Search Results (31)

Professional soccer imposes substantial physiological demands eliciting complex neuroendocrine responses. This review synthesizes evidence on hormonal adaptations in professional soccer players, with emphasis on ethnic and national differences and underlying pathophysiological mechanisms. We analyzed 21 key studies investigating testosterone, cortisol, the testosterone-to-cortisol (T:C) ratio, growth hormone (GH), and insulin-like growth factor-1 (IGF-1) responses to training and competition. Acute cortisol elevations that may persist for up to 72 h post-match in some professional populations and T:C ratio reductions following congested fixture periods are reported across available studies, while somatotropic responses vary considerably across studies. Preliminary evidence suggests that ethnic and geographic background may influence circulating testosterone and urinary steroid excretion profiles, with UGT2B17 genetic polymorphisms identified as one contributing factor; however, the evidence base is limited and requires replication. Approximately 7.4% of elite junior cohorts—though not necessarily professional adult populations—develop non-functional overreaching (NFOR), characterized by blunted GH and ACTH responses. Pathophysiological mechanisms involve hypothalamic–pituitary––adrenal (HPA) and hypothalamic–pituitary–gonadal (HPG) axis dysregulation producing anabolic–catabolic imbalance. Individualized, longitudinal T:C monitoring and post-match load moderation may be warranted; future research should establish ethnicity-specific normative values and investigate links between hormonal dysregulation and injury risk. Full article

Shearing is a stressful procedure for sheep, combining isolation, restraint, and the mechanical action of shearing, which activates the hypothalamic–pituitary–adrenal axis and induces oxidative stress. This study investigated whether melatonin—a pleiotropic hormone with well-documented antioxidant properties—administration could modulate the stress response and oxidative stress in Sarda sheep during shearing. Forty lactating ewes (aged 3–5 years, mean body weight 41 ± 1.1 kg) were randomly assigned to four groups (n = 10 each): two groups received a subcutaneous melatonin implant (18 mg); two remained untreated as controls. Within each category, one group was shorn and the other subjected only to restraint. Blood samples were collected before, during, and after shearing to measure cortisol, glucose, reactive oxygen metabolites (ROMs), biological antioxidant potential (BAP), and oxidative stress index (OSI). Procedures elevated cortisol, glucose, ROMs, and OSI in all groups, but melatonin treatment significantly reduced these parameters and increased BAP relative to untreated animals at all sampling points (p < 0.05). No significant differences were observed between shorn and unshorn animals within the same treatment, suggesting that the handling, restraint, and isolation associated with the shearing procedure represent the major sources of stress, rather than the mechanical act of shearing itself. In conclusion, melatonin administration blunts the stress response and reduces oxidative stress in sheep during routine shearing-related handling procedures, suggesting its potential as a practical tool to improve animal welfare during routine management practices. Full article

Background/Objectives: A blunted growth hormone (GH) response in stimulation tests (GHSTs) in obese patients is well documented, with less evidence for insulin-like growth factor-1 (IGF-1) concentrations. The aim of this study was to assess the relationships between nutritional status, GH peak in GHST, and IGF-1 concentrations, and to develop machine learning prediction models of GH deficiency (GHD) in children with short stature. Methods: A case–control study included 1592 children with short stature, whose height, weight, body mass index (BMI), GH peak in two GHSTs, IGF-1 concentration and bone age (BA) were assessed. The cut-off of GH peak in two GHSTs between GHD and idiopathic short stature (ISS) was 10.0 µg/L; additionally, a lower cut-off of 7.0 µg/L was used in repeated analysis. Univariate statistical analyses and classification models were used to identify variables related to the normal and subnormal results of GHST. Results: Depending on the cut-off of GH peak (10.0 vs. 7.0 µg/L), GHD was diagnosed in 604 vs. 279 patients (37.9% vs. 17.5%). Children with GHD had significantly lower (p < 0.001) BMI SDS and IGF-1 SDS than ones with ISS for both cut-offs of GH peak. Overnutrition was associated with the lowest GH peak but the highest IGF-1 SDS; the opposite results were observed in undernutrition. A decision tree predicted GHD in 156 patients, in 149 based on BMI SDS > 0.91. A Naïve Bayes classifier predicted GHD in 118 cases, with BMI SDS and IGF-1 SDS being the only significant variables. The best multilayer perceptron (MLP) neural network predicted GHD in 310 patients, while a logistic regression model did so in 269 patients. Conclusions: Interpretation of GHST should include the patient’s nutritional status in order to avoid overdiagnosis of GHD in overweight and obese children. Full article

