Podcasts about corticotropin

Die Anzahl effektiver, gezielter Pharmakotherapien im septischen Schock, einem Krankheitsbild mit einer Mortalität über 30%, ist immer noch limitiert. Die aktuellen Leitlinien der Surviving Sepsis Campaign geben eine schwache Empfehlung mit i.v.-Hydrocortison 200mg/d, basierend auf Evidenz von moderater Qualität. Die sogenannte HPA-Achse, also das System zur Regulation der Stresshormone, scheint aber bei differenzierter Betrachtung von größerer Bedeutung für die Immunmodulation in der Sepsis zu sein als bisher angenommen. Über neueste Studien sprechen wir mit Prof. Briegel von der LMU München. Diskutierte Studien zum Nachlesen:Bosch NA, Teja B, Law AC, Pang B, Jafarzadeh SR, Walkey AJ. Comparative Effectiveness of Fludrocortisone and Hydrocortisone vs Hydrocortisone Alone Among Patients With Septic Shock. JAMA Intern Med. 2023;183(5):451-459. doi:10.1001/jamainternmed.2023.0258Annane D, Renault A, Brun-Buisson C, et al. Hydrocortisone plus Fludrocortisone for Adults with Septic Shock. N Engl J Med. 2018;378(9):809-818. doi:10.1056/NEJMoa1705716Venkatesh B, Finfer S, Cohen J, et al. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock (ADRENAL). N Engl J Med. 2018;378(9):797-808. doi:10.1056/NEJMoa1705835Sprung CL, Annane D, Keh D, et al. Hydrocortisone therapy for patients with septic shock (CORTICUS). N Engl J Med. 2008;358(2):111-124. doi:10.1056/NEJMoa071366Briegel J, Möhnle P, Keh D, et al. Corticotropin-stimulated steroid profiles to predict shock development and mortality in sepsis: From the HYPRESS study. Crit Care. 2022;26(1):343. Published 2022 Nov 7. doi:10.1186/s13054-022-04224-5Dequin PF, Meziani F, Quenot JP, et al. Hydrocortisone in Severe Community-Acquired Pneumonia. N Engl J Med. 2023;388(21):1931-1941. doi:10.1056/NEJMoa2215145

Noradrenaline (norepinephrine) is a neurotransmitter and hormone that plays a role in the body's "fight or flight" response.  Acetylcholine is a neurotransmitter (“brain” +” across” + “to send”) that helps transmit signals in the brain and body. Its name comes from its chemical structure, an acetate group and a choline molecule.  Dopamine is a neurotransmitter that plays a role in motivation, reward, and movement. Its name comes from its chemical structure, a combination of two molecules called dihydroxyphenylalanine and dopamine. Adrenaline (epinephrine) is a hormone and neurotransmitter that helps the body respond to stress. Its name comes from its source, the adrenal glands.  Serotonin is a neurotransmitter that is involved in mood, appetite, and sleep. Its name comes from its chemical structure, a combination of sero- (meaning "serum") and -tonin (meaning "tonic" or "substance that modifies").  Corticotropin-releasing hormone (CRH) is a hormone that stimulates the release of cortisol, a stress hormone. The name comes from its function of stimulating the release of corticotropin, a hormone that stimulates the adrenal glands. Also, it gets its name from its role in stimulating the release of adrenocorticotropic hormone (ACTH) from the pituitary gland, which in turn stimulates the release of cortisol from the adrenal gland. Vasopressin is a hormone that regulates water balance in the body. Its name comes from its ability to constrict blood vessels (vasoconstriction) and increase blood pressure. Vasopressin, also known as antidiuretic hormone (ADH), is so named because it regulates water balance by causing the kidneys to reabsorb water. Thyrotropin-releasing hormone (TRH) is a hormone that stimulates the release of thyroid-stimulating hormone (TSH), which regulates the thyroid gland. Its name comes from its function of stimulating the release of thyrotropin.  Oxytocin is a hormone that is involved in social bonding, childbirth, and lactation. Its name comes from its ability to stimulate uterine contractions (oxytocic) and milk ejection (lactogenic).  Gonadotropin-releasing hormone (GnRH) is a hormone that stimulates the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which regulate the reproductive system. Its name comes from its function of stimulating the release of gonadotropins.  Growth hormone–releasing hormone (GHRH) is a hormone that stimulates the release of growth hormone (GH), which regulates growth and metabolism. Its name comes from its function of stimulating the release of growth hormone.  Catecholamines are a group of hormones and neurotransmitters that includes adrenaline, noradrenaline, and dopamine. Their name comes from their chemical structure, which includes a catechol group and an amine group.  Histamine is a neurotransmitter and hormone that is involved in inflammation, allergies, and gastric acid secretion. ACTH (adrenocorticotropic hormone) is a hormone that stimulates the release of cortisol from the adrenal glands.  Orexin (hypocretin) is a neurotransmitter that is involved in wakefulness and appetite. Its name comes from its discovery in the hypothalamus and its ability to stimulate food intake (orexigenic).  Glutamic acid (glutamate) is a neurotransmitter that is involved in learning, memory, and neural plasticity. Its name comes from its chemical structure, a combination of glutamine and an acid group.  Galanin is a neuropeptide that is involved in pain perception, mood, and appetite. Its name comes from its discovery in the galanin-containing neurons of the hypothalamus.  Neurotensin comes from the words "neuro," meaning related to nerves, and "tensin," which refers to its ability to cause contraction in smooth muscle. Neurotensin is a neuropeptide that is found in the central nervous system and gastrointestinal tract. --- Support this podcast: https://podcasters.spotify.com/pod/show/liam-connerly/support

