Journal of Neuroendocrinology最新文献

Dyslipidemia is a potential unfavorable prognostic factor in neuroendocrine tumors (NETs); conversely, statins proved to have antiproliferative effects in NET cell lines and could be a helpful therapeutic strategy for these patients. The main objective of this observational cohort retrospective study is to explore the associations between dyslipidemia and NET progression and evaluate the potential influence of statins in this context. 393 patients with histologically confirmed gastroenteropancreatic or bronchopulmonary NETs from six Italian centres didicated to NET diagnosis and therapy were included. The cohort included 123 patients with dyslipidemia, 81 of which were taking statins. Clinicopathological data, including patient demographics, tumor characteristics, and treatment details as well as the prevalence, timing of dyslipidemia and hypolipemic therapy were collected. The main outcome measure used is progression-free survival (PFS). Among the 393 patients, 123 (31.3%) had dyslipidemia. Statins were used by 81 (65.8%) dyslipidemic patients, mostly atorvastatin. Median PFS was 87 months overall, 124 months in non-dyslipidemic patients, and 72 months in dyslipidemic patients (p = .268). Dyslipidemic patients on statins had a significantly better median PFS (108 months) than those not on statins (26 months; p = .024). Recurrence-free survival (RFS) was also evaluated, but no significant differences were found. In conclusion, while PFS was lower in dyslipidemic patients compared to non-dyslipidemic patients, the difference was not statistically significant. Statin therapy was associated with improved PFS among dyslipidemic patients, suggesting a potential antiproliferative effect of statins in NETs. These findings warrant further investigation to substantiate the role of statins in the management of NETs.

Poultry production is confronting real challenges, including a lofty projected high demand for animal proteins to feed the future, and the need to adapt to planetary boundaries (global warming) with limited natural resources (land, energy, water). Among the most challenging stressors to poultry production sustainability are heat stress (HS) and water uncertainty, that need extensive fundamental and applied research to identify effective strategies. In that regard, our group has recently developed a high-water-efficient broiler (meat-type) chicken line using water conversion ratio (WCR) as a phenotypic trait and defined the hypothalamic molecular mechanisms controlling drinking water under heat stress conditions. In response to the invitation from the Organizing Committee of the 13th International Symposium on Avian Endocrinology (ISAE 2024), the present review summarizes these data and closes the chapter by asking questions for future investigations. Data showed that HS exposure increased core body temperature (CBT) of both lines, with higher degree in HWE than in LWE counterparts. Despite this increase in CBT, HWE line drank less water but had superior performance with better feed conversion ratio (FCR) and WCR than LWE line. Molecular analyses showed that hypothalamic drinking-related neuropeptides (arginine vasopressin system, aquaporin system, renin, and angiotensin system) are affected in line- and/or environmental-dependent manner. Together, our research outcome indicates that the divergent selection for water efficiency could be an effective strategy to preserve water while maintaining optimal growth performance and could be applied to other poultry species and livestock.

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.

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.

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.

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.

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).

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.

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.