Porcine epidemic diarrhea virus (PEDV) causes acute diarrhea, dehydration and death in piglets, resulting in significant economic losses in the pig industry. It is crucial to identify the pathogenesis and mechanism between host–PEDV interactions. In our study, we performed transcriptomic and metabolomic analyses in PEDV-infected Large White (LW) pigs. PEDV infection caused blunted and fused intestinal villi, necrosis of the intestinal mucosal epithelial cells and atrophy of intestinal glands. Transcriptomic and metabolomic analyses revealed 692 differentially expressed genes and 1485 differential metabolites, respectively. Among them, differentially expressed genes were enriched in virion assembly, lipoprotein metabolic process and PPAR signaling pathway. Differential metabolites were enriched in primary bile acid biosynthesis and lipoic acid metabolism. An integrated analysis of the transcriptome and metabolome revealed that differentially expressed genes and metabolites were co-enriched in steroid hormone biosynthesis and bile secretion. In addition, key metabolites Dehydroepiandrosterone (DHEA) and Estriol in steroid hormone biosynthesis both inhibited PEDV infection and alleviated the excessive inflammatory response in vitro. Collectively, our study constructed a multi-omics landscape of PEDV infection in LW pigs, providing potential targets for developing metabolic-targeted antiviral interventions. Full article

Background/Objectives: Insulin and glucagon are key hormones in metabolic regulation. There are limited comparative data on how common rodent anesthetic regimens influence hormone secretion, leading to misinterpretation of results. We aimed to compare the effects of several anesthetic regimens on insulin and glucagon secretion using the physiologically relevant isolated perfused rat pancreas model. Methods: Six commonly used rodent anesthetic regimens were assessed for their ability to induce surgical depth of anesthesia. Once achieved, the pancreas was vascularly isolated and perfused. After euthanasia, the pancreas was stimulated with glucose and glucagon-like peptide-1 (GLP-1). Insulin and glucagon were measured in the effluent using radioimmunoassay. Results: Anesthesia with Hypnorm^® (fentanyl/fluanisone)/midazolam produced the most physiological responses, meaning that insulin was secreted in response to hyperglycemia and GLP-1, and glucagon was secreted under hypoglycemia. Ketamine/dexmedetomidine anesthesia abolished insulin dynamic secretion and blunted glucagon secretion. Isoflurane/buprenorphine anesthesia partially suppressed insulin secretion, but it still followed a physiological pattern in response to glucose fluctuations. However, it abolished the dynamic glucagon responses to glucose. Three additional anesthetic regimens failed to produce surgical depth anesthesia and were therefore not further analyzed. Conclusions: Different anesthetic regimens altered pancreatic hormone secretion. Fentanyl/fluanisone/midazolam was associated with dynamic insulin and glucagon secretion, whereas ketamine/dexmedetomidine and isoflurane/buprenorphine altered the pattern and/or magnitude of hormone secretion. Overall, the choice of anesthesia is a critical variable in animal experimentation for metabolic studies and may confound the interpretation of results. Full article

Ghrelin is a regulator of appetite and growth hormone secretion, rising during fasting and decreasing after food intake. Children born small for gestational age (SGA) who undergo postnatal catch-up growth are at increased risk of obesity and metabolic disturbances, which may be related to impaired ghrelin regulation. This study assessed fasting and post-glucose ghrelin responses during an oral glucose tolerance test (OGTT) in prepubertal SGA children in relation to obesity and metabolic syndrome components. Ninety-eight children aged 5–9 years were included. Anthropometry, blood pressure, fasting lipids, glucose, insulin, and ghrelin were measured; BMI SDS and HOMA-IR were calculated. Ghrelin concentrations were assessed at baseline and 120 min after glucose ingestion. Ghrelin levels declined significantly during OGTT. Obese SGA children showed lower fasting and post-load ghrelin levels and a smaller decline compared with non-obese peers. Fasting and post-load ghrelin correlated inversely with BMI SDS, waist circumference, and insulin levels. In regression analyses, fasting ghrelin and its suppression were independently associated with HOMA-IR, whereas post-load ghrelin was determined by post-load insulin. These findings indicate that ghrelin dynamics in SGA children are more closely related to insulin sensitivity than adiposity and are blunted in the presence of obesity. Full article