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.10.535848v1?rss=1 Authors: Hon, O. J., Flanigan, M., Roland, A., Caira, C., Sides, T., D'Ambrosio, S., Lee, S., Simpson, Y., Buccini, M., Machinski, S., Yu, W., Boyt, K., Kash, T. Abstract: Fear is a protective response to perceived danger that allows an organism to identify and respond to threats to avoid harm. Though fear is critical for survival, excessive fear can impede normal biological processes; thus, accurate risk assessment is key for well-being. Here we investigate the neural underpinnings of two distinct behavioral states: phasic and sustained fear. Phasic fear is considered an adaptive response and is characterized by response to a clear and discrete cue that dissipates rapidly once the threat is no longer present. Conversely, sustained fear or anxiety is a heightened state of arousal and apprehension that is not clearly associated with specific cues and lasts for longer periods of time. Here, we directly examine the contribution of BNST CRF signaling to phasic and sustained fear in male and female mice using a partially reinforced fear paradigm to test the overarching hypothesis that plasticity in BNST CRF neurons drive distinct behavioral responses to unpredictable threat in males and females. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.07.531566v1?rss=1 Authors: Metwalli, A. H., Pross, A., Desfilis, E., Abellan, A., Medina, L. Abstract: Understanding the neural mechanisms that regulate the stress response is critical to know how animals adapt to a changing world and is one of the key factors to be considered for improving animal welfare. Corticotropin releasing factor (CRF) is crucial for regulating physiological and endocrine responses, triggering the activation of the sympathetic nervous system and the hypothalamo - pituitary - adrenal axis (HPA) during stress. In mammals, several telencephalic areas, such as the amygdala and the hippocampus, regulate the autonomic system and the HPA responses. These centers include subpopulations of CRF containing neurons that, by way of CRF receptors, play modulatory roles in the emotional and cognitive aspects of stress. CRF binding protein also plays a role, buffering extracellular CRF and regulating its availability. CRF role in activation of the HPA is evolutionary conserved in vertebrates, highlighting the relevance of this system to help animals cope with adversity. However, knowledge on CRF systems in the avian telencephalon is very limited, and no information exists on detailed expression of CRF receptors and binding protein. Knowing that the stress response changes with age, with important variations during the first week posthatching, the aim of this study was to analyze mRNA expression of CRF, CRF receptors 1 and 2, and CRF binding protein in chicken telencephalon throughout embryonic and early posthatching development, using in situ hybridization. Our results demonstrate an early expression of CRF and its receptors in pallial areas regulating sensory processing, sensorimotor integration and cognition, and a late expression in subpallial areas regulating the stress response. However, CRF buffering system develops earlier in the subpallium than in the pallium. These results help to understand the mechanisms underlying the negative effects of noise and light during prehatching stages in chicken, and suggest that stress regulation becomes more sophisticated with age. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.23.529717v1?rss=1 Authors: Maita, I., Bazer, A., Chae, K., Parida, A., Mirza, M., Sucher, J., Phan, M., Liu, T., Hu, P., Soni, R., Roepke, T. A., Samuels, B. A. Abstract: Corticotropin-releasing factor (CRF) in the anterior bed nucleus of the stria terminalis (aBNST) is associated with chronic stress and avoidance behavior. However, CRF+ BNST neurons project to reward- and motivation-related brain regions, suggesting a potential role in motivated behavior. We used chemogenetics to selectively activate CRF+ aBNST neurons in male and female CRF-ires-Cre mice during an effort-related choice task and a concurrent choice task. In both tasks, mice were given the option either to exert effort for high value rewards or to choose freely available low value rewards. Acute chemogenetic activation of CRF+ aBNST neurons reduced barrier climbing for a high value reward in the effort-related choice task in both males and females. Furthermore, acute activation of CRF+ aBNST neurons also reduced effortful lever pressing in high-performing males in the concurrent choice task. These data suggest a novel role for CRF+ aBNST neurons in effort-based decision and motivated behavior. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.28.517564v1?rss=1 Authors: Carson, K. E., Alvarez, J., Mackley, J., Travagli, A., Browning, K. N. Abstract: Perinatal high fat diet (pHFD) exposure is known to affect the development of vagal neurocircuits that control gastrointestinal (GI) motility and reduce stress resiliency in offspring. Descending oxytocin (OXT; prototypical, anti-stress peptide) and corticotropin releasing factor (CRF; prototypical, stress peptide) inputs from the paraventricular nucleus (PVN) of the hypothalamus to the dorsal motor nucleus of the vagus (DMV) modulate the GI stress response. However, how these descending inputs, and their associated changes to GI motility and stress responses, are altered following pHFD exposure are unknown. The present study used in vivo recordings of gastric tone and motility, in vivo assays of gastric emptying rates, in vitro electrophysiological recordings from brainstem slice preparations, and retrograde neuronal tracing experiments to investigate the hypothesis that pHFD alters descending PVN-DMV inputs, dysregulating DMV neuronal responses and subsequent gastric motility. Basal gastric emptying rates were found to be significantly delayed in pHFD rats, which also demonstrating an inability to mount an appropriate response to acute stress with a further delay in gastric emptying. Neuronal tracing experiments suggested that pHFD reduced PVNOXT neurons that project to the DMV but increased PVNCRF projections. Whole cell patch clamp recordings of DMV neurons demonstrated that, following pHFD, PVNCRF projections are tonically active, altering GABAergic inputs to DMV neurons. Lastly, blocking DMV CRF receptors in pHFD rats restored the appropriate gastric response to brainstem oxytocin application. Taken together, these results indicate that pHFD exposure leads to an upregulating of CRF inputs to the DMV, resulting in tonic CRF activation on the system and altering gastric motility. These results suggest that pHFD exposure leads gastric dysmotility, leading to a maladaptive gastric stress response and reduced stress resiliency. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Taking a minor break from ruffling the f*cking cages and feathers of what we call modern society these days and I wanted to talk about something a bit more conventional but important nevertheless and that is sleep. I have a multitude of studies for you to do your own research as I want to present this topic as clear cut as possible.   Time Stamps:   (0:28) Are You Enjoying the Podcast? (2:30) Going On a Journey With Sleep (6:40) Adverse Effects From Poor Sleep (16:30) Stress and the Blood-Brain Barrier (18:50) Naps ---------------------------- Resources: [i] Pilcher JJ, Walters AS. How sleep deprivation affects psychological variables related to college students' cognitive performance. J Am Coll Health. 1997 Nov;46(3):121-6. View Abstract [ii] Walker MP, et al. Practice with sleep makes perfect: sleep-dependent motor skill learning. Neuron. 2002 Jul 3;35(1):205-11. View Abstract [iii] Rosen IM, et al. Evolution of sleep quantity, sleep deprivation, mood disturbances, empathy, and burnout among interns. Acad Med. 2006 Jan;81(1):82-5. View Abstract [iv] Cohen S, et al. Sleep habits and susceptibility to the common cold. Arch Intern Med. 2009 Jan 12;169(1):62-7. View Full Paper [v] Patel SR, et al. Association between reduced sleep and weight gain in women. Am J Epidemiol. 2006 Nov 15;164(10):947-54. View Full Paper [vi] Donga E, et al. A single night of partial sleep deprivation induces insulin resistance in multiple metabolic pathways in healthy subjects. J Clin Endocrinol Metab. 2010 Jun;95(6):2963-8. View Abstract [vii] Williamson AM, Feyer AM. Moderate sleep deprivation produces impairments in cognitive and motor performance equivalent to legally prescribed levels of alcohol intoxication. Occup Environ Med. 2000 Oct;57(10):649-55. View Full Paper [viii] Kim TW, Jeong JH, Hong SC. The impact of sleep and circadian disturbance on hormones and metabolism. Int J Endocrinol. 2015;2015:591729. View Full Paper [ix] Vgontzas AN, et al. IL-6 and its circadian secretion in humans. Neuroimmunomodulation. 2005;12(3):131-40. View Abstract [x] Meier-Ewert HK, et al. Absence of diurnal variation of C-reactive protein concentrations in healthy human subjects. Clin Chem. 2001 Mar;47(3):426-30. View Full Paper [xi] Meier-Ewert HK, et al. Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk. J Am Coll Cardiol. 2004 Feb 18;43(4):678-83. View Abstract [xii] van Leeuwen WM, et al. Sleep restriction increases the risk of developing cardiovascular diseases by augmenting proinflammatory responses through IL-17 and CRP. PLoS One. 2009;4(2):e4589. View Full Paper [xiii] Chennaoui M, et al. Effect of one night of sleep loss on changes in tumor necrosis factor alpha (TNF-α) levels in healthy men. Cytokine. 2011 Nov;56(2):318-24. View Abstract [xiv] Vgontzas AN, et al. Chronic insomnia is associated with a shift of interleukin-6 and tumor necrosis factor secretion from nighttime to daytime. Metabolism. 2002 Jul;51(7):887-92. View Abstract [xv] He J, et al. Sleep restriction impairs blood-brain barrier function. J Neurosci. 2014 Oct 29;34(44):14697-706. View Full Paper [xvi] Zlokovic BV. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron. 2008 Jan 24;57(2):178-201. View Abstract [xvii] Hurtado-Alvarado G, et al. Blood-Brain Barrier Disruption Induced by Chronic Sleep Loss: Low-Grade Inflammation May Be the Link. J Immunol Res. 2016;2016:4576012. View Full Paper [xviii] Esposito P, et al. Corticotropin-releasing hormone and brain mast cells regulate blood-brain-barrier permeability induced by acute stress. J Pharmacol Exp Ther. 2002 Dec;303(3):1061-6. View Full Paper [xix] Steiger A. Sleep and the hypothalamo-pituitary-adrenocortical system. Sleep Med Rev. 2002 Apr;6(2):125-38. View Abstract [xx] Vgontzas AN, et al. Daytime napping after a night of sleep loss decreases sleepiness, improves performance, and causes beneficial changes in cortisol and interleukin-6 secretion. Am J Physiol Endocrinol Metab. 2007 Jan;292(1):E253-61. View Full Paper ---------------------------- Follow Me on Instagram! @tayloredwellbeing ---------------------------- Click Here to Apply to Work with Me or visit taylorsappington.com/application

