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BioRxiv : the Preprint Server For... Jan 2024Chromaffin cells of the adrenal medulla transduce sympathetic nerve activity into stress hormone secretion. The two neurotransmitters principally responsible for...
Chromaffin cells of the adrenal medulla transduce sympathetic nerve activity into stress hormone secretion. The two neurotransmitters principally responsible for coupling cell stimulation to secretion are acetylcholine and pituitary adenylate activating polypeptide (PACAP). In contrast to acetylcholine, PACAP evokes a persistent secretory response from chromaffin cells. However, the mechanisms by which PACAP acts are poorly understood. Here, it is shown that PACAP induces sustained increases in cytosolic Ca which are disrupted when Ca influx through L-type channels is blocked or internal Ca stores are depleted. PACAP liberates stored Ca via inositol trisphosphate receptors (IP3Rs) on the endoplasmic reticulum (ER), thereby functionally coupling Ca mobilization to Ca influx and supporting Ca -induced Ca -release. These Ca influx and mobilization pathways are unified by an absolute dependence on phospholipase C epsilon (PLCε) activity. Thus, the persistent secretory response that is a defining feature of PACAP activity, , is regulated by a signaling network that promotes sustained elevations in intracellular Ca through multiple pathways.
PubMed: 38260572
DOI: 10.1101/2024.01.03.574069 -
International Journal of Molecular... Dec 2023Hypertension is a global civilization disease and one of the most common causes of death in the world. Organ dysfunction is a serious health consequence of hypertension,...
Evaluation of the Expression and Localization of the Multifunctional Protein CacyBP/SIP and Elements of the MAPK Signaling Pathway in the Adrenal Glands of Rats with Primary and Secondary Hypertension.
Hypertension is a global civilization disease and one of the most common causes of death in the world. Organ dysfunction is a serious health consequence of hypertension, which involves damage to the heart, kidneys and adrenals. The interaction of recently discovered multifunctional protein-CacyBP/SIP with ERK1/2 and p38 kinases by regulating the activity and intracellular localization of these kinases may play an important role in the signaling pathways involved in the pathogenesis of hypertension. Due to the lack of data on this subject, we decided to investigate the localization, expression and possible relationship between the studied parameters in the adrenals under arterial hypertension. The study was conducted on the adrenals of rats with spontaneous and DOCA-salt hypertension. The expression of CacyBP/SIP, p-ERK1/2 and p-p38 was detected by immunohistochemistry and qRT-PCR. The results show a statistically significant decrease in CacyBP/SIP expression in the adrenal glands of hypertensive rats. With ERK1/2, there was a decrease in cortical immunoreactivity and an increase in the adrenal medulla of primary hypertensive rats. In contrast, in the adrenals of DOCA-salt rats, ERK1/2 immunoreactivity increased in the cortex and decreased in the medulla. In turn, p38 expression was higher in the adrenal glands of rats with primary and secondary hypertension. The obtained results may suggest the involvement of CacyBP/SIP in the regulation of signaling pathways in which MAP kinases play an important role and provide new insight into molecular events in hypertension. Moreover, they show the participation of CacyBP/SIP in response to oxidative stress.
Topics: Animals; Rats; MAP Kinase Signaling System; Desoxycorticosterone Acetate; Signal Transduction; Adrenal Glands; Hypertension; Sodium Chloride; Sodium Chloride, Dietary; Intracellular Signaling Peptides and Proteins
PubMed: 38203261
DOI: 10.3390/ijms25010084 -
Nutrients Dec 2023During the COVID-19 pandemic, an increase in the incidence of overweight and obesity in children was observed. It appears that unhealthy food choices, an unbalanced... (Review)
Review
During the COVID-19 pandemic, an increase in the incidence of overweight and obesity in children was observed. It appears that unhealthy food choices, an unbalanced diet, and a sedentary lifestyle, as well as experiencing stress related to the pandemic, may be contributing to this disturbing trend. Chronic stress is a significant factor contributing to eating disorders and obesity in youngsters, involving medical, molecular, and psychological elements. Individuals under chronic stress often focus on appearance and weight, leading to negative body image and disrupted relationships with food, resulting in unhealthy eating behaviors. Chronic stress also impacts hormonal balance, reducing the satiety hormone leptin and elevating the appetite-stimulating hormone ghrelin, fostering increased hunger and uncontrolled snacking. Two systems, the hypothalamic-pituitary-adrenal axis and the sympathetic system with the adrenal medulla, are activated in response to stress, causing impaired secretion of noradrenaline and cortisol. Stress-related obesity mechanisms encompass oxidative stress, neuroinflammation, insulin resistance, and neurohormonal and neurotransmission disorders. Stress induces insulin resistance, elevating obesity risk by disrupting blood sugar regulation and fat storage. Stress also affects the gut microbiome, potentially influencing chronic inflammation and metabolic processes linked to obesity. In conclusion, chronic stress is a multifaceted risk factor for eating disorders and obesity in children, necessitating a comprehensive understanding of effective preventive and intervention strategies amid the escalating prevalence of childhood overweight and obesity.
