Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:040593 (CRH)
 2,662 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regulatory mechanisms of the hypothalamo-pituitary-adrenal (H-P-A) axis during and after major abdominal surgery were studied in a group of patients who underwent upper abdominal surgery. We first examined the general profile of the changes of the H-P-A axis from the day before surgery to the seventh day after surgery. On the day of surgery, plasma levels of CRH, ACTH, and cortisol were all significantly elevated after skin incision (phase I). During the next 2 days, plasma cortisol levels remained significantly elevated, and the both plasma CRH and ACTH levels were suppressed below the control levels obtained on the day before surgery (phase II). Several additional studies, carried out to analyze the mechanism that maintains the high plasma cortisol levels, revealed the following features of the H-P-A axis during phase II. Plasma free cortisol levels in this phase were higher than those during the preoperative period. The exogenously administered hydrocortisone clearance rate in phase II did not differ from that observed on the day before surgery. Dexamethasone administration resulted in a decrease in plasma cortisol levels similar to that observed preoperatively. Conversely, the ACTH-stimulated cortisol increase was significantly greater in phase II than that observed preoperatively. These results suggest that during and after major surgical stress, the H-P-A axis undergoes a biphasic change in the pattern of the stress response and during the second phase, not the continuous hypothalamo-pituitary drive but the increased adrenal responsiveness to ACTH is responsible at least in part for maintaining the elevated plasma cortisol level.
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PMID:Biphasic changes in hypothalamo-pituitary-adrenal function during the early recovery period after major abdominal surgery. 164 14

Mifepristone (RU 486) is a compound with progesterone as well as cortisol-blocking activities. We investigated the endocrine effects of long-term therapy of 10 patients with meningiomas with 200 mg mifepristone daily for 1 yr. Most patients initially complained of nausea, vomiting, and/or tiredness. In four patients prednisone (7.5 mg/day) had to be given simultaneously in order to overcome these side-effects. In retrospect those patients who presented with the most severe side-effects showed the most rapidly occurring activation of the hypothalamo-pituitary-adrenal-axis, as measured by an increase of circulating cortisol levels as well as of urinary cortisol excretion. Therapy with RU 486 activated the hypothalamo-pituitary-adrenal axis, resulting in a resetting of this system at a higher level at which the diurnal rhythm and the responsiveness to CRH stimulation were maintained, whereas the sensitivity to dexamethasone had diminished. Secondarily the production of androstenedione and estradiol increased considerably. These endocrine changes were caused by the induction of partial cortisol receptor resistance during therapy with RU 486. The compensatory overproduction of androgens and consequently of estrogens during long-term RU 486 therapy might limit its use as a single treatment in the treatment of estrogen-dependent cancer.
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PMID:The endocrine effects of long-term treatment with mifepristone (RU 486). 164 17

Inferior petrosal sinus blood sampling for ACTH measurement (IPSS) is used for the differential diagnosis of ACTH-dependent Cushing's syndrome and for the preoperative location of pituitary microadenomas. Intermittent ACTH secretion from pituitary adenomas may result in insignificant differences between petrosal and peripheral ACTH levels at the time of sampling. Thus, pituitary stimulation during IPSS may improve the procedure. The aim of the study was to evaluate the usefulness of CRH injection in combination with IPSS. Twenty-two patients with Cushing's disease (CD; 5 macroadenomas, 16 microadenomas, and 1 corticotroph hyperplasia) and 5 patients with ectopic ACTH syndrome were studied. Bilateral IPSS was successfully carried out on 25 patients. Patients with ectopic ACTH syndrome had, before and after CRH injection, central to peripheral ACTH gradients below 1.7. Four patients with CD had basal gradients below 1.4. After CRH administration all patients with CD had gradients above 3.2. Despite correct location of central catheters, the predicted location of pituitary microadenomas was erroneous in 41% of the cases. It was not improved after CRH injection. In conclusion, the combination of CRH injection with IPSS was useful for the differential diagnosis of ACTH-dependent Cushing's syndrome, as it increased the discrimination of the procedure. On the contrary, it was useless for the preoperative location of pituitary microadenomas, which was poorly predicted by IPSS.
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PMID:Usefulness of the corticotropin-releasing hormone test during bilateral inferior petrosal sinus sampling for the diagnosis of Cushing's disease. 164 18