References Cell Tissue Res. 2019 Jan; 375(1): 143–172. Int. J. Mol. Sci. 2021, 22(21), 11465 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

References Dr Guerra's neuroscience lectures Neurosci BiobehavRev. 2019 Aug; 103: 50–59 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

In this podcast, Dhiman Basu, MD, highlights current treatment options for patients with rheumatoid arthritis (RA), findings from a phase 4 clinical trial that assessed the safety and efficacy of repository corticotropin injection among patients with refractory disease, and more.

Homeostatic chronic low stress results in low to moderate levels of CRF in the LC in association with enhanced Extra-Dimensional Shifting and optimal executive decision making. However, acute or chronic severe stress is linked to high levels of CRF in the LC and this may contribute to a shift from optimal executive function necessary for goal-directed behavior toward an iterative decision response. In healthy environments, this variable tonicity is a readout for adaptation when goal-oriented behavior is relaxed so that the individual uses pro-forma decisions even when novel environmental stimuli are encountered. During aging these pathways lose flexibility due to a decrease in executive decision making linked to the senescence phenotype that may impair neural circuitry via inflammation, over or under activation and lack of control over immune cell responses. J Neurosci. 2008 Nov 5; 28(45): 11517–11525. GeroScience. 2017 Feb; 39(1): 61–72. Neuroscience. 2017 Mar 14; 345: 12–26. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Adaptation to stress-such as the fear response obtains dopaminergic input to striatum and prefrontal cortex and is thought to signal unexpected events and facilitate a shift in attention to promote new learning within the contralateral primary somatosensory cortex (SI) which has been associated with the agentic categories of both the quality and quantity of thought event ontology. This process works in conjunction with the bilateral secondary somatosensory cortex (SII) process involved in executive decision making. Where stimulated, the primary sensory motor-neuronal process is integrated with novel extra-dimensional learning . Recall that this fear stress response can lose functional valency upon immune-regulating, senescent secretory phenotypes. In the aging brain, where CRF axon terminals are widely distributed, (including within catecholamine and serotonin nuclei) there are widespread cortical projections into the medial prefrontal cortex; linking executive functional responses to adverse stimuli. Dr. Daniel J. Guerra Authentic Biochemistry Published 20 Jan 2021 Refs Neuroimage. 2008 May 1;40(4):1765-71. Biol Psychiatry. 2009 Sep 15; 66(6): 586–593. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

•Intensive and chronic or excessive stress diminishes intellectual performance and general cognition: this is a form of negative reinforcement and can be related to learning disability and anxiety about future events. Indeed, •Individual responses and the magnitude of stressor as well as its association with self identity and goals will influence endurance, resilience, and self-empowerment vs. dissatisfaction and defeat. •Stresses first become recognized in the developing fetus since the fetal brain attains awareness during the first trimester and maternal stress is well established as an epigenetic mechanism involved in fetal neural development and stress is lifelong , contributing to one’s character and ability to overcome fear and anxiety. •Stress response is an element of the hypothalamic-pituitary-adrenocortical (HPA) axis where Corticotropin-releasing factor (CRF) serves as a gate keeper for fear conditioning playing dual roles as hormone and as neuromodulator. •CRH exerts multiple effects on the adult brain, often spatiotemporal, as shown by secretion site-specific responses in that CRH after binding to its GPCR's: CRHR1 and CRHR2 which subsequently regulates the formation of neuronal dendrites; neurite elongation, synaptogenesis, and circuit integration of adult-born neurons thus organizing and modifying excitatory transmission in a neuronal type-specific manner Transl Psychiatry. 2019; 9: 272. Cell Reports Oct 2019, 29, 932–945 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

