Growth Hormone Research Articles

Growth hormone improves the pregnancy outcomes in poor ovarian responders undergoing in vitro fertilization: an umbrella review.

Poor ovarian response (POR) significantly impacts the success of assisted reproductive technology (ART), and growth hormone (GH) has been proposed as an adjuvant treatment to improve outcomes in POR patients undergoing in vitro fertilization (IVF). A systematic review and meta-analysis were conducted to evaluate the effectiveness of GH in enhancing pregnancy outcomes, registering a protocol on PROSPERO and searching multiple databases up to September 2023. Twelve systematic reviews/meta-analysis and 20 randomized controlled trials (RCTs) involving 1984 patients were included. Quality assessment was performed using AMSTAR 2, GRADE, and RoB tools. The meta-analysis revealed that GH significantly increased live birth rates [OR=1.80, 95% CI (1.22, 2.64)] and clinical pregnancy rates [OR=1.92, 95% CI (1.51, 2.43)] compared to the control group. Subgroup analysis indicated that administering 5-10 IU/d of GH combined with a long protocol during the middle and late follicular stages maximized these benefits. Despite these promising findings, most outcome indicators exhibited low-quality evidence, highlighting the need for improved research standards to ensure solid evidence supports treatment strategies for POR, thereby promoting reliable application of GH in IVF treatments.

Host Manipulations Within Mutualisms: Role of Plant Hormones in Selective Resource Allocation.

In some mutualisms involving host plants, photoassimilates are provided as rewards to symbionts. Endophagous organisms often manipulate host plants to increase access to photoassimilates. Host manipulations by endophagous organisms that are also mutualists are poorly understood. We show host plant manipulations by symbionts and the role of phytohormones, i.e. the auxin indole-3-acetic acid (IAA), and the cytokinin trans-zeatin (tZ), in the brood-site pollination mutualism between fig trees and pollinator fig wasps. In this interaction, pollinator wasps pollinate Ficus flowers within an enclosed inflorescence called a syconium, in exchange for flowers that develop into galls nourishing pollinator offspring. To examine host manipulation by pollinator galls by affecting host fitness through seed reduction, we compared growth hormones released by syconial occupants within three experimentally produced treatment groups of syconia: S (containing only seeds), G (containing only pollinator galls) and SG (containing seeds and pollinator galls). We harvested syconia from each treatment in early and mid-phases of syconial maturation when maximal growth occurs and measured hormone levels. Hormones were reduced by mid-phase in general; however, their levels were mostly sustained in G syconia in the mid-phase, suggesting that galls manipulate the host to continuously access resources. We found no difference in IAA and tZ levels of S and G syconia. IAA concentrations were higher in SG syconia. From the perspective of the maintenance of mutualism, syconium volume and hormone concentrations were highest when both seeds and galls were present (SG treatment), indicating that both partners control allocation of resources to syconia.

24-epibrassinolide regulates oxytetracycline-induced phytotoxicity and its detoxification mechanism.

Oxytetracycline (OTC), a crop-absorbable antibiotic, poses a health risk to humans through the food chain. Conversely, 24-epibrassinolide (EBL), a plant growth hormone, mitigates the toxic effects of various pollutants on plants. However, the mechanism by which exogenous EBL affects the growth of rape seedlings exposed to OTC remains largely unknown. In this study, we found that environmental OTC concentrations significantly inhibited plant growth and metabolism, whereas exogenous EBL could restore plant growth characteristics. Exogenous EBL significantly decreased reactive oxygen species (ROS) accumulation, alleviating OTC-induced cell membrane lipid peroxidation. This was achieved by increasing the antioxidant capacity and secondary metabolism levels. Notably, our findings suggested that EBL stimulated glutathione S-transferase (GST) and glutathione reductase (GR) activities, enhancing reduced glutathione synthesis and participating in plant OTC detoxification. OTC residues in EBL + OTC-treated seedlings at 21 d were significantly reduced by 29 % compared with OTC alone. Further transcriptomic and metabolomic analyses revealed that the differentially expressed genes and metabolites in the EBL and OTC alone or combined treatment groups were primarily involved in the regulation of phenylpropanoid biosynthesis, glutathione metabolism, and lant hormone signal transduction pathways in response to phytotoxic effects and detoxification mechanisms, as compared to the control group.

