Disrupting actin filaments enhances glucose-stimulated insulin secretion independent of the cortical actin cytoskeleton.

Just under the plasma membrane of most animal cells lies a dense meshwork of actin filaments called the cortical cytoskeleton. In insulin-secreting pancreatic ß cells, a long-standing model posits that the cortical actin layer primarily acts to restrict access of insulin granules to the plasma membrane. Here we test this model and find that stimulating ß cells with pro-secretory stimuli (glucose and/or KCl) has little impact on the cortical actin layer. Chemical perturbations of actin polymerization, by either disrupting or enhancing filamentation, dramatically enhance glucose-stimulated insulin secretion. Using scanning electron microscopy, we directly visualize the cortical cytoskeleton, allowing us to validate the effect of these filament-disrupting chemicals. We find the state of the cortical actin layer does not correlate with levels of insulin secretion, suggesting filament disruptors act on insulin secretion independently of the cortical cytoskeleton.

Mitochondrial metabolism and dynamics in pancreatic beta cell glucose sensing.

Glucose-regulated insulin secretion becomes defective in all forms of diabetes. The signaling mechanisms through which the sugar acts on the ensemble of beta cells within the islet remain a vigorous area of research after more than 60 years. Here, we focus firstly on the role that the privileged oxidative metabolism of glucose plays in glucose detection, discussing the importance of 'disallowing' in the beta cell the expression of genes including Lactate dehydrogenase (Ldha) and the lactate transporter Mct1/Slc16a1 to restrict other metabolic fates for glucose. We next explore the regulation of mitochondrial metabolism by Ca2+ and its possible role in sustaining glucose signaling towards insulin secretion. Finally, we discuss in depth the importance of mitochondrial structure and dynamics in the beta cell, and their potential for therapeutic targeting by incretin hormones or direct regulators of mitochondrial fusion. This review, and the 2023 Sir Philip Randle Lecture which GAR will give at the Islet Study Group meeting in Vancouver, Canada in June 2023, honor the foundational, and sometimes under-appreciated, contributions made by Professor Randle and his colleagues towards our understanding of the regulation of insulin secretion.

Combined effects of copper and cadmium exposure on ovarian function and structure in Nile Tilapia (Oreochromis niloticus).

With the rapid development of industrialization and urbanization, the issue of copper (Cu) and cadmium (Cd) pollution in aquatic ecosystems has become increasingly severe, posing threats to the ovarian tissue and reproductive capacity of aquatic organisms. However, the combined effects of Cu and Cd on the ovarian development of fish and other aquatic species remain unclear. In this study, female Nile tilapia (Oreochromis niloticus) were individually or co-exposed to Cu and/or Cd in water. Ovarian and serum samples were collected at 15, 30, 60, 90, and 120 days, and the bioaccumulation, ovarian development, and hormone secretion were analyzed. Results showed that both single and combined exposure significantly reduced the gonadosomatic index and serum hormone levels, upregulated estrogen receptor (er) and progesterone receptor (pr) gene transcription levels, and markedly affected ovarian metabolite levels. Combined exposure led to more adverse effects than single exposure. The data demonstrate that the Cu and Cd exposure can impair ovarian function and structure, with more pronounced adverse effects under Cu and Cd co-exposure. The Cu and Cd affect the metabolic pathways of nucleotides and amino acids, leading to ovarian damage. This study highlights the importance of considering combined toxicant exposure in aquatic toxicology research and provides insights into the potential mechanisms underlying heavy metal-induced reproductive toxicity in fish.

Association between Intracellular Calcium Signaling and Tumor Recurrence in Human Non-Functioning Pituitary Adenomas.

Clinically non-functioning pituitary adenomas (CNFPAs) are the second most frequent sellar tumor among studies on community-dwelling adults. They are characterized by the absence of hormonal hypersecretion syndrome, and patients present with compressive symptoms, such as a headache and visual field defects. Immunohistochemically, most CNFPAs are of gonadotrope differentiation, with only a few of them being truly null cell adenomas. Although these tumors express receptors for one or more hypothalamic releasing hormones, to what extent this has an impact on the biological and clinical behavior of these neoplasms remains to be defined. In this research, we evaluated the basal and hypothalamic secretagogue-stimulated intracellular calcium mobilization in 13 CNFPAs, trying to correlate this response to the phenotypic features of the patients. Our results indicate that the recurrence of a CNFPA correlates positively with cellular responsiveness, as measured by spontaneous intracellular calcium activity and the ability to respond to multiple hypothalamic secretagogues. We conclude that this finding may be a useful tool for predicting the clinicopathologic behavior of CNFPAs, by testing the variation of cellular responsiveness to hypothalamic secretagogues.

