Distribution and Characterization of Immunoreactive Corticotropin-Releasing Factor in Human Tissues*

Suda, Toshio; Tomori, Naoki; Tozawa, Fumiko; Mouri, Toraichi; Demura, Hiroshi; Shizume, Kazuo

doi:10.1210/jcem-59-5-861

Cited by 177 publications

(75 citation statements)

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“…This is the first study investigating the ontogeny of irCRH in the primate. These findings are consistent with the report of Suda et al (19) describing irCRH in the adrenal, lung, liver, and pituitary in human adults. Our findings show that the pituitary, which contained the pituitary stalk, had the greatest levels and was at least 10-fold greater than any other tissue tested.…”

Section: Discussionsupporting

confidence: 93%

Distribution of Corticotropin Releasing Hormone in the Fetus, Newborn, Juvenile, and Adult Baboon

et al. 2004

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Corticotropin releasing hormone (CRH) has previously been identified in extrahypothalamic tissues and may act in a paracrine fashion within these tissues. To date, CRH production and its role in the fetus and newborn have not been investigated. The aim of this study was to explore the distribution and ontogeny of CRH in extrahypothalamic tissues of the fetus, newborn, juvenile, and adult baboon. Pituitary, adrenal, kidney, liver, and lung tissues from baboons at 125 d gestation, 140 d gestation, 185 d gestation (term), juveniles, and adults were obtained at necropsy. The tissues were quantified for protein and immunoreactive CRH was determined by a RIA. CRH levels were normalized to the protein content of each tissue. CRH was present in all tissues and varied over a 100-fold range according to tissue type. The highest concentration of CRH was found in the pituitary, which did not differ with the gestation and/or age of the animal. In the lung tissues of 125-and 140-d gestation animals, CRH was greater than the term, juvenile, and adult lung (p Ͻ 0.02). CRH in the adrenal gland of the 125-d samples was greater than the other four ages tested (p Ͻ 0.02). Liver CRH levels were higher in the term animals compared with the juvenile baboons. Our study documents the existence of CRH in extrahypothalamic tissues of the baboon from 125 d of gestation to adulthood. Given its presence and distribution, we speculate that CRH may exert ongoing paracrine and/or autocrine actions in these tissues from the time of intrauterine life throughout adulthood. CRH is a 41-amino acid neuropeptide first characterized from the hypothalami of sheep (1). The cell bodies of the neurons that synthesize CRH are located mainly in the paraventricular nucleus of the hypothalamus. CRH is conducted to the median eminence, where it is transported to the anterior pituitary to promote the production of ACTH. ACTH is then released into the blood and acts upon the adrenal cortex to produce cortisol (2). This endocrine axis regulates carbohydrate and amino acid metabolism, maintains blood pressure, and modulates and restrains the inflammatory response (3). In the fetus, cortisol is essential for normal fetal tissue maturation and survival (4).In addition to classical hypothalamic CRH production, extrahypothalamic secretion of CRH has been identified. In 1982, irCRH in placenta extracts was found (5), and it is now known that the placenta and fetal membranes of primates synthesize CRH (6, 7). The role of placenta CRH has been studied and is likely involved in vasoregulation in the placenta and ultimately in parturition (8,9). Extrahypothalamic CRH has also been identified in rats (10 -14), mice (15), dogs (16), cows (17), baboons (18), monkeys (6), and humans (19 -22). Some of the cell types in which irCRH and/or CRH mRNA expression have been identified include macrophages, tissue fibroblasts, endothelial cells, circulating monocytes, and lymphocytes (20,23,24). Furthermore, there is evidence that CRH may act in an autocrine/paracrine fashion to modulate...

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Section: Discussionsupporting

confidence: 93%

Distribution of Corticotropin Releasing Hormone in the Fetus, Newborn, Juvenile, and Adult Baboon

et al. 2004

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“…Synthetic rat CRF-41 itandards (covering the range 0.4 to 200 pmol/l), rat tissue extract dilutions or human plasma ized material in the sample. The presence of oxidized CRF-41 in a range o f tissue extracts has previously been shown by HPLC (22,23) and was confirmed in this study for rat hypothalamic and human placental tissue. The oxidized form of ovine CRF-41 has been shown to have one-tenth of the potency of CRF-41 in bioassays ( I ) and it is clear that measurement of irCRF-41 should take account of the potential for a form with reduced biological activity having different cross-reactivities in different immunoassays.…”

Section: Crf-41 Eaiasupporting

confidence: 85%

“…The resultant extract was diluted to 35% acetonitrile in 0.065% TFA prior to loading on to a p-Bondapak C,, HPLC column (22). A gradient of 35% to 70% acetonitrile in 0.65% TFA was run for 70 min at a flow rate of 0.5 ml/min.…”

