Journal of Neuroendocrinology最新文献

{"title":"Sustained induction of PMOS-like phenotype in mice exposed to letrozole in drinking water.","authors":"Kennedy A Stevenson, Romy Kerbus, Greg M Anderson, Caroline Decourt","doi":"10.1111/jne.70294","DOIUrl":"10.1111/jne.70294","url":null,"abstract":"<p><p>Polyendocrine metabolic ovarian syndrome (PMOS; formerly polycystic ovary syndrome) is the most common endocrinopathy affecting women of reproductive age, characterized by ovarian dysfunction and hyperandrogenism, with metabolic disturbances including insulin resistance and obesity also present for 50% of PMOS patients. Effective preclinical models are crucial for evaluating therapeutic interventions. However, current mouse models of hyperandrogenemia induced by aromatase inhibition typically rely on subcutaneous letrozole implants, which require surgical procedures and struggle to sustain PMOS-like phenotypes over an extended period necessary for thorough drug assessment. We hypothesized that an oral letrozole administration would provide extended maintenance of syndrome-like features. Female mice received letrozole either via subcutaneous implant (~1.67 mg/kg/day for 70 days) or orally in drinking water (~1 mg/kg/day for up to 130 days). Estrous cyclicity was monitored by vaginal cytology. Hormonal, metabolic, and histological assessments were performed. While a subcutaneous letrozole implant only sustained hyperandrogenic, metabolic and reproductive phenotypes for ~50 days, oral letrozole administration sustained complete anovulation for at least 100 days, maintaining a persistent diestrus stage. The oral letrozole treatment produced comprehensive PMOS-like features, including significantly elevated testosterone levels, increased luteinizing hormone concentration, pulse frequency and amplitude, enhanced hypothalamic androgen receptor expression, decreased hypothalamic progesterone receptor expression, cystic-like ovarian morphology, increased body weight, impaired insulin sensitivity, and elevated adiposity during the entire time of the treatment period (18 weeks), compared to the placebo treatment. Uterine weight was not decreased, suggesting normal circulating estrogen concentrations. These findings demonstrate that oral letrozole delivery offers a more accessible method of administration, resulting in a sustained induction of PMOS-like phenotypes. This approach effectively maintains both reproductive and metabolic features essential for comprehensive evaluation, thereby enhancing the model's utility for investigating therapeutic interventions in PMOS.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 10","pages":"e70294"},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estrogen/Esr2b signaling-dependent, female-biased expression of a neuropeptide Y gene in the medaka brain","authors":"Yuki Homan,&nbsp;Yuji Nishiike,&nbsp;Mika Sato-Tsukamoto,&nbsp;Daisuke Saito,&nbsp;Mikita Suyama,&nbsp;Yasuyuki Ohkawa,&nbsp;Fumiya Takahashi,&nbsp;Takashi Baba,&nbsp;Ken-ichirou Morohashi,&nbsp;Kataaki Okubo","doi":"10.1111/jne.70279","DOIUrl":"10.1111/jne.70279","url":null,"abstract":"<p>A recent study showed that female medaka lacking the estrogen receptor gene <i>esr2b</i> are unreceptive to male courtship and instead court other females. In this study, we investigated the brain transcriptome of <i>esr2b</i>-deficient females to explore the underlying mechanisms of this behavioral phenotype, and identified <i>npyb</i>, one of the two neuropeptide Y (NPY) genes in teleosts, as substantially downregulated. Follow-up analyses revealed that <i>npyb</i> is expressed in a markedly female-biased manner, dependent on estrogen/Esr2b signaling, in a ventral telencephalic nucleus implicated in mating behavior. These findings led us to hypothesize that <i>npyb</i> may mediate the phenotypic consequence of <i>esr2b</i> deficiency. To test this, we generated <i>npyb</i>-deficient medaka and assessed their mating behavior; however, no notable abnormalities were observed. Given that <i>npya</i>, the other NPY gene in teleosts, is also expressed in the same brain nucleus, we considered the possibility that <i>npya</i> compensates for the loss of <i>npyb</i> function. Nevertheless, even medaka lacking both <i>npya</i> and <i>npyb</i> showed no discernible deficits in mating behavior. While the precise physiological roles of NPY in medaka remain elusive, our findings establish <i>npyb</i> as a downstream target of estrogen/Esr2b signaling and demonstrate its female-biased expression in a behaviorally relevant brain region.