Endothelin-3 (ET-3) is a member of the novel vasoconstrictive peptide family, identified in porcine central nervous system. Intravenous bolus injection of 1000 pmol/kg of ET-3 in freely moving rats caused significant increases in plasma ACTH and corticosterone levels, almost equivalent to those of 100 pmol/kg of rat corticotropin-releasing hormone (rCRH). The action of ET-3 was virtually abolished by pretreatment of CRH-antagonist, alpha-helical CRH. When ET-3 was added to cultured anterior pituitary cells, neither direct stimulation of ACTH release nor potentiation of rCRH action was noted. The results indicate that ET-3 may function as a neuropeptide and stimulation of the CRH-neurons, direct or inderect, is mainly responsible for activation of ACTH and corticosterone release.
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PMID:Endothelin-3 stimulates the hypothalamic-pituitary-adrenal axis. 164 64

CRH (corticotropin-releasing hormone) is a hypothalamic polypeptide that stimulates ACTH secretion by the anterior pituitary and, subsequently, cortisol secretion by the adrenal cortex. CRH test administration is indicated in the differential diagnosis of Cushing syndrome and in the assessment of corticotropic function in different pituitary conditions. Both human CRH (hCRH) and ovine CRH (oCRH) can be used by i.v. injection. Intrinsic ACTH-releasing activities of the two molecular forms are similar. Nevertheless, and contrary to hCRH, oCRH does not interact with the human CRH specific binding protein (CRH-BP) and the use of this ovine form could be useful in testing pituitary function while avoiding possible changes in peptide activity due to protein binding. The present study was conducted in 3 distinct groups of human volunteers to evaluated the ACTH and cortisol responses to i.v. oCRH (1 micrograms per kg body weight) at noon (oCRH test). 24 healthy, nonobese subjects, not under medication, participated in the study. The first group consisted of 8 young men, the second of 8 women of childbearing age and the third of 8 menopausal women. Tolerance to the oCRH test was excellent in all 3 groups. A significant increase in plasma ACTH and cortisol was observed in all the subjects, with peak occurrence for ACTH between 15 and 60 minutes after oCRH and between 20 and 120 minutes for cortisol. The responses were not sex-related among the young subjects, but the menopausal women displayed a higher cortisol increase than the other 2 groups.
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PMID:[Test with ovine corticotropin-releasing hormone (oCRH): clinical application and reference values in the young adult and the postmenopausal women]. 164 82

