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Vitamins and Hormones 2024The adrenal gland is composed of two distinctly different endocrine moieties. The interior medulla consists of neuroendocrine chromaffin cells that secrete...
The adrenal gland is composed of two distinctly different endocrine moieties. The interior medulla consists of neuroendocrine chromaffin cells that secrete catecholamines like adrenaline and noradrenaline, while the exterior cortex consists of steroidogenic cortical cells that produce steroid hormones, such as mineralocorticoids (aldosterone), glucocorticoids (cortisone and cortisol) and androgens. Synthesis of steroid hormones in cortical cells requires substantial amounts of cholesterol, which is the common precursor for steroidogenesis. Cortical cells may acquire cholesterol from de novo synthesis and uptake from circulating low- and high-density lipoprotein particles (LDL and HDL). As cholesterol is part of the plasma membrane in all mammalian cells and an important regulator of membrane fluidity, cellular levels of free cholesterol are tightly regulated. To ensure a robust supply of cholesterol for steroidogenesis and to avoid cholesterol toxicity, cortical cells store large amounts of cholesterol as cholesteryl esters in intracellular lipid droplets. Cortical steroidogenesis relies on both mobilization of cholesterol from lipid droplets and constant uptake of circulating cholesterol to replenish lipid droplet stores. This chapter will describe mechanisms involved in cholesterol uptake, cholesteryl ester synthesis, lipid droplet formation, hydrolysis of stored cholesteryl esters, as well as their impact on steroidogenesis. Additionally, animal models and human diseases characterized by altered cortical cholesteryl ester storage, with or without abnormal steroidogenesis, will be discussed.
Topics: Animals; Humans; Cholesterol Esters; Lipid Droplets; Cholesterol; Steroids; Hydrocortisone; Mammals
PubMed: 38408810
DOI: 10.1016/bs.vh.2023.06.007 -
Vitamins and Hormones 2024The adrenal glands are key components of the mammalian endocrine system, helping maintain physiological homeostasis and the coordinated response to stress. Each adrenal... (Review)
Review
The adrenal glands are key components of the mammalian endocrine system, helping maintain physiological homeostasis and the coordinated response to stress. Each adrenal gland has two morphologically and functionally distinct regions, the outer cortex and inner medulla. The cortex is organized into three concentric zones which secrete steroid hormones, including aldosterone and cortisol. Neural crest-derived chromaffin cells in the medulla are innervated by preganglionic sympathetic neurons and secrete catecholamines (epinephrine, norepinephrine) and neuropeptides into the bloodstream, thereby functioning as the neuroendocrine arm of the sympathetic nervous system. In this article we review serotonin (5-HT) and the serotonin transporter (SERT; SLC6A4) in the adrenal gland. In the adrenal cortex, 5-HT, primarily sourced from resident mast cells, acts as a paracrine signal to stimulate aldosterone and cortisol secretion through 5-HT/5-HT receptors. Medullary chromaffin cells contain a small amount of 5-HT due to SERT-mediated uptake and express 5-HT receptors which inhibit secretion. The atypical mechanism of the 5-HT receptors and interaction with SERT fine tune this autocrine pathway to control stress-evoked catecholamine secretion. Receptor-independent signaling by SERT/intracellular 5-HT modulates the amount and kinetics of transmitter release from single vesicle fusion events. SERT might also influence stress-evoked upregulation of tyrosine hydroxylase transcription. Transient signaling via 5-HT receptors during embryonic development can limit the number of chromaffin cells found in the mature adrenal gland. Together, this emerging evidence suggests that the adrenal medulla is a peripheral hub for serotonergic control of the sympathoadrenal stress response.
Topics: Animals; Humans; Serotonin; Serotonin Plasma Membrane Transport Proteins; Aldosterone; Hydrocortisone; Adrenal Glands; Mammals
PubMed: 38408804
DOI: 10.1016/bs.vh.2023.06.002 -
Vitamins and Hormones 2024Without knowledge of the spatial [three-dimensional, (3D)] organization of an organ at the tissue and cellular levels, it is impossible to form a complete picture of its...
