Nycterohemeral difference in inhibition of stress-induced ACTH in adrenalectomized rats

1983 ◽  
Vol 244 (2) ◽  
pp. E186-E189 ◽  
Author(s):  
M. M. Wilson ◽  
S. E. Greer ◽  
M. A. Greer
Keyword(s):  
Feedback Inhibition ◽  
Daily Variation ◽  
Plasma Corticosterone ◽  
Circadian Rhythmicity ◽  
Feedback Signal ◽  
Plasma Acth ◽  
Acth Secretion ◽  
Corticosterone Concentration ◽  
Feedback Suppression ◽  
Adrenalectomized Rats

To determine the interactions among the determinants of ACTH secretion, we examined the influence of circadian rhythmicity on glucocorticoid suppression of ACTH. Adrenalectomized rats were injected with the same amount of corticosterone at 0900 and 1800 h, and plasma ACTH concentrations were determined under basal conditions and after a standard ether stress. At 0900 h, corticosterone suppressed both basal and stress-induced plasma ACTH concentrations. At 1800 h, the same treatment suppressed basal ACTH secretion but not the stress-induced rise. Although the same amount of corticosterone was injected at both times of day, the plasma corticosterone concentration 5 min after injection was higher at 1800 h than at 0900 h. This study indicates that there is a nycterohemeral difference in feedback suppression of stress-induced ACTH secretion by a given dose of corticosterone. The daily variation in feedback inhibition may be due to the additive effect of the evening surge stimulus and the stress stimulus that together override the feedback signal.

INTERRELATIONSHIPS OF PITUITARY AND PLASMA CORTICOTROPHIN AND PLASMA CORTICOSTERONE IN ADRENALECTOMIZED AND STRESSED, ADRENALECTOMIZED RATS

1974 ◽  
Vol 63 (1) ◽  
pp. 213-222 ◽  
Author(s):  
JULIA C. BUCKINGHAM ◽  
J. R. HODGES
Keyword(s):  
Plasma Corticosterone ◽  
Prolonged Treatment ◽  
Delayed Effect ◽  
Plasma Acth ◽  
Corticosterone Concentration ◽  
Before And After ◽  
Small Rise ◽  
Acth Concentration ◽  
Corticosterone Treatment ◽  
Adrenalectomized Rats

SUMMARY Changes in pituitary and plasma corticotrophin (ACTH), estimated by redox bioassay, were correlated with changes in plasma corticosterone in adrenalectomized rats, with and without corticosterone treatment, before and after exposure to stress. After adrenalectomy, the plasma ACTH concentration was persistently increased. The pituitary ACTH content declined and then increased markedly. These changes were prevented by physiological doses of corticosteroids. Stress caused only a small rise in the plasma ACTH concentration in intact and sham-operated rats but a marked increase in adrenalectomized animals. This exaggerated response was reduced to normal by physiological doses of corticosterone. Prolonged treatment with higher doses of corticosterone was necessary to abolish completely the adrenocorticotrophic response to stress. However, one injection of the steroid, in a dose sufficient to raise the plasma corticosterone concentration to a similar level, did not impair the stress-induced release of ACTH. The results suggest that the synthesis and the basal release of ACTH are directly controlled by the concentration of corticosteroid in the blood, but the corticosteroids exert only a delayed effect in modulating the stress-induced release of the hormone.

Interleukin 1 stimulation of the hypothalamic-pituitary-adrenal axis

1990 ◽  
Vol 258 (1) ◽  
pp. E65-E70 ◽  
Author(s):  
A. R. Gwosdow ◽  
M. S. Kumar ◽  
H. H. Bode
Keyword(s):  
Interleukin 1 ◽  
Plasma Corticosterone ◽  
Male Rats ◽  
Plasma Acth ◽  
Organ Cultures ◽  
Intact Male ◽  
Corticosterone Concentration ◽  
Protein Binding Assay ◽  
Hypophysectomized Rats ◽  
Induced Changes