CRH is secreted by the placenta into the maternal and fetal circulation during pregnancy in humans and non-human primates. ACTH and cortisol responses to exogenous CRH are blunted during pregnancy. In the present study we examined the pituitary-adrenal response to another corticotropin releasing factor, vasopressin. Studies were performed in chronically catheterized female baboons moving freely in their home cages; 13 studies were performed in 4 pregnant animals, and 8 studies were performed in 6 nonpregnant animals. Vasopressin was administered iv in 2 doses (0.3 and 3.0 U), and plasma samples were obtained for CRH, ACTH, and cortisol measurements. Results are expressed as the mean +/- SEM. Baseline plasma CRH was 240 +/- 20 pmol/L in the pregnant animals and unmeasurable (less than 20) in the nonpregnant animals. In the pregnant animals, ACTH concentrations rose from a baseline of 6.4 +/- 1.3 pmol/L to 10.1 +/- 0.4 after 0.3 U vasopressin and to 24.9 +/- 5.2 after 3.0 U vasopressin. In the nonpregnant animals, ACTH levels were 5.8 +/- 1.3 at baseline, 6.7 +/- 1.3 after the 0.3-U dose, and 14.6 +/- 2.4 after the 3.0-U dose. The peak ACTH response after each dose of vasopressin was higher in the pregnant animals than in the nonpregnant animals (P less than 0.05). The baseline cortisol level in the pregnant animals was 960 +/- 80 nmol/L and rose to 1370 +/- 110 and 1535 +/- 165 after the 2 doses of vasopressin, respectively. The baseline cortisol concentration in the nonpregnant animals was 910 +/- 86 nmol/L. The cortisol level was 990 +/- 75 after the 0.3-U vasopressin dose and 1380 +/- 140 after the 3.0-U dose. The peak cortisol response after the 0.3-U dose was significantly higher in the pregnant animals (P less than 0.02), while the peak cortisol responses after the 3.0-U dose were similar in the 2 groups of animals. In a single animal, vasopressin was administered sequentially at 4 gestational ages during pregnancy and then 2 times in the postpartum period. The ACTH response to vasopressin increased as pregnancy progressed and then decreased in the postpartum period. In summary, the ACTH and cortisol responses to 0.3 and 3.0 U vasopressin, iv, are enhanced during pregnancy in the baboon, although the responses to exogenous CRH are blunted during gestation. We conclude that the chronic placental CRH stimulation of the pituitary-adrenal axis during pregnancy leads to an enhanced response to vasopressin and a down-regulation of the response to exogenous CRH.
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PMID:Adrenocorticotropin and cortisol responses to vasopressin during pregnancy. 164 36

Using autoradiography combined with immunocytochemistry, we demonstrated that the target cells of CRH in the human pituitary were proopiomelanocortin cells. Scatchard analysis of [125I]Tyr0-oCRH saturation binding revealed the presence of one class of saturable, high affinity sites on pituitary tissue homogenate. The equilibrium dissociation constant (Kd) for [125I]Tyr0-oCRH ranged from 1.1-1.6 nM, and the receptor density was between 200-350 fmol/mg protein. Fixation of cryostat sections with 4% paraformaldehyde before tracer incubation improved both tissue preservation and localization of the CRH receptor at the cellular level. Additional postfixation with 1% glutaraldehyde inhibited tracer diffusion during subsequent immunocytochemistry and autoradiography. [125I]Tyr0-oCRH was found in cytoplasmic inclusions or at the cell periphery of ACTH/beta-endorphin cells in the anterior pituitary. Single cells of the posterior pituitary were also CRH receptor positive. Cells staining for PRL or GH were CRH receptor negative. We conclude that CRH binds only to high affinity receptors on ACTH/beta-endorphin cells in the human pituitary.
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PMID:Receptors for corticotropin-releasing hormone in human pituitary: binding characteristics and autoradiographic localization to immunocytochemically defined proopiomelanocortin cells. 164 37

To determine whether CRH is the sole mediator of ACTH release during exercise, five men and five women were given, in a subject-blinded random manner at separate visits, both a 6-h infusion of ovine CRH (1 microgram/kg.h) and a saline infusion as a placebo. After the fourth hour of each infusion, when plasma concentrations of ovine CRH were sufficiently elevated to saturate the capacity of the corticotroph to respond further to CRH, each subject completed a high intensity intermittent run. Plasma ACTH and cortisol levels increased significantly during the CRH infusion from 4.6 +/- 0.8 (mean +/- SE) to 8.6 +/- 1.6 pmol/L and from 361 +/- 39 to 662 +/- 70 nmol/L, respectively (P less than 0.05). Despite elevated preexercise cortisol levels during the CRH infusion, plasma ACTH rose to 32.0 +/- 8.5 pmol/L after exercise. During the saline infusion, plasma ACTH rose from 3.4 +/- 0.6 pmol/L before exercise to 18.1 +/- 4.2 after exercise. Time-integrated responses for postexercise values of ACTH and cortisol were higher during the CRH infusion than during the saline infusion (P less than 0.05). No significant exercise-induced differences in heart rate or plasma concentrations of lactate, epinephrine, and norepinephrine were observed between the two tests. The findings suggest that some factor(s) in addition to CRH causes ACTH release during exercise. Vasopressin, produced by the magnocellular and/or parvocellular neurons of the hypothalamus, is a likely candidate.
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PMID:Corticotropin-releasing hormone is not the sole factor mediating exercise-induced adrenocorticotropin release in humans. 164 38