Topics: Child; Humans; Adolescent; Pediatric Obesity; Hypothalamo-Hypophyseal System; Insulin Resistance; Pandemics; COVID-19; Pituitary-Adrenal System; Feeding Behavior
PubMed: 38201884
DOI: 10.3390/nu16010054 -
The Journal of Histochemistry and... Jan 2024The present study investigated the localization and the adenosine 5'-triphosphate (ATP)-degrading function of the plasma membrane-bound ecto-nucleotidase, ectonucleoside...
ADP-mediated Modulation of Intracellular Calcium Responses in Chromaffin Cells: The Role of Ectonucleoside Triphosphate Diphosphohydrolase 2 on Rat Adrenal Medulla Function.
The present study investigated the localization and the adenosine 5'-triphosphate (ATP)-degrading function of the plasma membrane-bound ecto-nucleotidase, ectonucleoside triphosphate diphosphohydrolase 2 (NTPDase2), in the rat adrenal medulla. The effect of ATP degradation product, adenosine 5'-diphosphate (ADP), on carbachol (CCh)-induced intracellular Ca ([Ca]) responses in adrenal chromaffin cells was examined using calcium imaging. NTPDase2-immunoreactive cells were distributed between chromaffin cells. NTPDase2-immunoreactive cells were immunoreactive for glial fibrillary acidic protein and S100B, suggesting that they were sustentacular cells. NTPDase2-immunoreactive cells surrounded chromaffin cells immunoreactive for vesicular nucleotide transporter and P2Y12 ADP-selective purinoceptors. In ATP bioluminescence assays using adrenal medullary slices, ATP was rapidly degraded and its degradation was attenuated by the NTPDase inhibitors sodium polyoxotungstate (POM-1) and 6-, -diethyl-d-β,γ-dibromomethylene ATP (ARL67156). ADP inhibited CCh-induced [Ca] increases of chromaffin cells in adrenal medullary slices. The inhibition of CCh-induced [Ca] increases by ADP was blocked by the P2Y12 purinoceptor antagonist AZD1283. CCh-induced [Ca] increases were also inhibited by the P2Y1, P2Y12, and P2Y13 purinoceptor agonist 2-methylthioadenosine diphosphate trisodium (2MeSADP), in combination with the P2Y1 purinoceptor antagonist MRS2179. These results suggest that sustentacular cells express NTPDase2 to degrade ATP released from adrenal chromaffin cells, and ADP modulates the excitability of chromaffin cells via P2Y12 purinoceptors to regulate catecholamine release during preganglionic sympathetic stimuli. .
Topics: Animals; Rats; Adenosine; Adenosine Triphosphate; Adrenal Medulla; Calcium; Chromaffin Cells; Diphosphates; Adenosine Triphosphatases
PubMed: 38158780
DOI: 10.1369/00221554231221872 -
Ochsner Journal 2023Malignant pheochromocytomas are rare and aggressive tumors that arise from the adrenal medulla and secrete catecholamines. Patients exhibit episodic symptoms of...
Malignant pheochromocytomas are rare and aggressive tumors that arise from the adrenal medulla and secrete catecholamines. Patients exhibit episodic symptoms of hypertension, headaches, sweating, and palpitations. The diagnosis is supported by elevated levels of urinary metanephrines, and imaging is used to determine the stage. Treatment involves surgical resection when possible. A 57-year-old male presented with hematemesis and melena, and endoscopy revealed upper gastrointestinal bleeding. Imaging showed a malignant pheochromocytoma that had infiltrated the upper lobe of the right kidney and the right lobe of the liver, with a tumor thrombus extending into the hepatic inferior vena cava, the right atrium, and the right ventricle. The patient denied surgery and was treated with palliative medical therapy until he died 3 months later. Although rare, malignant pheochromocytomas may present with upper gastrointestinal bleeding. While metastasis to the liver is a typical manifestation of malignant pheochromocytomas, invasion of the inferior vena cava with infiltration to the right ventricle resulting in tricuspid valve malfunction is a rare finding.
PubMed: 38143552
DOI: 10.31486/toj.23.0049 -
International Journal of Molecular... Dec 2023The adrenal gland is paired peripheral end organs of the neuroendocrine system and is responsible for producing crucial stress hormones from its two functional...