Thermoregulatory dysfunction is a major pathophysiological consequence of aging, affecting many elderly individuals. Growth hormone secretagogue receptor (GHSR) regulates energy homeostasis and immune function. We previously showed that global GHSR deletion improves thermogenic adaptation of brown adipose tissue (BAT) in aging, but the responsible cell type remained unclear. GHSR is expressed in macrophages, and its expression in macrophages increases with aging. Here, we studied myeloid-specific Ghsr-deleted male mice (LysM-Cre; Ghsr^f/f denoted as “KO”) to assess their metabolic and immune responses to cold stress at young and old ages. Old mice showed impaired thermogenesis, marked by reduced core body temperature under 4 °C cold exposure, a blunted cold-induced increase in glucose levels, reduced BAT mass, and increased infiltration of pro-inflammatory CD38⁺ macrophages in BAT. In contrast, KO mice exhibited enhanced cold tolerance in both young and old mice. Notably, aged KO mice showed preserved BAT mass and a pronounced shift in resident macrophages toward an anti-inflammatory state. Consistently, aged KO mice showed reduced pro-inflammatory markers (Ccl2, Nos2) and increased expression of the thermogenic gene Ppargc1a and UCP1 protein under cold exposure. Together, these findings demonstrate that macrophage GHSR drives age-associated pro-inflammatory remodeling of BAT, and that its deletion promotes an immune environment favorable for thermogenic activation. Thus, targeting macrophage GHSR may offer a new therapeutic strategy to restore thermogenesis and enhance thermal resilience in aging. Full article

Background: Mini-puberty is a transient but critical postnatal activation of the hypothalamic–pituitary–gonadal axis, essential for male gonadal maturation, penile and testicular growth, and future reproductive potential: this physiological hormonal surge is absent or blunted in congenital hypogonadotropic hypogonadism (CHH), often manifesting as micropenis, cryptorchidism, and impaired Sertoli cell proliferation. Objective: The aim of this review is to summarize current evidence on the impact of early gonadotropin therapy in male infants with CHH. Methods: We conducted a comprehensive literature review using PubMed, including studies reporting on male infants with confirmed or suspected CHH receiving gonadotropin therapy. Keywords included “mini-puberty and hypogonadism”, “gonadotropins and infancy,” and “gonadotropin therapy in CHH.” Eligible studies reported biochemical outcomes (luteinizing hormone, follicle-stimulating hormone, testosterone, inhibin B, anti-Müllerian hormone) and clinical measures (penile length, testicular volume, testicular descent). Data extraction focused on endocrine responses, genital growth, and safety. Results: Twelve studies including 95 infants were analyzed. Early gonadotropin therapy effectively restored postnatal hormonal levels, with consistent increases in testosterone, inhibin B, and anti-Müllerian hormone. Clinically, treatment induced significant penile growth, increased testicular volume and partial or complete testicular descent in the majority of cases. Both continuous infusion and intermittent injection regimens were effective, though hormone kinetics and growth responses varied. No serious adverse events were reported, and therapy was generally well tolerated. Conclusions: Early gonadotropin therapy during mini-puberty represents a safe and effective intervention to replicate the physiological postnatal hormonal surge in male infants with CHH. Prospective longitudinal studies are warranted to evaluate sustained effects on puberty, fertility, and adult reproductive function. Full article

Background/Objectives: Growth hormone (GH) secretion and activity are closely modulated by sex steroids, particularly during puberty, when GH response to stimulation tests (GHSTs) may be blunted in children with low circulating sex steroids. This systematic review evaluates the role of sex steroid priming in enhancing GH secretion during GHST and improving diagnostic accuracy especially in peripubertal children with GH deficiency (GHD). Methods: We conducted a medical literature review to assess the use of sex steroid priming in children undergoing GHST; our search was carried out via PubMed after paper selection based on strict eligibility criteria. Results: Seventeen studies published between 1969 and 2022 were analyzed overall, which corresponded to a total number of 1097 participants. Most studies reported a significant increase in GH peak levels after priming, reducing false-positive GHD diagnoses. However, protocols varied considerably in hormone type, dosage, and administration, and some studies showed no benefit in the case of a true GHD. Conclusions: While sex steroid priming appears to improve GHST specificity in GHD without negatively impacting growth outcomes, standardized guidelines about pre-administration of exogenous sex steroids are currently lacking, and further prospective studies are needed to define its diagnostic potential. Full article

