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Wylie Vale - One of the best experts on this subject based on the ideXlab platform.
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cloning and functional expression of a rat brain Corticotropin releasing factor crf receptor
Endocrinology, 1993Co-Authors: Marilyn H Perrin, Ruoping Chen, Kathy A Lewis, Cynthia J Donaldson, Wylie ValeAbstract:Corticotropin releasing factor (CRF), a key neuroregulator of the hypothalamic-pituitary-adrenal cortical axis, also displays a broad range of effects on the endocrine, central nervous and immune systems. Having recently characterized the human pituitary CRF receptor by expression cloning of cDNA from a human Cushing's corticotropic adenoma, we report here the structure of the cDNA for a rat brain CRF receptor (rCRF-R) which was cloned by hybridization from a rat brain cDNA library. The sequence of the rCRF-R encodes a 415 amino acid protein comprising seven membrane spanning domains. The rCRF-R is 97% identical at the amino acid level to the human pituitary tumor CRF receptor, differing by only 12 amino acids. When expressed in COSM6 cells, the rCRF-R binds CRF with high affinity (Kd = 1.7 (0.8-3.8)nM). The receptor transduces a CRF stimulated accumulation of intracellular cAMP which is inhibited by the CRF antagonist, alpha helCRF(9-41). These results suggest that the brain expresses a CRF receptor simi...
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expression cloning of a human Corticotropin releasing factor receptor
Proceedings of the National Academy of Sciences of the United States of America, 1993Co-Authors: Ruoping Chen, Kathy A Lewis, Marilyn H Perrin, Wylie ValeAbstract:Abstract Corticotropin-releasing factor (CRF) is the principal neuroregulator of the hypothalamic-pituitary-adrenocortical axis and plays an important role in coordinating the endocrine, autonomic, and behavioral responses to stress and immune challenge. We report here the cloning of a cDNA coding for a CRF receptor from a human corticotropic tumor library. The cloned cDNA encodes a 415-amino acid protein comprising seven putative membrane-spanning domains and is structurally related to the calcitonin/vasoactive intestinal peptide/growth hormone-releasing hormone subfamily of G protein-coupled receptors. The receptor expressed in COS cells binds rat/human CRF with high affinity (Kd = 3.3 +/- 0.45 nM) and specificity and is functionally coupled to adenylate cyclase. The CRF antagonist alpha-helCRF-(9-41) inhibits the CRF-stimulated increase in intracellular cAMP. Northern blot analysis reveals that the CRF receptor is expressed in the rat pituitary and brain as well as in the mouse AtT20 corticotropic cells. We also describe an alternatively spliced form of the receptor which includes an insert of 29 amino acids in the first intracellular loop.
Nilay D Shah - One of the best experts on this subject based on the ideXlab platform.
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older drugs with limited trial evidence are they worth the expense the case of repository Corticotropin marketed as h p acthar gel
Annals of Internal Medicine, 2019Co-Authors: Ali Duartegarcia, Eric L Matteson, Nilay D ShahAbstract:Repository Corticotropin (rACTH), a long-acting form of Corticotropin approved by the U.S. Food and Drug Administration in 1952, was once used to treat rheumatoid arthritis and other inflammatory c...
Verena A Briner - One of the best experts on this subject based on the ideXlab platform.
