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.

THE EFFECTS OF HYPOPHYSECTOMY ON THE METABOLISM OF ADRENAL STEROIDS IN THE PIGEON (COLUMBA LIVIA)

1972 ◽  
Vol 52 (3) ◽  
pp. 435-450 ◽  
Author(s):  
MO YIN CHAN ◽  
E. L. BRADLEY ◽  
W. N. HOLMES
Keyword(s):  
Replacement Therapy ◽  
Methylene Chloride ◽  
Compartment Model ◽  
Columba Livia ◽  
Plasma Corticosterone ◽  
Volume Of Distribution ◽  
Model Systems ◽  
Metabolic Clearance ◽  
Corticosterone Concentration ◽  
Plasma Fractions

SUMMARY The distribution and disappearance of radioactivity after the intravenous administration of [1,2-3H]corticosterone and [1,2-3H]aldosterone to the pigeon were studied according to one- and two-compartment model systems. The volume of distribution (AVD) of the total and methylene chlorideextractable radioactivity in the plasma of hypophysectomized pigeons injected with labelled corticosterone was significantly increased. Also the biological half-life (T½) of each radioactive fraction in plasma was significantly prolonged. No significant change in the metabolic clearance rate (MCR) of labelled corticosterone was observed in the hypophysectomized pigeon. The AVD of the total and methylene chloride-extractable tritium in the plasma of the hypophysectomized pigeon injected with labelled aldosterone was unchanged but the T½ of both plasma fractions was significantly prolonged. The estimated MCR of labelled aldosterone was significantly diminished. The concentration of total fluorogenic corticosteroid in plasma from the chronically hypophysectomized pigeon was reduced to one-third of that in the sham-operated bird, and corticotrophin-replacement therapy restored the concentration to normal. After hypophysectomy, the plasma corticosterone concentration was reduced to 20% of the concentration in the sham-operated birds, and replacement therapy with corticotrophin again restored the plasma levels to normal. Estimation of the endogenous corticosterone secretory rates indicated that chronic hypophysectomy was accompanied by a decline commensurate with the reduction in the plasma corticosterone concentration.

ANALYSIS OF THE INHIBITION OF THE ACTH RELEASE BY HYPOTHALAMIC IMPLANTS OF ATROPINE

1973 ◽  
Vol 73 (4) ◽  
pp. 651-659 ◽  
Author(s):  
J. Kaplanski ◽  
P. G. Smelik
Keyword(s):  
Adrenal Glands ◽  
Plasma Corticosterone ◽  
Corticosterone Concentration ◽  
Hypothalamic Region ◽  
Adrenal System ◽  
Cholinergic Synapses ◽  
Adrenocortical Responses ◽  
Acth Release

ABSTRACT The effect of anterior hypothalamic atropine implants on the secretion of corticotrophin in the rat, as indicated by the corticosteroid production by adrenal glands incubated in vitro and/or by the plasma corticosterone concentration, was studied. It was found that atropine implants markedly inhibit the adrenocortical responses evoked by all the stress stimuli tested, except for that to a CRF preparation. The onset of the blockade was very fast; the duration of the inhibition lasted for about 2 h. Smaller amounts of atropine (2×15 μg) were also effective when implanted bilaterally into the anterior hypothalamic region. It is concluded that cholinergic synapses in the hypothalamus may be involved in the activation of the pituitary-adrenal system after stressful stimuli.

THE EFFECTS OF HYPOPHYSECTOMY ON ADRENOCORTICAL FUNCTION IN THE DUCK (ANAS PLATYRHYNCHOS)

1971 ◽  
Vol 49 (3) ◽  
pp. 437-457 ◽  
Author(s):  
E. L. BRADLEY ◽  
W. N. HOLMES
Keyword(s):  
Mammalian Species ◽  
Compartment Model ◽  
Liver Glycogen ◽  
Plasma Corticosterone ◽  
Adrenocortical Function ◽  
Metabolic Clearance ◽  
General Effect ◽  
Corticosterone Concentration ◽  
Peripheral Plasma ◽  
Corticosterone Secretion

SUMMARY The general effect of chronic hypophysectomy on organ and body weights, liver glycogen, blood glucose, peripheral plasma corticosterone concentrations, and blood pressure in the duck were similar to those described for several mammalian species. The disappearance and distribution of radioactivity after the administration of [1,2-3H]corticosterone and [1,2-3H]aldosterone was studied according to a single compartment model system. When compared with sham-operated ducks, the apparent volumes of distribution and the biological half-lives of radioactivity in hypophysectomized ducks were significantly increased, and the estimated metabolic clearance rates of [1,2-3H] corticosterone and [1,2-3H]aldosterone were significantly decreased. The patterns of distribution of radioactivity and the rate of metabolism of both hormones returned towards normal when the chronically hypophysectomized ducks were treated with corticotrophin (ACTH). Fourteen days after hypophysectomy the peripheral plasma concentration of corticosterone and the estimated rate of corticosterone secretion by the adrenal fell to 10 and 4%, respectively, of the values observed in sham-operated birds. Examinations of the peripheral plasma corticosterone concentration during the first 30 min after the removal of the adenohypophysis indicated a mean biological half-life for endogenous corticosterone of 13·7 min. The rates of appearance of radioactivity in the bile, intestine and cloaca of the hypophysectomized birds suggested substantial declines in the rates of aldosterone and corticosterone metabolism. These declines could not be accounted for by the reduced rate of glomerular filtration in the hypophysectomized bird. Replacement therapy with ACTH restored the excretory patterns of both steroids towards normal. The quantitative similarities between the effects of hypophysectomy in the duck and several mammalian species make it unnecessary to postulate either a high degree of adrenal autonomy or an extrahypophysial source of ACTH in the control of adrenocortical function in the duck.

