Inhibition by dexamethasone of arginine vasopressin and ACTH responses to insulin-induced hypoglycemia and cigarette smoking in normal men

1990 ◽  
Vol 123 (5) ◽  
pp. 487-492 ◽  
Author(s):  
P. Chiodera ◽  
V. Coiro
Keyword(s):  
Cigarette Smoking ◽  
Plasma Concentrations ◽  
Peak Level ◽  
Inhibitory Effect ◽  
Dexamethasone Treatment ◽  
Plasma Acth ◽  
The Mean ◽  
Normal Men ◽  
Circulating Levels ◽  
Acth Release

Abstract. Glucocorticoids are known to inhibit the AVP response to osmotic and hemodynamic stimuli in humans. In the present study, we examined whether the AVP response to other primary stimuli, such as insulin-induced hypoglycemia and cigarette smoking was sensitive to inhibition by dexamethasone. The plasma ACTH responses were also measured. Twenty-four normal men were randomly divided into 3 groups of 8 subjects. One group was tested with insulin (0.15 IU/kg in an iv bolus) and another group with cigarette smoking (2 non-filter cigarettes smoked in succession within 10 min) with and without pretreatment with dexamethasone (2 or 4 mg in an iv bolus 10 min before insulin or smoking). The third group was tested with dexamethasone alone (2 or 4 mg in an iv bolus). The administration of dexamethasone (2 or 4 mg) alone did not modify the circulating levels of AVP and ACTH at any time during the next hour. The hypoglycemic response to insulin was similar regardless of dexamethasone treatment. AVP rose sharply in response to both hypoglycemia and smoking, reaching mean peak levels at 45 and 30 min, respectively. After both stimuli, the mean peak levels of AVP were 2.25 times higher than baseline. Pretreatment with dexamethasone (2 or 4 mg) significantly decreased the AVP responses to both hypoglycemia and cigarette smoking. Following pretreatment with dexamethasone (2 or 4 mg) the AVP increments in response to hypoglycemia or cigarette smoking were only 1.7 times higher than baseline. The plasma concentrations of ACTH were strikingly increased by hypoglycemia. The mean peak level was 3.5 times higher than baseline and was reached at 45 min. Pretreatment with dexamethasone (2 or 4 mg) significantly reduced hypoglycemia-induced ACTH increase, with a mean peak response 2.8 times higher than baseline. Cigarette smoking significantly increased the plasma ACTH concentrations. The mean peak level was observed at 20 min and was 1.3 times higher than baseline. The ACTH response to smoking was not significant following pretreatment with dexamethasone (2 or 4 mg). These data show a partial inhibitory effect of dexamethasone on hypoglycemia-and cigarette smoking-stimulated AVP secretion. In addition, the data show suppression by dexamethasone of the ACTH response to cigarette smoking and confirm previous observations of a partial inhibition by glucocorticoids of hypoglycemia-induced ACTH release.

Adrenal and gonadal function in hypothyroid adult male rats

1997 ◽  
Vol 152 (1) ◽  
pp. 147-154 ◽  
Author(s):  
A Tohei ◽  
M Akai ◽  
T Tomabechi ◽  
M Mamada ◽  
K Taya
Keyword(s):  
Adult Male ◽  
Functional Relationship ◽  
Plasma Concentrations ◽  
Gonadal Hormones ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Male Rats ◽  
Plasma Acth ◽  
Corticosterone Release ◽  
Acth Release

Abstract The functional relationship between thyroid, adrenal and gonadal hormones was investigated using adult male rats. Hypothyroidism was produced by the administration of 4-methyl-2-thiouracil (thiouracil) in the drinking water for 2 weeks. Plasma concentrations of TSH dramatically increased, whereas plasma concentrations of tri-iodothyronine and thyroxine decreased in thiouracil-treated rats as compared with euthyroid rats. Hypothyroidism increased basal levels of plasma ACTH and pituitary content of ACTH. The pituitary responsiveness to CRH for ACTH release markedly increased, whereas the adrenal responsiveness to ACTH for corticosterone release decreased. These results indicated that hypothyroidism causes adrenal dysfunction in adult male rats. Pituitary contents of LH and prolactin decreased in hypothyroid rats as compared with euthyroid rats. In addition, hypothyroidism lowered pituitary LH responsiveness to LHRH. Testicular responsiveness to human chorionic gonadotrophin for testosterone release, however, was not different between euthyroid and hypothyroid animals. These results indicated that hypothyroidism causes adrenal dysfunction and results in hypersecretion of ACTH from the pituitary gland. Adrenal dysfunction may contribute to the inhibition of LHRH secretion from the hypothalamus, possibly mediated by excess CRH. Journal of Endocrinology (1997) 152, 147–154

