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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence exerted by somatostatin on the secretion of ACTH and opioid peptides has still to be clarified. To gain further information on this issue, we performed in 10 normal volunteers two CRF tests (100 micrograms i.v.) one of which was preceded by s.c. injection of 100 micrograms of the long-acting somatostatin analogue SMS 201-995 (Sandostatin, Sandoz) (SMS), given 30 minutes before CRF. Premedication with SMS markedly inhibited the response of beta-EP to CRF, leaving unchanged the response of beta-LPH, ACTH and cortisol; mean incremental areas of beta-EP were 199.8 +/- 49.31 (SEM) vs 532.9 +/- 95.91 pmol 120 min (P less than 0.01) in the CRF test with and without SMS, respectively. To interpret the selective inhibitory effect of SMS on CRF-stimulated beta-EP secretion, it can be hypothesized that: a) the action of SMS was confined to a population of pituicytes preferentially secreting beta-EP; b) SMS interfered with the processing of POMC inhibiting the formation of beta-EP; c) SMS acted on extrapituitary, possibly peripheral, sources of beta-EP. In conclusion, this study indicates that, in man, somatostatin selectively inhibits the CRF-induced secretion of beta-EP, but not that of ACTH and beta-LPH, by an action that may be exerted at pituitary or extrapituitary level. This is a further example of dissociated secretion of POMC-derived peptides.
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PMID:Effect of sandostatin on CRF-stimulated secretion of ACTH, beta-lipotropin and beta-endorphin. 165 95

Low amplitude, long-lasting epochs of myometrial activity, contractures, occur throughout the majority of pregnancy in all species studied to date. Contractures are associated with a fall in fetal oxygenation and changes in fetal behavioral state. In the present study we observed that contractures produced by the administration of 70 mU oxytocin iv to the pregnant ewe at 125-139 days gestational age (term 145-150 days) result in a fall in fetal carotid arterial PO2 of approximately 2.5 mm Hg and are followed by a rise in fetal carotid arterial plasma ACTH of 16.3 +/- 9.6 pg.ml-1 (mean +/- SEM). When the contracture-induced fall in fetal arterial PO2 was prevented by administration of oxygen to the ewe, fetal ACTH did not rise after the contracture. In conclusion, these observations demonstrate that the relatively small fall in fetal PO2 that accompanies a contracture can be sensed by the fetus and is an essential part of the stimulus to the increased secretion of fetal ACTH that accompanies a contracture. These findings support the view that myometrial activity is one of the factors that influence fetal ACTH secretion.
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PMID:Myometrial contracture-related increases in plasma adrenocorticotropin in fetal sheep in the last third of gestation are abolished by maintaining fetal normoxemia. 165 81

Cells obtained from 6 adult human adrenals or adrenal fragments were cultured in serum-free synthetic medium (McCoy's) in order to study the isolated effects of IGF-I on steroidogenesis and its interactions with ACTH. After addition of peptide, changes in the activities of steroidogenic enzymes were assessed by measuring certain steroids in the spent medium. These included pregnenolone, 17-hydroxypregnenolone (17-OH-Preg), dehydroepiandrosterone (DHA), 17-hydroxyprogesterone (17-OH-P), androstenedione (AD), 11-deoxycortisol and glucocorticoids (chiefly cortisol and its immediate precursors, 11-deoxycortisol and 17-OH-P) and cortisol itself. The steroid responses obtained with repeated doses of IGF-I (40 ng/ml approximately 10(-9) M), added at 0, 48 and 72 h, over 4 days' culture were quite different from those obtained with repeated doses of ACTH (0.25 ng/ml approximately 10(-10) M). All the steroids measured increased with time of culture under the influence of ACTH and, apart from pregnenolone which peaked, tended to reach a plateau. With IGF-I, by contrast, DHA, AD, 11-deoxycortisol and glucocorticoid production increased initially, then decreased progressively, whereas pregnenolone, 17-OH-Preg and 17-OH-P production was either absent or negative. Cumulative steroid production over 4 days reached similar levels in response to a single dose of IGF-I and/or ACTH, with two major exceptions: pregnenolone dropped significantly with IGF-I [46% +/- 6 (SEM) as opposed to 93% +/- 11 with ACTH, P less than 0.005, n = 5], as did 17-OH-P (48% +/- 11 vs 113% +/- 8 with ACTH, P less than 0.001, n = 6). Increased formation of down-stream metabolites (DHA, AD, 11-deoxycortisol and glucocorticoids) would suggest that IGF-I induced stimulation of the 17 alpha-, 21- and 11 beta-hydroxylases. The responses to ACTH stimulation of cells which 4 days previously had been pre-treated with an initial and single dose of IGF-I and/or ACTH emphasized the impact of IGF-I on the 3-hydroxylation steps in cortisol biosynthesis. Compared with ACTH pre-treatment, the effects of which faded in the long term, pre-treatment with IGF-I resulted in a significantly increased steroidogenic response (P between less than 0.05 and less than 0.01). With the single exception of pregnenolone (43% +/- 4.7), production of all the metabolites was amplified: 17-OH-Preg: 348% +/- 88; DHA: 643% +/- 127; 17-OH-P: 193% +/- 36; AD: 725% +/- 200; 11-deoxycortisol: 573% +/- 110; cortisol: 1000%.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of insulin-like growth factor I (IGF-I) on enzymatic activity in human adrenocortical cells. Interactions with ACTH. 166 Nov 28

