Jordan E Hamden, Melody Salehzadeh, Hitasha Bajaj, Michael X Li, Kiran K Soma
{"title":"Lipopolysaccharide differentially alters systemic and brain glucocorticoid levels in neonatal and adult mice.","authors":"Jordan E Hamden, Melody Salehzadeh, Hitasha Bajaj, Michael X Li, Kiran K Soma","doi":"10.1111/jne.13481","DOIUrl":"https://doi.org/10.1111/jne.13481","url":null,"abstract":"<p><p>Glucocorticoids (GCs) are secreted by the adrenal glands and increase in response to stressors (e.g., infection). The brain regulates local GC levels via GC synthesis, regeneration and/or metabolism. Little is known about local GC regulation within discrete brain regions at baseline or in response to stress. We treated male and female C57BL/6J mice at postnatal day 5 (PND5) or PND90 with lipopolysaccharide (LPS; 50 μg/kg bw i.p.) or vehicle and collected blood and brain after 4 h. We microdissected the prefrontal cortex, hippocampus, hypothalamus and amygdala. We measured seven steroids, including corticosterone, via liquid chromatography-tandem mass spectrometry and measured transcripts for key steroidogenic enzymes (Cyp11b1, Hsd11b1, Hsd11b2) via qPCR. At both ages, LPS increased GC levels in blood and all brain regions; however, the increases were much greater at PND90 than at PND5. Interestingly, PND5 corticosterone levels were lower in prefrontal cortex than in blood, but higher in amygdala than in blood. These changes in corticosterone levels align with local changes in steroidogenic enzyme expression, demonstrating robust regional heterogeneity and a possible mechanism for the region-specific effects of early-life stress. In contrast, PND90 corticosterone levels were lower in all brain regions than in blood and similar among regions, and steroidogenic enzyme mRNA levels were generally not affected by LPS. Together, these data indicate that local GC levels within discrete brain regions are more heterogeneous at baseline and in response to LPS at PND5 than at PND90, as a result of increased local GC production and metabolism in the neonatal brain.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e13481"},"PeriodicalIF":3.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854519","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}
Grace Kraatz, Henry Tian Hao Xie, Hong Long, Claire-Dominique Walker
{"title":"Neonatal estradiol and early adversity interact to modify basolateral amygdala morphology and adult behavior in female rats.","authors":"Grace Kraatz, Henry Tian Hao Xie, Hong Long, Claire-Dominique Walker","doi":"10.1111/jne.13483","DOIUrl":"https://doi.org/10.1111/jne.13483","url":null,"abstract":"<p><p>Being raised under adverse conditions during infancy and childhood represents a significant risk factor for developing later psychopathologies and dysfunctions in emotional, affective, and cognitive abilities. Depending on the type, timing, and duration of early adversity, different consequences emerge across the sexes in both human and animal models, although our understanding of the underlying interactions between sex and early life stress (ELS) is still incomplete. In this study, we used the limited bedding (LB) paradigm, a well-described model of ELS in rat pups during the first 10 days of life, and tested whether masculinization of the female brain by neonatal injections of estradiol benzoate (EB) would recapitulate the ELS-induced vulnerability phenotype of males on morphology of the basolateral amygdala (BLA) principal neurons and pre-adolescent and adult behavior. Our results show that LB-induced morphological changes in BLA neurons of weaning female rats were eliminated by EB treatment independently of early changes in estrogen receptor (ERα) expression in this region. EB treatment synergized with LB to enhance play behavior of pre-adolescent females to levels far greater than those observed in control males. In adult offspring, LB reduced time spent in the center in males and EB tended to increase social contact time compared to normal females, but only in LB conditions. Our findings indicate that neonatal masculinization of the female brain modifies specific, but not all aspects of BLA morphology and both pre-adolescent and adult behavior that are altered by ELS.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e13483"},"PeriodicalIF":3.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854494","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}
Qiaorui Yang, Shengxiao Jia, Jing Tao, Jinfu Zhang, Zhenliang Fan