Regulation of CRH-induced secretion of ACTH and corticosterone by SOM230 in rats

2005 ◽  
Vol 153 (3) ◽  
pp. R7-R10 ◽  
Author(s):  
A P Silva ◽  
P Schoeffter ◽  
G Weckbecker ◽  
C Bruns ◽  
H A Schmid
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Plasma Concentrations ◽  
Inhibitory Effect ◽  
Corticotropin Releasing Hormone ◽  
Acth Secretion ◽  
Releasing Hormone ◽  
Corticosterone Secretion ◽  
Corticosterone Release ◽  
Acth Release

Objective: Adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome is biochemically characterized by increased plasma concentrations of ACTH inducing hypersecretion of cortisol. Somatostatin is known to inhibit ACTH secretion, and in vitro data have shown the inhibition of ACTH secretion by agonists activating sst2 and sst5 receptors. The present study aimed to determine the inhibitory effect of the multireceptor ligand SOM230, compared with the sst2-preferring agonist octreotide, on corticotropin-releasing hormone (CRH)-stimulated secretion of ACTH and corticosterone in rats. Methods: Secretion of ACTH and corticosterone was induced by i.v. application of CRH (0.5 μg/kg) in rats pretreated 1 h before by i.v. application of SOM230 (1, 3, or 10 μg/kg), octreotide (10 μg/kg) or NaCl 0.9%. Results: SOM230 (3 and 10 μg/kg) inhibited CRH-induced ACTH release by 45±3% and 51±2%, respectively, and corticosterone release by 43±5% and 27±16%, respectively. 10 μg/kg of octreotide tended to be less potent at inhibiting ACTH release (34±6% inhibition) and did not alter the secretion of corticosterone. Conclusion: SOM230 has a stronger inhibitory effect on ACTH and corticosterone secretion than octreotide in rats. This difference can be explained by its higher affinity to sst1, sst3 and especially sst5 receptors compared with octreotide.

Mechanism of restoration of ACTH release in rats with long-term lesions of the paraventricular nuclei

1986 ◽  
Vol 111 (1) ◽  
pp. 75-82 ◽  
Author(s):  
J. Dohanics ◽  
G. Kapócs ◽  
T. Janáky ◽  
J. Z. Kiss ◽  
G. Rappay ◽  
...  
Keyword(s):  
Median Eminence ◽  
Plasma Concentrations ◽  
Plasma Acth ◽  
Corticotrophin Releasing Factor ◽  
Paraventricular Nuclei ◽  
Basal Plasma ◽  
Corticosterone Response ◽  
Intact Rats ◽  
Acth Release

