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Endocrines Mar 2024GHRH regulates the secretion of GH from the anterior pituitary gland, previously associated with cancer progression and inflammation. An emerging body of evidence...
GHRH regulates the secretion of GH from the anterior pituitary gland, previously associated with cancer progression and inflammation. An emerging body of evidence suggests that GHRHAnt support endothelial barrier function, but the mechanisms mediating these events are not completely understood. In the present study, it is demonstrated that the GHRHAnt JV-1-36 counteracts barrier dysfunction due to LPS or LTA treatment in HUVECs, utilizing the Dextran-FITC assay. Moreover, it is shown in BPAECs that these bacterial toxins increase ROS generation, and that this effect is counteracted by JV-1-36, which reinstates the redox balance. The possible involvement of NEK2 in the beneficial activities of GHRHAnt in IFN-γ- and LPS-triggered hyperpermeability was also assessed, since that kinase is involved in inflammatory responses. NEK2 was increased in the inflamed cells, and JV-1-36 counteracted those endothelial events. Our data support the beneficial effects of GHRHAnt in toxin-induced endothelial injury.
PubMed: 38895505
DOI: 10.3390/endocrines5010008 -
BioRxiv : the Preprint Server For... Jun 2024In vertebrates, the glucocorticoid response through the hypothalamic-pituitary-adrenal (HPA) axis controls many essential functions, including behavior, metabolism, and...
UNLABELLED
In vertebrates, the glucocorticoid response through the hypothalamic-pituitary-adrenal (HPA) axis controls many essential functions, including behavior, metabolism, and ontogenetic transitions. However, there are tradeoffs associated with high levels of glucocorticoids, including reduced growth rate and lowered immunity. These tradeoffs drive variation in the timing of the development of the HPA axis across taxa. In anurans (frogs and toads), corticosterone has critical roles in development and behavior, and concentrations can fluctuate in response to environmental stressors. Given the role of corticosterone in ontogenetic changes and behaviors, we hypothesized that species with immediate habitat transitions and challenges would develop an HPA axis early in development. To test this hypothesis, we studied tadpoles of the dyeing poison frog ( ), a species in which tadpoles hatch terrestrially and are transported to pools of water by their parent. We measured the excretion rate and whole-body concentration of corticosterone and the corticosterone response to adrenocorticotropic hormone (ACTH). We found no significant differences in excretion rates and whole-body concentration of corticosterone, nor physiological response to ACTH injection across tadpole development. These findings indicate that the glucocorticoid response is developed early in ontogeny. These findings generally differ from those found in other species of tadpoles, which may suggest the unique ecological pressures of has shaped the development of its HPA axis. More broadly, this study illustrates how life history strategies and tradeoffs of glucocorticoids impact the timing of the development of the HPA axis.
HIGHLIGHTS
The timing of HPA axis development differs across species. We studied the HPA axis across tadpole development in . No difference in corticosterone concentration across development.No difference in corticosterone response to ACTH across development.Results suggest an early developed HPA axis is essential for their life history.
PubMed: 38895357
DOI: 10.1101/2024.05.31.596457 -
Frontiers in Endocrinology 2024Gonadotropin-releasing hormone (GnRH) is a key stimulator for gonadotropin secretion in the pituitary and its pivotal role in reproduction is well conserved in...
Differential involvement of cAMP/PKA-, PLC/PKC- and Ca/calmodulin-dependent pathways in GnRH-induced prolactin secretion and gene expression in grass carp pituitary cells.
Gonadotropin-releasing hormone (GnRH) is a key stimulator for gonadotropin secretion in the pituitary and its pivotal role in reproduction is well conserved in vertebrates. In fish models, GnRH can also induce prolactin (PRL) release, but little is known for the corresponding effect on PRL gene expression as well as the post-receptor signalling involved. Using grass carp as a model, the functional role of GnRH and its underlying signal transduction for PRL regulation were examined at the pituitary level. Using laser capture microdissection coupled with RT-PCR, GnRH receptor expression could be located in carp lactotrophs. In primary cell culture prepared from grass carp pituitaries, the native forms of GnRH, GnRH2 and GnRH3, as well as the GnRH agonist [D-Arg, Pro, NEt]-sGnRH were all effective in elevating PRL secretion, PRL mRNA level, PRL cell content and total production. In pituitary cells prepared from the rostral pars distalis, the region in the carp pituitary enriched with lactotrophs, GnRH not only increased cAMP synthesis with parallel CREB phosphorylation and nuclear translocation but also induced a rapid rise in cytosolic Ca by Ca influx via L-type voltage-sensitive Ca channel (VSCC) with subsequent CaM expression and NFAT dephosphorylation. In carp pituitary cells prepared from whole pituitaries, GnRH-induced PRL secretion was reduced/negated by inhibiting cAMP/PKA, PLC/PKC and Ca/CaM/CaMK-II pathways but not the signalling events via IP and CaN/NFAT. The corresponding effect on PRL mRNA expression, however, was blocked by inhibiting cAMP/PKA/CREB/CBP and Ca/CaM/CaN/NFAT signalling but not PLC/IP/PKC pathway. At the pituitary cell level, activation of cAMP/PKA pathway could also induce CaM expression and Ca influx via VSCC with parallel rises in PRL release and gene expression in a Ca/CaM-dependent manner. These findings, as a whole, suggest that the cAMP/PKA-, PLC/PKC- and Ca/CaM-dependent cascades are differentially involved in GnRH-induced PRL secretion and PRL transcript expression in carp lactotrophs. During the process, a functional crosstalk between the cAMP/PKA- and Ca/CaM-dependent pathways may occur with PRL release linked with CaMK-II and PKC activation and PRL gene transcription caused by nuclear action of CREB/CBP and CaN/NFAT signalling.