{"title":"Multiple effects of kisspeptin on neuroendocrine, reproduction, and metabolism in polycystic ovary syndrome.","authors":"Qiaorui Yang, Shengxiao Jia, Jing Tao, Jinfu Zhang, Zhenliang Fan","doi":"10.1111/jne.13482","DOIUrl":"https://doi.org/10.1111/jne.13482","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a highly prevalent and heterogeneous disease characterized by a combination of reproductive and endocrine abnormalities, often associated with metabolic and mental health disorders. The etiology and pathogenesis of PCOS remain unclear, but recent research has increasingly focused on the upstream mechanisms underlying its development. Among these, kisspeptin (KISS) signaling has emerged as a pivotal component in the regulation of the hypothalamic-pituitary-gonadal axis, with significant roles in reproductive function, energy regulation, and metabolism. Women with PCOS commonly exhibit disruptions in gonadotropin secretion, including elevated luteinizing hormone (LH) levels, imbalanced LH/follicle-stimulating hormone (FSH) ratios, and increased androgen levels, all of which are usually parallel with abnormal KISS signaling. Furthermore, alterations in the KISS/KISS1R system within the central and circulatory systems, as well as peripheral tissues, have been implicated in the development of PCOS. These changes affect multiple pathophysiological domains, including reproductive function, energy regulation, metabolic homeostasis, inflammatory response, and emotional disorders, and are further influenced by lifestyle and environmental factors. This review aims to comprehensively summarize the existing experimental and clinical evidence supporting these roles of KISS in PCOS, with the goal of establishing a foundation for future research and potential clinical applications.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e13482"},"PeriodicalIF":3.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854485","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":"Using digital PCR to investigate the prevalence of KRAS variants in pituitary tumours.","authors":"Veronica Aran, Elisa Lamback, Renan Lyra Miranda, Alexandro Guterres, Isabel Souza Barbosa, Leila Chimelli, Mônica Roberto Gadelha, Vivaldo Moura Neto","doi":"10.1111/jne.13484","DOIUrl":"https://doi.org/10.1111/jne.13484","url":null,"abstract":"<p><p>Pituitary tumours (PT) are formed in the pituitary gland, a small gland situated at the base of the brain. These tumours can be categorized according to their histological origin and hormone production. In surgical series, non-functioning PT are the commonest subtype, followed by functioning somatotroph and corticotroph tumours. Different somatic alterations have been implicated in the pathogenesis of these tumours and the objective of our study was to expand our previous new finding of KRAS pathogenic genetic variants in pituitary tumours. We conducted a digital polymerase chain reaction (PCR) analysis on formalin-fixed paraffin-embedded tissue blocks belonging to 189 patients. The results showed that, from the 184 pituitary tumours with good quality samples, 13 tumours (7.1%) presented mutant KRAS. The median age of the mutated group was 47 years old (range 19-77) and most patients with mutant KRAS tumours were from the female gender (61.5%, 8/13) and non-functioning subtype. For the first-time, mutant KRAS in corticotroph and somatotroph tumours were detected, and the variants showed low allele frequencies. In conclusion, we demonstrated that pituitary tumours might have mutant KRAS, and these data were not previously described probably due to lack of sensitivity of previous technologies. By identifying these variants, even at minimal levels, we open doors to a deeper understanding of the tumour microenvironment, clonal evolution and potential therapeutic targets.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e13484"},"PeriodicalIF":3.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854597","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}
Santiago Ronchetti, Florencia Labombarda, Julian Del Core, Paulina Roig, Alejandro F De Nicola, Luciana Pietranera