Dietary phytosterols increased the rate of weight gain, antioxidant capacity and growth of beneficial strains of bacteria in the gut and suppressed the population of potentially pathogenic bacteria in largemouth bass (Micropterus salmoides).

This study was to evaluate the effects of dietary adding of phytosterol (PS) on growth, antioxidant capacity, tissue morphology and gut microbiota of largemouth bass (Micropterus salmoides). A total of 540 largemouth bass (13.75 ± 0.37g) were selected and randomly divided into six groups and fed with diets supplemented with 0, 0.01 %, 0.02 %, 0.03 %, 0.04 % and 0.05 % of PS (ontrol, PS1-PS5) for 56 d. The results showed that the rate of weight gain (WGR) and condition factor (CF) of largemouth bass increased significantly (P < 0.05) with the increasing PS addition levels. In addition, PS significantly increased the activities of superoxide dismutase (SOD) and catalase (CAT) in serum compared to group C (P < 0.05), as well as increased relative expression of pituitary Insulin-like growth factor (igf1ra, igf1rb, and igf2r), hypothalamic growth hormone gh and insulin receptor ir, compared with group C (P < 0.05). Histopathological analysis showed that the addition of 0.04 % PS to the feed resulted in a tighter cellular arrangement and a significant reduction in vacuolisation in the liver of largemouth bass. It also significantly increased intestinal fold width and muscle wall thickness (P < 0.05). Analysis of the intestinal flora showed a significant decrease in the α-diversity of the flora in the PS4 group compared to the C group (P < 0.05). Notably, at the phylum level, the addition of PS to feed significantly reduced the relative abundance of Proteobacteria and Bacteroidota. At the genus level, PS significantly increased the relative abundance of Cetobacterium (P < 0.05). The addition of 0.04 % PS to the feed promotes growth, antioxidant capacity, improved tissue morphology and increased abundances of beneficial gut microbiotas in largemouth bass.

Clinical outcomes of switching to lonapegsomatropin from somatropin for treatment of pediatric growth hormone deficiency.

This study aimed to assess differences in insulin-like growth factor 1 (IGF-1) levels following the transition from somatropin to lonapegsomatropin in patients with pediatric growth hormone deficiency (GHD). Secondary objectives included the evaluation of dose titrations based on IGF-1 levels, changes in annualized height velocity (AHV) and body mass index (BMI), and assessing reported adverse effects associated with lonapegsomatropin therapy. A single-center, retrospective review was conducted including patients diagnosed with pediatric GHD initially treated with somatropin who transitioned to lonapegsomatropin between January 1, 2022, and December 31, 2023. Fourteen patients (median age: 9 years) were included. The median somatropin dose was 0.18 mg/kg/week (range, 0.09 to 0.29) at the time of transition and patients were initiated on a median lonapegsomatropin dose of 0.23 mg/kg/week (range, 0.15 to 0.26). This resulted in an IGF-1 increase of 2.3 SDS post-switch. Dose adjustments were made based on IGF-1 levels. Five patients required immediate dose reductions; four of these required further adjustments due to persistent elevation. There were no serious adverse effects reported. Lonapegsomatropin may be a favorable option to reduce injection burden for those with pediatric GHD, though the manufacturer's recommended starting dose of 0.24 mg/kg/week may require individualization. Careful monitoring and dose adjustment based on IGF-1 levels are necessary to maintain safety and efficacy.