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suppression and recovery of adrenal response after short term high dose glucocorticoid treatment
The Lancet, 2000Co-Authors: Christoph Henzen, Alex Suter, Erika Lerch, Ruth Urbinelli, Xaver H Schorno, Verena A BrinerAbstract:Summary Background Suppression of the adrenal response is an unpredictable consequence of glucocorticoid treatment. To investigate the kinetics of the adrenal response after shortterm, high-dose glucocorticoid treatment, we measured the adrenal response to the low-dose (1 μg) Corticotropin stimulation test. Methods We studied 75 patients who received the equivalent of at least 25 mg prednisone daily for between 5 days and 30 days. After discontinuation of glucocorticoid treatment, 1 μg Corticotropin was administered intravenously, and stimulated plasma cortisol concentrations were measured 30 min later. In patients with a suppressed response to 1 μg Corticotropin, the test was repeated until stimulated plasma cortisol concentrations reached the normal range. Findings The adrenal response to 1 μg Corticotropin was suppressed in 34 patients and normal in 41. Subsequent lowdose Corticotropin tests showed a steady recovery of the adrenal response within 14 days. In two patients, the adrenal response remained suppressed for several months. There was no correlation between plasma cortisol concentrations and the duration or dose of glucocorticoid treatment. Interpretation Suppression of the adrenal response is common after short-term, high-dose glucocorticoid treatment. The low-dose Corticotropin test is a sensitive and simple test to assess the adrenal response after such treatment.
George P Chrousos - One of the best experts on this subject based on the ideXlab platform.
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cerebrospinal fluid levels of Corticotropin releasing hormone in women with functional hypothalamic amenorrhea
American Journal of Obstetrics and Gynecology, 2000Co-Authors: Sarah L Berga, Tammy L Loucksdanielsa, Lauri J Adler, Judy L Cameron, Karen A Matthews, George P Chrousos, Marsha D MarcusAbstract:Abstract Objective: Women with functional hypothalamic amenorrhea are anovulatory because of reduced gonadotropin-releasing hormone drive. Several studies have documented hypercortisolemia, which suggests that functional hypothalamic amenorrhea is stress-induced. Further, with recovery (resumption of ovulation), cortisol decreased and gonadotropin-releasing hormone drive increased. Corticotropin-releasing hormone can increase cortisol and decrease gonadotropin-releasing hormone. To determine its role in functional hypothalamic amenorrhea, we measured Corticotropin-releasing hormone in cerebrospinal fluid along with arginine vasopressin, another potent adrenocorticotropic hormone secretagog, and β-endorphin, which is released by Corticotropin-releasing hormone and can inhibit gonadotropin-releasing hormone. Study Design: Corticotropin-releasing hormone, vasopressin, and β-endorphin levels were measured in cerebrospinal fluid from 14 women with eumenorrhea and 15 women with functional hypothalamic amenorrhea. Results: Levels of Corticotropin-releasing hormone in cerebrospinal fluid and of vasopressin were comparable and β-endorphin levels were lower in women with functional hypothalamic amenorrhea. Conclusions: In women with established functional hypothalamic amenorrhea, increased cortisol and reduced gonadotropin-releasing hormone are not sustained by elevated cerebrospinal-fluid Corticotropin-releasing hormone, vasopressin, or β-endorphin. These data do not exclude a role for these factors in the initiation of functional hypothalamic amenorrhea. (Am J Obstet Gynecol 2000;182:776-84.)
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Reproductive placental Corticotropin-releasing hormone and its clinical implications.