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Father knows stress: Interactions among stress, glucocorticoids, and paternal care in mammals","authors":"Wendy Saltzman,&nbsp;Breanna N. Harris","doi":"10.1111/jne.70271","DOIUrl":"10.1111/jne.70271","url":null,"abstract":"<p>In female mammals, motherhood and maternal care have bidirectional interactions with stress and glucocorticoid hormones: exposure to stressors and elevated glucocorticoid levels can impair parenting by mothers, while, conversely, pregnancy and lactation blunt mothers' neural, hormonal, and behavioral responses to stressors. In contrast, little is known about the effects of stress and glucocorticoids on paternal care in mammalian fathers or how fatherhood affects the activity of the hypothalamic–pituitary–adrenal (HPA) axis and responses to stressors. We review the available findings on interactions among stress, the HPA axis, and fathering in males of biparental mammalian species, including humans. Overall, we find remarkably little consistency across studies. Although chronic stress can impair parenting in men, very few studies address the effects of acute or chronic stress or glucocorticoid elevations on paternal care in other species, and those few studies yield inconsistent results. Almost no studies address the effects of fatherhood on the HPA stress response. Fatherhood and acute interactions with infants can influence basal glucocorticoid levels in many species, but the patterns are, again inconsistent, both within and among species. Overall, relationships among stress, HPA activity, and parenting appear to be less pronounced and less consistent in males than in females. We discuss these findings in the context of the “value-of-reproduction” hypothesis, which posits that reproductive attempts should be terminated under highly stressful conditions. Finally, we consider factors that might contribute to the pronounced variability of findings and suggest promising directions for future studies.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural and behavioral responses to fearful faces in men transitioning to first-time fatherhood","authors":"Sarah A. Stoycos,&nbsp;Philip Newsome,&nbsp;Anthony G. Vaccaro,&nbsp;Elizabeth J. Kim,&nbsp;Tim R. Hu,&nbsp;Jonas T. Kaplan,&nbsp;Darby E. Saxbe","doi":"10.1111/jne.70276","DOIUrl":"10.1111/jne.70276","url":null,"abstract":"<p>Fearful facial expressions signal vulnerability and may be especially salient in caregiving contexts. Like women, men undergo neurobiological transformation as they become parents, but no study has focused on how expectant and new fathers process fearful faces. To fill this gap, we administered a behavioral and fMRI emotion perception task to characterize fear responses in men transitioning to fatherhood. First-time fathers completed a forced-choice behavioral emotion recognition task and an fMRI emotion perception task before (<i>n</i> = 38, <i>M</i>_age = 32.33 years) and after (<i>n</i> = 34, <i>M</i>_age = 33.25 years) their child's birth. We examined behavioral fear recognition and neural responses to fearful adult faces prenatally and ~8 months postpartum. Additionally, we examined whether fathers' fear recognition and postpartum bonding difficulties were associated with neural response. Before their child's birth, fathers showed heightened neural activation to fearful expressions (versus rest) in the inferior frontal gyrus, anterior cingulate, insula, amygdala, periaqueductal gray, pre and postcentral gyri, fusiform gyrus, and visual cortex. Fathers who exhibited stronger periaqueductal gray activation towards fearful faces also showed more accurate fear recognition. After their child's birth, fathers responded to fearful faces in