Search Results (207)

Background: Central precocious puberty (CPP), defined as the onset of secondary sexual characteristics before age 8 in girls, is increasingly prevalent worldwide. CPP is often caused by early activation of the HPG axis, leading to accelerated growth and bone maturation. However, the diagnostic accuracy of standard bone age (BA) methods remains uncertain in this context. Objective: To compare the diagnostic accuracy of the Greulich–Pyle atlas (GPA) and Tanner–Whitehouse 3 (TW3) methods in estimating skeletal age in girls with CPP and to assess the predictive value of serum hormone levels for estimating chronological age (CA). Methods: An observational, cross-sectional diagnostic study was conducted, involving n = 109 girls aged 6–12 years with confirmed CPP (Ethics Committee approval: CHUC_2023_86; 13 July 2023). Left posteroanterior hand–wrist (PA–HW) radiographs were assessed using the GPA and TW3 methods. Anthropometric measurements were recorded, and serum concentrations of estradiol, LH, FSH, DHEA-S, cortisol, TSH, and free T4 were obtained. Comparisons between CA and BA estimates were conducted using repeated-measures ANOVA, and ANCOVA was applied to examine the hormonal predictors of CA. Results: Both GPA and TW3 overestimated CA between 7 and 12 years, with the GPA showing larger deviations (up to 4.8 months). The TW3 method provided more accurate estimations, particularly at advanced pubertal stages. Estradiol (η²_p = 0.188–0.197), LH (η²_p = 0.061–0.068), and FSH (η²_p = 0.008–0.023) emerged as the strongest endocrine predictors of CA, significantly enhancing the explanatory power of both radiological methods. Conclusions: The TW3 method demonstrated superior diagnostic accuracy over GPA in girls with CPP, especially between 7 and 12 years. Integrating estradiol, LH, and FSH into BA assessment significantly improved the accuracy, supporting a more individualized and physiologically grounded diagnostic approach. Full article

Obstructive sleep apnea (OSA) is a prevalent disorder linked to metabolic complications such as diabetes and cardiovascular disease. By fragmenting normal sleep architecture, OSA perturbs the growth hormone/insulin-like growth factor (GH/IGF) axis and alters circulating levels of IGF-binding proteins (IGFBPs). A prior clinical observation of elevated IGFBP4 in OSA patients motivated the present investigation in a controlled animal model. Building on the previously reported protocol, OSA was induced in male C57BL/6 mice (9–12 weeks old) through intralingual injection of polytetrafluoroethylene (PTFE), producing tongue hypertrophy, intermittent airway obstruction, and hypoxemia. After 8–10 weeks, the study assessed (1) hypoxia biomarkers—including HIF-1α and VEGF expression—and (2) neurobehavioral outcomes in anxiety and cognition using the open-field and novel object recognition tests. PTFE-treated mice exhibited a significant increase in circulating IGFBP4 versus both baseline and control groups. Hepatic Igfbp4 mRNA was also upregulated. Behaviorally, PTFE mice displayed heightened anxiety-like behavior and impaired novel object recognition, paralleling cognitive deficits reported in human OSA. These findings validate the PTFE-induced model as a tool for studying OSA-related hypoxia and neurocognitive dysfunction, and they underscore IGFBP4 as a promising biomarker and potential mediator of OSA’s systemic effects. Full article

The available literature data indicate that obestatin, a peptide derived from the preproghrelin precursor, may modulate neuroendocrine function, particularly in appetite regulation and somatotrophic/gonadotrophic pathways. This review synthesizes animal studies assessing the influence of obestatin on central neuroendocrine systems. Obestatin has been shown to affect the hypothalamic appetite-regulating center through neuropeptides such as neuropeptide Y and agouti-related peptide, yet findings remain inconsistent between species. In rodents, its effects on food intake and energy balance are inconclusive, whereas sheep models demonstrate significant alterations in orexigenic gene expression and peptide immunoreactivity. Regarding the somatotrophic axis, obestatin showed no significant effect on growth hormone (GH) secretion in rodents; however, in sheep, it modulated growth hormone-releasing hormone and somatostatin mRNA expression, elevated pituitary GH synthesis, and increased circulating GH levels. Studies involving the gonadotrophic axis demonstrated the presence of obestatin in Leydig and pituitary cells, with in vitro evidence suggesting its ability to modulate intracellular pathways implicated in gonadoliberin, luteinizing hormone, and follicle-stimulating hormone release. The collective findings discussed in this article indicate that obestatin interacts with multiple hypothalamic–pituitary axes, though its effects vary depending on species and experimental conditions. This review highlights the complexity of obestatin’s central actions and the need for further research to elucidate its functional relevance in neuroendocrine regulation. Full article