1. Corticotropin releasing factor (CRF) or hormone (CRH) is one of several neurohormones synthesized by specific hypothalamic nuclei in the brain and released into the portal system which bathes the anterior pituitary 2. CRF has marked CNS effects by acting at higher centers in the brain: cortical regions where there is a widespread distribution of CRF neurons. 3. Major role of CRF is to prepare the organism for an appropriate response to various stressors such as physical trauma, insults to the immune system and social interactions 4. It is the hyper- or hyposensitivity of the system that can lead to human pathologies such as anxiety, depression and feeding disorders 5. The hypothalamus induced combined pituitary hormone deficiency, which is responsible for systemic hypoplasia is the result of a neutral sphingomyelinase (SMPD3)deficiency 6. SMPD3 deficiency triggers acid sphingomyelinase (ASM) plus de novo CER synthesis and salvage CER production from sphingosine with concomitant alterations in membrane PLC mediated DAG enrichment of VLCPUFA’s and their SFA counterparts thus diturbing membrane raft-mediated signaling and cell death and an appropriate local immune response thus disturbing glucocorticoid (and a host of other) HPA axis hormones. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.24.219451v1?rss=1 Authors: Yu, W., Stanhope, C. M., Rivera Sanchez, N. d. R., Moseley, G. A., Kash, T. L. Abstract: The bed nucleus of the stria terminalis (BNST) plays an emerging yet understudied role in pain. Corticotropin-releasing factor (CRF) is an important source of pain modulation in the BNST, with local pharmacological inhibition of CRF receptors impacting both the sensory and affective components of pain. Knowledge on how pain dynamically engages CRF neurons in the BNST and is influenced by intra-BNST production of CRF remains unknown. In the present study, we utilized in vivo calcium imaging to show robust and synchronized recruitment of BNSTCRF+ neurons during acute exposure to noxious heat. Distinct patterns of recruitment were observed by sex, with males exhibiting a greater magnitude of heat responsive activity in BNSTCRF+ neurons than females. We then established the necessity of CRF for intact pain behaviors by genetically deleting Crf in the BNST, which reduced thermal and mechanical nociceptive sensitivity for both sexes, and increased paw attending responses to thermal nociception in female mice, suggesting a divergent role for CRF with respect to pain-related affective-motivational behaviors. Together, these findings demonstrate that CRF in the BNST contributes to multiple facets of the pain experience and may play a key role in the sex-specific expression of pain-related behaviors. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.22.215947v1?rss=1 Authors: Rouzer, S. K., Diaz, M. R. Abstract: Adolescents are phenotypically characterized with hyper-sensitivity to stress and inappropriate response to stress-inducing events. Despite behavioral distinctions from adults, investigations of developmental shifts in the function of stress peptide corticotrophin-releasing factor (CRF) are generally limited. Rodent models have determined that CRF receptor 1 (CRFR1) activation within the central amygdala is associated with a stress response and induces increased GABAergic synaptic neurotransmission within adult males. To investigate age-specific function of this system, we performed whole-cell patch clamp electrophysiology in brain slices from naive adolescent (postnatal days (P) 40-49) and adult (>P70) male and female Sprague Dawley rats to assess GABAergic activity in the medial central amygdala (CeM). Our results indicate a dynamic influence of age and sex on neuronal excitability within this region, as well as basal spontaneous and miniature (m) inhibitory post-synaptic currents (IPSCs) in the CeM. In addition to replicating prior findings of CRFR1-regulated increases in mIPSC frequency in adult males, we found that the selective CRFR1 agonist, Stressin-1, attenuated mIPSC frequency in adolescent males, at a concentration that did not affect adult males. Importantly, this age-specific distinction was absent in females, as Stressin-1 attenuated mIPSC frequency in both adolescent and adult females. Finally, only adult males exhibited an increase in mIPSC frequency in response to the CRF1R antagonist, NBI 35965, suggestive of tonic CRFR1 activation in the CeM of adult males. Together, these data emphasize the robust influence of age and sex on neurophysiological function of a brain region involved in the production of the stress response. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.23.168310v1?rss=1 Authors: Wang, Y., Hu, P., Shan, Q., Huang, C., Huang, Z., Chen, P., Li, A., Gong, H., Zhou, J.-N. Abstract: Corticotropin-releasing hormone (CRH) is an important neuromodulator with wide distribution in the brain. Here, we screened the CRH-IRES-Cre;Ai32 mouse line to reveal the morphologies of individual CRH neurons throughout the mouse brain by using fluorescence micro-optical sectioning tomography (fMOST) system. Diverse dendritic morphologies and projection fibers were found in various brain regions. Reconstructions showed hypothalamic CRH neurons had the smallest somatic volumes and simplest dendritic branches, and CRH neurons in several regions shared a bipolar morphology. Further investigations in the medial prefrontal cortex unveiled somatic depth-dependent morphologies that exhibited three types of connections and CRH neurons in the anterior parvicellular area of hypothalamus had fewer and smaller Herring bodies whereas in the periventricular area had more and larger Herring bodies that were present within fibers projecting to the third ventricle. Our findings provide the most comprehensive intact morphologies of CRH neurons throughout the mouse brain that is currently available. Copy rights belong to original authors. Visit the link for more info