many of the same regions, but also showed activation in the dorsal striatum. Higher dorsal striatum activation was associated with fewer father-infant bonding problems. A longitudinal region-of-interest analysis revealed a trend towards increased nucleus accumbens activation to fearful expressions from prenatal to postpartum. An exploratory whole-brain analysis also found that responses to fearful faces increased in the angular gyrus and decreased in the secondary visual cortex over the transition to fatherhood. Consistent with theory proposing caregivers must be willing to approach others in distress, our findings suggest that first-time fathers recruit reward regions in addition to canonical fear processing regions after their child's birth, and that striatal responding to fearful faces is linked with father-child bonding. This is the first longitudinal study to examine fear processing across the transition to fatherhood and provides insight into how men adapt to the fatherhood role.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolactin receptor signalling contributes to the attenuation of stress-induced hyperthermia during pregnancy","authors":"Andrew M. Stewart,&nbsp;David R. Grattan,&nbsp;Teodora R. Georgescu","doi":"10.1111/jne.70261","DOIUrl":"10.1111/jne.70261","url":null,"abstract":"<p>During pregnancy, thermoregulation is tightly controlled to protect the foetus from harmful elevated temperatures. Stress-induced hyperthermia is a component of the stress response that increases alertness to a perceived threat. Previous literature has shown that like other aspects of the stress response, stress-induced hyperthermia is attenuated in late pregnancy. We sought to investigate how stress-induced hyperthermia is attenuated in pregnancy of mice. The lactogenic hormones, prolactin and placental lactogen, have been previously shown to act through the prolactin receptor (Prlr) to keep maternal temperature in pregnancy low to ensure successful reproductive outcomes. We hypothesised that Prlr signalling in the brain would attenuate stress-induced hyperthermia during pregnancy. To investigate this, we specifically knocked out Prlr from glutamatergic (Vglut2) neurons in mice (<i>Prlr</i>^lox/lox/<i>Vglut2</i>^Cre). These neurons have been implicated in maternal adaptations and in stress-induced hyperthermia. Using radiotelemetry to record core temperature (<i>T</i>_core) and activity levels, non-pregnant and pregnant mice were handled daily by scruffing the skin on the back of the neck to elicit a stress-induced hyperthermic response. In pregnant control mice (<i>Prlr</i>^lox/lox), stress-induced hyperthermia became attenuated from day 12 of pregnancy. This was not due to habituation to the stressor, as non-pregnant mice did not show any attenuation of the stress-induced <i>T</i>_core response following repeated handling for up to 20 days. In the <i>Prlr</i>^lox/lox/<i>Vglut2</i>^Cre mice, the pregnancy-induced attenuation of stress-induced <i>T</i>_core was markedly delayed, only appearing at day 14 of pregnancy. The changes were specific to the temperature response to stress, as both genotypes displayed similar levels of stress-induced activity following handling. Together, these data demonstrate that stress-induced hyperthermia is attenuated during pregnancy in mice and that this effect is at least partially mediated by Prlr signalling in glutamate neurons. However, as the stress-induced <i>T</i>_core response of the knockout mice was eventually attenuated in late pregnancy (gestation day 15–17), comparable to controls, other factors may also be involved.