Prenatal and postnatal skeletal muscle development in ruminants is coordinated by interactions between genetic, nutritional, epigenetic, and endocrine factors. This review focuses on the influence of maternal nutrition during gestation on fetal myogenesis, satellite cell dynamics, and myogenic regulatory factors expression, including MYF5, MYOD1, and MYOG. Studies in sheep and cattle indicate that nutrient restriction or overnutrition alters muscle fiber number, the cross-sectional area, and the transcriptional regulation of myogenic genes in offspring. Postnatally, muscle hypertrophy is primarily mediated by satellite cells, which are activated via PAX7, MYOD, and MYF5, and regulated through mechanisms such as CARM1-induced chromatin remodeling and miR-31-mediated mRNA expression. Hormonal signaling via the GH–IGF1 axis and thyroid hormones further modulate satellite cell proliferation and protein accretion. Genetic variants, such as myostatin mutations in Texel sheep and Belgian Blue cattle, enhance muscle mass but may compromise reproductive efficiency. Nutritional interventions, including the plane of nutrition, supplementation strategies, and environmental stressors such as heat and stocking density, significantly influence muscle fiber composition and carcass traits. This review provides a comprehensive overview of skeletal muscle programming in ruminants, tracing the developmental trajectory from progenitor cell differentiation to postnatal growth and maturation. These insights underscore the need for integrated approaches combining maternal diet optimization, molecular breeding, and precision livestock management to enhance muscle growth, meat quality, and production sustainability in ruminant systems. Full article

The thyroid gland plays a crucial role in regulating metabolism and supporting development through the production of the hormones T4 and T3. These hormones are essential during childhood for nervous system myelination, physical growth, puberty, skeletal and dental maturation, and overall metabolic balance. In early infancy, when the hypothalamic–pituitary–thyroid axis is still immature, thyroid dysfunction can result in a range of long-term complications. The metabolism and action of thyroid hormones depend not only on iodine but also on other vital micronutrients, particularly selenium (Se). This narrative review aims to comprehensively examine the role of selenium in maintaining thyroid health from fetal life through adolescence. Selenium is a key micronutrient involved in thyroid development, hormone synthesis, antioxidant defense, and immune regulation, especially during pregnancy and childhood. Inadequate selenium levels may contribute to the onset, progression, and clinical management of various thyroid disorders, particularly hypothyroidism and autoimmune thyroid diseases. Although scientific evidence supports selenium’s critical functions in hormone metabolism and antioxidant protection, public awareness and monitoring of selenium intake remain insufficient. Beyond the need for further research, there is an urgent call for integrated public health strategies, ranging from sustainable, food-based approaches to targeted clinical screening and educational programs. Promoting awareness of selenium’s importance and incorporating selenium status into maternal and pediatric care protocols could play a significant role in preventing deficiencies and supporting long-term endocrine and neurodevelopmental health. Full article

Background: Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by mutations in the DMD gene, leading to progressive muscle degeneration, loss of ambulation, and multi-systemic complications. Beyond its impact on mobility, DMD is associated with significant endocrine and metabolic dysfunctions that develop over time. Objective: To provide a comprehensive analysis of growth disturbances, endocrine dysfunctions, and metabolic complications in DMD including bone metabolism, considering the underlying mechanisms, clinical implications, and management strategies for daily clinical guidance. Methods: In this narrative review, an evaluation of the literature was conducted by searching the Medline database via the PubMed, Scopus, and Web of Science interfaces. Results: Growth retardation is a hallmark feature of DMD, with patients exhibiting significantly shorter stature compared to their healthy peers. This is exacerbated by long-term glucocorticoid therapy, which disrupts the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and delays puberty. Obesity prevalence follows a biphasic trend, with increased risk in early disease stages due to reduced mobility and corticosteroid use, followed by a decline in body mass index (BMI) in later stages due to muscle wasting. Metabolic complications, including insulin resistance, altered lipid metabolism, and hepatic steatosis, further characterize disease burden. Osteoporosis and increased fracture risk, primarily due to reduced mechanical loading and glucocorticoid-induced bone resorption, are major concerns, needing early screening and intervention. The RANK/RANKL/OPG signaling pathway has emerged as a critical factor in bone deterioration, providing potential therapeutic targets for improving skeletal health. Conclusions: Growth and endocrine disorders in DMD are complex and multifactorial, requiring proactive monitoring and early intervention. Addressing these issues requires a multidisciplinary approach integrating endocrine, nutritional, and bone health management. Further research is essential to refine treatment strategies that mitigate growth and metabolic disturbances while preserving overall patient well-being. Full article