{"title":"The phytoestrogen genistein improves hippocampal neurogenesis and cognitive impairment and decreases neuroinflammation in an animal model of metabolic syndrome.","authors":"Santiago Ronchetti, Florencia Labombarda, Julian Del Core, Paulina Roig, Alejandro F De Nicola, Luciana Pietranera","doi":"10.1111/jne.13480","DOIUrl":"https://doi.org/10.1111/jne.13480","url":null,"abstract":"<p><p>Metabolic syndrome (MS) is the medical term for the combination of at least three of the following factors: obesity, hyperlipidemia, hyperglycemia, insulin resistance, and hypertension. The spontaneously hypertensive rat (SHR) is an accepted animal model for the study of human MS that reveals all the features of the syndrome when fed high-fat, high-carbohydrate diets. The intake of high-fat diets in rats has been shown to produce brain neuropathology. In humans, MS increases the risk of cognitive impairment, dementia, and Alzheimer's disease. Genistein (GEN) is a phytoestrogen found in soy that lacks feminizing and carcinogenic effects and was found to have neuroprotective and anti-inflammatory effects in many pathological conditions. Considering that multiple data support that natural phytoestrogens may be therapeutic options for CNS maladies, we aim to elucidate if these properties also apply to a rat model of MS. Thus, GEN effects on neuroinflammation, neurogenesis, and cognition were evaluated in SHR eating a fat/carbohydrate-enriched diet. To characterize the neuropathology and cognitive dysfunction of MS we fed SHR with a high-fat diet (4520 kcal/kg) along with a 20% sucrose solution to drink. MS rats displayed a significant increase in body weight, BMI and obesity indexes along with an increased in fasting glucose levels, glucose intolerance, high blood pressure, and high blood triglyceride levels. MS rats were injected with GEN during 2 weeks a dose of 10 mg/kg. We found that MS rats showed a decreased number of DCX+ neural progenitors in the dentate gyrus and treatment with GEN increased this parameter. Expression of GFAP was increased in the DG and CA1 areas of the hippocampus and treatment decreased astrogliosis in all of them. We measured the expression of IBA1+ microglia in the same regions and classified microglia according to their morphology: we found that MS rats presented an increased proportion of the hypertrophied phenotype and GEN produced a shift in microglial phenotypes toward a ramified type. Furthermore, colocalization of IBA1 with the proinflammatory marker TNFα showed increased proportion of proinflammatory microglia in MS and a reduction with GEN treatment. On the other hand, colocalization with the anti-inflammatory marker Arg1 showed that MS has decreased proportion of anti-inflammatory microglia and GEN treatment increased this parameter. Cognitive dysfunction was evaluated in rats with MS using a battery of behavioral tests that assessed hippocampus-dependent spatial and working memory, such as the novel object recognition test (NOR), the novel object location test (NOL), and the free-movement pattern Y-maze (FMP-YMAZE) and the d-YMAZE. In all of them, MS performed poorly and GEN was able to improve cognitive impairments. These results indicate that GEN was able to exert neuroprotective actions increasing neurogenesis and improving cognitive impairments while decreasing astrogliosis, microgliosis, and neuroin","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e13480"},"PeriodicalIF":3.3,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829081","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":"Daily and seasonal changes in steroidogenic markers in the hypothalamus and testes of tree sparrow (Passer montanus).","authors":"Subu Yatung, Amit Kumar Trivedi","doi":"10.1111/jne.13478","DOIUrl":"https://doi.org/10.1111/jne.13478","url":null,"abstract":"<p><p>The population responds to environmental variability largely determined by the dynamic interactions between fitness components within- and among-individual variation in the expression of the environmentally sensitive phenotype. The study was conducted on daily and seasonal changes in the expression of steroidogenic gene markers and corresponding seasonal changes in the physiological characters in adult male tree sparrows. Two experiments were performed. In experiment one, birds (n = 5/time points) were sampled during the breeding season at 6-time points, i.e., ZT1, ZT5, ZT9, ZT13, ZT17, and ZT21 [Zeitgeber time (ZT) 0 = sun rise time at the respective time of the year], and daily variation in expression of steroidogenic markers was observed in hypothalamus and testes tissues. In experiment two, birds (n = 5/month) were sampled every month at mid-day for a year. Body mass, bill color, testes size, and molt in feathers were recorded. The hypothalamus and testes tissues were used for gene expression studies. Blood plasma cholesterol and testosterone levels were measured. Higher testicular volumes were recorded from March to May, whereas maximum molt was observed during the post-breeding phase. Plasma cholesterol