Welcome to The Nutritional Pearls Podcast! Focusing on topics that include digestion, adrenal fatigue, leaky gut, supplementation, electrolytes, stomach acid, and so much more, “The Nutritional Pearls Podcast” features Christine Moore, NTP and is hosted by Jimmy Moore, host of the longest running nutritional podcast on the Internet.  Sharing nuggets of wisdom from Christine's training as a Nutritional Therapy Practitioner and Jimmy's years of podcasting and authoring international bestselling health and nutrition books, they will feature a new topic of interest and fascination in the world of nutritional health each Monday. Listen in today as Christine and Jimmy talk all about the endocrine system in Episode 15. Here's what Christine and Jimmy talked about in Episode 15: 1. What is the Endocrine System? The collection of glands that produce hormones that regulate metabolism, growth and development, tissue function, sexual function, reproduction, sleep, and mood, among other things. 2. Definition of hormones: Regulatory substances produced in an organism and transported in tissue fluids such as blood to stimulate specific cells or tissues into action. 3. Glands of the endocrine system and the minerals they depend on: A. Hypothalamus: Located in the brain, this is the part of the brain that controls the endocrine system. Think of it as a control center. It links the nervous system to the endocrine system through the Pituitary Gland. It releases at least 7 to 8 hormones that control the Pituitary Gland. The hypothalamus needs chromium for good health. 1. Thyrotropin-releasing Hormone (TRH)-a releasing hormone produced by the hypothalamus that stimulates the release of thyrotropin (thyroid-stimulating hormone or TSH) and prolactin from the pituitary gland. 2. Gonadotropin-releasing Hormone (GnRH)-signals the pituitary gland to create two hormones called leutenizing hormone (LH) and follicle-stimulating hormone (FSH) 3. Growth Hormone-releasing Hormone (GHRH)-stimulates the pituitary gland to produce and release growth hormone into the bloodstream. Once growth hormone is releases into the blood, it has an affect on just about every tissue of the body to control metabolism and growth. 4. Corticotropin-releasing Hormone (CRH)-Its main function is to stimulate the pituitary gland to produce Adrenocorticotropic Hormone (ACTH) 5. Somatostatin - it regulates the secretion of hormones coming from the pituitary gland, including growth hormone and thyroid stimulating hormone. It also inhibits the secretion of pancreatic hormones which include Glucagon and Insulin 6. Dopamine - this functions as a neurotransmitter which is a chemical released by neurons or nerve cells to send signals to other nerve cells. The brain has many distinct dopamine pathways and one of these pathways plays a big role in reward-motivated behavior. B. The Pituitary Gland: Located in the brain, it has also been described as the “master gland” because it secretes hormones that control other endocrine glands. It needs manganese for good health 1. Oxytocin-controls key aspects of the reproductive system and some aspects of human behavior 2. Prolactin-hormone that helps women produce milk after childbirth and it's important to both male and female reproductive health 3. Leutenizing Hormone-triggers ovulation and stimulates the production of testosterone 4. Anti-diuretic Hormone (ADH)-tells your kidneys how much water to conserve; it also constantly regulates and balances the amount of water in your blood 5. Human Growth Hormone (HGH)-encourages growth in children and adolescents, helps to regulate body composition as well as bodily fluids and muscle and bone growth, helps regulate sugar and fat metabolism, and it possibly helps with heart function C. The Pineal Gland also known as the Third Eye: This gland is also in the brain and it produces melatonin which helps with circadian rhythm. It is also known as the Third Eye because the Third Eye chakra in the Hindu system is located in the center of the forehead which is near the pineal gland. It depends on iodine and boron for good health. D. The Thyroid Gland: It depends on iodine and tyrosine. It is located in the front of the neck just below the Adams apple and is considered to be one of the major glands in the regulation of metabolism. It produces: 1. thyroxine (T4) which gets converted to its active form, triiodothyronine (T3) with the help of selenium. T3 controls basil metabolic rate 2. Calcitonin-responsible for the uptake of calcium to the bone E. The Parathyroid Gland: It's located in the neck behind the thyroid and produces parathormone or PTH which is associated with the growth of muscle and bone and distribution of calcium and phosphate in the body. It depends on calcium for good health. F. The thymus: The thymus lays across the trachea and bronchi in the upper thorax. It produces thymosin which triggers the immune system by activating the T-Cells and T-Lymphocytes which are white blood cells associated with antibody production. The thymus needs zinc for good health. G. The pancreas: It lies behind the stomach and needs chromium for good health. The pancreas produces: 1. Insulin by the Beta Cells which is responsible for the conversion of glucose to glycogen, shuttling glucose into the cells, and the conversion of excess glucose to fat 2. Glucagon by the Alpha Cells which is responsible for the conversion of glycogen to glucose H. The adrenal glands: They are on top of the kidneys and they rely on copper for good health. They produce: 1. Adrenalin which prepares the body for fight or flight 2. noradrenalin-which has similar effects to adrenalin 3. corticosteroids that include cortisol, cortisone, and corticosterone I. The ovaries: They are located in the lower abdomen and they rely on selenium for good health. They produce: 1. Estrogen which is responsible for the break-down of the uterus wall 2. progesterone which builds up and maintains the uterus wall for embedding of fertilized egg and is also associated with body hair, breast enlargement, and physical changes in the body J. The testes: They're located outside the pelvic cavity and produce testosterone which is responsible for the development and function of male sex organs and is associated with body hair, muscle development, and voice change. They rely heavily on selenium for good health. K. The prostate: It's about the size of a walnut located between the bladder and the penis. It produces prostate-specific antigen (PSA) which help keep the sperm in liquid form. The prostate relies on zinc for good health. 4. People with different endocrine issues carry weight on specific parts of the body A. If someone has adrenal gland problems through prolonged stress, cortisol is released and stores fat around the most vital organs which are in your midsection. Thus, a person with adrenal issues will carry more weight around their midsection. B. People with thyroid issues tend to carry weight all over since the thyroid controls the metabolism in all of your cells. C. For people with problems with their ovaries, they will tend to carry extra weight around their hips and lower stomach area. D. If a person has liver problems, they will tend to carry extra weight around their body but have thin legs 5. Blood sugar imbalances mess up the entire endocrine system because not only are the pancreas, liver, and adrenal glands all necessary for blood sugar regulation but they are also heavily involved in the endocrine system. Nutritional Pearl for Episode 15: It is very important to make sure blood sugar levels are normalized and under control before addressing any endocrine problem you have because blood sugar imbalances disrupt the entire endocrine system. BECOME A NUTRITIONAL THERAPY PRACTITIONER Sign up for the 9-month program NOTICE OF DISCLOSURE: Paid sponsorship YOUR NEW KETO DIET ALLY NOTICE OF DISCLOSURE: Paid sponsorship LINKS MENTIONED IN EPISODE 15 – SUPPORT OUR SPONSOR: Complete nutriton for nutritional ketosis (COUPON CODE LLVLC FOR 10% OFF YOUR FIRST ORDER) – SUPPORT OUR SPONSOR: Become A Nutritional Therapy Practitioner – NutritionalTherapy.com