Arginine vasopressin, oxytocin and ACTH are released from the pituitary gland in response to acute hypoglycemia. To investigate the role of alpha-adrenergic mechanisms in mediating this response, 6 non-diabetic subjects were studied during hypoglycemia induced by 0.15 IU/kg i.v. insulin under control conditions, and during non-selective alpha-adrenergic blockade with phentolamine. In the control study plasma arginine vasopressin rose from 1.6 +/- 0.8 pmol/l (mean +/- SEM) basally to a maximum of 2.5 +/- 0.8 pmol/l following hypoglycemia (p less than 0.05). An exaggerated response was found during phentolamine blockade, with a maximum plasma vasopressin of 11.5 +/- 0.4 pmol/l (by analysis of variance, p less than 0.05). The plasma oxytocin response to hypoglycemia was similarly increased during phentolamine compared to control. Plasma growth hormone rose to 94 +/- 19 mU/l, and during blockade with phentolamine the response was significantly reduced reaching a peak of 34 +/- 7 mU/l (by analysis of variance, p less than 0.05). ACTH and prolactin both increased in response to hypoglycemia, but the increases were not affected by phentolamine. An alpha-adrenergic mechanism appears to inhibit the release of arginine vasopressin and oxytocin in response to hypoglycemia, but does not appear to affect the secretion of ACTH.
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PMID:Effect of alpha-adrenergic blockade on pituitary hormonal responses to insulin-induced hypoglycemia in humans. 168 2

Endothelin-1 is a 21 amino acid peptide originally isolated from porcine aortic endothelium and has recently been localized within the central nervous system. We have administered endothelin-1 in a dynamic perfusion system in order to study its possible effects on the rat hypothalamus and anterior pituitary. Tissue (hypothalami or quartered pituitaries) was placed into plastic chambers and was perfused with oxygenated Krebs-bicarbonate solution. After an interval to establish stable basal peptide release, endothelin-1 was administered at two doses (0.1 and 1 microM) and the release of substance P, vasoactive intestinal peptide, 7B2, and somatostatin was measured, the last being detectable only in hypothalamic perfusates. Both concentrations of endothelin-1 led to a significant increase (P less than 0.01) in the release of substance P from the hypothalamus and pituitary, but not of vasoactive intestinal peptide, 7B2, or somatostatin. Thus after the 0.1 microM and 1 microM endothelin-1 perfusion substance P release from the hypothalamus increased by 125 +/- 5% and 215 +/- 15% (mean +/- SEM) of basal and from the pituitary by 168 +/- 8% and 276 +/- 15% (mean +/- SEM). No change occurred in the output of ACTH or other pituitary hormones. The release of substance P from hypothalamus or pituitary after stimulation with endothelin-1 was not blocked when a calcium free medium was used. Endothelin-1 binding sites were identified on rat pituitary cell membranes. These findings suggest the possibility that endothelin may act as a paracrine substance, neurotransmitter, or neuromodulator in the hypothalamo-pituitary axis.
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PMID:Release of substance P from rat hypothalamus and pituitary by endothelin. 169 95

