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The Corticotropin-releasing Hormone (CRH) mammalian family members include CRH, urocortin I, Stresscopin (SCP) and Stresscopin-related peptide (SRP), along with the CRH receptors type 1 (CRHR1) and type 2 (CRHR2), and CRH-binding protein (CRH-BP). These family members differ in their tissue distribution and pharmacology. Several studies have provided evidence supporting an important role of this family in the regulation of the neuroendocrine and behavioral responses to stress. Regulation of the relative contribution of CRH and its homologs and the two CRH receptors in brain CRH pathways may be essential in coordinating physiologic responses to stress. The development of disorders related to heightened stress sensitivity and dysregulation of stress-coping mechanisms appears to involve regulatory mechanisms of the CRH family members. Therapeutic agents that target CRH family members may offer a new approach to the treatment of these disorders. The purpose of this review is to summarize the most significant discoveries related to CRH over time. Keywords: CRH, urocortin, stresscopin, antalarmin, general adaptation syndrome, stress.
Letters and Corrections1 August 1982Late-Onset 21-Hydroxylase DeficiencyGEORGE P. CHROUSOS, M.D., ABRAHAM MUNABI, M.D., GORDON B. CUTLER JR., M.D., D. LYNN LORIAUX, M.D., PH.D.GEORGE P. CHROUSOS, M.D.Search for more papers by this author, ABRAHAM MUNABI, M.D.Search for more papers by this author, GORDON B. CUTLER JR., M.D.Search for more papers by this author, D. LYNN LORIAUX, M.D., PH.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-97-2-281_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Since our article on the diagnosis of late-onset 21-hydroxylase deficiency was published (1), we have been asked the best way to do the 30-minute adrenocorticotrophic hormone (ACTH) stimulation test (1). Most questions center around the intravenous ACTH infusion of 1.67 U over 30 minutes, which is low when compared to the usual dose of 25 U (0.25 mg) given as an intravenous bolus (2), and the mode of administration (continuous versus bolus). The dose of 1.67 U ACTH infused continuously over 30 minutes is a pharmacologic dose that causes maximal adrenal stimulation. Eik-Nes and associates (3) saw...References(1) CHROUSOS G, LORIAUX D, MANN D, and CUTLER G. Late-onset 21-hydroxylase deficiency mimicking idiopathic hirsutism or polycystic ovarian disease: An allelic variant of congenital virilizing adrenal hyperplasia with a milder enzymatic defect. Ann Intern Med. 1982;96:143-8. LinkGoogle Scholar(2) LINDHOLM J, KEHLET H, BLICHERT-TOFT M, DINESEN B, and RIISHEDE J. Reliability of the 30-minute ACTH test in accessing hypothalamic-pituitary-adrenal function. J Clin Endocrinol Metab. 1978;47:272-4. CrossrefMedlineGoogle Scholar(3) EIK-NES K, SANDBERG A, NELSON D, TYLER F, and SAMUELS L. Changes in plasma levels of 17-hydroxycorticosteroids during the intravenous administration of ACTH. I. A test of adrenocortical capacity in the human. J Clin Endocrinol Metab. 1954;33:1502-8. Google Scholar(4) BLANKSTEIN J, FAIMAN C, REYES F, SCHROEDER M, and WINTER J. Adult-onset familial adrenal 21-hydroxylase deficiency. Am J Med. 1980;68:441-8. CrossrefMedlineGoogle Scholar(5) LOBO R and GOEBELSMANN U. Adult manifestation of congenital adrenal hyperplasia due to incomplete 21-hydroxylase deficiency mimicking polycystic ovarian disease. Am J Obstet Gynecol. 1980;138:720-6. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: GEORGE P. CHROUSOS, M.D.; ABRAHAM MUNABI, M.D.; GORDON B. CUTLERJR., M.D.; D. LYNN LORIAUX, M.D., PH.D.Affiliations: National Institute of Child Health and Human Development Bethesda, MD 20205 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEndocrine profile and phenotype-genotype correlation in unrelated patients with non-classical congenital adrenal hyperplasiaRecovery of the hypothalamic-pituitary-adrenal (HPA) axis in patients with rheumatic diseases receiving low-dose prednisoneLate onset congenital adrenal hyperplasia: a gynecologist’s perspective 1 August 1982Volume 97, Issue 2Page: 281-282KeywordsAdrenocorticotropic hormone ePublished: 1 December 2008 Issue Published: 1 August 1982 PDF downloadLoading ...