The effect of varying doses of purified human interleukin 1 (IL-1) on rectal temperature (Tr), hypothalamic corticotropin-releasing hormone (CRH), pituitary and plasma adrenocorticotropic hormone (ACTH), and plamsa corticosterone was examined in intact male rats at 24 degrees C; plasma ACTH and corticosterone responses were also studied in hypophysectomized rats. In addition, IL-1-induced changes in corticosterone concentration were investigated by means of adrenal organ cultures. Tr was measured with thermocouples. CRH and ACTH levels were determined by radioimmunoassay, and corticosterone by protein-binding assay. Intravenous administration of IL-1 (0.063-1.0 ng) resulted in hyperthermia, which began 20 min postinjection and continued for an additional 30 min. IL-1 at a dose of 0.5 ng resulted in no change in hypothalamic CRH, pituitary ACTH, or plasma ACTH levels compared with saline-treated rats. Plasma corticosterone was significantly (P less than 0.05) elevated 30 min after IL-1 administration and returned to control levels after 1 h. The higher dose of IL-1 (1.0 ng) did not affect hypothalamic CRH content, but pituitary ACTH began to rise at 15 min and was significantly (P less than 0.05) elevated 30 min after injection. Rats receiving this dose displayed elevated (P less than 0.05) plasma ACTH and corticosterone levels 30 and 60 min postinjection. No change in plasma corticosterone was observed in hypophysectomized rats administered either 1 ng of IL-1 or 1 microgram of recombinant IL-1 beta (rIL-1 beta); adrenal organ cultures treated with IL-1 (10(-11) M) responded similarly.(ABSTRACT TRUNCATED AT 250 WORDS)

NEGATIVE, RATE-SENSITIVE FEEDBACK EFFECTS ON ADRENOCORTICOTROPHIN SECRETION BY CORTISOL IN NORMAL SUBJECTS

1982 ◽  
Vol 92 (3) ◽  
pp. 443-448 ◽  
Author(s):  
S. C. J. READER ◽  
J. ALAGHBAND-ZADEH ◽  
J. R. DALY ◽  
W. R. ROBERTSON
Keyword(s):  
Negative Feedback ◽  
Feedback Inhibition ◽  
Fast Rate ◽  
Normal Subjects ◽  
Constant Infusion ◽  
Stress Tests ◽  
Nacl Solution ◽  
Plasma Acth ◽  
Acth Secretion ◽  
Feedback Effects

Plasma ACTH and corticosteroid levels were measured in normal subjects during constant infusion of either 0·9% (w/v) NaCl solution or cortisol, and during insulin-induced hypoglycaemia. During infusions of 0·9% NaCl solution the secretion of ACTH and corticosteroids was episodic. Fast, rate-sensitive, negative feedback inhibition of ACTH secretion was observed during cortisol infusions, when the corticosteroid levels were within the physiological range (200–750 nmol/l) and were rising at a rate of between 5 and 10 nmol/l per min for 30 min or longer. When plasma corticosteroid levels were in a steady state, the initial fast feedback effects were abolished and ACTH secretion resumed. However, this recovery of ACTH secretion was not seen when the corticosteroid levels were persistently above 800 nmol/l. It appears that corticosteroid-induced negative feedback in man may be both rate- and level-sensitive. During insulin stress tests ACTH secretion fell at a time when the plasma corticosteroid level was rising rapidly (> 5 nmol/l per min) despite persistent hypoglycaemia.

Effect of ketoconazole on adrenocorticotrophic hormone secretion in vitro and in vivo

1986 ◽  
Vol 108 (1) ◽  
pp. 37-41 ◽  
Author(s):  
J. M. Burrin ◽  
T. H. Yeo ◽  
M. J. Ashby ◽  
S. R. Bloom
Keyword(s):  
Hormone Secretion ◽  
Plasma Corticosterone ◽  
In Vivo Studies ◽  
High Dose ◽  
Direct Effects ◽  
Acth Secretion ◽  
Steroid Synthesis ◽  
Oral Doses ◽  
Adrenalectomized Rats

