Corticosterone secretion after inhibition of prostaglandin synthesis by indomethacin

1981 ◽  
Vol 240 (2) ◽  
pp. E131-E135
Author(s):  
M. E. Thompson ◽  
G. A. Hedge

Systemic indomethacin (Ind) administration decreased prostaglandin F (PGF) content of the rat adrenal to less than 1.4 pg/mg. This was less than 5% of the adrenal PGF content in the gelatin-treated (Gel) control group (34 pg/mg). Basal plasma corticosterone levels were increased by the Ind treatment. Since the calculated metabolic clearance rate for corticosterone was unchanged, this increase was attributed to an enhanced adrenal secretion rate that was secondary to elevated plasma ACTH concentration. Ether exposure in the presence of Ind did not stimulate a normal rise in plasma corticosterone or adrenal corticosteroidogenesis. Adrenal responsiveness to exogenous ACTH was reduced after Ind treatment. There was a normal rise in plasma ACTH levels following ether exposure confirming the adrenal as the site of inhibition. Systemic Ind treatment thus appears to have two sites of action in altering plasma corticosterone levels: 1) a direct effect on the adrenal, inhibiting normal secretion in response to acute elevations of plasma ACTH, and 2) an action at the pituitary or hypothalamic level, eliciting an increase in basal ACTH secretion.

1974 ◽  
Vol 63 (1) ◽  
pp. 213-222 ◽  
Author(s):  
JULIA C. BUCKINGHAM ◽  
J. R. HODGES

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.


1997 ◽  
Vol 272 (4) ◽  
pp. R1128-R1134 ◽  
Author(s):  
C. J. Saoud ◽  
C. E. Wood

Parturition in sheep is initiated by increases in activity of the fetal hypothalamic-pituitary-adrenal axis. We have previously reported that cortisol negative feedback efficacy is decreased at the end of gestation. The present study was designed to test the hypothesis that increasing plasma estrogen and/or androgen concentrations in the fetus might increase plasma adrenocorticotropic hormone (ACTH) concentration, either by stimulating ACTH secretion or by altering the negative feedback effect of cortisol on ACTH. Fetal sheep were chronically catheterized and treated with no steroid (control), 17beta-estradiol, or androstenedione (each approximately 0.24 mg/day). After catheterization and implantation of steroid pellet, fetuses were subjected to two short (10 min) periods of sodium nitroprusside-induced hypotension with or without pretreatment with intravenous infusion of hydrocortisone sodium succinate (0.5 microg/min) to test fetal ACTH responsiveness to stress and cortisol negative feedback efficacy. Estradiol treatment significantly increased basal plasma ACTH and cortisol concentrations relative to control fetuses but did not interfere with the inhibition of ACTH secretion by cortisol. Fetal plasma ACTH responses to hypotension were significantly suppressed approximately 60% in both control and estradiol-treated groups. Androstenedione treatment significantly increased basal fetal plasma ACTH and decreased basal fetal plasma cortisol concentration. Androstenedione did not alter stimulated levels of fetal ACTH but did block the inhibition of stimulated ACTH by cortisol. We conclude that increased fetal cortisol and ACTH secretion at the end of gestation may be due to the combined effects of the gonadal steroids in that estradiol increases basal plasma ACTH secretion while androstenedione reduces cortisol negative feedback efficacy.


2013 ◽  
Vol 27 (10) ◽  
pp. 1655-1665 ◽  
Author(s):  
Gloria Laryea ◽  
Günther Schütz ◽  
Louis J. Muglia