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divergent effects of hyperandrogenemia on the female reproductive neuroendocrine axis under different physiological conditions","authors":"Lillian Rose,&nbsp;Alexander S. Kauffman","doi":"10.1111/jne.70267","DOIUrl":"10.1111/jne.70267","url":null,"abstract":"<p>The hypothalamic–pituitary–gonadal (HPG) axis coordinates reproductive function and incorporates gonadal sex steroid feedback to regulate gonadotropin secretion in a homeostatic manner. In females, ovarian estrogens and progestins act as the primary negative feedback signals to suppress luteinizing hormone (LH) release, whereas in males, androgens, such as testosterone (T), typically provide this feedback. However, androgens can also exert feedback effects on the female HPG axis, particularly in conditions where circulating T levels exceed that of the normal female physiological range. Three clinically relevant examples are anabolic substance abuse, testosterone therapy, and polycystic ovary syndrome (PCOS; recently renamed polyendocrine metabolic ovarian syndrome [PMOS]). Despite shared exposure to “androgen excess,” these different hyperandrogenic states are associated with strikingly different neuroendocrine phenotypes. In testosterone therapy and anabolic substance abuse, high exogenous androgen exposure in or above the male physiological range typically suppresses LH secretion and disrupts ovulatory cycling, mimicking enhanced negative feedback on the HPG axis. Conversely, in PMOS, endogenous elevations in T, high for a female but below the male physiological range, are associated with increased LH secretion, acyclicity, and anovulation. The mechanisms underlying these divergent LH outcomes remain unclear but may reflect, in part, differences in the source of androgens (exogenous vs. endogenous), circulating androgen concentrations, and development timing and/or duration of androgen exposure. This review synthesizes current clinical and preclinical evidence to compare distinct models of hyperandrogenemia with respect to the female HPG axis and aims to illuminate how endogenous and exogenous androgens with different features differentially alter female neuroendocrine function.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictors of in vitro response to somatostatin and dopamine receptor-targeted treatments are lacking in clinically non-functioning pituitary tumors","authors":"Claudia Campana,&nbsp;Jessica Amarù,&nbsp;Diego Criminelli Rossi,&nbsp;Anna Arecco,&nbsp;Paolo Nozza,&nbsp;Mara Boschetti,&nbsp;Gianluigi Zona,&nbsp;Diego Ferone,&nbsp;Marica Arvigo,&nbsp;Federico Gatto","doi":"10.1111/jne.70272","DOIUrl":"https://doi.org/10.1111/jne.70272","url":null,"abstract":"<p>Clinically non-functioning pituitary neuroendocrine tumors (NF-PitNETs) lack effective medical therapies, and the role of somatostatin receptor ligands (SRLs) and dopamine agonists (DAs) in this setting is controversial. We evaluated the in vitro response of NF-PitNETs to multiple SRL and/or DA treatments, focusing on the role of receptor expression and tumor characteristics in driving tumor response. Forty-four NF-PitNET primary cultures were treated (72 h, 10 nM) with octreotide (OCT), pasireotide (PAS), OCT + PAS, BIM-53097 (D2R agonist), BIM-53097 + PAS, and BIM-23B065 (SSTR2/SSTR5/D2R preferential ligand) to evaluate cell proliferation inhibition. Tumors were considered responders to a treatment when a ≥20% reduction in cell proliferation was observed (vs. control); responder tumors to at least one tested condition were classified into the “responder group” for further analysis. Somatostatin (SSTRs) and dopamine type 2 receptor (D2R) expression were evaluated through immunohistochemistry. Data on radiological invasiveness, proliferation indices (Ki67%, mitoses), and p53 immunostaining were collected. Tumor grade was determined using Trouillas and PANOMEN-3 classifications. Median patient age at surgery was 60.3 years (IQR 49.7–70.7), 29 were males (71%). Overall, no significant in vitro inhibition of cell proliferation was observed [ranging from −4.2% (OCT and PAS) to −7.4% (BIM-53097 + PAS)]. However, 13 cultures (30%) were included in the “responder group” [mean inhibition ranging from −18.6% (OCT) to −27.7% (BIM-53097 + PAS)]. D2R was the most expressed receptor (median IRS 8, IQR 6–8), followed by SSTR1 and SSTR2 (median IRS 4, IQR 3–6); SSTR3 and SSTR5 expression was low. In the whole cohort, OCT and PAS efficacy directly correlated with SSTR2 (<i>p</i> = .013 and <i>p</i> = .027, respectively). D2R and SSTR2 expression was higher in responders vs. non-responders to BIM-23B065 (<i>p</i> = .017 and <i>p</i> = .042, respectively). ROC