Without knowledge of the spatial [three-dimensional, (3D)] organization of an organ at the tissue and cellular levels, it is impossible to form a complete picture of its structure and function. At the same time, tissue components hidden in the thickness of the organ are the most difficult to study. The rapid development of computer technologies has contributed both to the development and implementation of new methods for studying 3D microstructures of organs, and the improvement of classical ones but the most complete picture can still be obtained only by recreating 3D models from serial histological sections. This fully applies to the important, but hidden in the thickness of the organ, and difficult to study 3D organization of the adrenal medulla. Only 3D reconstruction from serial sections makes it possible to identify all the main tissue components of the adrenal medulla simultaneously and with good resolution. Of particular importance to this method is the ability to reliably differentiate and study separately the 3D organization of the two main subpopulations of medulla endocrinocytes: adrenaline-storing (A-) cells and noradrenaline-storing (NA-) cells. In this chapter, we discuss the 3D organization of the adrenal medulla based on these original serial section 3D reconstructions and correlating them with data obtained by other methods.
Topics: Rats; Animals; Adrenal Medulla; Norepinephrine; Epinephrine
PubMed: 38408803
DOI: 10.1016/bs.vh.2023.06.003 -
Adaptive remodeling of the stimulus-secretion coupling: Lessons from the 'stressed' adrenal medulla.Vitamins and Hormones 2024Stress is part of our daily lives and good health in the modern world is offset by unhealthy lifestyle factors, including the deleterious consequences of stress and...
Stress is part of our daily lives and good health in the modern world is offset by unhealthy lifestyle factors, including the deleterious consequences of stress and associated pathologies. Repeated and/or prolonged stress may disrupt the body homeostasis and thus threatens our lives. Adaptive processes that allow the organism to adapt to new environmental conditions and maintain its homeostasis are therefore crucial. The adrenal glands are major endocrine/neuroendocrine organs involved in the adaptive response of the body facing stressful situations. Upon stress episodes and in response to activation of the sympathetic nervous system, the first adrenal cells to be activated are the neuroendocrine chromaffin cells located in the medullary tissue of the adrenal gland. By releasing catecholamines (mainly epinephrine and to a lesser extent norepinephrine), adrenal chromaffin cells actively contribute to the development of adaptive mechanisms, in particular targeting the cardiovascular system and leading to appropriate adjustments of blood pressure and heart rate, as well as energy metabolism. Specifically, this chapter covers the current knowledge as to how the adrenal medullary tissue remodels in response to stress episodes, with special attention paid to chromaffin cell stimulus-secretion coupling. Adrenal stimulus-secretion coupling encompasses various elements taking place at both the molecular/cellular and tissular levels. Here, I focus on stress-driven changes in catecholamine biosynthesis, chromaffin cell excitability, synaptic neurotransmission and gap junctional communication. These signaling pathways undergo a collective and finely-tuned remodeling, contributing to appropriate catecholamine secretion and maintenance of body homeostasis in response to stress.
Topics: Humans; Adrenal Medulla; Chromaffin Cells; Synaptic Transmission; Catecholamines; Gap Junctions
PubMed: 38408800
DOI: 10.1016/bs.vh.2023.05.004 -
Metabolites Jan 2024Hypoglycaemia-associated autonomic failure (HAAF) is characterised by an impairment in adrenal medullary and neurogenic symptom responses following episodes of recurrent... (Review)
Review
Hypoglycaemia-associated autonomic failure (HAAF) is characterised by an impairment in adrenal medullary and neurogenic symptom responses following episodes of recurrent hypoglycaemia. Here, we review the status quo of research related to the regulatory mechanisms of the adrenal medulla in its response to single and recurrent hypoglycaemia in both diabetic and non-diabetic subjects with particular focus given to catecholamine synthesis, enzymatic activity, and the impact of adrenal medullary peptides. Short-term post-transcriptional modifications, particularly phosphorylation at specific residues of tyrosine hydroxylase (TH), play a key role in the regulation of catecholamine synthesis. While the effects of recurrent hypoglycaemia on catecholamine synthetic enzymes remain inconsistent, long-term changes in TH protein expression suggest species-specific responses. Adrenomedullary peptides such as neuropeptide Y (NPY), galanin, and proenkephalin exhibit altered gene and protein expression in response to hypoglycaemia, suggesting a potential role in the modulation of catecholamine secretion. Of note is NPY, since its antagonism has been shown to prevent reductions in TH protein expression. This review highlights the need for further investigation into the molecular mechanisms involved in the adrenal medullary response to hypoglycaemia. Despite advancements in our understanding of HAAF in non-diabetic rodents, a reliable diabetic rodent model of HAAF remains a challenge.
PubMed: 38392992
DOI: 10.3390/metabo14020100 -
Journal of Kidney Cancer and VHL 2024This systematic review aims to investigate the clinical presentation, diagnostic methods, and management strategies for pheochromocytoma in patients with von...