We have investigated the central effects of substance P (SP) on plasma concentrations of immunoreactive ACTH and on immunoreactive and bioactive arginine vasopressin (AVP) in the rat. The injection of SP (20 nmol) into the lateral ventricle intracerebroventricular, (i.c.v.) of ethanol-anaesthetised rats produced a prolonged antidiuresis lasting at least 30 min, associated with an increase in plasma AVP (from 7.8 +/- 0.6 to 12.5 +/- 1.9 fmol/ml, mean +/- SEM, n = 6). Concentrations of plasma ACTH were significantly decreased 30 min following SP (from 320 +/- 70 to 135 +/- 15 fmol/ml, n = 12). In rats anaesthetised with urethane, a significant decrease in plasma ACTH was observed 15 and 30 min following i.c.v. injection of SP (20 nmol); a downward trend was also observed in ACTH following a 40 nmol dose, but this was not significant. No effect of SP was observed on either basal or CRF-41-stimulated ACTH release from isolated rat anterior pituitary cells in vitro. These results demonstrate for the first time that SP exerts opposite effects upon the release of ACTH and AVP in the same animal, and suggest that these actions occur at the level of the hypothalamus.
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PMID:Substance P stimulates arginine vasopressin and inhibits adrenocorticotropin release in vivo in the rat. 169 61

Hormones of the hypothalamo-pituitary-adrenocortical (HPA-) axis are considered to be of physiological and clinical relevance in regulating spontaneous growth hormone (GH) secretion. To further investigate interdependencies between both systems, we studied the effects of adrenocorticotropin [ACTH(1-24)] and human corticotropin-releasing hormone (h-CRH) upon spontaneous GH secretion in 10 male volunteers. Administration of 1 microgram ACTH (1-24), 10 micrograms h-CRH or saline (control: CTL) every hour from 9.00 to 6.00 p.m. resulted in significant differences of cortisol secretion during the entire observation period (8.00 a.m.-3.00 a.m.) between the three groups (p less than 0.001, Friedman two-way ANOVA). Mean area under the time course curve (AUC) values (+/- SEM) for cortisol expressed as ng x 1,000 x min/ml showed also significant differences between the three treatments from 8.00 a.m. to 3.00 a.m.: CTL 64.0 +/- 6.4, ACTH(1-24) 178.5 +/- 9.4 (p less than 0.01, Wilcoxon test), h-CRH 88.5 +/- 5.6 (p less than 0.01). The main portion of cortisol was released during daytime from 8.00 a.m. to 11.00 p.m., where the most significant differences in the AUC values emerged: CTL 59.6 +/- 5.8, ACTH(1-24) 171.5 +/- 8.8 (p less than 0.01, Wilcoxon test), h-CRH 80.2 +/- 5.1 (p less than 0.01). With regard to GH secretion, significant differences became obvious between the three treatments during daytime from 8.00 a.m. to 11.00 p.m. and the sleep-related period from 11.00 p.m. to 3.00 a.m. (p less than 0.01 and p less than 0.02, Friedman two-way ANOVA).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of human corticotropin-releasing hormone and adrenocorticotropin upon spontaneous growth hormone secretion. 174 61

Cardio-respiratory physiology in sleep was examined in eight preterm lambs born at 133-135 (134 +/- 1, mean SEM) days of gestation after 3-5 days of pulsatile ACTH/TRH infusion, and contrasted with eight lambs born at term (147 +/- 1 days). Lambs were instrumented with electrodes for recording electrocorticogram, electro-oculogram and nuchal electromyogram to define behavioural states, as well as carotid arterial catheters for determination of arterial pressure, heart rate and arterial blood gases. Compared to full-term lambs, the preterm lambs exhibited extended active sleep times, elevated PaCO2 and faster heart rate in all behavioural states than full-term lambs; with increasing postnatal age, sleep times and heart rate declined. As similar differences are found in preterm human infants, the preterm lamb will be a useful model to study the underlying physiology of these cardio-respiratory alterations.
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PMID:Preterm birth in lambs: sleep patterns and cardio-respiratory changes. 179 20