Background: Low-glycemic index (GI) carbohydrates like isomaltulose (ISO) are known to enhance incretin release and to improve postprandial glucose control at the following meal (an effect known as second meal effect, or SME), which is particularly beneficial for individuals with metabolic syndrome (MetS). This study aimed to assess the most effective preprandial interval of ISO- or saccharose (SUC) snacks (1 h vs. 3 h preload) to enhance prandial incretin responses to a subsequent meal. Methods: In a randomized crossover design, 15 participants with MetS completed four experimental conditions on four non-consecutive days, combining two preload types (ISO or SUC) and two preload timings (Intervention A: 3 h preload; Intervention B: 1 h preload). Specifically, the four conditions were (1) ISO + Intervention A, (2) SUC + Intervention A, (3) ISO + Intervention B, and (4) SUC + Intervention B. The order of conditions was randomized and separated by a 3–7-day washout period to minimize carryover effects. On each study day, participants consumed two mixed meal tests (MMT-1 and MMT-2) with a standardized preload (50 g ISO or SUC) administered either 3 h or 1 h prior to MMT-2. Blood samples were collected over 9 h at 15 predefined time points for analysis of glucose, insulin, C-peptide, and incretin hormones (GLP-1, GIP, and PYY). Results: The unique digestion profile of ISO resulted in a blunted glucose ascent rate (ΔG/Δt: 0.28 vs. 0.53 mmol/L/min for SUC, p < 0.01), paralleled by synonyms PYY elevation over 540 min monitoring, compared with SUC. ISO also led to higher and more sustained GLP-1 and PYY levels, while SUC induced a stronger GIP response. Notably, the timing of ISO consumption significantly influenced PYY secretion, with the 3 h preload showing enhanced PYY responses and a more favorable SME compared to the 1 h preload. Conclusions: ISO, particularly when consumed 3 h before a meal (vs. 1 h), offers significant advantages over SUC by elevating PYY levels, blunting the glucose ascent rate, and sustaining GLP-1 release. This synergy enhances the second meal effect, suggesting ISO’s potential for managing postprandial glycemic excursions in MetS. Full article

Obesity is a multifactorial condition that influences metabolic, endocrine, inflammatory, circadian, and behavioral systems. These disruptions can adversely affect the initiation of lactogenesis II—the critical process marking the onset of copious milk secretion following childbirth. In mothers with obesity, prolonged inflammation within the mammary gland, a blunted hormonal response (notably of prolactin), altered progesterone and estrogen dynamics, high leptin levels, and misaligned circadian rhythms contribute significantly to delayed lactogenesis. In addition, mechanical difficulties and psychological factors further hinder effective breastfeeding. This report synthesizes evidence from human epidemiological studies and animal models that elucidate the diverse mechanisms linking maternal obesity to delayed lactogenesis. We review the role of obesity-associated inflammatory mediators in impairing mammary tissue remodeling, the endocrine aberrations that impair lactogenic signaling, the consequences of circadian disruption on hormonal rhythmicity, and the behavioral influences that challenge effective breastfeeding. Finally, we discuss the clinical implications of these findings and propose future research directions targeting endocrine modulation, anti-inflammatory therapy, circadian interventions, and enhanced lactation support strategies for mothers with obesity. Full article

Background: The long-term effects of a perinatal high-fat diet on the cardiovascular function of offspring are not well elucidated. We hypothesize that perinatal exposure to a high-fat diet alters adult cardiovascular and immune responses in a sex-specific manner. Methods: Male and female offspring were born to perinatal high-fat (pHFD) or control diet (pCD)-fed C57BL/6 mothers and weaned to a control diet. Cardiovascular function (baseline and response to an acute isoproterenol stress test) was quantified at 8 weeks of age, and acute blood inflammatory response to a single low dose of lipopolysaccharide at 9 weeks of age. Results: Male pHFD offspring had identical baseline cardiovascular function compared to pCD mice but a blunted response to isoproterenol (20–45% reductions in cardiac output, stroke volume, and left ventricular fractional shortening). In contrast, baseline cardiovascular parameters were reduced in female pHFD compared to pCD offspring, but there was no effect of perinatal diet on response to isoproterenol. Concentrations of TNF-α and IL-6 in plasma two hours after a low-dose LPS administration were highest in female pCD mice. Conclusions: Perinatal high-fat diet exposure resulted in sex-specific adaptations in cardiovascular function and immune response. Female offspring displayed baseline impairments, whereas male offspring showed latent vulnerability under stress. These differences may reflect underlying hormonal or epigenetic mechanisms that diverge by sex. Future studies should examine the roles of sex hormones and gene regulation pathways to better understand these dimorphic outcomes. These findings emphasize the importance of maternal diet in shaping offspring cardiometabolic risks and highlight potential avenues for nutritional interventions during pregnancy. Full article