BCL6 coordinates muscle mass homeostasis with nutritional states

Nutritional status is a determining factor for growth during development and homeostatic maintenance in adulthood. In the context of muscle, growth hormone (GH) coordinates growth with nutritional status; however, the detailed mechanisms remain to be fully elucidated. Here, we show that the transcriptional repressor B cell lymphoma 6 (BCL6) maintains muscle mass by sustaining GH action. Muscle-specific genetic deletion of BCL6 at either perinatal or adult stages profoundly reduces muscle mass and compromises muscle strength. Conversely, muscle-directed viral overexpression of BCL6 significantly reverses the loss of muscle mass and strength. Mechanistically, we show that BCL6 transcriptionally represses the suppressor of cytokine signaling 2 to sustain the anabolic actions of GH in muscle. Additionally, we find that GH itself transcriptionally inhibits BCL6 through the Janus kinase and signal transducer and activator of transcription 5 (JAK/STAT5) pathway. Supporting the physiologic relevance of this feedback regulation, we show the coordinated suppression of muscle Bcl6 expression with the induction of GH in the fasted state. These findings reveal the complexity of the feedback controls modulating GH signaling and identify BCL6 as a key homeostatic regulator coordinating muscle mass with nutrient availability. Moreover, these studies open avenues for targeted therapeutic strategies to combat muscle-wasting conditions.

Integrating immunity, antioxidative status, and gene regulation against nickel and high-temperature stress in fish: selenium nanoparticles for mitigation.

Fish face health hazards due to high-temperature (T) stress and the toxicity associated with nickel (Ni), both of which can occur in aquatic ecosystems. The accumulation of nickel in fish may pose risks to human health when contaminated fish are consumed. Consequently, the goal of this study was to clarify how selenium nanoparticles (Se-NPs) help Pangasianodon hypophthalmus by reducing the effects of nickel and high-temperature stress. The fish were reared under different experimental conditions as follows: a control group (no exposure to Ni and T, and fed a control diet); a group concurrently exposed to Ni and T while fed a control diet; and groups concurrently exposed to Ni and T while being fed supplemented diets with Se-NPs at 0.5mgkg-1 and 1.0mgkg-1 for 38days. The growth performance of fish exposed to nickel and high-temperature (Ni + T) stress was significantly improved by supplementation with selenium nanoparticles (Se-NPs) at 0.5mgkg-1. This supplementation also upregulated the expression of growth hormone (GH) and growth hormone receptor (GHR1) genes, while considerably downregulating the myostatin (MYST) gene. Fish subjected to Ni + T stress exhibited markedly elevated cortisol levels, which were notably reduced by Se-NPs at 0.5mgkg-1. Moreover, Se-NPs at 0.5mgkg-1 significantly downregulated the expression of stress-related genes, including Caspase 3a (Cas 3a), CYP450, iNOS, and HSP70. Fish fed Se-NPs supplemented diet and exposed to Ni + T stress demonstrated enhanced levels of TNFα and total immunoglobulins, indicating an improved immune response. Dietary Se-NPs also led to a significant reduction in oxidative stress markers, such as glutathione-S-transferase, catalase, and superoxide dismutase, in stressed fish. While Ni + T stress reduced acetylcholine esterase activity, dietary Se-NPs restored these activities. Furthermore, the inclusion of Se-NPs in the diet markedly enhanced the detoxification of nickel in various fish tissues. In conclusion, the study demonstrates that dietary supplementation with Se-NPs at 0.5mgkg-1 effectively mitigates the adverse effects of Ni + T stress in fish by modulating gene expression, alleviating cellular metabolic stress, and enhancing physiological functions.

Short- and long-term glycemic effects of pasireotide in patients with acromegaly: a comprehensive case study with review of literature.