ABSTRACT The direct effects of ketoconazole on ACTH secretion have been investigated using a rat pituitary cell culture system. Ketoconazole had no significant effects on basal ACTH secretion, corticotrophin-releasing factor- or arginine vasopressin-stimulated ACTH secretion, nor did it affect dexamethasone inhibition of ACTH secretion. In-vivo studies demonstrated an increased ACTH level (168 vs 76 ng/l) accompanied by a fall in plasma corticosterone (193 vs 307 μg/l) in normal rats given ketoconazole (24 mg/kg, five oral doses given 8 hourly). No effects were seen in adrenalectomized rats or at lower doses (6 mg/kg) in normal or adrenalectomized rats. A high dose of ketoconazole (24 mg/kg, twice daily oral doses) also caused increased ACTH levels in normal rats (129 vs 86 ng/l) when given for 7 days. No effects were seen in adrenalectomized rats or on plasma corticosterone levels in normal rats. Our data suggest that ketoconazole at these doses has no direct effects on pituitary ACTH secretion but causes an increase in plasma ACTH due to its inhibition of adrenal steroid synthesis. J. Endocr. (1986) 108, 37–41

Feedback Inhibition of Adrenocorticotropin Release by Corticosterone Infusions in the Adrenalectomized Rat

1975 ◽  
Vol 53 (3) ◽  
pp. 475-478 ◽  
Author(s):  
William Rotsztejn ◽  
Josée Lalonde ◽  
Maurice Normand ◽  
Claude Fortier
Keyword(s):  
Body Weight ◽  
Infusion Rate ◽  
Feedback Inhibition ◽  
Inhibitory Effect ◽  
Plasma Corticosterone ◽  
Rat Plasma ◽  
Metabolic Clearance ◽  
Experimental Conditions ◽  
Corticosterone Concentration ◽  
Acth Release

Advantage was taken of a specific and sensitive bioassay for rat plasma adrenocorticotropin (ACTH) based on the dispersion of rat adrenal cells with trypsin, to investigate the relationship between plasma corticosterone concentration and inhibition of ACTH release under steady-stale conditions achieved by graded rates (0–5.12 μg/min per 100 g body weight) of intravenous infusion of the steroid for 45 min in 28-day adrenalectomized rats. In contrast to prior reports involving suppression of stress-induced ACTH release, the inhibitory effect of corticosterone was shown, under our experimental conditions, to be exerted also on the basal rate of ACTH secretion. Indeed, a slight though not significant decrease of plasma ACTH concentration was observed with the corticosterone infusion rate of 0.64 μg/min per 100 g body weight, and further progressive and highly significant drops in concentration were recorded for infusion rates of 2.56 and 5.12 μg/min per 100 g body weight. An increase of the metabolic clearance rate of corticosterone, observed as a function of the infusion rate, was ascribed to saturation by the steroid of the plasma transcortin binding sites.

Fast, rate-sensitive corticosteroid negative feedback during stress

1978 ◽  
Vol 234 (1) ◽  
pp. R39-R45
Author(s):  
M. Kaneko ◽  
T. Hiroshige
Keyword(s):  
Negative Feedback ◽  
Feedback Inhibition ◽  
Fast Rate ◽  
Feedback Regulation ◽  
Plasma Corticosterone ◽  
Absolute Level ◽  
Corticosterone Concentration ◽  
Negative Feedback Regulation ◽  
Control Response ◽  
The Absolute

Characteristics of the fast, rate-sensitive, negative-feedback regulation of adrenocorticotropin secretion during stress was quantitatively analyzed using rats anesthetized with pentobarbital sodium. Various levels of plasma corticosterone were achieved during morning hours by infusing corticosterone solutions of different concentrations. Blood was sampled serially from the carotid artery. An increase in plasma corticosterone concentration 15 min after intravenous, pulsed injection of histamine (230 microgram) during saline intravenous infusion was defined as the “control response”. When plasma corticosterone was rising during corticosterone infusion, the response to histamine stimulus was distinctly inhibited (fast, rate-sensitive feedback inhibition), whereas such an inhibition was not observed when plasma corticosterone levels were not rising, regardless of the absolute level. The critical rate of rise of plasma corticosterone, at or above which the fast rate-sensitive feedback was manifested, was 4-6 microgram/100 ml per min. When three graded doses of histamine were injected while plasma corticosterone levels were increasing at a rate of 6 microgram/100 ml per min, the absolute value of the inhibition observed was indepxendent of the administered dose of the stressor. A hypothetical model for the mechanism of this feedback inhibition, based on the assumption that the hormone effect was proportional to the rate of formation of hormone-receptor complex, satisfied the quantitative characteristics of the inhibition experimentally observed in this study.