ABSTRACT The effects of lesions in the paraventricular nucleus (PVN) on the adrenocortical response to ether stress were investigated in neurohypophysectomized and intact rats. During the first 4 days after placement of lesions in the PVN, the corticosterone response to ether stress was almost completely inhibited. It then gradually increased and, within 4–6 weeks of surgery, was restored to about 60% of that in sham-operated rats. Basal plasma concentrations of corticosterone were low in rats after placement of lesions in the PVN and/or after neurointermediate lobectomy (NILX). Corticosterone responses to ether stress were similar in groups submitted to PVN lesions and/or NILX, and lower than those in the appropriate sham-operated groups. In all lesioned groups, plasma ACTH concentrations after a combination of stressors (ether plus laparotomy) were also lower than those in the sham-operated groups. Six weeks after lesioning of the PVN, immunoreactive rat corticotrophin-releasing factor-41 (rCRF-41) concentrations in stalk-median eminence (SME) extract fell to about 5% of that in sham-operated rats, while immunoreactive arginine vasopressin (AVP) concentrations did not change. Immunohistochemistry revealed a substantial decrease in rCRF-41 immunostaining of the median eminence 6 weeks after lesioning of the PVN, though randomly located clusters of stained terminals were still seen in the whole rostro-caudal extent of the median eminence. A mixture containing synthetic rCRF-41 and AVP, in proportions similar to those in SME extracts from sham-operated rats, caused significantly less release of ACTH from anterior pituitary cell cultures than did SME extracts from sham-operated rats. Extracts of SME from PVN-lesioned rats released as much ACTH as a mixture containing synthetic rCRF-41 and AVP in proportions similar to those in the SME extracts from PVN-lesioned rats. Extracts of SME from either PVN-lesioned or sham-operated rats did not cause a significant increase in the amount of ACTH released when preincubated with antisera to both rCRF-41 and AVP. It is suggested that (1) the restoration of the adrenocortical reponse to ether stress, evident within a few days of placement of lesions in the PVN, occurs independently of neurohypophysial function; (2) the full corticosterone and ACTH response to ether or ether plus laparotomy stress requires not only an intact PVN but also an intact neurointermediate lobe; (3) SME extracts from sham-operated rats contain a factor(s) with the ability to potentiate the ACTHreleasing effect of rCRF-41 and AVP; and (4) the ACTH-releasing activity of SME extract obtained from rats with long-term PVN lesions is probably due to its remaininJ content of rCRF-41 and AVP. J. Endocr. (1986) 111, 75–82

Coordinate activation of the corticotropic axis by insulin-induced hypoglycemia: simultaneous estimates of β-endorphin, adrenocorticotropin and cortisol secretion and disappearance in normal men

1993 ◽  
Vol 128 (6) ◽  
pp. 521-528 ◽  
Author(s):  
Ali Iranmanesh ◽  
German Lizarralde ◽  
Johannes D Veldhuis
Keyword(s):  
Plasma Concentrations ◽  
Metabolic Stress ◽  
Fold Increase ◽  
Volume Of Distribution ◽  
Mean Value ◽  
Cortisol Secretion ◽  
Daily Production ◽  
Deconvolution Analysis ◽  
The Mean ◽  
Normal Men

In the present study, we investigated the coordinate kinetic response of the corticotropic axis to the acute metabolic stress of hypoglycemia by applying deconvolution analysis to adrenocorticotropin (ACTH), β-endorphin and cortisol concentration-time series generated in seven normal men after intravenous administration of insulin. Hypoglycemic stress resulted in a 22-fold increase in the mean plasma concentration of ACTH to a maximum of 77±15 pmol/l, in conjunction with a 7.5-fold increase in the mean plasma β-endorphin concentration, the maximal value of which was 96±11 pmol/l. Plasma cortisol concentrations increased by 2.6-fold with a mean value of 734±14 nmol/l. Maximal plasma ACTH and β-endorphin concentrations were preceded by discrete secretory bursts with peak amplitudes of 10.5±2.7 and 10.6±2.0 pmol·I−1·min−1 (20-fold and ninefold increases compared to control), respectively. The mass of ACTH released was 114±20 pmol/l (3.4-fold increase), which corresponds to a total amount of 1.25 μg (50% of daily production and 0.5% of reported pituitary stores), assuming a distribution volume of 40 ml/kg. A total amount of 4.4±0.7 mg of cortisol was released after insulin-induced hypoglycemia, based on a mean cortisol secretory mass of 1088±137 nmol/l and a presumed 11.3-1 volume of distribution. Deconvolution-based estimates of the endogenous half-lives of ACTH, β-endorphin and cortisol were 17±0.6, 22±1.7 and 65±5.3 min, respectively. In summary, deconvolution analysis revealed a rapid coordinate activation of ACTH, β-endorphin and cortisol secretion after hypoglycemic stress, which correlated closely but temporally preceded increases in the respective plasma concentrations. Our inference that only a small fraction of pituitary ACTH content is released during hypoglycemic stress emphasizes the large reserve capability of the pituitary corticotropes. The percentage response of adrenal gland to the metabolic stress of hypoglycemia was of lesser magnitude, possibly owing to the rate-limiting properties of cortisol biosynthesis. We conclude that kinetic responses of the hypothalamic—pituitary—adrenal axis to hypoglycemic stress exhibit exquisite temporal synchrony and manifest a marked reserve capacity.