curve analysis discriminates BIM-23B065 responders based on D2R and SSTR2 expression with acceptable ability (AUC = 0.784 and AUC = 0.743, respectively). However, the “responder group” did not differ significantly from the “non-responder group” with respect to patient demographics, tumor clinical–pathological characteristics, receptor expression, and grading. In conclusion, we confirm the limited efficacy of SRL and DA treatment in NF-PitNETs. D2R and SSTR2 can discriminate tumors responsive to BIM-23B065. As concerns the other tested compounds, none of the tumor parameters evaluated demonstrated robust predictive value for NF-PitNET in vitro response.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.70272","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ethanolamine plasmalogens increase luteinising hormone pulsatility and are associated with GPR61 expression in bovine gonadotrophin-releasing hormone neurons","authors":"Hiroya Kadokawa,&nbsp;Tomoaki Kubo,&nbsp;Kana Kobayashi,&nbsp;Denis Karani Wanjiru,&nbsp;Yvan Bienvenu Niyonzima","doi":"10.1111/jne.70273","DOIUrl":"https://doi.org/10.1111/jne.70273","url":null,"abstract":"<p>Pulsatile secretion of luteinising hormone (LH) reflects episodic activity of hypothalamic gonadotrophin-releasing hormone (GnRH) neurons and is essential for reproductive function. Plasmalogens are ether phospholipids enriched in neuronal membranes; however, their role in neuroendocrine regulation of reproduction remains unclear. We examined the effects of ethanolamine and choline plasmalogens on LH pulsatility in vivo and investigated GPR61 expression in bovine hypothalamic tissues and relevant cell lines. The oestrous cycles of 15 Holstein heifers were synchronised, and blood samples were collected at 10 min intervals for 8 h. Ethanolamine plasmalogens, choline plasmalogens or vehicle were administered intravenously. LH concentrations were measured by radioimmunoassay, and LH pulses were identified using the Pulsar algorithm. GPR61 expression was examined by RT-PCR, Western blotting and immunofluorescence in bovine hypothalamic tissues and in cell lines. LH pulse frequency showed a significant treatment × time interaction (<i>p</i> &lt; .01) and increased after ethanolamine plasmalogen administration (Holm-adjusted <i>p</i> = .0084), whereas no significant changes were observed after choline plasmalogen or control treatments. Mean LH concentrations showed a significant effect of time (<i>p</i> &lt; .01), whereas neither the treatment effect nor the treatment × time interaction was significant. LH pulse amplitude was unaffected. GPR61 was expressed in GnRH neurons in the bovine hypothalamus, including the preoptic area, arcuate nucleus and median eminence, and was also detected in GT1-7 and LβT2 cells. Ethanolamine plasmalogens are associated with increased LH pulsatility in vivo and GPR61 expression in GnRH neurons, suggesting a potential role for plasmalogen composition in the neuroendocrine regulation of reproduction.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.70273","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic landscape of a neonatal hypogonadotropic hypogonadism series: Novel variants and phenotypic spectrum","authors":"Karine Aouchiche,&nbsp;Laure Van Wormhoudt,&nbsp;Kevin Perge,&nbsp;Joanne Dornberger,&nbsp;Cindy Colson,&nbsp;Marine Delagrange,&nbsp;Clara Leroy,&nbsp;Jennifer Ledmazel,&nbsp;Vanessa Menut,&nbsp;Jessica Benarrous Jaillet,&nbsp;Djamel Bendifallah,&nbsp;Mohamad Hage Chehade,&nbsp;Christelle Dib,&nbsp;Anne Barlier,&nbsp;Thierry Brue,&nbsp;Rachel Reynaud,&nbsp;Alexandru Saveanu","doi":"10.1111/jne.70274","DOIUrl":"https://doi.org/10.1111/jne.70274","url":null,"abstract":"<p>To describe clinical presentation and genetic findings in a cohort of infants with congenital hypogonadotropic hypogonadism (CHH) diagnosed before 2 years of age. From a large cohort of patients who underwent next-generation sequencing (NGS) for CHH between 2019 and 2025, we identified all patients tested at ≤2 years of age. Genetic analysis consisted of a targeted CHH gene panel, followed by a CPHD-NGS panel. In one remaining patient