspeptin and early pregnancy: Insights from animal models into hormonal regulation and miscarriage.
Decourt C, Heads K
J Neuroendocrinol · 2026 Jan · PMID 41310413 · Publisher ↗
Miscarriage, defined as spontaneous pregnancy loss before 20 weeks of gestation, affects 10-15% of pregnancies in women under 30, rising to over 50% in women over 45. Implantation failure and early placental dysfunction...
Miscarriage, defined as spontaneous pregnancy loss before 20 weeks of gestation, affects 10-15% of pregnancies in women under 30, rising to over 50% in women over 45. Implantation failure and early placental dysfunction are major contributors, yet the precise mechanisms remain incompletely understood. Kisspeptin, encoded by KISS1, is a critical regulator of the reproductive axis and is highly expressed in the placenta, where it modulates trophoblast proliferation, migration, invasion, and vascular remodelling. Human studies indicate that reduced placental kisspeptin is associated with recurrent pregnancy loss, while circulating kisspeptin levels increase dramatically throughout gestation and may serve as a biomarker for pregnancy viability. Mouse models, including CBA/J × DBA/2 matings and Kiss1/Kiss1r knockout lines, have provided mechanistic insights, showing that loss of kisspeptin signalling impairs decidualization, trophoblast invasion, and embryo implantation. These studies also highlight kisspeptin's role in modulating maternal immune responses and in coordinating hormonal cues, including progesterone, oestrogen, and prolactin, necessary for uterine receptivity. Despite shared features of placentation signal and endocrine regulation, significant species-specific differences exist (e.g. mice lack hCG, exhibit embryo-dependent decidualization, have less invasive trophoblasts) limiting direct extrapolation to human pregnancy. This review synthesizes current evidence on kisspeptin's paracrine and endocrine roles during early gestation, emphasizing the insights gained from murine models while highlighting the translational challenges in applying these findings to human miscarriage research.
Cardiac fibrosis induced by high-fat diet in ApoE-deficient male mice is exacerbated by genetic deletion of PACAP-PAC1 signaling.
Schubart JM, Schaefer MKH, Bonaterra GA … +9 more , Mey L, Schwarzbach H, Pankuweit S, Ausbuettel F, Eiden LE, Weyand S, Weihe E, Kinscherf R, Waechter C
J Neuroendocrinol · 2026 Jan · PMID 41292235 · Full text
Cardiac fibrosis is characterized by an excessive accumulation of extracellular matrix proteins and occurs in a variety of cardiac diseases, such as the highly prevalent syndrome heart failure with preserved ejection fra...
Cardiac fibrosis is characterized by an excessive accumulation of extracellular matrix proteins and occurs in a variety of cardiac diseases, such as the highly prevalent syndrome heart failure with preserved ejection fraction (HFpEF) and other cardiac disorders. Interstitial fibrosis has been identified as a central pathophysiological factor induced and maintained by metabolic stress and chronic inflammation. Considering the limited treatment options for cardiac fibrosis, new therapeutic targets are urgently needed. Mounting evidence for the cardioprotective effects of the neuropeptide pituitary adenylate cyclase-activating peptide (PACAP) provides a rationale to elucidate its role and that of its receptor PAC1 in metabolic stress-mediated cardiac fibrosis. Metabolic stress was induced by feeding a cholesterol-enriched diet (CED) to PACAP/ApoE, PAC1/ApoE and ApoE mice and cardiac tissue subjected to analyses of fibrosis. Under CED feeding, a statistically significant (p < .001) increase in myocardial fibrosis was observed in PACAP/ApoE and PAC1/ApoE compared to ApoE mice. These findings suggest a role for PACAP signaling in the mitigation of metabolically induced cardiac fibrosis. The antifibrotic effect of PACAP is dependent on the expression of the PAC1 receptor and only emerges under metabolic stress conditions. PAC1 receptor agonists may have the potential to attenuate metabolically triggered cardiac fibrosis arising after a chronic high-fat diet.
Intravenous kisspeptin 112-121 bolus does not acutely impact circulating vasopressin in humans.
Galbiati F, Plessow F, Plummer L … +10 more , Campbell MB, Nazarloo S, Carter CS, Davis JM, Miller KK, Carroll RS, Kaiser UB, Seminara SB, Aulinas A, Lawson EA
J Neuroendocrinol · 2026 Jan · PMID 41273106 · Full text
Arginine-vasopressin (AVP) deficiency (AVP-D) is caused by hypothalamic-pituitary damage of vasopressinergic neurons leading to polyuria and polydipsia. Diagnostic tests for AVP-D are limited by low accuracy and/or toler...
Arginine-vasopressin (AVP) deficiency (AVP-D) is caused by hypothalamic-pituitary damage of vasopressinergic neurons leading to polyuria and polydipsia. Diagnostic tests for AVP-D are limited by low accuracy and/or tolerability. Kisspeptin (KP) stimulates AVP release in animals, but no study has investigated KP as a provocative test for AVP-D in humans. We investigated circulating AVP levels in response to intravenous (IV) KP in adults. We also explored sex differences in AVP response to KP. Twelve healthy adults (50% female) received an IV KP bolus. Serum AVP was measured pre- and 10, 20, 40, and 60 min post-KP. AVP levels were higher in males at all time points (p = .028) and did not change in response to KP. KP did not stimulate AVP, possibly due to dose, administration route, or cross-species differences in the AVP system. Our study does not support IV KP bolus of 0.24 nmol/kg as a provocative test for AVP-D. CLINICAL TRIAL REGISTRATION: Our study was registered on ClinicalTrials.gov (NCT00914823).
