Immunoreactive corticotropin-releasing factor in human plasma.

Suda, Toshio; Tomori, Naoki; Yajima, Fumiko; Sumitomo, Takashi; Nakagami, Yuriko; Ushiyama, Tsuyako; Demura, Hiroshi; Shizume, Kazuo

doi:10.1172/jci112204

Cited by 93 publications

(39 citation statements)

References 18 publications

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“…However, evidence of the presence of immunoreactivities against ACTH and its related peptides in tumor cells strongly suggested that the high level of plasma ACTH was caused by ectopic (metastatic) tumors in the liver. The plasma CRH concentration is also known to be increased in certain patients with Nelson's syndrome (Suda et al, 1985). Since we do not know the CRH level before adrenalectomy in this patient, it was impossible to define whether the high level of CRH was induced by adrenalectomy or was due to hypersecretion which was associated with MEN-I (Lips et al, 1984, Yamaguchi et al, 1980.…”

Section: Discussionmentioning

confidence: 84%

Somatostatin Analogue(SMS 201-995) Decreases Plasma Levels of Corticotropin(ACTH) and Corticotropin-Releasing Hormone in a Patient with Ectopic ACTH-Producing Tumors.

et al. 1990

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Effects of long-acting somatostain analogue (SMS 201-995) on plasma corticotropin (ACTH) and corticotropin-releasing hormone (CRH) levels were studied in a patient (63-year-old woman) with ectopic ACTH-producing tumors associated with type I multiple endocrine neoplasia (MEN-I). The patient had undergone bilateral adrenalectomy.Plasma CRH, as well as plasma ACTH, beta-endorphin and alpha-MSH, increased.The hormone levels were dramatically decreased by acute administration of SMS 201-995.Moderately higher doses of dexamethasone (0.05 or 0.1mg/kg a day) did not decrease plasma CRH or ACTH. An extremely high dose of dexamethasone (0.2mg/kg a day), however, decreased plasma ACTH, but failed to decrease plasma CRH.Acute administration of SMS 201-995 further lowered the level of plasma ACTH even in this condition.In addition to the decrease inACTH, SMS 201-995 decreased plasma CRH. Chronic administration of SMS 201-995 continuously decreased plasma CRH, ACTH and beta-endorphin. The decrease in these hormone concentrations accompanied the disappearance of hyperpigmentation.These results suggested that SMS 201-995 inhibits hypersecretion not only of ACTH but also of CRH, and that the agent is therapeutically useful in normalizing the hypersecretion of these hormones.

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Section: Discussionmentioning

confidence: 84%

Somatostatin Analogue(SMS 201-995) Decreases Plasma Levels of Corticotropin(ACTH) and Corticotropin-Releasing Hormone in a Patient with Ectopic ACTH-Producing Tumors.

et al. 1990

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“…This also enables sequential addition of samples, antibody-enzyme conjugate and substrate allowing potentially interfering substances to be removed by washing (18). The ability of the assay to measure CRF-41 without the need for an extraction procedure is a significant improvement on RIA since differences in sample extraction have been implicated in the discrepancies between measurements?by different groups (8,9,19,20). The plasma Extracts were separated on a p-Bondapak C,, reverse-phase column using a gradient of 35% to 70% acetonitrile in 0.065% trifluoroacetic acid.…”

Section: Discussionmentioning

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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“…However, this approach requires acute anesthesia and surgery, thus precluding studies of the axis in a basal state or of examining the effects of emotional stressors on function. Alternative approaches, including transnasal collection of hypophysial-portal blood from the awake sheep (8,9) and peripheral sampling in a variety of species (10)(11)(12)(13)(14)(15)(16)(17) have been attempted. In the present study, we have critically evaluated the validity of peripheral irCRF-41 measurements as an index of hypothalamic secretory activity by comparing peripheral and hypophysial-portal plasma irCRF-41 concentrations under a variety of conditions.…”

Section: Discussionmentioning

confidence: 99%

“…However, the relative inaccessibility of this specialized vascular link in species other than the sheep (8,9) prevents direct determination of irCRF-41 secretory profiles in the circulation at this level in the unanesthetized, ambulatory animal. Several laboratories have reported the presence of irCRF-41 in human or rat peripheral plasma (10)(11)(12)(13)(14)(15)(16)(17). During pregnancy, peripheral irCRF-41 appears to be derived from the placenta (18)(19)(20).…”

mentioning

confidence: 99%

“…During pregnancy, peripheral irCRF-41 appears to be derived from the placenta (18)(19)(20). The source of peripheral irCRF-41 in non-pregnant animals is unknown and it has been postulated that it may reflect, at least in part, hypothalamic irCRF-41 secretion (13,14,16,17); other sources include the gastrointestinal tract (21), the pancreas (22) and the adrenal gland (23,24). In the present study, the relationship between peripheral and hypophysial-portal plasma concentration profiles of irCRF-41 was evaluated by direct measurements in both circulatory compartments under a variety of experimental conditions.…”

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confidence: 99%

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Lack of Correlation Between Immunoreactive Corticotropin‐Releasing Factor Concentration Profiles in Hypophysial‐Portal and Peripheral Plasma

Plotsky¹,

Otto²,

Toyama³

et al. 1990

J Neuroendocrinology

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Corticotropin-releasing factor (CRF-41) is the primary mediator of adrenocorticotropin secretion from the adenohypophysis. This 41-amino-acid peptide is synthesized in perikarya of the paraventricular nuclei, transported to nerve terminals in the external zone of the median eminence and released into the hypophysial-portal circulation. It is also synthesized in multiple extrahypothalamic and peripheral sites. In addition, immunoreactive (ir) CRF-41 is present in the systemic circulation, raising the possibility that systemic measurements might provide a useful index of hypothalamic irCRF-41 secretion. This hypothesis was tested in several rat models. Neither bilateral destruction of hypothalamic irCRF-41 producing perikarya, nor infundibular stalk transection altered peripheral plasma irCRF-41 concentration. Furthermore, central administration of norepinephrine, an agent previously shown to evoke irCRF-41 secretion into the portal circulation, was without effect on peripheral irCRF-41 concentration. Finally, while increased irCRF-41 levels in both the hypophysial-portal and the peripheral circulation were associated with nitroprusside-induced hypotension, bilateral paraventricular nuclei lesions blocked irCRF-41 secretion into the hypophysial-portal circulation without blunting the rise observed in the peripheral circulation. The source of peripheral irCRF-41 remains undetermined; however, the adrenals may be excluded as bilateral adrenalectomy failed to alter circulating irCRF-41 levels. Therefore, our observations do not support the concept that peripheral irCRF-41 levels provide a useful index of hypothalamic secretion of this peptide into the hypophysial-portal circulation under the conditions tested.

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Immunoreactive corticotropin-releasing factor in human plasma.

Cited by 93 publications

References 18 publications

Somatostatin Analogue(SMS 201-995) Decreases Plasma Levels of Corticotropin(ACTH) and Corticotropin-Releasing Hormone in a Patient with Ectopic ACTH-Producing Tumors.

Somatostatin Analogue(SMS 201-995) Decreases Plasma Levels of Corticotropin(ACTH) and Corticotropin-Releasing Hormone in a Patient with Ectopic ACTH-Producing Tumors.

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

Lack of Correlation Between Immunoreactive Corticotropin‐Releasing Factor Concentration Profiles in Hypophysial‐Portal and Peripheral Plasma

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