Idiopathic short stature (ISS) represents one of the most frequent yet enigmatic conditions in pediatric endocrinology. Traditionally defined by auxological parameters in the absence of identifiable causes, ISS has long served as a diagnosis of exclusion. However, with the advent of next-generation sequencing, our understanding of the etiological landscape has significantly evolved. Recent studies have revealed that many children previously labeled as idiopathic actually harbor monogenic variants in genes related to the growth hormone–insulin-like growth factor axis, extracellular matrix components, or growth plate signaling pathways. This review integrates auxological assessment with current knowledge on molecular diagnostics to propose a more accurate and individualized approach to short stature. We examine emerging genotype–phenotype correlations, criteria for selecting candidates for genetic testing, and implications for recombinant human growth hormone therapy. Additionally, we advocate for a shift in clinical mindset: from a descriptive to a biologically grounded framework. ISS should be regarded as a transitional label pending further endocrine and genetic clarification. Recognizing this paradigm shift will improve diagnostic accuracy, personalize treatment strategies, and ultimately enhance care for children with growth failure in the genomic era. Full article

It is well established that different fasting strategies offer a range of benefits and may even serve as potential therapeutic approaches for metabolic diseases. The biological effects of intermittent fasting (IF) are multidimensional, involving the induction of metabolic switching from glucose to fatty acid and ketone utilization, thereby enhancing fat metabolism and improving glucose tolerance and insulin sensitivity. In addition, IF modulates the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis by lowering IGF-1 levels, a change associated with enhanced cellular protection, reduced tumorigenesis, and delayed aging. Moreover, IF modulates key signaling pathways, including mitogen-activated protein kinases, Notch, and nuclear factor kappa B, which collectively contribute to reduced oxidative stress, attenuated inflammation, and hepatoprotection. Although fasting may present certain challenges, it is essential to be adequately informed about its potential benefits and appropriate preparatory strategies before undertaking various fasting protocols. This review summarizes the current knowledge on various IF protocols and periodic short-term fasting (PSTF) lasting more than 24 h and up to 72 h, highlighting the signaling pathways through which these interventions affect metabolic processes. Additionally, it aims to provide a practical guide for the safe preparation for PSTF lasting more than 24 h and up to 72 h. Full article

Mini-puberty refers to the transient activation of the hypothalamic–pituitary–gonadal (HPG) axis during early infancy, lasting up to six months in boys and 12–24 months in girls. This phase represents the second activation of the HPG axis, following its initial activation during the second half of fetal life. At birth, the removal of the suppressive effect of placental estrogens on the HPG axis prompts a rise in both gonadotropins and sex steroid hormones, resulting in distinct clinical and laboratory markers of mini-puberty. While the clinical significance of mini-puberty remains partially understood, emerging evidence underscores its essential role in several aspects of human growth and development. In boys, testosterone influences penile growth, increases Sertoli cell numbers in the testes, and lays the foundation for future spermatogenesis. In girls, the increase in estradiol levels promotes follicular maturation and stimulates breast and uterine growth. Beyond the gonadal effects, mini-puberty appears to impact body composition, affecting body weight and promoting accelerated growth. Additionally, it may affect early psychosomatic and neural maturation, playing a role in several key aspects of the infantile brain. This narrative review examines recent findings on the physiology of the activation of the HPG axis before and after birth along with its significance in various aspects of human growth and development. In addition, mini-puberty-unique features in specific groups, such as preterm and small-for-gestational-age infants, are presented. Full article