American Journal of Obstetrics and Gynecology, 1999Co-Authors: George P ChrousosAbstract:The hypothalamic-pituitary-adrenal axis and the reproductive system exhibit a complex relationship in both nonpregnant and pregnant women.1,2 The hypothalamic-pituitary-adrenal axis exerts profound, mostly inhibitory, effects on the reproductive axis, with Corticotropin-releasing hormone and Corticotropin-releasing hormone–induced pro-opiomelanocortin peptides inhibiting hypothalamic gonadotropin-releasing hormone secretion and with glucocorticoids inhibiting pituitary luteinizing hormone and ovarian estrogen and progesterone secretion and rendering estrogen-target tissues, such as the endometrium, resistant to the gonadal steroid. Conversely, estrogen directly stimulates the hypothalamic Corticotropin-releasing hormone gene, which may explain the slight hypercortisolism seen in women and the preponderance of depression, anxiety disorders, and anorexia nervosa among women.3 Interestingly, several components of the hypothalamicpituitary-adrenal axis and their receptors are present in reproductive tissues as autacoid regulators of their various functions2, 4-7 (Table I). These include ovarian and endometrial Corticotropin-releasing hormone, which may participate in the regulation of steroidogenesis and the inflammatory processes of the ovary (ovulation and luteolysis) and of the endometrium (blastocyst implantation and menstruation), and placental Corticotropin-releasing hormone, which is secreted mostly in the latter half of pregnancy and is responsible for the physiologic hypercortisolism seen during this period (Fig 1). Most circulating Corticotropin-releasing hormone is neutralized by Corticotropin-releasing hormone binding protein produced by the liver. Between weeks 34 and 35 of gestation, however, the concentrations of this protein fall by about 60%, leading to elevations of free Corticotropin-releasing hormone. Subsequently plasma free Corticotropin-releasing hormone concentrations rise further, to peak at labor and delivery. In addition to the hypercortisolism of pregnancy, placental Corticotropin-releasing hormone causes vasodilation of the fetoplacental circulation by activating nitric oxide synthase and participates in labor by stimulating secretion of prostaglandin F2α and prostaglandin E2 by the fetal membranes and by promoting constriction of myometrial cells. Placental Corticotropin-releasing hormone secretion is stimulated by glucocorticoids, inflammatory cytokines, and anoxic conditions and therefore by noninflammatory or inflammatory stress, including the stress of preeclampsia or eclampsia.2,6 Premature elevation of placental Corticotropin-releasing hormone level has been associated with premature labor and birth. Potent Corticotropin-releasing hormone antagonists are in the making and could be tested as labor retardants. The hypercortisolism of pregnancy is followed by a transient suppression of hypothalamic Corticotropin-releasing hormone secretion in the postpartum period, which may explain the blues or depression and autoimmune phenomena seen during this period.2,7 Estrogen administration has been shown to ameliorate postpartum depression, probably by returning to normal the secretion of the suppressed Corticotropin-releasing hormone neuron. From Section on Pediatric Endocrinology, Developmental Endocrinology Branch, National Institute of Child Health and Development, National Institutes of Health. Reprint requests: G. P. Chrousos, MD, Section on Pediatric Endocrinology, National Institutes of Health, Bethesda, MD 20892-1862. Am J Obstet Gynecol 1999;180:S249-50. 0002-9378/99 $8.00 + 0 6/0/90865 Table I. Reproductive Corticotropin-releasing hormone and its potential physiologic functions
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aberrant interleukin 1 receptors in a cortisol secreting adrenal adenoma causing cushing s syndrome
The New England Journal of Medicine, 1998Co-Authors: Holger S Willenberg, George P Chrousos, Constantine A Stratakis, Christian Marx, Monika Ehrhartbornstein, Stefan R BornsteinAbstract:Cortisol-secreting adrenal adenomas are an uncommon cause of Cushing's syndrome. Little is known about the events leading to the formation of these tumors, but molecular defects, including activating mutations of receptors for corticotropic factors, have been suspected in this process. Structural mutations of the Corticotropin-receptor gene have not been detected in these tumors,1 but some have had gastric inhibitory polypeptide,2,3 vasopressin,4 and more recently, β-adrenergic receptors.5 In this report, we provide evidence of the involvement of immune cells and one of their cytokine products in the formation of an adrenocortical adenoma in a patient with Cushing's syndrome. A striking . . .
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Corticotropin-secreting carcinoid tumors of the thymus: diagnostic unreliability of thymic venous sampling.