This systematic review aims to investigate the clinical presentation, diagnostic methods, and management strategies for pheochromocytoma in patients with von Hippel-Lindau (VHL) disease, an autosomal dominant disorder that predisposes individuals to the development of various tumors, including pheochromocytomas. Pheochromocytoma is a rare neuroendocrine tumor of the adrenal medulla that occurs sporadically or as part of an inherited syndrome. The incidence of pheochromocytoma in VHL patients is estimated to be between 10-20%, making it the second most common tumor associated with VHL. Early detection and management of pheochromocytoma in VHL patients are critical for patient outcomes, as these tumors can cause severe hypertension, cardiovascular complications, and death. This review highlights the importance of screening for pheochromocytoma in VHL patients and discusses the current diagnostic and management strategies to optimize patient care.
PubMed: 38344311
DOI: 10.15586/jkcvhl.v11i1.275 -
International Journal of Molecular... Jan 2024Dichlorodiphenyltrichloroethane (DDT) is a wide-spread systemic pollutant with endocrine disrupting properties. Prenatal exposure to low doses of DDT has been shown to...
Postnatal Exposure to the Endocrine Disruptor Dichlorodiphenyltrichloroethane Affects Adrenomedullary Chromaffin Cell Physiology and Alters the Balance of Mechanisms Underlying Cell Renewal.
Dichlorodiphenyltrichloroethane (DDT) is a wide-spread systemic pollutant with endocrine disrupting properties. Prenatal exposure to low doses of DDT has been shown to affect adrenal medulla growth and function. The role of postnatal exposure to DDT in developmental disorders remains unclear. The aim of the present investigation is to assess growth parameters and the expression of factors mediating the function and renewal of chromaffin cells in the adult adrenal medulla of male Wistar rats exposed to the endocrine disruptor o,p'-DDT since birth until sexual maturation. The DDT-exposed rats exhibited normal growth of the adrenal medulla but significantly decreased tyrosine hydroxylase production by chromaffin cells during postnatal period. Unlike the control, the exposed rats showed enhanced proliferation and reduced expression of nuclear β-catenin, transcription factor Oct4, and ligand of Sonic hedgehog after termination of the adrenal growth period. No expression of pluripotency marker Sox2 and absence of Ascl 1-positive progenitors were found in the adrenal medulla during postnatal ontogeny of the exposed and the control rats. The present findings indicate that an increase in proliferative activity and inhibition of the formation of reserve for chromaffin cell renewal, two main mechanisms for cell maintenance in adrenal medulla, in the adult DDT-exposed rats may reflect a compensatory reaction aimed at the restoration of catecholamine production levels. The increased proliferation of chromaffin cells in adults suggests excessive growth of the adrenal medulla. Thus, postnatal exposure to DDT alters cell physiology and increases the risk of functional insufficiency and hyperplasia of the adrenal medulla.
Topics: Pregnancy; Female; Rats; Animals; Male; Rats, Wistar; Endocrine Disruptors; DDT; Hedgehog Proteins; Adrenal Medulla; Chromaffin Cells; Cell Physiological Phenomena
PubMed: 38338771
DOI: 10.3390/ijms25031494 -
Radiology Case Reports Apr 2024Pheochromocytomas are rare catecholamine-secreting neuroendocrine tumors that originate from chromaffin cells in the adrenal medulla. They cause severe hypertension and...
Pheochromocytomas are rare catecholamine-secreting neuroendocrine tumors that originate from chromaffin cells in the adrenal medulla. They cause severe hypertension and various clinical manifestations. While most arise in the adrenal medulla, some occur in extra-adrenal locations.We present a case report with clinical, laboratory and radiographic data, along with a brief literature review. We report a 33-year-old woman who presented with flushing and sharp lower abdominal pain. Abdominal ultrasound and urinary metanephrines suggested a pheochromocytoma. Subsequent Computed tomography (CT) and Ga-DOTATATE Positron emission tomography/Computed tomography (PET/CT) scans confirmed a pheochromocytoma in the organ of Zuckerkandl with distant bony metastasis. Extra-adrenal pheochromocytomas, or paragangliomas, are rare tumors found in specific anatomical locations. Their diagnostic challenges stem from variable clinical presentations and imaging findings. CT scans and Ga-DOTATATE PET/CT scans are crucial in diagnosis and prognosis. Surgical resection can cure localized cases, while metastatic disease requires palliative options, such as chemotherapy and I131-MIBG, due to a poorer prognosis.