Pasireotide (PAS), a multireceptor somatostatin analog, has been demonstrated to effectively control hormone levels, including those of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), in patients with acromegaly. However, it induces hyperglycemia by inhibiting insulin secretion via somatostatin receptor 5 (SSTR5). Despite the extensive literature on the occurrence of PAS-induced hyperglycemia, there is still no consensus on the optimal first-line treatment for this complication. Herein, we present two cases of acromegaly treated with PAS and highlight its short- and long-term effects on glucose metabolism. In the first case, postprandial hyperglycemia manifested rapidly following the commencement of PAS treatment and was effectively managed with dulaglutide under continuous glucose monitoring (CGM). In the second case, long-term PAS therapy resulted in a dose-dependent glycemic response that was controlled by different GLP-1 receptor agonists (GLP-1RAs), including semaglutide. CGM facilitated the early detection of significant glycemic fluctuations, underscoring the necessity for close monitoring in patients receiving PAS therapy. These cases demonstrate the efficacy of GLP-1RAs in managing PAS-induced hyperglycemia and highlights the value of CGM in early detection and intervention. Our findings suggest that GLP-1RAs, particularly semaglutide, are a valuable treatment option for this condition. Further research is needed to determine the optimal treatment strategy, particularly in East Asian populations, and to establish a clear consensus on the first-line therapy for PAS-induced hyperglycemia.

Therapeutic Potential of Plant Phenolic Acids Combating Cancer Drug Resistance.

Despite notable progress in treatment modalities, cancer continues to be a prom-inent cause of death globally. Chemotherapy is the main method used to treat cancer, and chemotherapeutic medications are categorized according to how they work. Nevertheless, the issue of multidrug resistance (MDR) is a significant obstacle, impacting almost 90% of cancer patients who receive chemotherapy or innovative targeted medicines. MDR pro-cesses involve the quick metabolism of foreign substances, the accelerated removal of drugs from cells, the stimulation of growth hormones, the enhancement of DNA repair ability, and the influence of genetic variables. Recent studies have mostly concentrated on studying the anticancer effects of dietary phytoconstituents as a possible remedy for overcoming multidrug resistance (MDR). Various bioactive compounds, such as phenolic acids, phe-nylpropanoids, flavonoids, stilbenes, terpenoids, and organo-sulfur compounds, have shown potential in fighting cancer. It is worth mentioning that a number of phenylpro-panoids are now being tested in clinical trials to evaluate their effectiveness in fighting cancer. This review presents a comprehensive summary of the existing knowledge regard-ing dietary phytoconstituents as possible agents for treating cancer, particularly their ability to overcome MDR. This discussion will focus on the mechanisms by which these com-pounds work, as well as the data from both preclinical and clinical studies. Additionally, we have explored the potential future applications of these compounds in the development of cancer therapeutics.

Synergistic effects of Vachellia nilotica-derived zinc oxide nanoparticles and melatonin on drought tolerance in Fragaria × ananassa

This study investigates the synergistic effects of zinc oxide nanoparticles (ZnO NPs) and melatonin (MT) on Fragaria × ananassa (strawberry) plants under drought stress, focusing on growth, fruit biomass, and stress tolerance. ZnO NPs enhance nutrient uptake and stress resistance, while MT regulates growth hormones and boosts photosynthetic efficiency. Seven treatments were evaluated: T1 (no stress, 0.5 g/L ZnO NPs + 0.1 g/L MT), T2 (no stress, 0.5 g/L ZnO NPs), T3 (no stress, 0.1 g/L MT), T4 (drought stress, no application), T5 (drought stress, 0.5 g/L ZnO NPs + 0.1 g/L MT), T6 (drought stress, 0.5 g/L ZnO NPs), and T7 (drought stress, 0.1 g/L MT). Growth and stress parameters included shoot/root length, fruit biomass, bud number, chlorophyll content, oxidative stress markers (H₂O₂, MDA), and antioxidant enzyme activities in the leaves of Fragaria × ananassa. The combined treatment (ZnO NPs + MT) consistently outperformed others, achieving the highest growth metrics under both conditions: shoot length (22.33 ± 1.53 cm non-stress, 15.00 ± 1.53 cm drought), root length (18.67 ± 1.53 cm non-stress, 12.00 ± 1.53 cm drought), and fruit biomass (9.55 ± 0.31 g non-stress, 5.02 ± 0.23 g drought). Bud formation peaked at 3.33 ± 0.58 buds/plant non-stress and 2.00 ± 0.00 buds/plant drought. Under drought, the combined treatment also enhanced chlorophyll content (2.47 ± 0.20 mg/g FW) and significantly reduced H₂O₂ (28.67 ± 2.52 µmol/g FW) and MDA (4.21 ± 0.10 µmol/g FW) levels, while maximizing antioxidant enzyme activities (SOD: 121.67 ± 7.64 U/g FW, POD: 206.33 ± 14.84 U/g FW, CAT: 48.00 ± 3.61 U/g FW). These findings highlight the combined application of ZnO NPs and MT as a promising strategy to enhance growth and stress tolerance in strawberry plants, warranting further research on optimized concentrations, delivery methods, and molecular mechanisms.

