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acth physiology

Alexandra Ahmet, Vincent Brienza, Audrey Tran, Julie Lemieux, Mary Aglipay, Nick Barrowman, Ciaran Duffy, Johannes Roth, Roman Jurencak
OBJECTIVE: Adrenal suppression (AS), a glucocorticoid (GC) side effect with potentially significant morbidity, is poorly understood. The purpose of our study was to determine frequency, duration and predictors of AS following a gradual taper of GC in children with rheumatologic conditions. METHODS: Prospective observational cohort study was conducted. All patients ≤16 years ready to discontinue GC after >4weeks of therapy were included. Morning cortisol was tested 4 weeks after GC taper to physiologic doses and then repeatedly until normalization...
October 9, 2016: Arthritis Care & Research
Ludovic Giloteaux, Maureen R Hanson, Betsy A Keller
BACKGROUND Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) present with profound fatigue, flu-like symptoms, pain, cognitive impairment, orthostatic intolerance, and post-exertional malaise (PEM), and exacerbation of some or all of the baseline symptoms. CASE REPORT We report on a pair of 34-year-old monozygotic twins discordant for ME/CFS, with WELL, the non-affected twin, and ILL, the affected twin. Both twins performed a two-day cardiopulmonary exercise test (CPET), pre- and post-exercise blood samples were drawn, and both provided stool samples for biochemical and molecular analysis...
October 10, 2016: American Journal of Case Reports
Rebecca Dumbell, Alexei Leliavski, Olga Matveeva, Christopher Blaum, Anthony H Tsang, Henrik Oster
The circadian rhythm of glucocorticoids affects diverse physiological systems, including stress responses and the coordination of rhythmic functions in peripheral and central tissues. Circadian clocks are considered to be important coordinators of glucocorticoid release and loss of the core clock component BMAL1 leads to ablation of behavioural and physiological rhythms, hypocortisolism, impaired ACTH and behavioural stress responses. Transplantation and conditional clock gene knock-down studies in mice suggest an important role of local adrenocortical clock function in this context...
October 3, 2016: Endocrinology
Aikaterini A Nella, Ashwini Mallappa, Ashley F Perritt, Verena Gounden, Parag Kumar, Ninet Sinaii, Lori-Ann Daley, Alexander Ling, Chia-Ying Liu, Steven J Soldin, Deborah P Merke
CONTEXT: Classic congenital adrenal hyperplasia (CAH) management remains challenging, as supraphysiologic glucocorticoid doses are often needed to optimally suppress the ACTH-driven adrenal androgen overproduction. OBJECTIVE: To approximate physiologic cortisol secretion via continuous subcutaneous hydrocortisone infusion (CSHI) and evaluate the safety and efficacy of CSHI in difficult-to-treat CAH patients. DESIGN: Eight adult patients with classic CAH participated in a single-center open label phase I-II study comparing CSHI to conventional oral glucocorticoid treatment...
September 28, 2016: Journal of Clinical Endocrinology and Metabolism
E Fazio, P Medica, C Cravana, And A Ferlazzo
AIM: The changes of the hypothalamic pituitary adrenal (HPA) axis response to a long distance transportation results in increase of adrenocorticotropic hormone (ACTH) and cortisol levels. The purpose of the study was to quantify the level of short-term road transport stress on circulating ACTH and cortisol concentrations, related to the effect of previous handling and transport experience of horses. MATERIALS AND METHODS: The study was performed on 56 healthy horses after short-term road transport of 30 km...
August 2016: Veterinary World
Jeffrey Wagner, Cara M Fleseriu, Aly Ibrahim, Justin S Cetas
BACKGROUND: Idiopathic intracranial hypertension (IIH) in patients with Cushing disease (CD), after treatment, is rarely described, in adults. The cause is believed to be multifactorial, potentially related to a relative decrease in cortisol after surgical resection or medical treatment of a corticotroph pituitary adenoma. We investigate our center's CD database (140 surgically and 60 medically [primary or adjunct] treated patients) for cases of IIH, describe our center's experience with symptomatic IIH, and review treatment strategies in adults with CD after transsphenoidal resection...
September 12, 2016: World Neurosurgery
Nobumasa Ohara, Masanori Kaneko, Hideyuki Kuriyama, Kazuhiro Sato, Hideki Katakami, Yutaka Oki, Kenzo Kaneko, Kyuzi Kamoi
A 73-year-old Japanese woman with untreated Graves' hyperthyroidism developed glucocorticoid-induced adrenal insufficiency (AI) after a supraphysiological dose of prednisolone therapy for bronchial asthma. Days later, she had high plasma adrenocorticotropic hormone (ACTH) levels and was expected to recover from glucocorticoid-induced AI. Her plasma ACTH levels remained high over 3 months during a physiological dose of hydrocortisone replacement. However, she suffered a further decrease in her serum cortisol level and was diagnosed with isolated adrenocorticotropin deficiency (IAD), in which bioinactive ACTH likely caused the high ACTH value...