Bone metastases from neuroendocrine neoplasms: Results of an Italian nationwide survey of natural history and management.
Fazio N, Maisonneuve P, Frezza AM … +26 more , Ranallo N, Ibrahim T, La Salvia A, Brizzi MP, De Divitiis C, Tafuto S, Pusceddu S, Marconcini R, Cives M, Ferrari C, Campana D, De Lisi D, Santini D, Faggiano A, Modica R, Massironi S, Bianchi A, Panzuto F, Antonuzzo L, Pellegrini E, Amoroso V, Puliafito I, Merola E, Silvestris N, Grana CM, Spada F
J Neuroendocrinol · 2026 Jan · PMID 41255062 · Full text
Bone metastases (BMs) were reported in <15% of cases of neuroendocrine neoplasms (NENs). Their clinical behavior is various and clinical management is still undefined. This study aimed to describe the clinical practical...
Bone metastases (BMs) were reported in <15% of cases of neuroendocrine neoplasms (NENs). Their clinical behavior is various and clinical management is still undefined. This study aimed to describe the clinical practical management and survival outcome of neuroendocrine neoplasm patients with BMs. This is a retrospective, observational, multicenter, nationwide study, in which clinical-pathological characteristics, diagnostic tools, skeletal-related events (SREs), bone targeted agents (BTAs) and their correlation with clinical outcome were collected. Data from 320 patients from 18 Italian centers diagnosed with bone metastases during 2000-2013 were captured. Most patients had a well/moderately differentiated NEN, with synchronous distant metastases, mostly hepatic, the majority of which originated from a gastroenteropancreatic primary site. Bone was the first metastatic site in 41% of patients. After a median follow-up of 27 months 122 patients died. The median overall survival (OS) was 62 months. In 22% of patients (n = 72), SREs were observed, and 31% of patients received a BTA. At multivariable analysis of factors associated with OS after the development of BMs, primary lung site, Ki-67 ≥55% versus ≤20%, >10 BMs, mixed pattern (osteoblastic/osteolytic) versus osteoblastic, prior lung metastases and SREs were found to be significant poor prognosis factors. At multivariable analysis Ki-67 ≥55% versus ≤20% remains significantly associated with the development of SREs. Our study represents a real-life nationwide scenario of a large series of NEN patients with BMs handled at dedicated centers. Several hypotheses generated by this study are warranted to be tested in future homogeneous studies, including objective criteria for the use of BTAs.
Plasticity and neuromodulation of neuroendocrine nerve terminals.
Iremonger KJ
J Neuroendocrinol · 2026 Jan · PMID 41251401 · Publisher ↗
Hypothalamic neuroendocrine neurons control diverse homeostatic functions that are essential for survival. While the cell bodies of these neurons are widely distributed, the nerve terminals converge on one specialised ar...
Hypothalamic neuroendocrine neurons control diverse homeostatic functions that are essential for survival. While the cell bodies of these neurons are widely distributed, the nerve terminals converge on one specialised area of the brain called the median eminence. It is here that releasing hormones are secreted into the blood to control the function of the anterior pituitary gland. This current review summarises studies which demonstrate that nerve terminals in the median eminence can undergo unique forms of plasticity under different physiological states. This includes changes in the types of neuropeptides produced, changes in morphology and changes in glial coverage. In addition, median eminence nerve terminals can also act as independent sites of integration of both synaptic and hormonal signals to control the output of the neuroendocrine axis. Together these mechanisms allow for regulation of neurosecretion in response to different physiological demands.
The gatekeepers of growth: The neural roles and regulation of growth hormone-releasing hormone neurons.
Jamieson BB
J Neuroendocrinol · 2026 Jan · PMID 41250802 · Full text
The neuroendocrine control of growth is mediated by the hypothalamic-pituitary-somatic (HPS) axis. This involves the hypothalamic release of growth hormone-releasing hormone (GHRH), which stimulates the pituitary secreti...
The neuroendocrine control of growth is mediated by the hypothalamic-pituitary-somatic (HPS) axis. This involves the hypothalamic release of growth hormone-releasing hormone (GHRH), which stimulates the pituitary secretion of growth hormone (GH). GH subsequently promotes growth both directly and indirectly by stimulating insulin-like growth factor 1 (IGF1) release from the liver. While extensive research has focused on the actions and mechanisms of GH and IGF1, comparatively little attention has been given to how GHRH neurons themselves are regulated. This review aims to provide insight into how GHRH neurons are controlled, emphasizing their intrinsic electrophysiological properties and the broader brain circuitry involved in detecting physiological signals such as hormonal and metabolic status. Central to this regulation is the balance of excitatory and inhibitory inputs that generate the pulsatile secretion pattern essential for growth regulation. Somatostatin (SST) provides critical inhibitory control over both GH secretion and GHRH neuronal activity. Feedback from peripheral hormones and integration of environmental and metabolic cues can further shape GHRH neuron function. Developmental, sex-dependent, and species-specific variations in GHRH neuron regulation are also discussed, highlighting important avenues for future research. This review offers a neuroendocrine perspective on growth regulation, with important implications for understanding the brain's role in regulating growth and development.
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