The Prevalence of Septo-Optic Dysplasia in Neonates with Absent Cavum Septi Pellucidi Identified During Routine Prenatal Imaging.

To determine the prevalence of septo-optic-dysplasia (SOD) in patients with prenatally identified absent cavum septi pellucidi (CSP), agenesis of the corpus callosum (ACC) or dysgenesis of the corpus callosum (DCC). This retrospective chart review investigated neonates prenatally diagnosed with an absent CSP, ACC, or DCC who were admitted to a single quaternary academic medical center in the Pacific Northwest between 2016-2023. This prenatal diagnosis prompted a routine and protocolized postnatal workup for SOD including laboratory evaluation, imaging, and specialty consultation. Sociodemographic and clinical data were collected for eligible neonates and their birthing person. The prevalence of SOD in patients with midline callososeptal anomalies was calculated. Of the 86 patients prenatally diagnosed with absent CSP, ACC and/or DCC, 36.0% (n=31) were diagnosed postnatally with SOD. Of those diagnosed with SOD, 71.0% (n=22) had isolated optic nerve hypoplasia, 9.7% (n=3) had pituitary hormone abnormalities, and 19.4% (n=6) had both. Seven patients required maintenance hydrocortisone, one required thyroid hormone replacement, and one required thyroid and growth hormones. Of the 26 patients with SOD who underwent genetic testing, 9 (34.6%) had one or more genetic differences detected. SOD was diagnosed in 36.0% of cases of prenatally-diagnosed midline callososeptal anomalies. For patients with prenatally-diagnosed midline callososeptal anomalies, a standardized, postnatal SOD evaluation allows timely diagnosis and prompts early intervention and hormone replacement, thus avoiding the consequences of a delayed diagnosis.

Clinical Manifestations and Challenges in Adolescent and Adult Females With Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency.

Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) is a rare genetic condition that results in cortisol deficiency and excess production of adrenal androgens. While the introduction of newborn screening for CAH has reduced morbidity and mortality, management of CAH remains challenging. Lifelong treatment with glucocorticoids is required to replace the endogenous cortisol deficiency and reduce excess adrenal androgens. Undertreatment or overtreatment with glucocorticoids can lead to multiple disease- and treatment-related comorbidities, including impaired growth and compromised final height, menstrual irregularities and reduced fertility in females, and long-term cardiometabolic complications. In addition to avoiding adrenal crisis and sudden death, treatment goals in adolescent females with CAH are to obtain normal growth and bone maturation and normal timing of puberty. Management of adolescents is particularly challenging due to changes in growth and sex hormone levels that can lead to inadequate suppression of adrenal androgens and increasing independence that can affect treatment adherence. During the transition to adult care, treatment goals focus on preventing symptoms of hyperandrogenism, preserving menstrual regularity and fertility, and providing education and support for issues related to sexuality, atypical genitalia, and/or complications from previous surgical treatment. In addition, patients must be monitored continuously to prevent long-term complications such as decreased bone mineral density, obesity, diabetes, and hypertension. In this review, we discuss the challenges faced by adolescent and adult females with CAH and provide guidance to health-care professionals to help patients to navigate these challenges.