Introduction: Traumatic brain injuries (TBIs) are conditions affecting brain function caused by blunt or penetrating forces to the head. Symptoms may include confusion, impaired consciousness, coma, seizures, and focal or sensory neurological motor injuries. Objective: This study evaluated sex hormone profiles and their predictive role in returning consciousness after severe traumatic brain injury. Materials and Methods: We included 120 patients with TBIs and collected comprehensive information about each patient, including the cause of the trauma, age, gender, Glasgow Coma Scale (GCS) score, Injury Severity Score (ISS), and neuroradiological imaging data. The ISS was used to assess the severity of the trauma. At the same time, the lowest GCS score was recorded either before sedation and intubation in the emergency room or by emergency medical services personnel. For female participants, samples were collected during the luteal phase of the menstrual cycle (days 18 to 23). Results: The mean age of male patients was 33.40 years, ranging from 23 to 45 years, while female patients had an average age of 34.25 years, ranging from 25 to 48 years. The primary cause of injury for both genders was motor vehicle accidents. In male patients, testosterone levels were significantly higher in those classified as responsive (RC) compared to those non-responsive (NRC), with levels of 2.56 ± 0.47 ng/mL versus 0.81 ± 0.41 ng/mL (p = 0.003). A cut-off point of 1.885 ng/mL for testosterone levels in males was established, achieving a sensitivity and specificity of 86.7% and 86.7%, respectively. In female patients, progesterone levels were elevated in those who regained consciousness, measuring 1.80 ± 0.31 ng/mL compared to 0.62 ± 0.31 ng/mL (p = 0.012). A cut-off point of 1.335 ng/mL for progesterone levels in females was determined, with a sensitivity and specificity of 93.3% and 86.7%, respectively. Conclusions: We can conclude that sex hormone levels in the acute phase of TBIs can vary between males and females. Notably, serum testosterone levels in males and progesterone levels in females with TBIs are significant prognostic factors for assessing the likelihood of regaining consciousness after such injuries. These findings underscore the importance of considering sex hormone profiles in TBI recovery prognosis. Full article

GLP-1 is a gastro-intestinal hormone acting within the gut/brain axis for energy balance regulation. We aimed to evaluate the role of the vagus nerve in whole-body energy homeostasis and in mediating GLP-1 effects. For this, rats submitted to truncal vagotomy and sham-operated controls underwent a comprehensive evaluation, including eating behavior, body weight, percentage of white (WAT) and brown adipose tissue (BAT), resting energy expenditure (REE) and acute response to GLP-1. Truncal vagotomized rats had significantly lower food intake, body weight, body weight gain, WAT and BAT, with a higher BAT/WAT ratio, but no significant difference in REE when compared to controls. Vagotomized rats also had significantly higher fasting ghrelin and lower glucose and insulin levels. After GLP-1 administration, vagotomized rats depicted a blunted anorexigenic response and higher plasma leptin levels, as compared to controls. However, in vitro stimulation of VAT explants with GLP-1 resulted in no significant changes in leptin secretion. In conclusion, the vagus nerve influences whole-body energy homeostasis by modifying food intake, body weight and body composition and by mediating the GLP-1 anorectic response. The higher leptin levels in response to acute GLP-1 administration observed after truncal vagotomy suggest the existence of a putative GLP-1-leptin axis that relies on the integrity of gut–brain vagal pathway. Full article

The urban overheating phenomenon in Mediterranean cities is a societal challenge with vast implications for the protection of public health. An additional analysis of the pilot TEMP randomized 2 × 2 cross-over trial was set up, using wearable sensor-based skin temperature measurements (n = 14). The study objectives were to: (i) assess the recurrence patterns of skin temperature measurements in individuals spending time in two climatologically contrasting settings (urban versus mountainous), and (ii) evaluate the association between the diurnal nonlinear recurrence quantification analysis (RQA) metrics and metabolic hormone levels. The intervention was a short-term stay (5–7 days) in a mountainous, climate-cooler setting (range 600–900 m altitude), which is about a 1 h drive from the main urban centres of Cyprus. The RQA analysis showed a blunting phenomenon on the nonlinear temporal dynamics of skin temperature time series observed in the urban setting. Compared with the mountainous setting, a more stable (and thus less adaptive) profile of skin temperature dynamics in the urban setting appeared, being less deterministic and with a smaller degree of complexity. No significant (p > 0.05) associations were observed between the leptin or cortisol and any of the skin temperature dynamical descriptors. However, there were marginal associations between the adiponectin and laminarity (beta = 0.24, 95%CI: −0.02, 0.50, p = 0.07) and with determinism (beta = 0.23, 95%CI: −0.037, 0.50, p = 0.09). We found dysregulations in skin temperature temporal dynamics of the study population while residing in the urban setting when compared with the cooler mountainous setting; these dysregulations took the form of reduced cycle duration and complexity, while skin temperature dynamics became less responsive to perturbations and less regular in magnitude. More research is needed to better understand heat stress temporal dynamics and their influence on human health. Trial registration: This trial is registered with ClinicalTrials.gov; number: NCT03625817. Full article