Die Hypothalamus-Hypophysen-Nebennierenrinden-Achse (HPA-Achse) ist ein hierarchisch organisiertes, neuroendokrines System, das unter anderem die Freisetzung des Nebennierenrindenhormons Kortisol, dem zentralen Hormon der Stressantwort und der Homöostase des Organismus in Bezug auf die Anpassung an Umweltanforderungen, regelt. Die HPA-Achse ist in ein komplexes System von Regulationsnetzwerken eingebunden, über die der Organismus die Anpassung an ständig wechselnde Anforderungen erfasst und steuert. Fehlanpassungen der HPA-Achse sind hierbei von großer klinischer Bedeutung, da sie zu psychiatrischen Erkrankungen führen können. Ziel der vorliegenden Arbeit war es daher, HPA-Achsen-regulierende kortikale Netzwerke mithilfe der funktionalen Magnetresonanztomographie (fMRT) in verschiedenen Versuchansätzen zu identifizieren. Der Stand der bisherigen Forschungsergebnisse deutet darauf hin, dass es grundsätzlich einen mit der Methode der fMRT messbaren Zusammenhang zwischen diesen kortikalen Netzwerken im Gehirn und der neuroendokrinologischen Stressregulationsachse (HPA-Achse) gibt. Wichtige Knotenpunkte solcher kortikaler Netzwerke sind dabei insbesondere Kerne der Amygdala, Teile des Hippokampus und des Hypothalamus sowie Bereiche des präfrontalen Kortex. Diese Regionen üben zum einen Einfluss auf die Freisetzung des Corticotropin-releasing-Hormons (CRH) im Hypothalamus aus, zum anderen werden sie durch Kortisol rekursiv in ihrer Funktion durch ein negatives Feedback beeinflusst. Diese beiden Aspekte wurden im Rahmen dieser Arbeit in separaten Analysen bearbeitet: Es wurde zunächst untersucht, ob die Aktivität der kortikalen Netzwerke des Gehirns in Ruhe das Ergebnis des kombinierten Dexamethason-Suppressions-CRH-Stimulations-Tests (Dex/CRH-Test) als sensitiven endokrinologischen Stresstest vorhersagen kann. Ferner wurde untersucht, ob sich die Aktivität der Ruhenetzwerke durch eine experimentelle Modulation des Kortisolspiegels signifikant verändert, wobei sowohl der Effekt einer intravenösen Applikation von Kortisol im Vergleich zu Placebo als auch der Effekt einer durch Dexamethason herbeigeführten Suppression von Kortisol untersucht wurde. Bei der hierfür durchgeführten Studie handelt es sich um ein placebo-kontrolliertes, endokrinologisches fMRT-Experiment im Cross-Over-Design mit kombinierter EEG. Zusätzlich zu den EEG/fMRT-Ruhe-Messungen wurde ein Dex/CRH-Test außerhalb des MRT aufgenommen, um die Funktionalität der HPA-Achse in den Probanden zu quantifizieren. Es wurden 20 gesunde männliche Probanden untersucht. An den Messtagen 1 und 3 wurde je eine knapp einstündige kombinierte EEG/fMRT-Messung durchgeführt, wobei einmal 20 mg Kortisol, gelöst in 10 ml Kochsalzlösung, und einmal 0,9%-ige Kochsalzlösung (10 ml) während der Messung durch eine Bolusinjektion verabreicht wurden. Am Messtag 2 wurden die EEG/fMRT-Ruhe-Daten (~ 15 Minuten) im Status der Kortisolsuppression durch Dexamethason aufgenommen. Die kombinierte EEG-Messung diente hier vor allem der Vigilanzüberwachung der Probanden, da aus verschiedenen Studien bekannt ist, dass sich die Ruhenetzwerke des Gehirns in Abhängigkeit des Vigilanzstatus verändern. An einem zusätzlichen 4. Messtag wurde außerhalb des MRT an einer Teilgruppe der Probanden die Wirkung einer Kortisolbolusinjektion (20 mg) auf Blutdruck, Puls und Sauerstoffsättigung bestimmt und zusätzlich auch die Wirksamkeit des extern zugeführten Kortisols auf die HPA-Achse ermittelt. Die fMRT-Ruhe-Daten wurden mit komplementären Methoden aus dem Bereich der Konnektivitätsanalysen untersucht. Dabei wurden sowohl hypothesengeleitete Analysen von Ruhenetzwerken über die Seed-Methode als auch Kreuzkor-relationsanalysen definierter Regionen, oder - im explorativen Ansatz - des gesamten Gehirns einschließlich voxelbasierter Verfahren, angewandt. Die Analysen zur Modulierung des Kortisolmilieus insgesamt betrachtet lassen den Schluss zu, dass sich die funktionelle Konnektivität des Gehirns in Ruhe durch die Änderung des Kortisolmilieus ändert, sei es durch direkte exogene Kortisolgabe, oder indirekten Kortisolentzug durch die Dexamethasonsuppression. Der Schwerpunkt dieser kortisolabhängigen Modulation lag dabei in präfrontal basierten Ruhenetzwerken. In den Analysen, in denen die drei Zustände der Kortisolmilieuänderungen (Kortisol, Placebo, Kortisolsuppression) verglichen wurden, zeigten sich stärkere Effekte durch die Kortisolsuppression als durch das exogen zugeführte Kortisol. Diese Effekte hatten ihren regionalen Schwerpunkt für die hypothesenbasierte Seedanalyse im medialen präfrontalen Kortex/anterioren cingulären Kortex (ACC), und in der explorativen Analyse im dorsolateralen präfrontalen Kortex. Effekte auf den Hippokampus und die Amygdala waren dabei relativ schwach ausgeprägt. Die Analysen der dynamischen Änderung nach Kortisolgabe im Vergleich zu Placebo zeigten Effekte im subcallosalen/ subgenualen ACC und im dorsalen ACC, sowohl im hypothesengesteuerten als auch im explorativen Ansatz. Da der Analyseschwerpunkt bisheriger Arbeiten auf der Hippokampus/Amygdala-Region lag wird neu postuliert, dass Akuteffekte nach 20 mg Kortisol möglicherweise auf ACC-Regionen stärker wirken als auf den Hippokampus. Ebenfalls hergestellt werden konnte ein prädiktiver Zusammenhang zwischen der Stärke der funktionellen Konnektivität in limbischen und paralimbischen Regionen in Ruhe, insbesondere hippokampaler Netzwerke, und dem Ergebnis des Dex/CRH-Tests. Da der Dex/CRH-Test das gesamte zerebrale Feedbacksystem belastet, kann hieraus abgeleitet werden, dass spezifische Netzwerke in beiden Korrelationsrichtungen einen Einfluss auf das Ergebnis des Dex/CRH-Tests haben. Damit wurde erstmals indirekt das Regulationssystem sichtbar gemacht, das durch den Dex/CRH-Test belastet wird. In zukünftigen Studien können die konzentrations- und zeitabhängige Sensitivität der Ruhenetzwerke gegenüber Kortisol, zusammen mit der funktionellen Konnektivität, die die individuelle Regulation der HPA-Achse vorhersagt, als Grundlage zur Etablierung eines Stressbiomarkes verwendet werden.