Interpreting IGF-1 in children treated with recombinant growth hormone: challenges during early puberty

Interpreting IGF-1 in children treated with recombinant growth hormone: challenges during early puberty

Development of Neuroblastoma During Growth Hormone Therapy for Short Stature in a Girl With Mosaic Turner Syndrome

Development of Neuroblastoma During Growth Hormone Therapy for Short Stature in a Girl With Mosaic Turner Syndrome

Dietary rosemary oil with/without zymogen forte improves water quality, growth hormones, immune-physiological response, stress resilience, and health status of Chelon ramada grown in groundwater

With freshwater resources becoming scarce worldwide, mariculture is a promising avenue to sustain aquaculture development, especially by incorporating brackish and saline groundwater (GW) use into fish farming. A 75-day rearing trial was conducted to evaluate fish growth, immune response, overall health, and water quality of Chelon ramada cultured in brackish GW and fed on a basal diet (BD) augmented with rosemary oil (RO) or RO + zymogen forte™ (ZF) as an anti-flatulent. Five treatments were administrated in triplicate: T1: fish-fed BD without additives (control group); T2: fish-fed BD + 0.5 g RO /kg diet; T3: fish-fed BD + 0.5 g RO and 1 g ZF /kg diet; T4: fish-fed BD + 1 g RO /kg diet; T5: fish-fed BD + 1 g RO and 1 g ZF /kg diet. Three hundred fish (8.51 ± 0.01 g/fish) were housed in 15 fiberglass tanks (1500-L tank). The results revealed significant improvements (P < 0.05) in growth performance, survival, growth hormone, and insulin-like growth factor-1. Additionally, there were decreases in the feed conversion ratio (FCR) and the levels of nitrogen by-products (NH4, NH3, and NO2) and pathogenic bacterial counts in the rearing water when fish were fed diets supplemented with RO and RO + ZF. Furthermore, significant reductions in the levels of plasma stress indicators (cortisol, creatinine, and glucose) were detected. In addition, there were significant enhancements observed in the levels of innate immune markers, such as white blood cells, total protein, albumin, and immunoglobulin. The complement system, specifically complement 3 and complement 4, also showed considerable improvements. Furthermore, there were increases in plasma heat shock proteins HSP70 and HSP90, as well as enhanced antioxidant activity. These gains were associated with healthier liver and intestines. The investigation demonstrated that adding 0.5–1 g RO / kg diet or RO + ZF to a C. ramada diet has many benefits, including reducing the levels of nitrogen by-product chemicals and pathogenic bacterial load in GW used in growth tanks. Furthermore, significant improvements were observed in the rates of growth and associated hormones, efficiency of feed utilization, blood indicators, immune function, condition of internal organs (namely the intestine and liver), and overall health of the fish.

Ontogeny of adenohypophyseal cells, pituitary gland development, and structure in adults of Astyanax lacustris (Teleostei, Characiformes): an emerging Neotropical model fish species.