levels were highest before the breeding phase. Higher testosterone levels corresponded with the breeding phase. Higher expressions of thyroid-stimulating hormone subunit beta (tshβ), type 2 deiodinase (dio2), and gonadotropin-releasing hormone (gnrh) during the breeding phase and higher expression of type 3 deiodinase (dio3) and gonadotropin-inhibitory hormone (gnih) were observed during the non-breeding phase. The steroidogenic transcripts showed seasonal changes in their expression in the hypothalamic and testicular tissue and were upregulated either during the pre-breeding or breeding phase. The study reveals that mRNA levels of steroidogenic enzymes exhibit daily rhythmicity both in the hypothalamus and testis tissues. Further, steroidogenic transcripts show seasonal variations that correspond to the annual reproductive cycle of the tree sparrow (Passer montanus).</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e13478"},"PeriodicalIF":3.3,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813456","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}
Vikas Prasad, Anna Koumarianou, Timm Denecke, Anders Sundin, Christophe M Deroose, Marianne Pavel, Emanuel Christ, Angela Lamarca, Martyn Caplin, Justo P Castaño, Clarisse Dromain, Massimo Falconi, Simona Grozinsky-Glasberg, Johannes Hofland, Ulrich Peter Knigge, Beata Kos-Kudla, Balkundi A Krishna, Nicholas Simon Reed, Aldo Scarpa, Rajaventhan Srirajaskanthan, Christos Toumpanakis, Andreas Kjaer, Rodney J Hicks, Valentina Ambrosini
{"title":"Challenges in developing response evaluation criteria for peptide receptor radionuclide therapy: A consensus report from the European Neuroendocrine Tumor Society Advisory Board Meeting 2022 and the ENETS Theranostics Task Force.","authors":"Vikas Prasad, Anna Koumarianou, Timm Denecke, Anders Sundin, Christophe M Deroose, Marianne Pavel, Emanuel Christ, Angela Lamarca, Martyn Caplin, Justo P Castaño, Clarisse Dromain, Massimo Falconi, Simona Grozinsky-Glasberg, Johannes Hofland, Ulrich Peter Knigge, Beata Kos-Kudla, Balkundi A Krishna, Nicholas Simon Reed, Aldo Scarpa, Rajaventhan Srirajaskanthan, Christos Toumpanakis, Andreas Kjaer, Rodney J Hicks, Valentina Ambrosini","doi":"10.1111/jne.13479","DOIUrl":"https://doi.org/10.1111/jne.13479","url":null,"abstract":"<p><p>Assessing the response to systemic therapy in neuroendocrine tumors (NET) is challenging since morphological imaging response is often delayed and not necessarily reflective of clinical benefit. Peptide receptor radionuclide therapy (PRRT) has a complex mechanism of action, further complicating response assessment. In response to these challenges, the European Neuroendocrine Tumor Society (ENETS) Theranostics Task Force conducted a statement-based survey among experts to identify the current landscape and unmet needs in PRRT response assessment. The survey, presented at the 2022 ENETS Advisory Board (AB) meeting in Vienna, was completed by 70% of AB members, most of whom (81%) were from ENETS Centers of Excellence (CoE). It comprised a set of 13 questions with two substatements in three questions. Six (46%) of the statements achieved more than 75% agreement, while five (39%) additional statements reached over 60% consensus. Key points from the survey include: AB members agreed that lesions deemed equivocal on computed tomography (CT) or magnetic resonance imaging (MRI) should be characterized by somatostatin receptor (SST) positron emission tomography (PET)/CT before being designated as target lesions. It was agreed that interim response assessments should occur after the second or third PRRT cycle. Over half (54%) preferred using both conventional cross-sectional imaging (CT and/or MRI) and hybrid imaging (SST PET/CT) for this purpose. Almost all AB members supported further response assessment 3 months after the final PRRT cycle. A majority (62%) preferred using a combination of conventional cross-sectional imaging and SST PET/CT. For cases showing equivocal progression (ambiguous lesions or nontarget lesions) on CT and/or MRI, further confirmation using SST PET/CT was recommended. A significant majority (74%) preferred assessing pseudo-progression and delayed response by combining SST PET with diagnostic CT and/ or MRI. Though just below the 75% consensus threshold, there was substantial agreement on selecting target lesions based on SST PET/CT uptake intensity and homogeneity. Sixty-nine percent noted the importance of documenting and closely following heterogeneity in lesions in liver, lymph nodes, primary tumors, or other organs. As to the statement on parameters for new response criteria, AB members recommended exploring maximum standard unit value, tumor-to-background ratio, Hounsfield Unit (Choi Criteria), total tumor burden, and novel serum or molecular markers for future response evaluation criteria. Sixty-five percent supported the use of a single SST PET/CT for response assessment of NET lesions treated with PRRT. These findings highlight the importance of integrating advanced imaging techniques and recognizing the need for more nuanced criteria in assessing the efficacy of PRRT in NET patients. This approach aims to enhance the accuracy of treatment monitoring and improve patient outcomes.