Journal of Neuroendocrinology最新文献

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.

The prevalence of gastric NEN is estimated worldwide at 8.9% of all gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) and only 0.3%-1% of all gastric neoplasms, but is rising in the last decades. The aim of this project was to map the epidemiology of gastric neuroendocrine neoplasm (gNEN) in Belgium. This is a population-wide retrospective cohort study over 10 years (2010-2019), based on data from the Belgian Cancer Registry. A total of 641 patients were included; 605 patients with gNEN and 36 with MiNEN. The AAIR of gNEN was 0.67 per 100,000 person-years, increasing over the years and with a slight female predominance (55.4%). Neuroendocrine carcinoma (NEC) accounted for 15.7% (N = 95), with an AAIR of 0.11 per 100,000 person-years. The other 510 patients were diagnosed with gNET: G1 NET was most prevalent (54.3%) followed by G2 (32.5%) and G3 NET (3.5%). Concerning the clinical classification (type) of gNET, a diagnosis of type 1 tumors was presumed in 67.6%, type 3 tumors in 17.1% and type 2 tumors in 0.6% of patients. In only 3.8% of patients, the clinical classification was explicitly stated in the pathology report. Stage IV tumors were diagnosed in 13.4% (N = 81). A favorable evolution in pathology reporting is seen. Some variables-for example, clinical classification of gNET-were heavily underreported, stressing the importance of registries integrating clinical and pathological information.

There are over 1000 varieties of steroids that have been reported in nature, including the endogenous sex steroid hormones (i.e., progesterone, testosterone, and 17β-estradiol) and corticosteroids which are mainly synthesized by gonads and adrenals, respectively. In addition, an extra-glandular steroidogenesis has been also reported in the brain and in the gastrointestinal tract (GIT). The reason why intestinal steroidogenesis and consequently gut steroids draw our attention is for the communication and interaction with the gut microbiota, which functions like a virtual endocrine organ, and it is also involved in the steroid production. Moreover, both GIT and gut microbiota communicate through neural, endocrine, and humoral ways with the brain, in the so-called gut-microbiota-brain axis. On this basis, in this review, we will discuss several aspects such as (1) intestinal steroidogenesis and its possible regulation, (2) the potential role of gut steroids in physiopathological conditions, and (3) the role of microbiome in steroidogenesis and steroid metabolism. Overall, this review highlights new points of view considering steroid molecules as potential therapeutic approach for gastrointestinal disorders and brain comorbidities.

Somatostatin receptor (SST) positron emission tomography with computed tomography (PET/CT) is the gold standard for functional imaging of neuroendocrine tumors (NETs), but FDG PET/CT is increasingly recognized for its prognostic value, particularly for higher-grade NETs and to detect disease heterogeneity. Despite the established role of pathological grading, clinical heterogeneity within the tumor burden often complicates accurate prognostication. Evidence suggests FDG PET/CT can outperform WHO grading in predicting outcomes by identifying aggressive, undifferentiated tumor clones that influence long-term prognosis and treatment decisions. Several grading systems integrating both SST and FDG PET/CT have been proposed to better capture tumor heterogeneity and guide clinical management. Studies demonstrate that FDG PET/CT can influence management in a significant subset of patients, although variably reported. Its use remains variable across centers, also affected by different reimbursement policies and local clinical practices. This review explores the indications to FDG PET/CT in NET and the clinical impact of combined SST and FDG PET/CT imaging.