Pituitary gland morphogenesis and the ontogeny of the adenohypophyseal (AH) cells of Astyanax lacustris are presented herein. This Characiformes species shows great ecological and commercial importance, and it has been increasingly used as animal model. For this study, A. lacustris specimens were collected from 0.5 to 120days after hatching (dah) (adults). The entire animal or its head was appropriately fixed, and after histological processing, the sections were subjected to histochemical and immunohistochemical reactions, using homologous and heterologous antibodies. The first AH cells of A. lacustris were detected at 1 dah by the immunostaining of prolactin (PRL)-producing cells. The morphology of the gland presented changes in shape throughout the development, starting with elongation but more oval at the end. The neurohypophysis was differentiated at 3 dah, along with the identification of adrenocorticotropic hormone (ACTH), melanotropic hormone (MSH), thyroid-stimulating hormone (TSH), and follicle-stimulating hormone (FSH)-producing cells. Identification of the immunoreactive cells to anti-luteinizing hormone (LH), anti-somatolactin (SL), and anti-growth hormone (GH) antibodies occurred at 5 dah. At 20 dah, an increase in pituitary proportions and the presence of the pituitary stalk were observed. At 60 dah, the pituitary gland already had the same shape and distribution of AH cells seen in the adult. The ontogeny of adenohypophyseal cells in A. lacustris corroborates the heterogeneity in the appearance of these cell types in teleosts and suggests that these hormones actively participate during the post-hatching development of this species, even before the establishment of all endocrine axes. Our findings contribute to understanding the morphogenesis of the hypothalamic-pituitary axis in South American teleosts, providing essential data for the development of future studies related to pituitary gland morphophysiology under normal or experimental conditions.

Impact of pubertal timing on growth progression and final height in subjects affected by RASopathies

BackgroundRASopathies, including Noonan syndrome and related disorders, are multisystem conditions caused by mutations in various genes encoding proteins involved in the RAS/MAPK signaling pathway resulting in increased signal flow. They are clinically characterized by failure to thrive, facial dysmorphisms, congenital heart defects, lymphatic malformations, skeletal anomalies, and variable cognitive impairment, with variable prevalence in the different conditions and subtypes. Pubertal development, which affects growth and final height, is often delayed in Noonan syndrome patients, though not universally. This study aimed to evaluate the timing and progression of puberty and its impact on growth and final height in patients with RASopathies.Subjects and methodsA retrospective longitudinal study was conducted involving 103 patients with molecularly confirmed RASopathies. A subgroup of 40 patients who had completed pubertal development was analyzed. Anthropometric, hormonal (FSH, LH, estradiol/testosterone), and radiological data were collected.ResultsAmong the 40 patients who had completed puberty, 75% had a diagnosis of Noonan syndrome. The median age at pubertal onset was 11.8 years in males and 13.2 years in females. Delayed puberty was observed in 27.8% of patients, with a higher incidence in females. Median final height was significantly lower in those with delayed pubertal onset compared to those with normal development (p &amp;lt; 0.01). No significant differences in final height were observed between patients with growth hormone deficiency treated with growth hormone and those who were untreated.ConclusionsDelayed pubertal onset negatively impacts final height in patients with RASopathies, with inadequate pubertal catch-up growth being a common outcome. While most patients initiate puberty spontaneously, careful monitoring of growth and pubertal progression is crucial to optimize therapeutic interventions and improve final height outcomes.

Critical Insights into LEAP2 Biology and Physiological Functions: Potential Roles Beyond Ghrelin Antagonism.

Liver-expressed antimicrobial peptide 2 (LEAP2) has recently emerged as a novel hormone that reduces food intake and glycemia by acting through the growth hormone secretagogue receptor (GHSR), also known as the ghrelin receptor. This discovery has led to a fundamental reconceptualization of GHSR's functional dynamics, now understood to be under a dual and opposing regulation. LEAP2 exhibits several distinctive features. LEAP2 is released by hepatocytes and enterocytes-two cell types that lack classical regulatory secretory mechanisms and may respond differently to nutrient signals. LEAP2 is also found in higher concentrations in plasma than ghrelin, even under energy-deficit conditions, and modulates GHSR by inhibiting both ghrelin-dependent and ghrelin-independent activities. Given these characteristics, LEAP2 appears to play a major role in regulating GHSR activity in vivo, extending beyond simple ghrelin antagonism and being crucial for the long-term regulation of energy balance. A deeper understanding of how LEAP2 functions may clarify the functional implications of GHSR in different physiological contexts and unlock new therapeutic strategies for treating obesity, diabetes, and other metabolic disorders.