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.

Corticosteroids mediate fast feedback of the rat hypothalamic-pituitary-adrenal axis via the mineralocorticoid receptor

2008 ◽  
Vol 294 (6) ◽  
pp. E1011-E1022 ◽  
Author(s):  
Helen C. Atkinson ◽  
Susan A. Wood ◽  
Emma S. Castrique ◽  
Yvonne M. Kershaw ◽  
Crispin C. R. Wiles ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Hpa Axis ◽  
Mineralocorticoid Receptor ◽  
Feedback Inhibition ◽  
Inhibitory Effect ◽  
Plasma Corticosterone ◽  
Time Of Day ◽  
Sampling System ◽  
Mineralocorticoid Receptor Antagonist ◽  
Hypothalamic Pituitary Adrenal

The aim of this study was to investigate fast corticosteroid feedback of the hypothalamic-pituitary-adrenal (HPA) axis under basal conditions, in particular the role of the mineralocorticoid receptor. Blood samples were collected every 5 min from conscious rats at the diurnal peak, using an automated blood sampling system, and assayed for corticosterone. Feedback inhibition by rapidly increasing concentrations of ligand was achieved with an intravenous bolus of exogenous corticosteroid. This resulted in a significant reduction in plasma corticosterone concentrations within 23 min of the aldosterone bolus and 28 min of methylprednisolone. Evaluation of the pulsatile secretion of corticosterone revealed that the secretory event in progress at the time of administration of exogenous steroid was unaffected, whereas the next secretory event was inhibited by both aldosterone and methylprednisolone. The inhibitory effect of aldosterone was limited in duration (1 secretory event only), whereas that of methylprednisolone persisted for 4–5 h. Intravenous administration of canrenoate (a mineralocorticoid receptor antagonist) also had rapid effects on the HPA axis, with an elevation of ACTH within 10 min and corticosterone within 20 min. The inhibitory effect of aldosterone was unaffected by pretreatment with the glucocorticoid receptor antagonist RU-38486 but blocked by the canrenoate. These data imply an important role for the mineralocorticoid receptor in fast feedback of basal HPA activity and suggest that mineralocorticoids can dynamically regulate basal corticosterone concentrations during the diurnal peak, a time of day when there is already a high level of occupancy of the cytoplasmic mineralocorticoid receptor.

Metabolic clearance rate of adrenocorticotropin in the rat

1977 ◽  
Vol 55 (5) ◽  
pp. 1079-1083 ◽  
Author(s):  
Josée Lalonde ◽  
Maurice Normand
Keyword(s):  
Body Weight ◽  
Steady State ◽  
Clearance Rate ◽  
Intravenous Infusion ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Plasma Acth ◽  
Adrenal Cells ◽  
Acth Concentration ◽  
Acth Release

The metabolic clearance rate (MCR) of adrenocorticotropin (ACTH) was estimated after the intravenous infusion of graded rates of the hormone (40–2560 μU/min per 100 g body weight) in rats pretreated with chlorpromazine, morphine, and Nembutal, a preparation which proved effective in blocking endogenous ACTH release. The hormone was infused over a period of 45 min, at which time the plasma ACTH concentration had reached a steady state. A specific and sensitive bioassay, based on the corticosterone production of dispersed adrenal cells, was used to measure the plasma ACTH concentration. With increasing infusion rates of ACTH, a threefold decrease in the MCR of ACTH was observed. Previous studies of our group have shown that the MCR of corticosterone increases as a function of the infusion rate of the steroid. It appears, therefore, that the metabolism of these two hormonal links of the hypothalarno–pituitary–adrenocortical axis vary in opposite fashions as a function of the secretion rate of the hormone.

The hypophyseal–adrenocortical response to various different stressing procedures in ACTH-treated rats

1968 ◽  
Vol 46 (4) ◽  
pp. 567-571 ◽  
Author(s):  
E. Stark ◽  
Zs. Ács ◽  
G. B. Makara ◽  
K. Mihály
Keyword(s):  
Corticosterone Level ◽  
Plasma Corticosterone ◽  
Release Mechanism ◽  
Significant Elevation ◽  
Plasma Corticosterone Level ◽  
Corticosterone Concentration ◽  
Corticotrophin Releasing Factor ◽  
Adrenocortical Response ◽  
The Difference ◽  
Acth Release

Twenty-four hours after the last of 14 daily injections of ACTH, the administration of ether, histamine, 1% formalin, or lysine-8-vasopressin produced no rise in the plasma corticosterone level in rats but raised it significantly in saline-treated control animals. As assayed by the plasma corticosterone concentration, ACTH release was found to be inhibited when hypophyseal–adrenocortical responsiveness was not impaired and the peripheral corticosterone level was normal or less than normal. Endotoxin induced nearly the same statistically significant elevation in the ACTH-treated and saline-treated animals. It would appear that it is the high corticosterone level produced by the last ACTH injection that suppresses the corticotrophin-releasing factor (CRF) 24 h later (feedback action) when this level returns to normal or less than normal; and that certain stressors liberate CRF whereas others do not. An explanation for the latter assumption may be found either in the difference in intensity between the stimuli or, more probably, in that the high corticosterone level inhibits the ACTH release mechanism for certain individual stressors, but not for others.

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.

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