Oxytocin reduces exercise-induced ACTH and cortisol rise in man

1988 ◽  
Vol 119 (3) ◽  
pp. 405-412 ◽  
Author(s):  
V. Coiro ◽  
M. Passeri ◽  
C. Davoli ◽  
A. Bacchi-Modena ◽  
L. Bianconi ◽  
...  
Keyword(s):  
Physical Exercise ◽  
Bolus Injection ◽  
Inhibitory Effect ◽  
Bicycle Ergometer ◽  
Endogenous Opioids ◽  
Cortisol Response ◽  
Plasma Acth ◽  
Exercise Induced ◽  
Normal Men ◽  
Response To Exercise

Abstract. The effect of oxytocin on the ACTH, cortisol, GH and PRL response to physical exercise was investigated in 6 normal men. In addition, the possible involvement of endogenous opioids in the mediation of oxytocin action was evaluated. After fasting overnight, each subject was tested on four mornings at least 1 week apart. Exercise was performed on a bicycle ergometer. The workload was gradually increased at 3-min intervals until exhaustion and lasted about 20 min in all subjects. Tests were carried out under administration of oxytocin (2000 mIU as an iv bolus injection plus 32 mIU/min per 30 min) or naloxone (10 mg as an iv bolus injection) alone; furthermore, the effect of oxytocin together with naloxone (10 mg as an iv bolus injection) was evaluated. In the remaining test, normal saline was given instead of drugs. Plasma ACTH, cortisol, PRL and GH concentrations were significantly increased by physical exercise. Administration of oxytocin, naloxone or their combination was without effect on the PRL and GH rise elicited by exercise. In contrast, the exercise-induced ACTH and cortisol response was significantly raised by naloxone and reduced by oxytocin. When oxytocin was preceded by administration of naloxone, the ACTH and cortisol response to exercise was not reduced by oxytocin. These data show that oxytocin is capable of inhibiting the rise in ACTH and cortisol, but not in GH and PRL induced by physical exercise. Since naloxone abolished the inhibitory effect of oxytocin, oxytocin action on ACTH and cortisol secretion might be supposed to be mediated by an opioid pathway. However, we cannot exclude that oxytocin and naloxone act at different sites in the hypothalamic-pituitary system.

THE EFFECT OF METYRAPONE ON CORTICOTROPHIN SECRETION

1972 ◽  
Vol 52 (3) ◽  
pp. 517-524 ◽  
Author(s):  
R. A. DONALD ◽  
E. A. ESPINER ◽  
D. W. BEAVEN
Keyword(s):  
Replacement Therapy ◽  
Diurnal Rhythm ◽  
Acth Level ◽  
Plasma Acth ◽  
Significant Difference ◽  
Acth Concentration ◽  
The Mean ◽  
Adrenal Disease ◽  
Normal Controls ◽  
Acth Release

SUMMARY The plasma immunoreactive corticotrophin (ACTH) response to metyrapone (1 g orally at 08.00 h, and 6 hourly thereafter for 48 h) was analysed in 20 patients with a normal oxogenic steroid response. A greater than threefold rise in the mean plasma ACTH concentration was observed within 24 h. The mean plasma ACTH level at 08.00 h on the 2nd day of the test was significantly higher than the mean level at 16.00 h, indicating that the diurnal rhythm in ACTH release persists despite metyrapone administration. The degree of rhythmicity, as assessed by the ratio of the means of the 08.00 and 16.00 h ACTH values on the 2nd day of metyrapone administration, was comparable to, but slightly less than that observed in untreated normal controls. The ACTH response to reduction of circulating cortisol levels was also studied by interrupting steroid replacement therapy for 24 h in eight patients with adrenal disease. The observed increase in plasma ACTH was more variable than that after metyrapone, the rapidity of the ACTH rise possibly being influenced by the details of previous replacement therapy and the severity of the adrenal disease. There was no significant difference in the plasma ACTH response to metyrapone and insulin-induced hypoglycaemia in 13 patients whose pituitary function had been assessed by each of these procedures.