2016: Internal Medicine
Antonio Magrì, Giovanni Tabbì, Alessandro Giuffrida, Giuseppe Pappalardo, Cristina Satriano, Irina Naletova, Vincenzo G Nicoletti, Francesco Attanasio
Semax is a heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) that encompasses the sequence 4-7 of N-terminal domain of the adrenocorticotropic hormone and a C-terminal Pro-Gly-Pro tripeptide. N-terminal amino group acetylation (Ac-Semax) modulates the chemical and biological properties of parental peptide, modifying the ability of Semax to form complex species with Cu(II) ion. At physiological pH, the main complex species formed by Ac-Semax, [CuLH-2](2-), consists in a distorted CuN3O chromophore with a weak apical interaction of the methionine sulphur...
August 27, 2016: Journal of Inorganic Biochemistry
Ferdinand Roelfsema, Paul Aoun, Johannes D Veldhuis
CONTEXT: Factors that regulate physiological feedback by pulses of glucocorticoids on the hypothalamic-pituitary unit are sparsely defined in humans in relation to gluco- or mineralocorticoid receptor pathways, gender, age and the sex-steroid milieu. OBJECTIVE: To test (the clinical hypothesis) that glucocorticoid (GR) and mineralocorticoid (MR) receptor-selective mechanisms differentially govern pulsatile cortisol-dependent negative feedback on ACTH output( by the hypothalamo-pituitary unit) in men and women studied under experimentally defined testosterone (T) and estradiol (E2) depletion and repletion, respectively...
August 22, 2016: Journal of Clinical Endocrinology and Metabolism
Mark Nixon, Scott D Mackenzie, Ashley I Taylor, Natalie Z M Homer, Dawn E Livingstone, Rabah Mouras, Ruth A Morgan, Damian J Mole, Roland H Stimson, Rebecca M Reynolds, Alistair P D Elfick, Ruth Andrew, Brian R Walker
The aim of treatment in congenital adrenal hyperplasia is to suppress excess adrenal androgens while achieving physiological glucocorticoid replacement. However, current glucocorticoid replacement regimes are inadequate because doses sufficient to suppress excess androgens almost invariably induce adverse metabolic effects. Although both cortisol and corticosterone are glucocorticoids that circulate in human plasma, any physiological role for corticosterone has been neglected. In the brain, the adenosine 5'-triphosphate-binding cassette transporter ABCB1 exports cortisol but not corticosterone...
August 17, 2016: Science Translational Medicine
K Kempker, A Güssow, R Neiger
A two year old male Labrador Retriever was treated with delmadinone acetate because of benign prostatic hyperplasia. Four days after the injection the dog showed gastrointestinal signs and a progressive lethargy. In the hospital for small animals of the Justus-Liebig-University of Gießen an ACTH stimulation test was done and a secondary hypoadrenocorticism was diagnosed. The dog was treated with prednisolone in physiological dose for 14 weeks after the injection. The clinical symptoms stopped immediately. A new ACTH stimulation test some weeks later showed a completely normal adrenal function...
March 2016: Schweizer Archiv Für Tierheilkunde
Emilie Pastel, Jean-Christophe Pointud, Antoine Martinez, A Marie Lefrançois-Martinez
Aldose reductase (AKR1B) proteins are monomeric enzymes, belonging to the aldo-keto reductase (AKR) superfamily. They perform oxidoreduction of carbonyl groups from a wide variety of substrates, such as aliphatic and aromatic aldehydes or ketones. Due to the involvement of human aldose reductases in pathologies, such as diabetic complications and cancer, AKR1B subgroup enzymatic properties have been extensively characterized. However, the issue of AKR1B function in non-pathologic conditions remains poorly resolved...
2016: Frontiers in Endocrinology
Hervé Lefebvre, Michaël Thomas, Céline Duparc, Jérôme Bertherat, Estelle Louiset
In the normal human adrenal gland, steroid secretion is regulated by a complex network of autocrine/paracrine interactions involving bioactive signals released by endothelial cells, nerve terminals, chromaffin cells, immunocompetent cells, and adrenocortical cells themselves. ACTH can be locally produced by medullary chromaffin cells and is, therefore, a major mediator of the corticomedullary functional interplay. Plasma ACTH also triggers the release of angiogenic and vasoactive agents from adrenocortical cells and adrenal mast cells and, thus, indirectly regulates steroid production through modulation of the adrenal blood flow...