Growth and rhGH use in children with congenital chronic kidney disease: a multicentric contemporary study.

Growth retardation is common in children with chronic kidney disease (CKD) and reflects CKD severity. Recombinant human growth hormone (rhGH) treatment was approved for CKD in 1995. We describe here treatment patterns and growth outcomes in children with congenital CKD in three pediatric nephrology departments. We included patients with kidney transplantation (KT) performed between 2015 and 2020 at an age of 3 to 18 years. Data were collected at four timepoints: CKD diagnosis, initiation of rhGH, initiation of dialysis, and transplantation. Among 87 patients, 42 (48%) received rhGH. The median height at treatment initiation was -2.0 SDS, with a median height gain of +0.7 SD (p<0.0001) in 1.7 years. Growth outcomes were negatively associated with older age and CKD stage 5. The 45 rhGH-untreated patients lost 0.6 SD (p=0.02) from diagnosis to transplantation but maintained their height in the normal range. At transplantation, 26% of rhGH-treated and 9% of rhGH-untreated patients had a height SDS below -2 SDS. rhGH was initiated by nephrologists in 52% of cases and endocrinologists in 48%. Deviations from marketing authorization criteria were observed in 68% of cases: endocrinologists typically prescribed rhGH for children under 2 years, while nephrologists prescribed it for patients with a height above -2 SDS. About half of CKD patients received rhGH treatment, resulting in significant height gain. Untreated patients were not adversely affected in terms of height. These data highlight the importance of careful monitoring of growth and rhGH treatment if needed in patients with CKD.

Emotional and Behavioural Adjustment in Children and Adolescents with Short Stature vs. Their Normal-Statured Peers.

Background/Objectives: the aim of the current cross-sectional study is to explore and compare the emotional and behavioural conditions of children and adolescents with short stature (i.e., familial short stature and constitutional delay of growth), idiopathic growth hormone deficiency (GHD), and normal height. Methods: Twenty-nine participants (15 males, 14 females; mean age ± standard deviation (SD) = 11.2 ± 1.96 years) with short stature (height standard deviation score (SDS): -2.10 ± 0.57), 10 age-matched participants (4 males, 6 females; mean age ± SD = 10.9 ± 2.35 years) with growth hormone deficiency (GHD; height SDS: -2.44 ± 0.29), and 36 age-matched participants (19 males, 17 females; mean age ± SD = 11.3 ± 1.93 years) with normal stature (height SDS: 0.56 ± 0.78) were admitted to this study. Psychological distress was evaluated using the Depression Anxiety and Stress Scale (DASS-21), and emotional and behavioural problems using the Child Behaviour Checklist for Children (CBCL) and the Strengths and Difficulties Questionnaire (SDQ). Results: Participants with GHD exhibited higher levels of the "withdrawn/depressed subscale" score of CBCL (H = 7.794, df = 2, p = 0.020), compared to their peers with normal height, while no significant differences were observed between participants with short stature and those with normal stature. Normal-statured participants reported higher levels of the "conduct problems" subscale score (H = 10.421, df = 2, p = 0.005) and the "rule-breaking behaviour" subscale score of CBCL (H = 10.358, df = 2, p = 0.006) compared to both short-statured groups. No significant differences among the three subgroups were found in the DASS-21 and SDQ scores questionnaires, suggesting the lack of short stature-dependent effects on psychological distress and emotional and behavioural adjustment. Conclusions: Although participants with GHD exhibited higher levels of the "withdrawn/depressed subscale" score of CBCL (H = 7.794, df = 2, p = 0.020) compared to their peers with normal height, participants with short stature did not experience the same problems. Although short-statured participants had lower levels of "conduct problems" and "rule-breaking behaviours" scores than their normal-statured peers, the psychological distress and emotional and behavioural adjustment were not affected by short stature, being comparable to those recorded in normal-statured participants.