Endometriosis is considered as a benign aseptic inflammatory disease, characterised by the presence of ectopic endometrium-like tissue. Its symptoms (mostly pain and infertility) are reported as constant stressors. Corticotropin releasing hormone (CRH) and urocortin (UCN) are neuropeptides, strongly related to stress and inflammation. The effects of CRH and UCN are mediated through CRHR1 and CRHR2 receptors which are implicated in several reproductive functions acting as inflammatory components. However, the involvement of these molecules to endometriosis remains unknown. The aim of this study was to examine the expression of CRHR1 and CRHR2 in endometriotic sites and to compare the expression of CRHR1 and CRHR2 in eutopic endometrium of endometriotic women to that of healthy women. We further compared the expression of CRH, UCN, CRHR1 and CRHR2 in ectopic endometrium to that in eutopic endometrium of women with endometriosis. Endometrial biopsy specimens were taken from healthy women (10 patients) and endometrial and endometriotic biopsy specimens were taken from women with endometriosis (16 patients). Τhe expression of CRH, UCN, CRHR1, and CRHR2 was tested via RT-PCR, immunohistochemistry and Western blotting. This study shows for the first time that CRH and UCN receptor subtypes CRHR1β and CRHR2α are expressed in endometriotic sites and that they are more strongly expressed (p

Early-life stress (ELS) can lead to enduring changes in the structure and function of neural circuits and endocrine pathways, resulting in altered vulnerability thresholds for stress-related disorders such as depression and anxiety. The question addressed in this work was whether epigenetic mechanisms contribute to the long-term programming of altered hypothalamus-pituitary-adrenal axis activity in ELS (maternal separated on postnatal days 1-10) mice. Adrenocorticotropic hormone (ACTH), a key pituitary mediator of the adrenocortical response to stress, is encoded by the proopiomelanocortin (Pomc) gene. Corticotropin releasing hormone (CRH) and arginine vasopressin (AVP) are the main upstream neural regulators of Pomc gene expression and the post-translational processing of its peptidergic products, whereas glucocorticoids, secreted by the adrenals in response to stress, exert negative feedback actions on Pomc synthesis and ACTH secretion. It was shown that Pomc mRNA level is persistently increased in ELS mice and leads to sustained hypersecretion of glucocorticoids. Interestingly, ELS causes a reduction in DNA methylation at a critical regulatory region of the Pomc gene; this occurs with some delay after onset of the stress and persists for up to 1 year. A series of experiments (including reporter-, EMSA-, IHC- and ChIP-assays) supported the concept that the adverse early-life event induces changes in Pomc gene methylation and results in persistently upregulated expression of the Pomc gene. Interestingly, stress-induced changes in DNA-methylation were found to be more pronounced in males than in females, raising the possibility that epigenetic encoding occurs in a sex-specific manner; this may help to explain sex differences in susceptibility to stress-related disorders. Collectively, the results of this study indicate that epigenetic mechanisms can serve to translate environmental cues into stable changes (“cellular memory”) in gene expression in post-mitotic tissues, without the need for alterations in the genetic code.

Wed, 19 Oct 2011 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/13447/ https://edoc.ub.uni-muenchen.de/13447/2/Wang_Xiao-Dong.pdf Wang, Xiao-Dong

The corticotropin-releasing hormone (CRH) is widely recognised as the major activator of the hypothalamic-pituitary-adrenocortical (HPA) axis, thereby mediating neuroendocrine, autonomic, and behavioural responses to stress. Dysregulation of the release of stress hormones, caused by excessive CRH secretion from the hypothalamus, is frequently observed in patients with affective disorders such as depression. One of the cardinal symptoms of major depression is a severe impairment of sleep (e.g. reduced sleep intensity, disinhibition of rapid eye movement sleep (REMS), and early morning awakenings). Consequently, besides a role of CRH in stress-induced arousal, its additional contribution to spontaneous sleep-wake regulation was suggested in literature. Due to the lack of highly specific CRH receptor antagonists and adequate CRH receptor knockout animal models, the mechanism and pathways by which CRH communicates its arousal function remained indistinct. Up to now it is unclear whether CRH interferes with sleep by a direct central action, or if the activation of the HPA axis and the subsequent release of peripheral stress hormones are mandatory. The present study with conditional CNS-specific CRH receptor type 1 (CRH-R1 CKO) and conventional CRH receptor type 2 knockout mice (CRH-R2 KO), allows assessment of CRH effects on wakefulness and sleep separately from a functional HPA axis together with various levels of CRH receptor system functionality. In addition, challenging sleep homeostasis in these mouse lines by sleep deprivation allows investigating the involvement of CRH and its receptor system in basic sleep-wake regulatory processes. Besides slight dissimilarities between the baseline sleep profiles in the various genotypes, CRH-R1 CKO displayed a markedly different response to intracerebroventricular (i.c.v.) CRH injections. The dose-dependent increases in wakefulness and decreases in non-REM sleep (NREMS), which could be observed in all other mouse lines, were almost totally absent in CRH-R1 CKO. The dose-dependent REMS suppression on the other hand persisted in all, even CRH-R1 CKO, animals. This suggests that the centrally expressed CRH receptor type 1 (CRH-R1) but not the CRH receptor type 2 (CRH-R2), mediates the crucial effects of CRH on wake induction and NREMS suppression. Since REMS inhibition by CRH still occurred in CRH-R1 CKO animals pretreated with a highly specific CRH-R2 antagonist, the clear role of central CRH and both receptors in REMS suppression remains elusive. Sleep deprivation induced significant increases in plasma corticosterone levels in all mouse lines, demonstrating HPA axis activation and suggesting that all mice perceived sleep loss as a stressor. After termination of sleep deprivation, all animals responded with a significant increase of slow wave activity (SWA), an indicator of sleep intensity, followed by a rebound of NREMS. With the exception of CRH-R1 CKO mice, all mice furthermore similarly displayed REMS rebound. Another difference in response to sleep deprivation constitutes the course of SWA in CRH-R1 CKO which was significantly increased over baseline levels for a longer period as compared to all other mouse lines. Accordingly CRH-R1 CKO animals presumably sleep more intensely or efficiently than mice of the other breeding lines. These results suggest that CRH mediates the effects, at least the stressful component, of sleep loss, and moreover that CRH-R1 is essentially involved in sleep homeostasis. This study is the first to show considerable evidence for a crucial involvement of central CRH and CRH-R1 in arousal and the suppression of NREMS. It could further be shown that activation of the HPA axis is not a prerequisite of these effects. Additionally, the action of central CRH, mediated by CRH-R1 seems to influence sleep quality. The role of CRH-R2 has to be regarded as of a minor nature. The impact of CRH on REMS regulation demands further investigation.