Section: Crf-41 Riamentioning

confidence: 99%

Corticotrophin‐Releasing Factor‐41 in the Human and Rat—Utility of a Highly Sensitive Enzyme Amplified Immunometric Assay

Milton

Hillhouse

Fuller³

et al. 1990

J Neuroendocrinology

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RbstractW e have developed a highly sensitive and specific immunoassay for humanlrat corticotrophin-releasing factor-41 (CRF-41) to enable determination of immunoreactive CRF-41 levels in biological samples. To achieve high specificity, sensitivity and s p e e dwe have used two antisera in a sandwich enzyme immunoassay combined with enzyme amplification. The assay h a s a sensitivity of 0.08 fmollwell compared with radioimmunoassay sensitivities of 0.5 fmol/tube and is highly specific for the intact CRF-41 molecule. Measurement of samples is complete within 24 h compared with the 5 days required to obtain sensitive radioimmunoassay measurement. The assay has been used to measure both rat hypothalamic CRF-41 tissue content and release in vitro with good correlation when compared to radioimmunoassay measurement using antisera rC70 (0.983) or R1 (0.953). The assay only measures immunoreactive CRF-41 coeluting with humanlrat CRF-41 and its oxidized form Met [02'~38]CRF-41 in human and rat tissue extracts separated by high-performance liquid chromatography. The ability to measure immunoreactive CRF-41 in unextracted plasma allows rapid measurement and eliminates multiple extraction steps.( 'orticotrophin-releasing factor-41 (CRF-41) is a 41 amino-acid pcptide originally isolated from ovine hypothalamic tissue ( I ) . 7hc amino-acid sequences of human and rat CRF-41 are identical and differ from the ovine sequence at 7 residues (2, 3). CRF-41 cilso shares considerable sequence homology with sauvagine, a fi.ogskin peptide which has corticotrophin-releasing activity (4). 1,'arly assays for C R F relied on bioassay techniques ( 5 ) and were, therefore, susceptible to interfercnce from substances such as :idrenaline or arginine vasopressin which also have corticotrophinlcleasing activity (4). The development of RIAs for CRF-41 (6) allowed more specific and sensitive assay. However, the RIA tcchnique is time consuming and can give elevated measurements in the presence of CRF-41 peptide fragments or peptides with dcgrees of sequence homology with CRF-41 (4). Such RIAs also 1-cquire extraction of the material from biological fluids to reduce interference (7-9). The development of a 'two-site' immunoradiometric assay (IRMA) for CRF-41 (10) was a significant advance, reducing interference from fragments and allowing direct measurement of the peptide in biological fluids including plasma (1 1) In this study, we sought to construct an enzyme amplified ilnmunometric assay (EAIA) for human/rat CRF-41 using two polyclonal antisera raised against the whole CRF-41 molecule. The technique uses one antibody bound to a solid phase with sequential addition of samples, second antibody-enzyme conjugate and substrate. The assay was based on the technique of enzyme amplification (12) to improve sensitivity and reduce assay time (13). The performance of this assay has been compared t o two RIAs for CRF-41 in the measurement of rat hypothalamic CRF-41 content and release. The ability of the EAIA to measure human CRF-41 in both unextracted gest...

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“…5,17 Within the adrenal itself, CRH-like immunoreactivity has been detected in the medulla of humans and other species. 18,19 This adrenal CRH is identical to the hypothalamic CRH and is released in response to physiological stimuli such as hemorrhage, 20 splanchnic nerve activation, 21,22 K + -induced depolarization, nicotine, 23 and various neuropeptides and cytokines. 24,25 Like the central CRH/ACTH system, the peripheral adrenal CRH/ACTH system is regulated via feedback mechMolecular Psychiatry anisms.…”

Section: Discussionmentioning

confidence: 99%

Effects of a novel corticotropin-releasing-hormone receptor type I antagonist on human adrenal function

et al. 2000

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Distribution and Characterization of Immunoreactive Corticotropin-Releasing Factor in Human Tissues*

Cited by 177 publications

References 0 publications

Distribution of Corticotropin Releasing Hormone in the Fetus, Newborn, Juvenile, and Adult Baboon

Distribution of Corticotropin Releasing Hormone in the Fetus, Newborn, Juvenile, and Adult Baboon

Corticotrophin‐Releasing Factor‐41 in the Human and Rat—Utility of a Highly Sensitive Enzyme Amplified Immunometric Assay

Effects of a novel corticotropin-releasing-hormone receptor type I antagonist on human adrenal function

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