The clinical, biochemical, and radiographic features of ectopic ACTH-dependent Cushing's syndrome are often indistinguishable from those of pituitary ACTH-dependent hypercortisolism (Cushing's disease). We prospectively evaluated 29 patients with ACTH-dependent hypercortisolism by means of bilateral inferior petrosal sinus ACTH sampling with ovine CRH (oCRH) stimulation. Patients with Cushing's disease (n = 20), had a maximal basal inferior petrosal sinus to peripheral ACTH ratio (IPS:P-ACTH) of 11.7 +/- 4.4 (+/- SE) from the dominant IPS, which increased to 50.8 +/- 18.3 after oCRH administration. Bilateral IPS sampling was necessary to correctly identify patients with Cushing's disease, since the maximal basal nondominant IPS:P-ACTH was less than 2.0 in over 50% of the patients and remained less than 2.0 after oCRH administration in one third. In contrast, patients with occult ectopic ACTH-secreting neoplasms (n = 9) had maximal basal IPS:P-ACTH of 1.2 +/- 0.1 that did not change after oCRH administration. Occult ectopic ACTH-secreting neoplasms were found in 7 of 9 patients from 0.4-14 yr after the recognition of Cushing's syndrome, and 4 of these patients had intermittent hypercortisolism with prolonged periods of remission. Selective endobronchial lavage for ACTH correctly localized a radiologically occult ACTH-secreting bronchial carcinoid in 1 patient, and magnetic resonance imaging identified a similar neoplasm in a patient with a normal chest computed tomographic scan. Basal ACTH and urinary free cortisol excretion were significantly higher in patients with ectopic ACTH than in those with Cushing's disease, but overlap existed between groups. High dose dexamethasone suppression testing inaccurately classified 24% of patients, and radiological imaging of the pituitary and adrenal glands was misleading. The occult ectopic ACTH syndrome is a common form of ACTH-dependent hypercortisolism that cannot be distinguished from Cushing's disease with routine clinical studies. The accurate differential diagnosis of ACTH-dependent Cushing's syndrome requires bilateral inferior petrosal sinus ACTH sampling with oCRH stimulation.
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PMID:Routine inferior petrosal sinus sampling in the differential diagnosis of adrenocorticotropin (ACTH)-dependent Cushing's syndrome: early recognition of the occult ectopic ACTH syndrome. 164 42

Blood borne hormones of the hypothalamus-pituitary-adrenal (HPA) axis form an afferent humoral system modulating a great variety of brain functions. In humans, bioassays consistently reflecting central nervous system actions have not been developed, so far. The present experiments are part of a series of studies which have been conducted to demonstrate the afferent influences of ACTH and CRH on brain activity by recording of auditory event-related brain potentials (ERPs) in healthy human subjects. In a double-blind within-subject comparison in 12 healthy male students, influences of 4 U ACTH and 100 micrograms CRH (infused within 2 h; the infusion starting 1 h prior to ERP recordings) were compared with the effects of a placebo infusion. Influences of the hormones were tested for the early, brain stem generated ERP components (BAEPs) and for the late components of the ERP associated with cortical stimulus processing. ACTH and CRH showed no consistent effect on BAEPs. ACTH, but not CRH, significantly reduced amplitudes of late ERP components, in particular, the Nd and P3 components which are considered signs of selective attention. These results are consistent with findings from previous studies demonstrating impaired ERP signs of selective attention in humans after administration of the 4-10 fragment of ACTH which lacks the peripheral adrenocorticotropic activity. Together with these foregoing studies, results from the present experiments further establish ERP methodology as a sensitive bioassay for CNS actions of hormones in humans.
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PMID:Brain evoked responses, a bioassay for central actions of adrenocorticotropin (ACTH 1-39) and corticotropin releasing hormone (CRH) in humans. 165 Jul 50


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