Die depressive Störung gehört den affektiven Störungen, die durch eine krankhafte Veränderung der Stimmung (Affektivität) gekennzeichnet ist. Die Punktprävalenz von Depressionen beträgt 5-10%. Das Lebenszeitrisiko an einer Depression zu erkranken beträgt ca. 15-17%. Unter den affektiven Störungen kommt den depressiven Erkrankungen bei weiten die größte Bedeutung zu. Sie gehören heute zu den häufigsten psychischen Erkrankungen. Nur 25% der Depressionen verlaufen einphasig, 75% der Erkrankungen rezidivieren. Bei unipolaren Depressionen muss im Mittel mit vier Episoden im Laufe eines Lebens gerechnet werden. Als eine biologische Ursache für eine depressive Störung werden Dysregulationen der HPA-Achse verantwortlich gemacht. Mit dem DEX/CRH-Test steht ein Verfahren zur Verfügung, mit dem sich die Veränderungen der HPA-Achse gut darstellen lassen. Ein deutlicher Anstieg des Cortisol- bzw. ACTH-Spiegels im DEX/CRH-Test wird als pathologisch gewertet. In der vorliegenden Arbeit wurde die Rolle des DEX/CRH-Tests in der Verlaufsbeobachtung bei 18 Patienten mit einer depressiven Störung erstmals über einen Zeitraum von drei Jahren untersucht. Anhand der Ergebnisse im DEX/CRH-Test bei Entlassung aus stationärer Behandlung erfolgte die Einteilung der Patienten in zwei Gruppen. Die Gruppe der "Suppressoren" zeigte sowohl im DEX/CRH-Test bei Entlassung als auch in den nach zwei und drei Jahren durchgeführten DEX/CRH-Tests ein signifikant von der Gruppe der "Nonsuppressoren" differierendes Verhalten der Cortisolspiegel. Es konnte erstmals festgestellt werden, dass der Unterschied zwischen der Gruppe der "Suppressoren" und der Gruppe der "Nonsuppressoren" hinsichtlich der Ergebnisse im DEX/CRH-Test auch über einen längeren Zeitraum von bis zu drei Jahren nach Entlassung aus stationärer Behandlung relativ stabil bleibt. In Kenntnis dieses Sachverhaltes besteht daher die Möglichkeit, in weiteren Studien mögliche Einflussfaktoren auf den DEX/CRH-Test genauer zu untersuchen und Hochrisikopatienten mit hohem Rückfallrisiko zu identifizieren und im Verlauf engmaschiger weiterzubetreuen.

Neben den klassischen kardiovaskulären Risikofaktoren wie arterielle Hypertonie oder Hypercholesterinämie kommen den psychosozialen Faktoren wie Stress oder Depression eine entscheidene Rolle als Risikofaktor für die Entwicklung der Atherosklerose zu. Obwohl das chronische Stresshormon Corticotropin-Releasing-Hormon im Rahmen der adaptiven Stressantwort als Hauptvertreter der Effektorhormone angesehen wird, sind die pathophysiologischen Mechanismen, die zu einer CRH/Stress-bedingten endothelialen Dysfunktion führen, weitgehend unbekannt. Diese Arbeit hatte zum Ziel, den Effekt von peripherem CRH auf die Monozyten/Endothel-Interaktion, beispielhaft die Adhäsion, herauszuarbeiten. Die Untersuchungen der Monozyten-Endothel-Adhäsion wurde in einem in-vitro-Modell unter Verwendung der Zelllinien HMEC-1 und THP-1 mit einer neuen, modifizierten fluorometrischen Methode untersucht, monozytäres MAC-1/CD11b, endotheliales ICAM-1/CD54 und VCAM-1/CD106 mit Hilfe der Durchflusszytometrie bestimmt. Der Nachweis der vermittelnden monozytären CRH-Rezeptoren R1/-R2 erfolgte mittels RT-PCR- und Immunfluoreszenztechnik. THP-1 konnte als Zielzelle für CRH mit Nachweis der CRH-Rezeptoren auf mRNA- und Proteinebene identifiziert werden. CRH induzierte eine signifikante zeit- und konzentrationsabhängige Adhäsionszunahme der THP-1 Zellen am HMEC-1 Monolayer. Der Effekt scheint Monozyten-vermittelt, da CRH, konzentrationsabhängig, zu einer monozytären MAC-1/CD11b-Freisetzung führte. Eine CRH-Stimulation nur von HMEC-1 führte hingegen zu keiner Adhäsionszunahme, erklärbar z. B. durch die hier dokumentierte fehlende Veränderung von endothelialem ICAM-1/CD54 und VCAM-1/CD106 unter Einfluß von CRH. Die Ergebnisse unterstreichen somit die Relevanz von peripherem CRH auf die Monozytenfunktion und Monozyten/Endothel-Interaktion. Sie können einen Beitrag zur Erklärung eines möglichen Zusammenhangs von chronischem Stress (mit konsekutiver Erhöhung des Stresshormons CRH) und der Initiation / Progression der endothelialen Dysfunktion leisten (Wilbert-Lampen, Straube et al., 2006).

Tue, 1 Jan 1991 12:00:00 +0100 https://epub.ub.uni-muenchen.de/7023/1/Reincke_Martin_7023.pdf Winkelmann, W.; Allolio, B.; Reincke, Martin ddc:610, Medizin

Three uncommon findings were observed in a case of Cushing's disease due to macroadenoma: no suppression of plasma ACTH during an 8-mg dexamethasone test, a negative corticotropin-releasing factor test, and a normal X-ray of the sella turcica. Despite these findings, the diagnosis of pituitary was confirmed Cushing's syndrome by computerized tomography and a transphenoidal operation.

Mit Hilfe von Saccharosedichtegradientenzentrifugation wurde die Bindung von tritiummarkiertem und nichtmarkiertem 1–23-Corticotropin gezeigt. Es handelt sich um eine Bindung an Albumin.

3H- 1–23-Corticotropin wurde an Dextrangel (Sephadex G-25) gebunden und konnte durch Serumproteine, Albumin oder 0,1 N HCl eluiert werden. Mittels Dextrangelfiltration wurde gefunden, daß3H-ACTH kompetitiv an Serumproteine (Albumin) und Dextrangel gebunden wurde. Auch für natürliches Schweine-ACTH und endogenes ACTH in Patientenplasma (Adrenalektomie) wurde mittels biologischer ACTH-Bestimmung die Bindung von ACTH an Proteine bestätigt.