Somatostatin Containing δ-Cell Number Is Reduced in Type-2 Diabetes.

Recent developments suggest that increased glucagon and decreased somatostatin secretion from the pancreas contribute to hyperglycaemia in type-2 diabetes (T2D) patients. There is a huge need to understand changes in glucagon and somatostatin secretion to develop potential anti-diabetic drugs. To further describe the role of somatostatin in the pathogenesis of T2D, reliable means to detect islet δ-cells and somatostatin secretion are necessary. In this study, we first tested currently available anti-somatostatin antibodies against a mouse model that fluorescently labels δ-cells. We found that these antibodies only label 10-15% of the fluorescently labelled δ-cells in pancreatic islets. We further tested six antibodies (newly developed) that can label both somatostatin 14 (SST14) and 28 (SST28) and found that four of them were able to detect above 70% of the fluorescent cells in the transgenic islets. This is quite efficient compared to the commercially available antibodies. Using one of these antibodies (SST10G5), we compared the cytoarchitecture of mouse and human pancreatic islets and found fewer δ-cells in the periphery of human islets. Interestingly, the δ-cell number was also reduced in islets from T2D donors compared to non-diabetic donors. Finally, with the aim to measure SST secretion from pancreatic islets, one of the candidate antibodies was used to develop a direct-ELISA-based SST assay. Using this novel assay, we could detect SST secretion under low and high glucose conditions from the pancreatic islets, both in mice and humans. Overall, using antibody-based tools provided by Mercodia AB, our study indicates reduced δ-cell numbers and SST secretion in diabetic islets.

Hormonal Imbalances in Prader-Willi and Schaaf-Yang Syndromes Imply the Evolution of Specific Regulation of Hypothalamic Neuroendocrine Function in Mammals.

The hypothalamus regulates fundamental aspects of physiological homeostasis and behavior, including stress response, reproduction, growth, sleep, and feeding, several of which are affected in patients with Prader-Willi (PWS) and Schaaf-Yang syndrome (SYS). PWS is caused by paternal deletion, maternal uniparental disomy, or imprinting defects that lead to loss of expression of a maternally imprinted region of chromosome 15 encompassing non-coding RNAs and five protein-coding genes; SYS patients have a mutation in one of them, MAGEL2. Throughout life, PWS and SYS patients suffer from musculoskeletal deficiencies, intellectual disabilities, and hormonal abnormalities, which lead to compulsive behaviors like hyperphagia and temper outbursts. Management of PWS and SYS is mostly symptomatic and cures for these debilitating disorders do not exist, highlighting a clear, unmet medical need. Research over several decades into the molecular and cellular roles of PWS genes has uncovered that several impinge on the neuroendocrine system. In this review, we will discuss the expression and molecular functions of PWS genes, connecting them with hormonal imbalances in patients and animal models. Besides the observed hormonal imbalances, we will describe the recent findings about how the loss of individual genes, particularly MAGEL2, affects the molecular mechanisms of hormone secretion. These results suggest that MAGEL2 evolved as a mammalian-specific regulator of hypothalamic neuroendocrine function.

Functional analysis of islet cells in vitro, in situ, and in vivo.

The islet of Langerhans contains at least five types of endocrine cells producing distinct hormones. In response to nutrient or neuronal stimulation, islet endocrine cells release biochemicals including peptide hormones to regulate metabolism and to control glucose homeostasis. It is now recognized that malfunction of islet cells, notably insufficient insulin release of ß-cells and hypersecretion of glucagon from α-cells, represents a causal event leading to hyperglycemia and frank diabetes, a disease that is increasing at an alarming rate to reach an epidemic level worldwide. Understanding the mechanisms regulating stimulus-secretion coupling and investigating how islet ß-cells maintain a robust secretory activity are important topics in islet biology and diabetes research. To facilitate such studies, a number of biological systems and assay platforms have been developed for the functional analysis of islet cells. These technologies have enabled detailed analyses of individual islets at the cellular level, either in vitro, in situ, or in vivo.

Sodium background currents in endocrine/neuroendocrine cells: Towards unraveling channel identity and contribution in hormone secretion.