The adrenal gland is paired peripheral end organs of the neuroendocrine system and is responsible for producing crucial stress hormones from its two functional compartments, the adrenal cortex, and the adrenal medulla under stimuli. Left-right asymmetry in vertebrates exists from the central nervous system to peripheral paired endocrine glands. The sided difference in the cerebral cortex is extensively investigated, while the knowledge of asymmetry of paired endocrine glands is still poor. The present study aims to investigate the asymmetries of bilateral adrenal glands, which play important roles in stress adaptation and energy homeostasis via steroid hormones produced from the distinct functional zones. Left and right adrenal glands from male C57BL/6J mice were initially histologically analyzed, and high-throughput RNA sequencing was then used to detect the gene transcriptional difference between left and right adrenal glands. Subsequently, the enrichment of functional pathways and ceRNA regulatory work was validated. The results demonstrated that the left adrenal gland had higher tissue mass and levels of energy expenditure, whereas the right adrenal gland appeared to be more potent in glucocorticoid secretion. Further analysis of adrenal stem/progenitor cell markers predicted that Shh signaling might play an important role in the left-right asymmetry of adrenal glands. Of the hub miRNAs, miRNA-466i-5p was identified in the left-right differential innervation of the adrenal glands. Therefore, the present study provides evidence that there are asymmetries between the left and right adrenal glands in glucocorticoid production and neural innervation, in which Shh signaling and miRNA-466i-5p play an important role.
Topics: Animals; Mice; Male; Glucocorticoids; Mice, Inbred C57BL; Adrenal Glands; Adrenal Cortex; MicroRNAs
PubMed: 38139285
DOI: 10.3390/ijms242417456 -
Virchows Archiv : An International... Feb 2024Tumors of the endocrine glands are common. Knowledge of their molecular pathology has greatly advanced in the recent past. This review covers the main molecular... (Review)
Review
Tumors of the endocrine glands are common. Knowledge of their molecular pathology has greatly advanced in the recent past. This review covers the main molecular alterations of tumors of the anterior pituitary, thyroid and parathyroid glands, adrenal cortex, and adrenal medulla and paraganglia. All endocrine gland tumors enjoy a robust correlation between genotype and phenotype. High-throughput molecular analysis demonstrates that endocrine gland tumors can be grouped into molecular groups that are relevant from both pathologic and clinical point of views. In this review, genetic alterations have been discussed and tabulated with respect to their molecular pathogenetic role and clinicopathologic implications, addressing the use of molecular biomarkers for the purpose of diagnosis and prognosis and predicting response to molecular therapy. Hereditary conditions that play a key role in determining predisposition to many types of endocrine tumors are also discussed.
Topics: Humans; Pathology, Molecular; Endocrine Gland Neoplasms; Mutation; Thyroid Gland; Adrenal Gland Neoplasms
PubMed: 38108848
DOI: 10.1007/s00428-023-03713-4 -
Indian Journal of Urology : IJU :... 2023Synchronous tumors comprising of cortical as well as medullary differentiation are rare in the adrenal gland. Collision tumors comprise of two independent neoplasms...
Synchronous tumors comprising of cortical as well as medullary differentiation are rare in the adrenal gland. Collision tumors comprise of two independent neoplasms arising from the cortex and the medulla without any histological admixture. Adrenal cortico-medullary mixed tumors are rare tumors comprising of adrenal cortical and chromaffin cells intermixed with each other. Ganglioneuroma is a rare benign tumor originating from the paravertebral sympathetic ganglia and is rarely seen in the adrenal medulla. The presence of a synchronous ganglioneuroma with an adrenal cortical adenoma in the ipsilateral adrenal gland is exceedingly rare. We report a collision tumor comprising of an adrenal cortical adenoma and a ganglioneuroma detected as an incidental finding in a pediatric patient who presented with hypertension and palpitations.
PubMed: 38077205
DOI: 10.4103/iju.iju_174_23 -
Cureus Nov 2023Phaeochromocytoma is indeed a rare and frequently misunderstood neuroendocrine tumor originating from chromaffin cells in the adrenal medulla. Its clinical presentation...
Phaeochromocytoma is indeed a rare and frequently misunderstood neuroendocrine tumor originating from chromaffin cells in the adrenal medulla. Its clinical presentation often includes paroxysmal hypertension, palpitations, headache, and diaphoresis, which can easily be mistaken for common medical conditions. Timely diagnosis and precise localization are paramount for ensuring the best possible outcomes for patients. In this case report, we describe an unusual presentation of phaeochromocytoma in a 36-year-old man who presented with acute myocarditis. This atypical manifestation underscores the diagnostic challenges associated with phaeochromocytoma, as its symptoms can mimic various other cardiac and non-cardiac conditions. Vigilant clinical evaluation and a multidisciplinary approach are essential for promptly recognizing and managing such cases, thus optimizing patient care and prognosis.
PubMed: 38073930
DOI: 10.7759/cureus.48554