Topics: Animals; Carps; Gonadotropin-Releasing Hormone; Prolactin; Pituitary Gland; Protein Kinase C; Cyclic AMP-Dependent Protein Kinases; Calcium; Type C Phospholipases; Cyclic AMP; Signal Transduction; Calmodulin; Cells, Cultured; Gene Expression
PubMed: 38894746
DOI: 10.3389/fendo.2024.1399274 -
Clinical and Translational Science Jun 2024Following SARS-CoV-2 infection, some patients develop lingering neurologic symptoms of post-acute sequelae of COVID-19 (PASC) that commonly include fatigue and "brain...
Following SARS-CoV-2 infection, some patients develop lingering neurologic symptoms of post-acute sequelae of COVID-19 (PASC) that commonly include fatigue and "brain fog." PASC symptoms are also linked with reduced growth hormone (GH) secretion, but GH treatment has not been tested to relieve symptoms. We enrolled 13 adults with neurologic PASC symptoms and peak stimulated GH secretion less than 10 ng/mL (glucagon stimulation) in a pilot study to receive 9 months of daily GH injections and an additional 3 months of off-treatment assessment. We compared peak stimulated GH secretion at baseline and 12 months and assessed measures of cognition, metabolism, body composition, and physical performance over the first 6 months of treatment. Patient-reported outcomes of fatigue, quality of life, sleep, and mood were recorded at baseline and compared with timepoints at 6, 9, and 12 months. GH treatment was associated with significantly improved scores for Brief Fatigue Inventory, Multidimensional Fatigue Symptom Inventory, Quality of Life Assessment of Growth Hormone Deficiency in Adults, Profile of Mood States, and Beck Depression Inventory-II, with no significant change in Pittsburgh Sleep Quality Index. Six months of adjunct GH treatment was not associated with significant changes in cognition, body composition, resting energy expenditure, or physical performance. Peak stimulated GH secretion was not altered at 12 months following 9 months of GH treatment. GH treatment significantly improved neurologic symptoms in PASC patients but cognition, sleep, and physical performance were not significantly altered.
Topics: Humans; Male; Female; COVID-19; Middle Aged; Human Growth Hormone; Post-Acute COVID-19 Syndrome; Pilot Projects; Quality of Life; Fatigue; Adult; SARS-CoV-2; Aged; Treatment Outcome; Body Composition
PubMed: 38894576
DOI: 10.1111/cts.13826 -
Nutrients May 2024The onset of puberty, which is under the control of the hypothalamic-pituitary-gonadal (HPG) axis, is influenced by various factors, including obesity, which has been... (Review)
Review
The onset of puberty, which is under the control of the hypothalamic-pituitary-gonadal (HPG) axis, is influenced by various factors, including obesity, which has been associated with the earlier onset of puberty. Obesity-induced hypothalamic inflammation may cause premature activation of gonadotropin-releasing hormone (GnRH) neurons, resulting in the development of precocious or early puberty. Mechanisms involving phoenixin action and hypothalamic microglial cells are implicated. Furthermore, obesity induces structural and cellular brain alterations, disrupting metabolic regulation. Imaging studies reveal neuroinflammatory changes in obese individuals, impacting pubertal timing. Magnetic resonance spectroscopy enables the assessment of the brain's neurochemical composition by measuring key metabolites, highlighting potential pathways involved in neurological changes associated with obesity. In this article, we present evidence indicating a potential association among obesity, hypothalamic inflammation, and precocious puberty.