As the most abundant fat-derived hormone, adiponectin plays an essential role in regulating energy homeostasis. Current evidence proposes the serum levels of adiponectin as a risk factor and a diagnostic/prognostic biomarker in cancer. Moreover, distinctive antineoplastic features have also been reported as a result of adiponectin supplementation in preclinical models. Mapping of the cancer-associated metabolic changes has elucidated a highly adaptable and interconnected system that allows malignant cells to sustain their growth and survival. Along with the pyruvate into acetyl-CoA conversion, downregulation of both lactate dehydrogenase and glycolysis-related genes depicts the main adiponectin-induced perturbations affecting glucose metabolism in cancer. Meanwhile, a multi-level approach involving lipid trafficking, catabolism, and de novo synthesis has been attributed to adiponectin in malignancies. The adiponectin receptor agonist AdipoRon has recently been recognized as a promising antineoplastic compound. Remarkably, AdipoRon-mediated changes in cancer metabolism occur together with its antiproliferative potential. This review aimed at recapitulating the modulatory effects of adiponectin, as well as those of its synthetic receptor agonists, in driving metabolic alterations in cancerous cells. A critical discussion is also conducted to deduce whether the adiponectin axis could serve as a putative target to address the metabolic reprogramming in cancer progression. Full article

Background/Objectives: Growth in childhood and adolescence is influenced by a complex interaction of genetic, environmental, and hormonal factors, with growth hormone (GH) and insulin-like growth factor 1 (IGF-1) playing crucial roles in linear growth and development. However, chronic inflammation, often detected in situations like inflammatory bowel disease and juvenile idiopathic arthritis, can significantly disrupt the GH/IGF-1 axis, causing a relevant growth impairment. Methods: We conducted a retrospective review focusing on the role of cytokines in the GH-IGF-1 axis and growth. Results: Inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 have been shown to contribute to GH resistance through an array of mechanisms that involve the downregulation of GH receptors and alterations in IGF-1 metabolism. This disruption negatively impacts the growth plate, particularly by impairing chondrocyte proliferation and differentiation, which are essential for proper bone elongation. This review delves into the intricate relationship among growth, chronic inflammation, and GH-IGF-1 axis, emphasizing the contribution of inflammatory cytokines in modulating GH signaling. It also highlights how cytokines can interfere with the molecular pathways that regulate skeletal growth, ultimately leading to growth disturbances in children suffering from chronic inflammatory diseases. Conclusions: The findings underscore the importance of controlling inflammation in affected individuals to mitigate its detrimental effects on growth and ensure that children may reach their growth full potential. Full article

This study systematically elucidates the regulatory mechanisms and potential therapeutic value of the exercise-induced hormone Irisin in the pathological progression of cardiac fibrosis. Through comprehensive analysis and multidimensional data integration, we constructed a complete regulatory network of Irisin within the cardiovascular system, spanning its secretion, signal transduction, and precise regulatory control. Our findings demonstrate that exercise intervention significantly elevates circulating Irisin levels via the skeletal muscle–peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)–fibronectin type III domain-containing protein 5 (FNDC5) signaling axis. Irisin establishes a multidimensional molecular barrier against cardiac fibrosis by targeting Sirtuin 1 (Sirt1) activation, inhibiting the transforming growth factor-beta (TGF-β)/Smad3 signaling pathway, and modulating the transcriptional activity of the mitochondrial biogenesis core factors PGC-1α and nuclear respiratory factor 1 (NRF-1). Moreover, the dual regulatory mechanism of the exercise–skeletal muscle–heart axis not only effectively suppresses the aberrant activation of cardiac fibroblasts but also significantly reduces collagen deposition, oxidative stress, and inflammatory infiltration by restoring mitochondrial dynamics balance. Taken together, this study reveals a novel exercise-mediated cardioprotective mechanism at the molecular interaction network level, thereby providing a theoretical basis for the development of non-pharmacological bio-intervention strategies targeting the Irisin signaling pathway and laying a translational foundation for precise exercise prescriptions in cardiovascular diseases. Full article