Evidence that endogenous SST inhibits ACTH and ghrelin expression by independent pathways

2006 ◽  
Vol 291 (2) ◽  
pp. E395-E403 ◽  
Author(s):  
Raul M. Luque ◽  
Manuel D. Gahete ◽  
Ute Hochgeschwender ◽  
Rhonda D. Kineman
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Inhibitory Effect ◽  
Mrna Levels ◽  
Adrenal Axis ◽  
Ghrelin Gene ◽  
Total Ghrelin ◽  
The Impact ◽  
Circulating Levels ◽  
Acth Release

Corticosterone and total ghrelin levels are increased in somatostatin (SST) knockout mice ( Sst −/−) compared with SST-intact controls ( Sst +/+). Because exogenous ghrelin can increase glucocorticoids, the question arises whether elevated levels of ghrelin contribute to elevated corticosterone levels in Sst −/− mice. We report that Sst −/− mice had elevated mRNA levels for pituitary proopiomelanocortin (POMC), the precursor of adrenocorticotropic hormone (ACTH), whereas mRNA levels for hypothalamic corticotropin-releasing hormone (CRH) did not differ from Sst +/+ mice. Furthermore, SST suppressed pituitary POMC mRNA levels and ACTH release in vitro independently of CRH actions. In contrast, it has been reported that ghrelin increases glucocorticoids via a central effect on CRH secretion and that n-octanoyl ghrelin is the form of ghrelin that activates the GHS-R1a and modulates CRH neuronal activity. Consistent with elevations in total ghrelin levels, Sst −/− mice displayed an increase in stomach ghrelin mRNA levels, whereas hypothalamic and pituitary expression of ghrelin was not altered. Despite the increase in total ghrelin levels, circulating levels of n-octanoyl ghrelin were not altered in Sst −/− mice. Because glucocorticoids and ghrelin increase in response to fasting, we examined the impact of fasting on the adrenal axis and ghrelin in Sst +/+ and Sst −/− mice and found that endogenous SST does not significantly contribute to this adaptive response. We conclude that endogenous SST inhibits basal ghrelin gene expression in a tissue specific manner and independently and directly inhibits pituitary ACTH synthesis and release. Thus endogenous SST exerts an inhibitory effect on ghrelin synthesis and on the adrenal axis through independent pathways.

Effects of a V1-vasopressin antagonist on ACTH release following vasopressin infusion or insulin-induced hypoglycemia in normal men

1990 ◽  
Vol 123 (6) ◽  
pp. 622-628 ◽  
Author(s):  
Oliver Hader ◽  
Volker Bähr ◽  
Johannes Hensen ◽  
Karl G. Hofbauer ◽  
Wolfgang K. H. Oelkers
Keyword(s):  
Plasma Cortisol ◽  
Peak Plasma ◽  
Control Group ◽  
Plasma Acth ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Infusion Experiment ◽  
The Difference ◽  
Normal Men ◽  
Acth Release