Topics: Humans; Pediatric Obesity; Hypothalamus; Child; Puberty, Precocious; Puberty; Inflammation; Female; Gonadotropin-Releasing Hormone; Male; Hypothalamo-Hypophyseal System
PubMed: 38892653
DOI: 10.3390/nu16111720 -
International Journal of Molecular... May 2024The main goal of this research was to determine whether there is a correlation between adherence to the Mediterranean diet (assessed by the Mediterranean Diet Serving...
The main goal of this research was to determine whether there is a correlation between adherence to the Mediterranean diet (assessed by the Mediterranean Diet Serving Score (MDSS)) and parameters indicating thyroid gland activity, such as concentration of thyroid-stimulating hormone (TSH), thyroid hormones (free triiodothyronine (fT3), free thyroxine (fT4)), thyroglobulin (Tg), antibodies to thyroid proteins (thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb)), and calcitonin (CT) in plasma and serum samples. An additional objective was to investigate whether there are differences in the values of the MDSS among clinical groups (euthyroid individuals, euthyroid individuals with positive TgAb and/or TPOAb, and hypothyroid and hyperthyroid participants). This cross-sectional study included 4620 participants over 18 years of age from the islands of Korčula and Vis, and the mainland city of Split. The MDSS was assessed from a food frequency questionnaire (FFQ). MDSS values were significantly higher in females compared to males and showed a positive association with the age of the participants. There was no significant difference in the MDSS values among the examined clinical groups. In the group of subjects with euthyroidism, a significant positive association was found between fT3 and the MDSS, while in the group of subjects with subclinical hypothyroidism, a significant positive association was observed between the MDSS and both fT3 and fT4. CT levels were also positively associated with the MDSS. Considering the significant positive association of the MDSS and both fT3 and fT4 levels in patients with subclinical hypothyroidism, the results of this study could be used to create guidelines for selecting an appropriate, potentially protective diet for these patients.
Topics: Humans; Diet, Mediterranean; Female; Male; Thyroid Gland; Middle Aged; Adult; Cross-Sectional Studies; Thyroglobulin; Autoantibodies; Aged; Thyrotropin; Triiodothyronine; Hypothyroidism; Thyroid Hormones; Thyroxine
PubMed: 38892060
DOI: 10.3390/ijms25115874 -
International Journal of Molecular... May 2024Inflammation, demyelination, and axonal damage to the central nervous system (CNS) are the hallmarks of multiple sclerosis (MS) and its representative animal model,...
Inflammation, demyelination, and axonal damage to the central nervous system (CNS) are the hallmarks of multiple sclerosis (MS) and its representative animal model, experimental autoimmune encephalomyelitis (EAE). There is scientific evidence for the involvement of growth hormone (GH) in autoimmune regulation. Previous data on the relationship between the GH/insulin like growth factor-1 (IGF-1) axis and MS/EAE are inconclusive; therefore, the aim of our study was to investigate the changes in the GH axis during acute monophasic EAE. The results show that the gene expression of and in the hypothalamus does not change, except for and , while at the pituitary level the , and genes are upregulated. Interestingly, the cell volume of somatotropic cells in the pituitary gland remains unchanged at the peak of the disease. We found elevated serum GH levels in association with low IGF-1 concentration and downregulated and expression in the liver, indicating a condition resembling GH resistance. This is likely due to inadequate nutrient intake at the peak of the disease when inflammation in the CNS is greatest. Considering that GH secretion is finely regulated by numerous central and peripheral signals, the involvement of the GH/IGF-1 axis in MS/EAE should be thoroughly investigated for possible future therapeutic strategies, especially with a view to improving EAE disease.
Topics: Animals; Encephalomyelitis, Autoimmune, Experimental; Female; Rats; Growth Hormone; Insulin-Like Growth Factor I; Hypothalamus; Pituitary Gland; Receptors, Somatotropin; Receptors, Pituitary Hormone-Regulating Hormone; Multiple Sclerosis; Growth Hormone-Releasing Hormone; Liver; Disease Models, Animal
PubMed: 38892024
DOI: 10.3390/ijms25115837 -
International Journal of Molecular... May 2024The testes serve as the primary source of androgens and the site of spermatogenesis, with their development and function governed by hormonal actions via endocrine and... (Review)
Review
The testes serve as the primary source of androgens and the site of spermatogenesis, with their development and function governed by hormonal actions via endocrine and paracrine pathways. Male fertility hinges on the availability of testosterone, a cornerstone of spermatogenesis, while follicle-stimulating hormone (FSH) signaling is indispensable for the proliferation, differentiation, and proper functioning of Sertoli and germ cells. This review covers the research on how androgens, FSH, and other hormones support processes crucial for male fertility in the testis and reproductive tract. These hormones are regulated by the hypothalamic-pituitary-gonad (HPG) axis, which is either quiescent or activated at different stages of the life course, and the regulation of the axis is crucial for the development and normal function of the male reproductive system. Hormonal imbalances, whether due to genetic predispositions or environmental influences, leading to hypogonadism or hypergonadism, can precipitate reproductive disorders. Investigating the regulatory network and molecular mechanisms involved in testicular development and spermatogenesis is instrumental in developing new therapeutic methods, drugs, and male hormonal contraceptives.