Background: Multiple genes can disrupt hypothalamic–pituitary axis development, causing multiple pituitary hormone deficiencies (MPHD). Despite advances in next-generation sequencing (NGS) identifying over 30 key genes, 85% of cases remain unsolved, indicating complex genotype–phenotype correlations and variable inheritance patterns. Objective: This study aimed to identify the MPHD genetics in three probands from two unrelated families. Methods: Family A had one affected child, while Family B had two affected siblings. All probands exhibited poor growth since birth, and family B’s probands were born small for gestational age. Growth hormone deficiency was confirmed in all subjects. Family B’s probands responded poorly to growth hormone treatment compared to the first patient. Furthermore, Family A’s proband and Family B’s younger sibling developed central hypothyroidism, while Family B’s older sibling presented hypogonadotropic hypogonadism. Brain magnetic resonance imaging (MRI) revealed pituitary hypoplasia, ectopic posterior pituitary gland, and small sella turcica in all probands. Patients and their available relatives underwent NGS. Results: NGS identified the same novel and likely pathogenic LHX4 variant (c.481C>G) in all probands despite the families being unrelated. Additionally, Family A’s proband carried a GLI2 variant (c.2105C>A), and Family B’s probands carried an IGF1R variant (c.166G>A), both interpreted as being of uncertain significance. Conclusions: This study confirms that heterozygous pathogenic variants of LHX4 can cause MPHD associated with a specific neuroradiological triad of abnormalities despite incomplete penetrance and variable phenotype. Moreover, the co-occurrence of the other two gene variants was debated. The IGF1R variant could explain the unusually poor response to growth hormone therapy in Family B, suggesting an oligogenic mechanism underlying the phenotype. Full article

Background/Objectives: The hog deer (Axis porcinus) is an endangered species facing significant threats from habitat loss and fragmentation, with only captive populations remaining in China. Expanding breeding programs and restoring wild populations are critical strategies for the species’ conservation. Achieving this requires the development of an effective health database and the identification of molecular biomarkers for their physiological traits. Methods: In this study, we present the largest blood metabolomics dataset to date for captive hog deer, comprising 73 healthy individuals. We conducted targeted metabolomics to quantify blood hormone levels and untargeted metabolomics to characterize blood metabolic profiles, aiming to evaluate the associations of sex, age, and weight with metabolic profiles. Results: Our results reveal distinct growth patterns between females and males, with males reaching their body weight plateau at a larger size. We observed significant sex differences (p < 0.05) in blood hormones and metabolic profiles. Females exhibited higher levels of progesterone, hydroxyprogesterone, stress hormones (e.g., cortisol), and proline, while males had higher levels of testosterone, uric acid, phenylalanine, and guanidinosuccinic acid. Notably, body weight emerged as a more important factor than gender in explaining variations in the metabolome, particularly in males. Several blood biomarkers were identified as correlating with age and body weight. Specifically, blood progesterone levels in females were linked to both age and body weight, while in males, uric acid, prolylhydroxyproline, and 3-methylhistidine were associated with these factors. The potential significance of these results for the artificial breeding and conservation of hog deer were discussed. Conclusions: Our study provides a metabolic reference for identifying abnormal individuals and offers potential biomarkers for determining the gender, age, and body weight of hog deer. These findings may have significant implications for the artificial breeding and conservation efforts of the species. Full article

Chronic stress poses threats to the physical and psychological well-being of dogs. Resveratrol (Res) is a polyphenol with antidepressant properties and has rarely been studied in dogs. This study aimed to investigate the stress-relieving effects and underlying mechanism of Res in dogs. Dogs were fed a basal diet supplemented with Res for 35 days. The fecal microbiota of the dogs was cultured with Res in vitro. The results show that Res improved the stress-related behaviors and increased the serum levels of 5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF), immunoglobulin A, and antioxidant capacity in dogs. Res downregulated the hormones of the hypothalamic–pituitary–adrenal axis. The abundance of butyric-producing bacteria, like Blautia, increased, while the growth of Fusobacterium related to gut inflammation was inhibited in the Res group. A higher content of fecal butyric acid was observed in the Res group. The metabolome indicated that Res increased the fecal and serum levels of tryptophan (Trp) and decreased the consumption of Trp by microorganisms. A chronic unpredictable mild stress mouse model was established, and Res was administered for 35 days. The results show that Res ameliorated the stress-related behavior and increased the levels of Trp and 5-HT in the whole brains of mice. The relative mRNA expression of genes associated with the tight junction protein, aryl hydrocarbon receptor, and Trp transporters in the colon were upregulated. In conclusion, Res could ameliorate canine stress by increasing 5-HT, BDNF, and the antioxidant capacity and improving the immune function and stress response, which was attributed to the role of Res in the restructuring of gut microbiota and the modulation of tryptophan metabolism. Full article