scholarly journals Pregnancy-induced adaptations of the central circadian clock and maternal glucocorticoids

2015 ◽  
Vol 228 (3) ◽  
pp. 135-147 ◽  
Author(s):  
Michaela D Wharfe ◽  
Peter J Mark ◽  
Caitlin S Wyrwoll ◽  
Jeremy T Smith ◽  
Cassandra Yap ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Hpa Axis ◽  
Clock Genes ◽  
Circadian Variation ◽  
Maternal Plasma ◽  
Plasma Corticosterone ◽  
Plasma Acth ◽  
Corticosterone Concentration ◽  
Physiological Adaptations ◽  
Acth Concentration

Maternal physiological adaptations, such as changes to the hypothalamic–pituitary–adrenal (HPA) axis, are central to pregnancy success. Circadian variation of the HPA axis is dependent on clock gene rhythms in the hypothalamus, but it is not known whether pregnancy-induced changes in maternal glucocorticoid levels are mediated via this central clock. We hypothesized that hypothalamic expression of clock genes changes across mouse pregnancy and this is linked to altered HPA activity. The anterior hypothalamus and maternal plasma were collected from C57Bl/6J mice prior to pregnancy and on days 6, 10, 14 and 18 of gestation (term=d19), across a 24-h period (0800, 1200, 1600, 2000, 0000, 0400 h). Hypothalamic expression of clock genes and Crh was determined by qPCR, plasma ACTH concentration measured by Milliplex assay and plasma corticosterone concentration by LC-MS/MS. Expression of all clock genes varied markedly across gestation, most notably at mid-gestation when levels of each gene were elevated. The pregnancy-induced increase in maternal corticosterone levels (by up to 14-fold on day 14) was not accompanied by a parallel shift in plasma ACTH (28% lower on day 14 compared with non-pregnant levels). Moreover, while circadian rhythmicity in corticosterone was maintained up to day 14 of gestation, this was effectively lost by day 18. Overall, our data show that the central circadian clock undergoes marked adaptations throughout mouse pregnancy, changes that are likely to contribute to maternal physiological adaptations. Importantly, however, neither hypothalamic clock genes nor plasma ACTH levels appear to drive the marked increase in maternal corticosterone after mid-gestation.

Corticosteroids and ACTH are not required for compensatory adrenal growth

1975 ◽  
Vol 229 (5) ◽  
pp. 1461-1464 ◽  
Author(s):  
WC Engeland ◽  
J Shinsako ◽  
MF Dallman
Keyword(s):  
Young Male ◽  
Dry Weight ◽  
Plasma Corticosterone ◽  
Male Rats ◽  
Adrenal Weight ◽  
Plasma Acth ◽  
Acth Secretion ◽  
Unilateral Adrenalectomy ◽  
Hypophysectomized Rats

We have tested the hypothesis that unilateral adrenalectomy results in decreased glucocorticoid secretion, reflexly elevated ACTH secretion, and consequently, compensatory adrenal growth. Plasma ACTH and corticosterone and right adrenal weight were measured during the first 10 days after left adrenalectomy or sham adrenalectomy in young male rats. There is a decrease in plasma corticosterone after unilateral adrenalectomy compared to sham adrenalectomy that persists for 1 h. ACTH is elevated only at 2 h after unilateral adrenalectomy compared to shamoperated rats. Treatment with dexamethasone, shown to abolish the ACTH and corticosterone responses to laparotomy with intestinal traction, resulted in significantly increased adrenal weight after unilateral adrenalectomy by 6 h (wet or dry weight), and at 24 h. Compensatory adrenal growth also occurs after unilateral adrenalectomy in hypophysectomized rats (wet or dry weight). We conclude the compensatory adrenal growth after unilateral adrenalectomy requires neither a virtual decrease in circulating corticosterone levels nor elevated ACTH levels, and speculate that the phenomenon is neurally mediated.