Topics: Humans; Male; Testis; Animals; Spermatogenesis; Follicle Stimulating Hormone; Hypothalamo-Hypophyseal System; Androgens; Testosterone
PubMed: 38891991
DOI: 10.3390/ijms25115805 -
International Journal of Molecular... May 2024In the majority of children with growth hormone (GH) deficiency (GHD), normal GH secretion may occur before the attainment of final height. The aim of the study was to...
Transient Isolated, Idiopathic Growth Hormone Deficiency-A Self-Limiting Pediatric Disease with Male Predominance or a Diagnosis Based on Uncertain Criteria? Lesson from 20 Years' Real-World Experience with Retesting at One Center.
In the majority of children with growth hormone (GH) deficiency (GHD), normal GH secretion may occur before the attainment of final height. The aim of the study was to assess the incidence of persistent and transient GHD and the effectiveness of recombined human GH (rhGH) therapy in children with isolated, idiopathic GHD with respect to the moment of therapy withdrawal and according to different diagnostic criteria of GHD. The analysis included 260 patients (173 boys, 87 girls) with isolated, idiopathic GHD who had completed rhGH therapy and who had been reassessed for GH and IGF-1 secretion. The incidence of transient GHD with respect to different pre- and post-treatment criteria was compared together with the assessment of GH therapy effectiveness. The incidence of transient GHD, even with respect to pediatric criteria, was very high. Normal GH secretion occurred before the attainment of near-final height. Application of more restricted criteria decreased the number of children diagnosed with GHD but not the incidence of transient GHD among them. Poor response to GH therapy was observed mainly in the patients with normal IGF-1 before treatment, suggesting that their diagnosis of GHD may have been a false positive. Further efforts should be made to avoid the overdiagnosis GHD and the overtreatment of patients.
Topics: Humans; Male; Child; Female; Human Growth Hormone; Insulin-Like Growth Factor I; Adolescent; Child, Preschool; Growth Disorders; Body Height
PubMed: 38891927
DOI: 10.3390/ijms25115739 -
The American Journal of Case Reports Jun 2024BACKGROUND Bartter syndrome is a rare, inherited salt-wasting tubulopathy caused by mutations in 1 of 6 genes that express ion transport channels in the thick ascending...
BACKGROUND Bartter syndrome is a rare, inherited salt-wasting tubulopathy caused by mutations in 1 of 6 genes that express ion transport channels in the thick ascending limb of nephrons. Excessive prostaglandin E2 and associated hyperreninemic hyperaldosteronism occurs, causing polyhydramnios, polyuria, prematurity, failure to thrive, and characteristic physical features. Hypokalemia, hypochloremic metabolic alkalosis, and, depending on the affected gene, hypercalciuria and nephrocalcinosis are hallmarks of Bartter syndrome. CASE REPORT A 9-month-old male infant, born prematurely due to polyhydramnios, presented in the Emergency Department with dehydration due to incoercible vomiting and significant polyuria. A 6-year-old male infant with a previous history of prematurity due to polyhydramnios was referred to the Pediatric Endocrinology Department due to short stature and notable polydipsia and polyuria. Considering these marked symptoms, both cases triggered suspicion and started workup for arginine-vasopressin insufficiency/resistance. However, during the investigations, a broader clinical revision revealed that both had dysmorphic physical features (triangularly shaped face, prominent forehead, protruding ears, drooping mouth), poor growth, impaired weight gain, and typical biochemical findings (hypokalemic metabolic alkalosis, hypercalciuria, secondary hyperaldosteronism) of Bartter syndrome. Genetic testing confirmed the diagnosis of Bartter syndrome types 1 and type 2, respectively, and this diagnosis allowed proper treatment and significant clinical improvements, personalized follow-up, and genetic counseling for parents desiring further healthy pregnancies. CONCLUSIONS Here, we present clinical and follow-up findings of 2 patients with Bartter syndrome types 1 and 2 discovered upon a broader clinical revision of suspected arginine-vasopressin insufficiency/resistance. We also review pertinent data on diagnosis and management of this challenging syndrome.
Topics: Humans; Bartter Syndrome; Male; Infant; Child; Arginine Vasopressin
PubMed: 38885190
DOI: 10.12659/AJCR.942872