Radiology, 1992Co-Authors: J L Doppman, George P Chrousos, Harvey I. Pass, L K Nieman, Donald L. Miller, Richard Chang, Gordon B. Cutler, G. Jaffe, Jeffrey A. NortonAbstract:Three patients with Cushing syndrome due to ectopic production of Corticotropin underwent total thymectomy on the basis of elevated concentrations of Corticotropin in selective samples from thymic veins but in the absence of a radiographically detectible thymic mass. In one patient, radiologic examination demonstrated hyperplasia of neuroendocrine cells staining positively for Corticotropin throughout the thymus but no discrete mass. This patient had complete remission after total thymectomy. The other two patients had no evidence of an intrathymic source of Corticotropin, and both had persistent Cushing syndrome. Elevated levels of Corticotropin in thymic vein samples may reflect Corticotropin production by pulmonary bronchial carcinoid tumors, mediastinal metastases, thymic carcinoids, or diffuse hyperplasia of intrathymic neuroendocrine elements. In the absence of a demonstrable intrathymic mass, Corticotropin gradients in thymic veins do not reliably indicate a thymic source of Corticotropin and shoul...
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Circadian patterns of plasma immunoreactive Corticotropin, beta-endorphin, corticosterone and prolactin after immunoneutralization of Corticotropin-releasing hormone.
Neuroendocrinology, 1991Co-Authors: Gyorgy Bagdy, George P Chrousos, Aldo E. CalogeroAbstract:To study the role of Corticotropin-releasing hormone (CRH) in the circadian rhythm of circulating Corticotropin (ACTH), β-endorphin (β-END), corticosterone, and prolactin (PRL), we measured the effect
Ruoping Chen - One of the best experts on this subject based on the ideXlab platform.
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cloning and functional expression of a rat brain Corticotropin releasing factor crf receptor
Endocrinology, 1993Co-Authors: Marilyn H Perrin, Ruoping Chen, Kathy A Lewis, Cynthia J Donaldson, Wylie ValeAbstract:Corticotropin releasing factor (CRF), a key neuroregulator of the hypothalamic-pituitary-adrenal cortical axis, also displays a broad range of effects on the endocrine, central nervous and immune systems. Having recently characterized the human pituitary CRF receptor by expression cloning of cDNA from a human Cushing's corticotropic adenoma, we report here the structure of the cDNA for a rat brain CRF receptor (rCRF-R) which was cloned by hybridization from a rat brain cDNA library. The sequence of the rCRF-R encodes a 415 amino acid protein comprising seven membrane spanning domains. The rCRF-R is 97% identical at the amino acid level to the human pituitary tumor CRF receptor, differing by only 12 amino acids. When expressed in COSM6 cells, the rCRF-R binds CRF with high affinity (Kd = 1.7 (0.8-3.8)nM). The receptor transduces a CRF stimulated accumulation of intracellular cAMP which is inhibited by the CRF antagonist, alpha helCRF(9-41). These results suggest that the brain expresses a CRF receptor simi...
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expression cloning of a human Corticotropin releasing factor receptor
Proceedings of the National Academy of Sciences of the United States of America, 1993Co-Authors: Ruoping Chen, Kathy A Lewis, Marilyn H Perrin, Wylie ValeAbstract:Abstract Corticotropin-releasing factor (CRF) is the principal neuroregulator of the hypothalamic-pituitary-adrenocortical axis and plays an important role in coordinating the endocrine, autonomic, and behavioral responses to stress and immune challenge. We report here the cloning of a cDNA coding for a CRF receptor from a human corticotropic tumor library. The cloned cDNA encodes a 415-amino acid protein comprising seven putative membrane-spanning domains and is structurally related to the calcitonin/vasoactive intestinal peptide/growth hormone-releasing hormone subfamily of G protein-coupled receptors. The receptor expressed in COS cells binds rat/human CRF with high affinity (Kd = 3.3 +/- 0.45 nM) and specificity and is functionally coupled to adenylate cyclase. The CRF antagonist alpha-helCRF-(9-41) inhibits the CRF-stimulated increase in intracellular cAMP. Northern blot analysis reveals that the CRF receptor is expressed in the rat pituitary and brain as well as in the mouse AtT20 corticotropic cells. We also describe an alternatively spliced form of the receptor which includes an insert of 29 amino acids in the first intracellular loop.