Pregnancy alters cortisol feedback inhibition of stimulated ACTH: studies in adrenalectomized ewes

2001 ◽  
Vol 280 (6) ◽  
pp. R1790-R1798 ◽  
Author(s):  
Maureen Keller-Wood ◽  
Charles E. Wood
Keyword(s):  
Plasma Cortisol ◽  
Feedback Inhibition ◽  
Plasma Acth ◽  
Acth Secretion ◽  
Feedback Effects ◽  
Low Concentrations ◽  
Pregnancy And Postpartum ◽  
Cortisol Levels

These studies test the hypothesis that pregnancy alters the feedback effects of cortisol on stimulated ACTH secretion. Ewes were sham-operated (Sham), or adrenalectomized (ADX) at ∼108 days gestation and replaced with aldosterone (3 μg · kg−1· day−1) and with cortisol at either of two doses (ADX + 0.6 and ADX + 1 mg · kg−1· day−1); ewes were studied during pregnancy and postpartum. Mean cortisol levels produced in ADX ewes were similar to normal pregnant ewes (ADX+1) or nonpregnant ewes (ADX+0.6), respectively. Plasma ACTH concentrations in response to infusion of nitroprusside were significantly increased in the pregnant ADX+0.6 ewes (1,159 ± 258 pg/ml) relative to pregnant Sham ewes (461 ± 117 pg/ml) or the ADX+1 ewes (442 ± 215 pg/ml) or the same ewes postpartum (151 ± 69 pg/ml). Plasma ACTH concentrations were not significantly different among the groups postpartum. Increasing plasma cortisol to 20–30 ng/ml for 24 h before hypotension produced similar inhibition of ACTH in all groups. Pregnancy appears to decrease the effectiveness of low concentrations of cortisol to inhibit ACTH responses to hypotension.

Feedback suppression of ACTH secretion by Cortisol in dogs: lags after large signals equal those following very small signals

1983 ◽  
Vol 61 (11) ◽  
pp. 1281-1288 ◽  
Author(s):  
John S. Cowan ◽  
Ross A. Layberry
Keyword(s):  
Insulin Infusion ◽  
Venous Blood ◽  
Control Period ◽  
Feedback Signal ◽  
Acth Secretion ◽  
Feedback Suppression ◽  
Physiological Limits ◽  
Single Compartment ◽  
Low Cortisol ◽  
Secretion Rates

Previously, low stepwise infusions of Cortisol in resting adrenalectomized dogs (plateaux ≤ 6 μg/dL) were shown to reduce ACTH secretion only after 20 min. In the present study, large, steep-sloped cortisol signals were used to try to evoke faster feedback. Adrenalectomized male mongrel dogs were maintained on exogenous steroids until 48 h before the experiment. Of the 23 experiments on 15 dogs (under light pentobarbital anesthesia), 12 were on resting dogs, 7 on dogs stressed by variable insulin infusion (keeping plasma glucose at 18–40 mg/dL), and 4 stressed as above but with 4 h of low cortisol infusion (plasma [Formula: see text] 5 μg/dL) before applying the feedback signal. After a 50-min control period, a 30-min feedback period was initiated by one of two i.v. cortisol signals: (a) injection of 0.3 mg/kg or (b) infusion of 46 μg kg−1 min−1. Both raised plasma cortisol above physiological limits (within 2 and 6 min, respectively). In each experiment, 23 timed venous blood samples were assayed for plasma ACTH and cortisol. ACTH secretion rates were calculated continuously using a validated single-compartment method. Results from both types of cortisol signals were indistinguishable, and were thus pooled. In the unstressed dogs, control-period ACTH secretion of 0.97 ± 0.12 mU kg−1 min−1 showed no significant decline due to the feedback signal for 20.3 ± 1.4 min. In the stressed dogs the comparable values were 3.18 ± 0.92 mU kg−1 min−1 and 21.9 ± 3.2 min, and in the stressed Cortisol preconditioned dogs 0.78 ± 0.23 mU kg−1 min−1 and 21.0 ± 3.2 min. Thus at rest or in stress, these large cortisol signals evoked no more evidence of fast, rate-sensitive feedback than did very small signals.

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