In endocrine/neuroendocrine tissues, excitability of secretory cells is patterned by the repertoire of ion channels and there is clear evidence that extracellular sodium (Na+) ions contribute to hormone secretion. While voltage-gated channels involved in action potential generation are well-described, the background 'leak' channels operating near the resting membrane potential are much less known, and in particular the channels supporting a background entry of Na+ ions. These background Na+ currents (called here 'INab') have the ability to modulate the resting membrane potential and subsequently affect action potential firing. Here we compile and analyze the data collected from three endocrine/neuroendocrine tissues: the anterior pituitary gland, the adrenal medulla and the endocrine pancreas. We also model how INab can be functionally involved in cellular excitability. Finally, towards deciphering the physiological role of INab in endocrine/neuroendocrine cells, its implication in hormone release is also discussed.

Rotating Day and Night Disturb Growth Hormone Secretion Profiles, Body Energy Metabolism, and Insulin Levels in Mice.

BACKGROUND: Insulin and growth hormone (GH) - 2 vital metabolic regulatory hormones - regulate glucose, lipid, and energy metabolism. These 2 hormones determine substrate and energy metabolism under different living conditions. Shift of day and night affects the clock system and metabolism probably through altered insulin and GH secretion. METHODS: Five-week-old male mice were randomly assigned to a rotating light (RL) group (3-day normal light/dark cycle followed by 4-day reversed light/dark cycle per week) and normal light (NL) group. Body weight and food intake were recorded every week. Series of blood samples were collected for pulsatile GH analysis, glucose tolerance test, and insulin tolerance test at 9, 10, and 11 weeks from the start of intervention, respectively. Indirect calorimetric measurement was performed, and body composition was tested at 12 weeks. Expressions of energy and substrate metabolism-related genes were evaluated in pituitary and liver tissues at the end of 12-week intervention. RESULTS: The RL group had an increased number of GH pulsatile bursts and reduced GH mass/burst. RL also disturbed the GH secretion regularity and mode. It suppressed insulin secretion, which led to a disturbed insulin/GH balance. It was accompanied by the reduced metabolic flexibility and modified gene expression involved in energy balance and substrate metabolism. Indirect calorimeter recording revealed that RL decreased the respiratory exchange ratio (RER) and oxygen consumption at the dark phase, which resulted in an increase in fat mass and free fatty acid levels in circulation. CONCLUSION: RL disturbed pulsatile GH secretion and decreased insulin secretion in male mice with significant impairment in energy, substrate metabolism, and body composition.

Effects of different DDE exposure paradigms on testicular steroid hormone secretion and hepatic oxidative stress in male Long-Evans rats.

Chronic exposure to low doses of anthropogenic chemicals in the environment continues to be a major health issue. Due to concerns about the effects in humans and wildlife, use of persistent organic pollutants, such as dichlorodiphenyltrichloroethane (DDT), is prohibited. However, their ubiquitous nature and persistence allows them to remain in the environment at low levels for decades. Dichlorodiphenyldichloroethylene (DDE) is the most persistent metabolite of DDT and has been shown to cause hepatotoxicity, nephrotoxicity, hormonal disorders, and induce oxidative stress in many organisms. Although the effects of acute exposure to DDT and its metabolite DDE have been extensively studied, the chronic effects of sub-lethal DDE exposure at levels comparable to those found in the environment have not been well documented. Long-Evans male rats were used to determine the effect of relatively chronic and short term DDE (doses ranged from 0.001 to 100 µg/L) exposure on endocrine function and oxidative stress at different developmental time points. We found that circulating serum testosterone (T) levels were significantly decreased and T secretion in testicular explants were significantly influenced in a dose dependent manner in both pre-pubertal and pubertal male rats after DDE exposure, with pubertal rats being the most affected contrary to our original prediction. Additionally, exposure to DDE increased expression of protein oxidation indicating a possible increase in cellular damage caused by oxidative stress. This study suggests that chronic exposures to environmentally relevant levels of DDE affected testicular function and decreased T secretion with implications for reproductive capacity.

Syndrome of inappropriate secretion of antidiuretic hormone following high dose rate brachytherapy for prostate cancer: a case report.