We have used the technique which we have developed for collecting pituitary venous blood from conscious, undisturbed horses to study the effect of acute vigorous exercise on the secretion of CRF, arginine vasopressin (AVP) and ACTH. Pituitary venous (pit) blood was collected every 1-5 min from nine trained racehorses at rest in the stable. The horses then trotted quietly for 10 min, after which they galloped as fast as possible for 4-6 min, before returning to the stable where sampling continued. In Exp 1 (n = 5) no blood samples were taken during exercise, whereas in Exp 2 (n = 4), pit blood was collected every 30 sec during exercise. Immediately after exercise, significant elevations in heart rate (P less than 0.001), body temperature (P less than 0.01) and hematocrit (P less than 0.001) were observed as compared with preexercise values. Jugular cortisol levels were higher after exercise (301.9 +/- 35.2 nmol/liter; mean +/- SEM) than before (187.3 +/- 34.8; P less than 0.01; n = 9). Likewise, jugular AVP levels increased with exercise (before, 0.65 +/- 0.11 pmol/liter; after 3.2 +/- 0.6; P less than 0.01; n = 6), whereas jugular CRF was not altered by exercise (before, 0.38 +/- 0.08 pmol/liter; after, 0.93 +/- 0.31; n = 6; NS). In Exp 1, no significant changes in pit ACTH, AVP, or CRF were observed after exercise. However in Exp 2 when pit blood was sampled during exercise all horses showed an immediate and dramatic rise in ACTH (P less than 0.01) and AVP (P less than 0.005) secretion which peaked during galloping with mean fractional changes above resting levels of 23.6 +/- 9.9 for ACTH and 51.7 +/- 24.0 for AVP. After exercise pit AVP levels were not different from resting, whereas ACTH remained elevated (11.4 +/- 6.9-fold above resting levels). By contrast, pit CRF levels were not altered by exercise. In both experiments together, pit AVP and ACTH concentrations were correlated in eight of the nine horses, whereas pit CRF and ACTH concentrations were positively correlated in only one of seven horses. We conclude that acute exercise causes a transient increase in ACTH secretion which occurs synchronously with an increase in AVP secretion. CRF does not appear to play a major role in mediating the initial ACTH response to exercise.
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PMID:The effect of acute exercise on the secretion of corticotropin-releasing factor, arginine vasopressin, and adrenocorticotropin as measured in pituitary venous blood from the horse. 184 16

To explore whether possible differences in central nervous system neuromodulators contribute to the differential presentation of affective symptomatology in Cushing's disease and major depression, we examined the levels of immunoreactive CRH and ACTH in the cerebrospinal fluid (CSF) of 11 patients with Cushing's disease, a patient with ectopic ACTH secretion, 34 patients with major depression, and 60 healthy subjects. We elected to measure these peptides not only because both are classically involved in pituitary-adrenal regulation, but also because their primarily arousal-producing and anorexigenic behavioral effects in experimental animals suggest that they may play a role in the symptom complex of depressive syndromes. We also explored whether the CSF levels of these peptides were more helpful in determining the often difficult differential diagnosis between major depression and Cushing's disease than the plasma ACTH response to ovine CRH, a currently used but somewhat insensitive laboratory means of distinguishing these disorders. CSF levels of immunoreactive CRH and ACTH were significantly lower in Cushing's disease patients [21.9 +/- 2.7 and 15.4 +/- 1.8 pg/mL, (mean +/- SEM), respectively] compared to patients with major depression [38.4 +/- 2.3 pg/mL (P less than 0.01) and 24.5 +/- 1.6 pg/mL (P less than 0.01), respectively] and controls [38.4 +/- 1.6 pg/mL (P less than 0.001) and 26.3 +/- 1.1 pg/mL (P less than 0.001), respectively]. The coexistence of high plasma ACTH and low CSF ACTH in Cushing's disease yielded a CSF/plasma ACTH ratio consistently less than that in depressed patients, with only 2 of 31 subjects comprising both groups showing values that overlapped. In contrast, 9 of the combined patients showed ACTH responses to ovine CRH that overlapped. These data suggest that differences in centrally directed CRH secretion may account for the differential presentation of the dysphoric syndromes seen in major depression and Cushing's disease. Hence, the classic form of major depression (melancholia), is often associated with evidence of pathological hyperarousal, such as intense anxiety, sleeplessness, and anorexia, while that of Cushing's disease is associated with evidence of pathological hyperarousal, including hyperphagia, fatigue, and inertia. Moreover, measurement of the CSF/plasma ACTH ratio may serve as a clinically useful adjunct to the ovine CRH stimulation test and other laboratory measures in determining the differential diagnosis between major depression and Cushing's disease.
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PMID:Cerebrospinal fluid immunoreactive corticotropin-releasing hormone and adrenocorticotropin secretion in Cushing's disease and major depression: potential clinical implications. 199 96


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