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e13479"},"PeriodicalIF":3.3,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801177","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":"From silence to song: Testosterone triggers extensive transcriptional changes in the female canary HVC.","authors":"Meng-Ching Ko, Carolina Frankl-Vilches, Antje Bakker, Nina Sohnius-Wilhelmi, Pepe Alcami, Manfred Gahr","doi":"10.1111/jne.13476","DOIUrl":"https://doi.org/10.1111/jne.13476","url":null,"abstract":"<p><p>Seasonal song production in canaries is influenced by gonadal hormones, but the molecular mechanisms underlying testosterone-induced song development in adult female canaries, which rarely sing naturally, remain poorly understood. We explored testosterone-induced song development in adult female canaries by comparing gene regulatory networks in the song-controlling brain area HVC at multiple time points (1 h to 14 days) post-treatment with those of placebo-treated controls. Females began vocalizing within 4 days of testosterone treatment, with song complexity and HVC volume increasing progressively over 2 weeks. Rapid transcriptional changes involving 2739 genes preceded song initiation. Over 2 weeks, 9913 genes-approximately 64% of the canary's protein-coding genome-were differentially expressed, with 98% being transiently regulated. These genes are linked to various biological functions, with early changes at the cellular level and later changes affecting the nervous system level after prolonged hormone exposure. Our findings suggest that testosterone-induced song development is accompanied by extensive and dynamic transcriptional changes in the HVC, implicating widespread neuronal involvement. These changes underpin the gradual emergence of singing behavior, providing insights into the neural basis of seasonal behavioral patterns.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e13476"},"PeriodicalIF":3.3,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794902","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":"Nomogram for predicting diabetes insipidus following endoscopic transsphenoidal surgery in pituitary adenomas.","authors":"Xinming Yu, Guangming Xu, Peng Qiu","doi":"10.1111/jne.13475","DOIUrl":"https://doi.org/10.1111/jne.13475","url":null,"abstract":"<p><p>Postoperative diabetes insipidus (DI) frequently complicates endoscopic transsphenoidal surgery (TSS) in pituitary adenoma (PA) patients, yet reliable predictive methods for DI risk remain lacking. This study aims to identify risk factors associated with DI following endoscopic transsphenoidal resection of PA and to develop a predictive nomogram for assessing postoperative DI risk. This study involved 600 PA patients underwent endoscopic TSS at Shandong Provincial Hospital from 2021 to 2023. Among these patients, 82 developed postoperative DI while 518 did not. The cohort was randomly divided into training (n = 360) and validation (n = 240) groups at 6:4 ratios by R software. Clinical parameters and radiographic features were evaluated using univariable and multivariable logistic regression to construct a predictive nomogram for post-endoscopic TSS DI risk. Model performance was assessed using ROC curves, calibration plots, and decision curve analysis. Subgroup analysis was used to evaluate the model's ability to discriminate between transient and permanent DI. Univariable and multivariable logistic regression analyses on the training group identified several independent risk factors for post-endoscopic TSS DI, including maximum tumor diameter, Knosp grade, Esposito grade, recurrent PA, and pituitary stalk deviation angle. A nomogram was developed based on these factors, demonstrating robust predictive accuracy with ROC areas under curve of 0.840 for the training group and 0.815 for the validation group. Calibration plots indicated excellent