2016: Frontiers in Endocrinology
Nada El Ghorayeb, Isabelle Bourdeau, André Lacroix
The major physiological regulators of aldosterone production from the adrenal zona glomerulosa are potassium and angiotensin II; other acute regulators include adrenocorticotropic hormone (ACTH) and serotonin. Their interactions with G-protein coupled hormone receptors activate cAMP/PKA pathway thereby regulating intracellular calcium flux and CYP11B2 transcription, which is the specific steroidogenic enzyme of aldosterone synthesis. In primary aldosteronism (PA), the increased production of aldosterone and resultant relative hypervolemia inhibits the renin and angiotensin system; aldosterone secretion is mostly independent from the suppressed renin-angiotensin system, but is not autonomous, as it is regulated by a diversity of other ligands of various eutopic or ectopic receptors, in addition to activation of calcium flux resulting from mutations of various ion channels...
2016: Frontiers in Endocrinology
Gregory P Boivin, Michael A Bottomley, Emily S Dudley, Patricia A Schiml, Christopher N Wyatt, Nadja Grobe
Rodent euthanasia with CO2 by using gradual displacement of 10% to 30% of the chamber volume per minute is considered acceptable by the AVMA Panel on Euthanasia. However, whether a 50% to 100% chamber replacement rate (CRR) of CO2 is more painful or distressful than 10% to 30% CRR is unclear. Therefore, we examined physiological and behavioral parameters, corticosterone and ACTH levels, and lung histology of mice euthanized at CRR of 15%, 30%, 50%, or 100%. Adult male C57BL/6N mice were euthanized at different CO2 CRR as physiological parameters were recorded telemetrically...
2016: Journal of the American Association for Laboratory Animal Science: JAALAS
Aurélia E Lewis, Reidun Aesoy, Marit Bakke
Adrenocorticotropic hormone regulates adrenal steroidogenesis mainly via the intracellular signaling molecule cAMP. The effects of cAMP are principally relayed by activating protein kinase A (PKA) and the more recently discovered exchange proteins directly activated by cAMP 1 and 2 (EPAC1 and EPAC2). While the intracellular roles of PKA have been extensively studied in steroidogenic tissues, those of EPACs are only emerging. EPAC1 and EPAC2 are encoded by the genes RAPGEF3 and RAPGEF4, respectively. Whereas EPAC1 is ubiquitously expressed, the expression of EPAC2 is more restricted, and typically found in endocrine tissues...
2016: Frontiers in Endocrinology
Qiuxiang Ou, Jie Zeng, Naoki Yamanaka, Christina Brakken-Thal, Michael B O'Connor, Kirst King-Jones
Steroid hormones are ancient signaling molecules found in vertebrates and insects alike. Both taxa show intriguing parallels with respect to how steroids function and how their synthesis is regulated. As such, insects are excellent models for studying universal aspects of steroid physiology. Here, we present a comprehensive genomic and genetic analysis of the principal steroid hormone-producing organs in two popular insect models, Drosophila and Bombyx. We identified 173 genes with previously unknown specific expression in steroid-producing cells, 15 of which had critical roles in development...
June 28, 2016: Cell Reports
A-C Schwinn, C H Knight, R M Bruckmaier, J J Gross
One of the most prominent physiological responses to stressors is the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis, currently assessed by measuring cortisol concentration in blood plasma. To reduce animal discomfort during sampling, which negatively affects stress biomarkers, current research focuses on noninvasive sampling of media other than blood, for example, saliva. The aim of this study was to assess the suitability of saliva cortisol as a biomarker under different physiological and immunological states in dairy cows...
June 2016: Journal of Animal Science
H Bobby Fokidis
The secretion of steroids from the adrenal gland is a classic endocrine response to perturbations that can affect homeostasis. During an acute stress response, glucocorticoids (GC), such as corticosterone (CORT), prepare the metabolic physiology and cognitive abilities of an animal in a manner that promotes survival during changing conditions. Although GC functions during stress are well established, much less is understood concerning how adrenal androgens, namely dehydroepiandrosterone (DHEA) are influenced by stress...
September 1, 2016: General and Comparative Endocrinology
John W Funder
Aldosterone is a homeostatic hormone, rising in volume depletion, sodium deficiency, and potassium loading, in response to angiotensin11 and elevation of plasma potassium. Pathophysiologically, in primary aldosteronism (PA) aldosterone levels are inappropriate for the patient's sodium and potassium status, and thus outside the normal feedback loop. ACTH is equivalent with A11 and [K(+)] in elevating aldosterone: its effects differ from those of the other secretagogues in four ways. First, it is not sustained; second, it raises aldosterone and cortisol secretion with equal potency; third, it is outside the normal feedback loops, reflecting the epithelial action of aldosterone; and finally its possible role in driving inappropriate aldosterone secretion (aka PA) is not widely recognized...
2016: Frontiers in Endocrinology
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