BACKGROUND: The syndrome of inappropriate secretion of antidiuretic hormone is a disorder characterized by the excess release of antidiuretic hormone and can result in hyponatremia. If managed inappropriately, severe hyponatremia can cause seizures, cerebral edema, and even death. There are various known causes of this inappropriate release of antidiuretic hormone, including malignancy, CNS disorders, and disturbances in the hypothalamic-pituitary-renal axis. However, reports of syndrome of inappropriate secretion of antidiuretic hormone after brachytherapy for prostate cancer are exceedingly rare. CASE PRESENTATION: We report a case of symptomatic hyponatremia secondary to the inappropriate secretion of antidiuretic hormone after prostate high-dose rate brachytherapy under general anesthesia in a patient with adenocarcinoma of the prostate. CONCLUSIONS: In rare instances, inappropriate secretion of antidiuretic hormone can occur after high-dose rate brachytherapy for prostate cancer. The cause is likely multifactorial, involving pain or discomfort ensuing from the surgical procedure, the general anesthesia or intraoperative drugs administered. However, due to the potential severity of the side effects, timely diagnosis is crucial to ensure prompt, and effective management.

Syndrome of inappropriate antidiuretic hormone secretion is associated with different proton pump inhibitor use: a pharmacovigilance study.

AIM: The objective of this study was to evaluate the reported associations between the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and a variety of proton pump inhibitors (PPI) through analysis of the reports extracted from the Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: FAERS reports from January 2004 to March 2020 were used to conduct disproportionality and Bayesian analyses. The definition of SIADH relied on the preferred terms provided by the Medical Dictionary for Regulatory Activities. The time to onset, mortality, and hospitalization rates of PPI-related SIADH were also investigated. RESULTS: The study identified a total of 273 reports of PPI-associated SIADH, which appeared to influence more elderly than middle-aged patients (71.1% vs. 12.5%). Women were more affected than men (48.7% vs. 41.8%). Rabeprazole had a stronger SIADH association than other PPIs based on the highest reporting odds ratio (reporting odds ratio = 13.3, 95% confidence interval (CI) = 7.2, 24.9), proportional reporting ratio (proportional reporting ratio = 13.3, χ2 = 113.7), and empirical Bayes geometric mean (empirical Bayes geometric mean = 13.3, 95% CI = 7.9). The median time to SIADH onset was 22 (interquartile range 6-692) days after PPI administration. PPI-associated SIADH generally led to a 2.95% fatality rate and a 79.7% hospitalization rate. The highest hospitalization death rate occurred in esomeprazole (91.2%). CONCLUSION: According to our findings, more attention should be paid to SIADH within the first several months after the administration of PPIs. For women older than 65 years, dexlansoprazole may reduce the incidence of PPI-associated SIADH. Nonetheless, larger epidemiological studies are suggested to verify this conclusion.

Short-Chain Fatty Acid Receptors and Cardiovascular Function.

Increasing experimental and clinical evidence points toward a very important role for the gut microbiome and its associated metabolism in human health and disease, including in cardiovascular disorders. Free fatty acids (FFAs) are metabolically produced and utilized as energy substrates during almost every biological process in the human body. Contrary to long- and medium-chain FFAs, which are mainly synthesized from dietary triglycerides, short-chain FFAs (SCFAs) derive from the gut microbiota-mediated fermentation of indigestible dietary fiber. Originally thought to serve only as energy sources, FFAs are now known to act as ligands for a specific group of cell surface receptors called FFA receptors (FFARs), thereby inducing intracellular signaling to exert a variety of cellular and tissue effects. All FFARs are G protein-coupled receptors (GPCRs) that play integral roles in the regulation of metabolism, immunity, inflammation, hormone/neurotransmitter secretion, etc. Four different FFAR types are known to date, with FFAR1 (formerly known as GPR40) and FFAR4 (formerly known as GPR120) mediating long- and medium-chain FFA actions, while FFAR3 (formerly GPR41) and FFAR2 (formerly GPR43) are essentially the SCFA receptors (SCFARs), responding to all SCFAs, including acetic acid, propionic acid, and butyric acid. As with various other organ systems/tissues, the important roles the SCFARs (FFAR2 and FFAR3) play in physiology and in various disorders of the cardiovascular system have been revealed over the last fifteen years. In this review, we discuss the cardiovascular implications of some key (patho)physiological functions of SCFAR signaling pathways, particularly those regulating the neurohormonal control of circulation and adipose tissue homeostasis. Wherever appropriate, we also highlight the potential of these receptors as therapeutic targets for cardiovascular disorders.

[Tactile communication within the father-mother-baby triad]. / La communication tactile au sein de la triade père-mère-bébé.

This literature review focuses on tactile interactions between parents and their infants. Research on the dyad has explored both cultural differences in touch and the relationship between touch style and hormonal secretion in both parents. The few studies that have examined this communicative modality within the triad have investigated the frequency and type of parent-infant touch, as well as the effect of skin-to-skin contact on tactile interactions at three months postpartum.