PubMed: 38322234
DOI: 10.1016/j.radcr.2024.01.026 -
International Journal of Surgery Case... Feb 2024Phaeochromocytomas are neuroendocrine neoplasms arising from chromaffin cells of the adrenal medulla and are known as intra-adrenal paragangliomas. On the contrary,...
INTRODUCTION AND IMPORTANCE
Phaeochromocytomas are neuroendocrine neoplasms arising from chromaffin cells of the adrenal medulla and are known as intra-adrenal paragangliomas. On the contrary, paragangliomas are non-epithelial neuroendocrine neoplasms that produce other peptide hormones such as norepinephrine, epinephrine, and dopamine. In a setting with limited resources, such a condition may result in inaccurate diagnosis and treatment, which may lose a patient life if left untreated. In addition, PPGLs present a surgical challenge to many surgeons who are not thoroughly prepared.
CASE PRESENTATION
We describe a case of extra-adrenal paraganglioma in a 27-year-old female who presented with symptoms of heartbeat awareness for almost a year and abdominal swelling for three months. Physical examination revealed a palpable mass around the umbilicus. Abdominal pelvic CT scan revealed a well-circumscribed mass in the central retroperitoneum displacing the IVC laterally and abdominal aorta medially with no invasion of surrounding structures. Results for pheochromocytoma workup showed elevated levels of 24-h urine Vanillylmandelic acid (VMA), and 24-h metanephrine excretion. Laparotomy through extended midline incision was done with successful excision of the tumor. The blood pressure, which was initially high normalized after surgery.
DISCUSSION
The diagnosis of a malignant EAP is commonly made based on recurrence and the development of metastasis to lymph nodes or to other organs. Our patient presented with similar symptoms as pheochromocytoma. Compared to the commonly stated 10 % risk for pheochromocytomas, people with EAPs have been observed to have a 20 % to 50 % incidence of malignancy. EAPs account for at least 15 % of adult and 30 % of pediatric pheochromocytomas and are frequently found in the Zuckerkandl organ. Pheochromocytoma symptoms may manifest asymptomatically in patients with EAPs, or they may occur because of compression of nearby tissues. Surgical excision of the tumor is always the best option in managing EAP.
CONCLUSION
Extra-adrenal paragangliomas can be successfully managed surgically, provided there is a multidisciplinary team, and the tumor location is well recognized and can reduce the chance of tumor metastasis.
PubMed: 38306874
DOI: 10.1016/j.ijscr.2024.109315 -
Psychoneuroendocrinology Apr 2024Existing research indicates that not only own stress leads to physiological stress reactions, but also observing stress in others. So far, a standardized paradigm to... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & OBJECTIVES
Existing research indicates that not only own stress leads to physiological stress reactions, but also observing stress in others. So far, a standardized paradigm to reliably induce physiological stress contagion based on direct face-to-face stress observation compared to an active placebo-stress observing control condition is lacking. Here, we tested a standardized randomized placebo-controlled experimental paradigm to investigate physiological reactivity to direct stress observation and characterized the stress contagion response of the major endocrine stress systems, including full reactivity kinetics.
METHODS
Healthy young male participants were randomly assigned to (1) undergo an adapted version of the Trier Social Stress Test ("TSST participants", n = 20), (2) observe it ("stress observers", n = 36), or (3) observe a corresponding placebo-stress control condition ("placebo-stress observers", n = 30). We repeatedly assessed heart rate, salivary alpha-amylase, salivary cortisol, and salivary aldosterone.
RESULTS
Stress observers exhibited greater physiological reactivity to stress observation as compared to placebo-stress observers to placebo-stress observation in heart rate, salivary alpha-amylase, and cortisol (p's ≤ .027), but not in aldosterone. We observed similar reactivity kinetics in TSST participants and stress observers but less pronounced in stress observers.
DISCUSSION
Extending previous literature, our findings indicate that independent of secondary effects of the observation setting, direct observation of stress in other individuals induces activation of the hypothalamus-pituitary-adrenal axis and the sympathetic-adrenal-medullary axis. Moreover, the physiological stress contagion response resembles the physiological reactivity to first-hand stress but is less pronounced. Potential implications of physiological stress contagion regarding health, cognition, or behavior, as well as modulating factors need to be further elucidated.
Topics: Humans; Male; Aldosterone; Hydrocortisone; Adrenal Medulla; Cognition; Stress, Physiological
PubMed: 38301381
DOI: 10.1016/j.psyneuen.2024.106964