Summary Nonlinear static procedures, which relate the seismic demand of a structure to that of an equivalent single‐degree‐of‐freedom oscillator, are well‐established tools in the performance‐based earthquake engineering paradigm. Initially, such procedures made recourse to inelastic spectra derived for simple elastic–plastic bilinear oscillators, but the request for demand estimates that delve deeper into the inelastic range, motivated investigating the seismic demand of oscillators with more complex backbone curves. Meanwhile, near‐source (NS) pulse‐like ground motions have been receiving increased attention, because they can induce a distinctive type of inelastic demand. Pulse‐like NS ground motions are usually the result of rupture directivity, where seismic waves generated at different points along the rupture front arrive at a site at the same time, leading to a double‐sided velocity pulse, which delivers most of the seismic energy. Recent research has led to a methodology for incorporating this NS effect in the implementation of nonlinear static procedures. Both of the previously mentioned lines of research motivate the present study on the ductility demands imposed by pulse‐like NS ground motions on oscillators that feature pinching hysteretic behaviour with trilinear backbone curves. Incremental dynamic analysis is used considering 130 pulse‐like‐identified ground motions. Median, 16% and 84% fractile incremental dynamic analysis curves are calculated and fitted by an analytical model. Least‐squares estimates are obtained for the model parameters, which importantly include pulse period T p . The resulting equations effectively constitute an R − μ − T − T p relation for pulse‐like NS motions. Potential applications of this result towards estimation of NS seismic demand are also briefly discussed. Copyright © 2016 John Wiley & Sons, Ltd.
Among the adverse effects arising from chronic high-dose glucocorticoid treatment, adrenal insufficiency secondary to suppression of the hypothalamic-pituitary-adrenal (HPA) axis is a cause for concern. Glucocorticoid-induced adrenal suppression is related to the duration of therapy, type of steroid used and dosage, and schedule of glucocorticoid administration. To evaluate the suppression and recovery time of the HPA axis in children with acute leukemia, we performed the ovine CRH (oCRH) stimulation test in 15 patients, who were given high doses of dexamethasone as part of their induction chemotherapy for 42 days. The oCRH tests were performed before, and 7 and 14 days after, discontinuation of the glucocorticoid. The ACTH levels were not significantly different among the 3 tests. The cortisol levels, however, were significantly (albeit mildly) lower, both basally and after oCRH, 1 and 2 weeks post treatment than before therapy. Six patients had cortisol values that remained suppressed 2 weeks after discontinuation of therapy. One of these patients had manifestations of mild adrenal insufficiency, 6–8 days after discontinuation of therapy, but required no glucocorticoid coverage. We conclude that up to 2 weeks after discontinuation of 6 weeks of high-dose dexamethasone administration, the HPA axis of patients with acute leukemia is mildly suppressed but infrequently associated with clinical manifestations of adrenal insufficiency. This may indicate that major stress, when concurrent with glucocorticoid treatment, may prevent clinically significant adrenal suppression.
A feasibility study is presented on mid-size onshore wind farms in Greece, taking into consideration two metrics for the evaluation of the profitability of the pertinent investment, namely the net present value, and the internal rate of return. An operationally complete wind park of ten 3.2 MW turbines is considered, incorporating all required power conversion/transmission, and transportation infrastructure that an owner would have to construct. Actual wind speed data are employed from 285 weather stations installed throughout the country and covering a period of 1 to 12 years. The costs of installation, operation, and financing are explicitly accounted for over a standard lifecycle of twenty years. Given the regulated wholesale price for renewable electrical power, the proximity of many sites to ports, and the relatively uniform cost of investing, it is the wind potential that remains the governing factor affecting the financial viability of the wind park. Accordingly, the most profitable areas are the Aegean islands, the south-central mainland coastline, east Peloponnese, and south Attica. Most other regions of mainland Greece are found to be either marginally profitable or to generate a net loss given the current wholesale prices, wind turbine technology and investment costs.