TGF-ß1/Smad2/3 signaling pathway modulates octreotide antisecretory and antiproliferative effects in pituitary somatotroph tumor cells.

Octreotide (OCT) is used to inhibit hormone secretion and growth in somatotroph tumors, although a significant percentage of patients are resistant. It has also been tested in nonfunctioning (NF) tumors but with poor results, with these outcomes having been associated with SSTR2 levels and impaired signaling. We investigated whether OCT inhibitory effects can be improved by TGF-ß1 in functioning and nonfunctioning somatotroph tumor cells. OCT effects on hormone secretion and proliferation were analyzed in the presence of TGF-ß1 in WT and SSTR2-overexpressing secreting GH3 and silent somatotroph tumor cells. The mechanism underlying these effects was assessed by studying SSTR and TGFßR signaling pathways mediators. In addition, we analyzed the effects of OCT/TGF-ß1 treatment on tumor growth and cell proliferation in vivo. The inhibitory effects of OCT on GH- and PRL-secretion and proliferation were improved in the presence of TGF-ß1, as well as by SSTR2 overexpression. The OCT/TGF-ß1 treatment induced downregulation of pERK1/2 and pAkt, upregulation of pSmad3, and inhibition of cyclin D1. In vivo experiments showed that OCT in the presence of TGF-ß1 blocked tumor volume growth, decreased cell proliferation, and increased tumor necrosis. These results indicate that SSTR2 levels and the stimulation of TGF-ß1/TGFßR/Smad2/3 pathway are important for strengthening the antiproliferative and antisecretory effects of OCT.

Head-to-head comparison of 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT in localizing tumors with ectopic adrenocorticotropic hormone secretion: a prospective study.

PURPOSE: Localizing the source of ectopic adrenocorticotropic hormone secretion (EAS) is challenging. This study compared the diagnostic value of 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT in tumors with EAS. METHODS: Thirty-six patients with a suspicion of EAS were enrolled to undergo both 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT within 4 weeks for comparison. Twenty-three underwent surgical resection or biopsy. Immunohistochemical staining for SSTR2 and Ki-67 was performed to correlate with 68Ga-DOTATATE uptake and 18F-FDG uptake, respectively. RESULTS: EAS tumors were observed in 20/23 patients. Among the 20 patients with histologically proven EAS tumors, 68Ga-DOTATATE PET/CT correctly identified the tumor in 15 (75.0%), with an SUVmax ranging from 1.4 to 20.7 (6.7 ± 5.5). 18F-FDG PET/CT correctly identified the tumor in 12 (60.0%) patients, with an SUVmax ranging from 1.8 to 10.0 (4.0 ± 2.1). Moreover, 68Ga-DOTATATE PET/CT unmasked the sources of EAS in 6 patients with negative 18F-FDG uptake, and 18F-FDG PET/CT unmasked the sources in 3 patients with negative 68Ga-DOTATATE uptake, resulting in EAS tumors being identified in 18 (90%) patients by combining 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT. CONCLUSIONS: 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT are complementary in localizing and discriminating the source of EAS. 68Ga-DOTATATE PET/CT combined with 18F-FDG PET/CT had higher detection rate than each alone. TRIAL REGISTRATION: 68Ga-DOTATATE PET/CT in Neuroendocrine Tumors (NCT04041882) URL OF REGISTRY: https://clinicaltrials.gov/ct2/show/NCT04041882.

Awareness of the use of hyponatraemia-inducing medications in older adults with hyponatraemia: a study of their prevalent use and association with recurrent symptomatic or severe hyponatraemia.

BACKGROUND: Cautious use or avoidance of hyponatraemia-inducing medications (HIMs) is recommended in older patients with hyponatraemia. OBJECTIVE: To evaluate the use of HIMs after treatment for symptomatic or severe hyponatraemia and to investigate the impact of HIMs on the recurrence of symptomatic or severe hyponatraemia in older patients. DESIGN AND SETTINGS: A cross-sectional and nested case-control study using data obtained from national insurance claims databases. METHODS: The rate of prescribing HIMs during the 3 months before and after the established index date was analysed in a cross-sectional analysis. Multivariable logistic regression was performed to investigate the association between HIM use and recurrence of symptomatic or severe hyponatraemia after adjusting for covariates in a case-control study. RESULTS: The cross-sectional study included 1,072 patients treated for symptomatic or severe hyponatraemia. The proportion of patients prescribed any HIMs after hyponatraemia treatment decreased from 76.9 to 70.1%. The prescription rates significantly decreased for thiazide diuretics (from 41.9 to 20.8%) and desmopressin (from 8.6 to 4.0%), but the proportion of patients prescribed antipsychotics increased from 9.2 to 17.1%. Of 32,717 patients diagnosed with hyponatraemia, 913 (2.8%) showed recurrent hyponatraemia. After adjusting for comorbid conditions, the use of any HIMs including proton pump inhibitors [adjusted odds ratio (aOR) 1.34, 95% confidence interval (CI) 1.15-1.57] and two or more HIMs (aOR 1.48, 95% CI 1.22-1.78) especially in combination with thiazide diuretics increased the likelihood of severe hyponatraemia recurrence. CONCLUSIONS: Prevalent use of HIMs after treatment for symptomatic or severe hyponatraemia and multiple HIM use increase the risk of recurrent hyponatraemia in geriatric patients.