agreement between predicted and observed probabilities of postoperative DI. DCA curves highlighted the nomogram's efficacy in guiding clinical decision-making. Subgroup analysis showed that the model was able to discriminate between transient and permanent DI, and the AUC was 0.652 (95% CI 0.525-0.794). This study presents a nomogram designed to predict postoperative DI risk in patients undergoing endoscopic TSS for PA. Internal and external validations underscored the model's high accuracy, calibration, and clinical utility. Simultaneously, the model can also assess the development risk of permanent DI. This predictive tool offers clinicians valuable support in identifying high-risk DI patients, optimizing postoperative care strategies, and tailoring treatment plans to improve patient outcomes.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e13475"},"PeriodicalIF":3.3,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769849","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}
Yugo Watanabe, Lorryn Fisher, Rebecca E Campbell, Christine L Jasoni
{"title":"Developmental expression patterns of gonadal hormone receptors in arcuate kisspeptin and GABA neurons of the postnatal female mouse.","authors":"Yugo Watanabe, Lorryn Fisher, Rebecca E Campbell, Christine L Jasoni","doi":"10.1111/jne.13477","DOIUrl":"https://doi.org/10.1111/jne.13477","url":null,"abstract":"<p><p>The arcuate nucleus of the hypothalamus (ARC) is central in the neuronal regulation of fertility and reproduction through translating gonadal steroid hormone cues into the GnRH signaling pathway in the brain. Evidence suggests that circulating gonadal steroids play an important role in modulating female reproduction via kisspeptin and γ-aminobutyric acid (GABA) neurons in the ARC in both development and adulthood. However, the temporal onset of these ARC neurons' sensitivity to gonadal steroids is unknown. Using RNAscope® in situ hybridization, we localized androgen receptor (Ar), estrogen receptor alpha (Esr1), and progesterone receptor (Pgr) expression in ARC kisspeptin or GABA neurons of female mice at postnatal day (P)4, P8, P12, P20, and P60. A probe that binds to kiss1 mRNA or vGat mRNA was used to produce signal in kisspeptin or GABA neurons, respectively. In adult, we identified that the vast majority of kisspeptin neurons coexpressed Esr1 (95%) and Pgr (93%), while a smaller proportion coexpressed Ar (66%). Similar proportions of Ar- or Esr1-positive kisspeptin neurons were seen from P4, suggesting that kisspeptin neurons develop adult-like sensitivity to androgen and estrogen in early postnatal life. In contrast, the proportion of Pgr-positive kisspeptin cells in early life was significantly lower than in adulthood, suggesting that progesterone sensitivity develops over time in the ARC kisspeptin population. ARC GABA neurons also colocalized with Ar (70%), Esr1 (64%), or Pgr (85%) in adulthood. GABA neurons continuously expressed Esr1 or Pgr from the postnatal stages to adulthood, while the proportion of Ar-positive GABA neurons gradually increased from P4 (24%) to P20 (59%). These results suggest that while ARC GABA neurons can respond to circulating estrogen and progesterone from early postnatal ages, this same population may become more sensitive to androgens during later postnatal life. Our findings identified the expression patterns of Ar, Esr1, and Pgr by ARC kisspeptin and GABA neurons during early postnatal life. These data provide the understanding for the hormone sensitivity of these populations during early postnatal life, the critical time for the formation and regulation of female reproductive physiology.Esr1 (95%) and Pgr (93%), while a smaller proportion coexpressed Ar (66%). Similar proportions of Ar- or Esr1-positive kisspeptin neurons were seen from P4, suggesting that kisspeptin neurons develop adult-like sensitivity to androgen and estrogen in early postnatal life. In contrast, the proportion of Pgr-positive kisspeptin cells in early life was significantly lower than in adulthood, suggesting that progesterone sensitivity develops over time in the ARC kisspeptin population. ARC GABA neurons also colocalized with Ar (70%), Esr1 (64%), or Pgr (85%) in adulthood. GABA neurons continuously expressed Esr1 or Pgr from the postnatal stages to adulthood, while the proportion of Ar-positive GABA neurons gradually increas","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e13477"},"PeriodicalIF":3.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739797","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}