Abstract. Experimental evidence indicates that arginine vasopressin contributes to the release of adrenocorticotropic hormone under certain conditions. We studied for the first time the AVP antagonist [d(CH2)5 Tyr(Me)AVP] in 6 normal men in order to evaluate the possible role of AVP as an ACTH-releasing hormone during insulin-induced hypoglycemia. To test the agent's capacity to inhibit an ACTH release by exogenous AVP, we compared the ACTH response to an infusion of 300 ng AVP/min a. 30 min after injection of 5 μg/kg of the antagonist, b. after injection of placebo (0.9% NaCl). Plasma ACTH levels during AVP infusion rose from 17.2±1.6 ng/l (3.8±0.35 pmol/l) to 31.7±4.2 ng/l (7.0±0.92 pmol/l) at 40 min after injection of the antagonist, the difference to the control-group (increment from 16.5±1.2 ng/l (3.6±0.26 pmol/l) to 41.8±3.5 ng/l) (9.2±0.77 pmol/l) being significant (p<0.05). Peak plasma cortisol levels were 323±42 and 529±52 nmol/l, respectively (p<0.05). We then tested the compound in the same subjects during an insulin-induced hypoglycemia; 30 min after administration of 10 μg/kg of the AVP antagonist or placebo, all subjects received 0.12 IU/kg of normal insulin, thus inducing a fall of blood glucose levels below 2 mmol/l. The AVP antagonist caused a moderate but insignificant reduction of the rise in plasma ACTH and a slightly greater, significant reduction of the increment in plasma cortisol (350±19 nmol/l with antagonist and 469±90 nmol/l with placebo, p<0.05) during insulininduced hypoglycemia. The results indicate that a. the AVP antagonist partly inhibits the stimulatory effect of infused AVP on ACTH release in normal men; b. a slightly higher dose of this competitive AVP antagonist inhibits ACTH and cortisol stimulation by hypoglycemia only very little. The importance of AVP as an ACTH-releasing factor in the latter condition may have been underestimated by our experiment, since AVP concentrations in hypophyseal portal blood during hypoglycemia probably were higher than during the AVP infusion experiment.

Relationship of nocturnal plasma bioactive and immunoactive ACTH concentrations to cortisol secretion in normal men

1989 ◽  
Vol 121 (6) ◽  
pp. 857-865 ◽  
Author(s):  
Russell E. Poland ◽  
Koichi Hanada ◽  
Robert T. Rubin
Keyword(s):  
Plasma Concentrations ◽  
Normal Male ◽  
Cortisol Secretion ◽  
Plasma Acth ◽  
Average Correlation ◽  
Adrenal Cell ◽  
Male Volunteers ◽  
Shared Variance ◽  
Normal Men ◽  
Relationship Of

Abstract. Plasma concentrations of ACTH and cortisol were measured at 15-min intervals from 22.30 to 07.00 h in 8 normal male volunteers. ACTH was measured both by a modified and sensitized isolated adrenal cell bioassay and by radioimmunoassay. Within-subject correlations between bioactive ACTH and cortisol concentrations ranged between 0.86 and 0.95, with an average correlation of 0.93 (86% shared variance). In contrast, within-subject correlations between immunoassayable ACTH and cortisol ranged between 0.03 and 0.92, with an average correlation of 0.69 (48% shared variance). These results suggest that plasma ACTH concentrations determined by RIA might not accurately reflect the capacity of plasma to regulate the secretion of adrenal glucocorticoids.

Plasma Thrombospondin as an Indicator of Intravascular Platelet Activation in Patients with Vasculitis

1987 ◽  
Vol 58 (03) ◽  
pp. 850-852 ◽  
Author(s):  
M B McCrohan ◽  
S W Huang ◽  
J W Sleasman ◽  
P A Klein ◽  
K J Kao
Keyword(s):  
Platelet Activation ◽  
Plasma Levels ◽  
Half Life ◽  
Degradation Products ◽  
Plasma Concentrations ◽  
Primary Source ◽  
Positive Correlation ◽  
Activation Marker ◽  
Fibrin Degradation Products ◽  
The Mean

SummaryThe use of plasma thrombospondin (TSP) concentration was investigated as an indicator of intravascular platelet activation. Patients (n = 20) with diseases that have known vasculitis were included in the study. The range and the mean of plasma TSP concentrations of patients with vasculitis were 117 ng/ml to 6500 ng/ml and 791±1412 ng/ml (mean ± SD); the range and the mean of plasma TSP concentrations of control individuals (n = 33) were 13 ng/ml to 137 ng/ml and 59±29 ng/ml. When plasma TSP concentrations were correlated with plasma concentrations of another platelet activation marker, β-thromboglobulin (P-TG), it was found that the TSP concentration inei eased exponentially as the plasma β-TG level rose. A positive correlation between plasma levels of plasma TSP and serum fibrin degradation products was also observed. The results suggest that platelets are the primary source of plasma TSP in patients with various vasculitis and that plasma TSP can be a better indicator than β-TG to assess intravascular platelet activation due to its longer circulation half life.

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