Toxicological Effects of BPDE on Dysfunctions of Female Trophoblast Cells.

Polycyclic aromatic hydrocarbons (PAHs) are widely spread persistent environmental toxicants. Its typical representative benzo[a]pyrene (BaP) is a human carcinogen. BaP can pass through the placental barrier and is finally metabolized into benzo[a]pyren-7, 8-dihydrodiol-9, 10-epoxide (BPDE). BPDE can form DNA adducts, which directly affect the female reproductive health. Based on the special physiological functions of trophoblast cells and its important effect on normal pregnancy, this chapter describes the toxicity and molecular mechanism of BPDE-induced dysfunctions of trophoblast cells. By affecting the invasion, migration, apoptosis, proliferation, inflammation, and hormone secretion of trophoblast cells, BPDE causes diseases such as choriocarcinoma, intrauterine growth restriction, eclampsia, and abortion. In the end, it is expected to provide a scientific basis and prevention approach for women's reproductive health and decision-making basis for the formulation of environmental health standards.

Effects of ammonia on hypothalamic-pituitary-ovarian axis in female rabbits.

BACKGROUND: As one of the most harmful gases in the livestock house, ammonia is recognized as an environmental stressor by Environmental Protection Agency (United States). The study aimed to explore the effect of ammonia on hypothalamic-pituitary-ovarian (HPO) axis of rabbits. A total of ninety two-month-old female IRA rabbits were randomly divided into three groups, and were kept in animal environment control rooms for four weeks at college of animal science and technology, Hebei Agricultural University (Baoding, China). The rabbits in the control group were kept under ammonia concentration of < 3 ppm. The two treatment groups were kept under ammonia concentration of 30 ppm and 50 ppm. Hypothalamus, pituitary, and ovary were collected for hematoxylin and eosin (HE) staining, immunohistochemistry, terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Serum was collected for enzyme-linked immunosorbent assay (ELISA). RESULTS: Histopathological examination revealed that exposed to excess ammonia damaged the morphology and structure of hypothalamus, pituitary, and ovary. TUNEL assay revealed that apoptosis rate increased in hypothalamus, pituitary, and ovary. The protein expression levels of Bcl-2associated X protein (Bax) and Caspase-9 increased, while B-cell lymphoma-2 (Bcl-2) decreased, resulting in apoptosis. Moreover, the concentration of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (PROG) reduced in plasma. The mRNA expression of FSH and LH in pituitary and follicle-stimulating hormone receptor (FSHR), E2, PROG in ovary as well as decreased, indicated hormone secretion disorder. CONCLUSIONS: The results indicated that ammonia exposure damaged hypothalamus, pituitary, and ovary, caused hormone secretion disorder and apoptosis.

Diagnosis and Management of Disorders of Body Tonicity-Hyponatremia and Hypernatremia: Core Curriculum 2020.

Overall body fluid concentration is regulated within a narrow range by the concerted action of the hypothalamic-pituitary axis to influence water intake through thirst and water excretion via the effect of vasopressin, or antidiuretic hormone, on renal collecting duct water permeability. Sodium is the principal extracellular cation; abnormalities in overall effective body fluid concentration, or tonicity, manifest as disturbances in serum sodium concentration. Depending on its severity and chronicity, hyponatremia can lead to significant symptoms, primarily related to central nervous system function. Failure to correct hyponatremia can lead to permanent neurologic damage, as can over rapid correction. It is thus essential to stay within specific limits for correction, particularly for chronic hyponatremia. Hypernatremia also leads to central nervous system dysfunction, although goals for its correction rate are less well established. This Core Curriculum article discusses the normal regulation of tonicity and serum sodium concentration and the diagnosis and management of hypo- and hypernatremia.