with neurodevelopmental defects, whole-exome sequencing was performed. Phenotypic data were collected through the GENHYPOPIT registry. Twelve male infants (1.5% of the total cohort) met the inclusion criteria; one additional patient via familial screening was included, for a total of 13 patients. All had micropenis; four had associated cryptorchidism (bilateral in half of cases). CHH was biologically confirmed during mini-puberty in 10 infants, at a median age of 6.8 weeks. Seven of these 10 infants received gonadotropin therapy, at an average of 4.1 months. MRI revealed bilateral olfactory bulb agenesis in five cases. A pathogenic or likely pathogenic variant was identified in 7 of 12 patients (58%), involving <i>TACR3</i> (<i>n</i> = 2), <i>ANOS1</i>, <i>FGFR1</i> (including two novel variants), <i>SOX10</i>, <i>GLI2</i> (through the CPHD panel), and <i>SOX11</i> (identified by exome sequencing). A genetic cause was identified in 58% of cases, a diagnostic yield higher than reported in pubertal cohorts. Early genetic diagnosis allowed anticipatory monitoring for syndromic manifestations and associated pituitary deficiencies—particularly relevant for <i>FGFR1</i> and <i>GLI2</i> variant carriers at risk of CPHD. Our findings support the inclusion of <i>GLI2</i> and <i>SOX11</i> in targeted HH gene panels.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.70274","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolactinomas in the transition from adolescence to young adulthood: A multicentre, retrospective study from the TALENT group","authors":"Dario De Alcubierre,&nbsp;Claudia Giavoli,&nbsp;Tiziana Feola,&nbsp;Lorenzo Cerroni,&nbsp;Ludovica Vincenzi,&nbsp;Eriselda Profka,&nbsp;Aurora Pedroli,&nbsp;Giulia Puliani,&nbsp;Rosa Pirchio,&nbsp;Marta Tenuta,&nbsp;Renata S. Auriemma,&nbsp;Maria Luisa Appetecchia,&nbsp;Rosario Pivonello,&nbsp;Giovanna Mantovani,&nbsp;Andrea M. Isidori,&nbsp;Marie-Lise Jaffrain-Rea,&nbsp;Ashley Grossman,&nbsp;Emilia Sbardella","doi":"10.1111/jne.70275","DOIUrl":"https://doi.org/10.1111/jne.70275","url":null,"abstract":"<p>Prolactinomas in the transition age present unique challenges; treatment strategies and long-term outcomes in this population remain incompletely characterised. This is a multicentre, retrospective study of 110 consecutive patients (33 males) with prolactinomas, aged 15–25 years, across five Italian referral centres (2010–2025). Clinical, hormonal, radiological, and treatment-related parameters were assessed at diagnosis and at follow-up. At diagnosis, the median age was 20 years; median prolactin 177 ng/mL [49–6646]; 55% of patients had micro-tumours. Male patients presented with larger tumours, higher prolactin levels, and greater invasiveness (<i>p</i> &lt; .001 for all comparisons). Cabergoline was first-line therapy in 95%, achieving prolactin normalisation in 75% and significant tumour shrinkage (≥50% volume and/or diameter reduction) in 66% of patients. Partial resistance (biochemical and/or radiological) occurred in 40% of patients. Treatment discontinuation occurred in 48% of cases; 61% of patients discontinuing cabergoline after prolonged normalisation experienced recurrence, which was predicted by younger age at diagnosis (OR 0.67/year, <i>p</i> = .040) and shorter treatment duration (OR 0.95/month, <i>p</i> = .050), the latter showed 93% sensitivity for recurrence at 45.5 months. Adverse events occurred in 12%, leading to treatment discontinuation in 6%. Surgery was required in 17%, achieving long-term remission in 31%, while 21% of surgical cases required radiotherapy. At last follow-up (median 72 months), 73% remained on cabergoline while 25% achieved complete radiological resolution. Transition-age prolactinomas demonstrate high cabergoline resistance rates and frequent recurrence after discontinuation. Treatment duration ≥45.5 months before withdrawal may reduce recurrence risk. Surgical remission is achievable, especially in non-invasive tumours, although multimodal therapy is often required for disease control.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.70275","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}