The glucocorticoid receptor (GR) regulates hypothalamic-pituitary-adrenal (HPA) axis activity during the stress response. The paraventricular nucleus (PVN) is a major site of negative feedback to coordinate the degree of the HPA axis activity with the magnitude of the exposed stressor. To define the function of endogenous PVN GR, we used Cre-loxP technology to disrupt different GR exons in Sim1-expressing neurons of the hypothalamus. GR exon 2-deleted mice (Sim1Cre-GRe2Δ) demonstrated 43% loss of PVN GR compared with an 87% GR loss in exon 3-deleted mice (Sim1Cre-GRe3Δ). Sim1Cre-GRe3Δ mice display stunted growth at birth but develop obesity in adulthood and display impaired stress-induced glucose release. We observed elevated basal and stress-induced corticosterone levels in Sim1Cre-GRe3Δ mice, compared with control and Sim1Cre-GRe2Δ mice, and impaired dexamethasone suppression, indicating an inability to negatively regulate corticosterone secretion. Sim1Cre-GRe3Δ mice also showed increased CRH mRNA in the PVN, increased basal plasma ACTH levels, and reduced locomotor behavior. We observed no differences in Sim1Cre-GRe2Δ mice compared with control mice in any measure. Our behavioral data suggest that GR deletion in Sim1-expressing neurons has no effect on anxiety or despair-like behavior under basal conditions. We conclude that loss of PVN GR results in severe HPA axis hyperactivity and Cushing's syndrome-like phenotype but does not affect anxiety and despair-like behaviors.


1971 ◽  
Vol 49 (3) ◽  
pp. 437-457 ◽  
Author(s):  
E. L. BRADLEY ◽  
W. N. HOLMES

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.


1981 ◽  
Vol 240 (4) ◽  
pp. E441-E446 ◽  
Author(s):  
G. B. Makara ◽  
E. Stark ◽  
M. Karteszi ◽  
M. Palkovits ◽  
G. Rappay

The effects of destroying the paraventricular nucleus (PVN) of the rat hypothalamus on pituitary-adrenal function were studied. Four days after PVN lesions were placed with a rotating knife, the basal plasma corticosterone level was normal, but the corticosterone response to electrical stimulation of the medial basal hypothalamus, surgical trauma, and ether-venesection stress was significantly inhibited. Four and 8 days after PVN lesioning and adrenalectomy, the basal plasma ACTH level was lower, and the rise of plasma ACTH level elicited by a 3-min ether inhalation was significantly smaller than in the adrenalectomized controls. Corticotropin-releasing factor (CRF) activity in the stalk-median eminence extracts from PVN-lesioned rats was significantly less than in the control extracts. The weight of the adrenals was decreased by both 2 and 4 wk after PVN destruction, and 2 wk after hemiadrenalectomy, the compensatory adrenal hypertrophy was inhibited. The plasma corticosterone response to ether-venesection stress was inhibited only temporarily because it returned to normal by the end of the 4th postoperative week. The results are consistent with the hypothesis that a substantial portion of CRF-containing fibers in the stalk-median eminence region either originate from or run though the PVN or its immediate vicinity.


1977 ◽  
Vol 55 (5) ◽  
pp. 1079-1083 ◽  
Author(s):  
Josée Lalonde ◽  
Maurice Normand

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.


1998 ◽  
Vol 158 (2) ◽  
pp. 285-293 ◽  
Author(s):  
AJ Douglas ◽  
HA Johnstone ◽  
A Wigger ◽  
R Landgraf ◽  
JA Russell ◽  
...  

Endogenous opioid regulation of neurohypophysial and hypothalamo-pituitary-adrenal (HPA) axis hormone secretion in response to forced swimming (90 s in deep water at 19 degrees C) was investigated in virgin and 21-day-pregnant rats. There was no difference in basal plasma oxytocin concentrations between pregnant and virgin rats, but the opioid antagonist, naloxone, increased basal oxytocin secretion in the pregnant rats. Forced swimming increased oxytocin secretion similarly in pregnant and virgin rats, and this response was enhanced by naloxone. In pregnant rats naloxone had a greater effect (by 3.1-fold) than in virgins, showing stronger endogenous opioid restraint of an enhanced oxytocin secretory response to stress in pregnancy. Vasopressin secretion was not increased with forced swimming in virgin or pregnant rats, and naloxone had no effect. ACTH and corticosterone secretion in response to forced swimming was attenuated in pregnant rats compared to virgin rats, measured at 5 min. Naloxone had no effect on basal plasma ACTH or corticosterone concentration, but it reduced ACTH secretion in virgin rats 5 min after forced swimming; in pregnant rats naloxone had no such effect. Naloxone removed the pregnancy-related attenuation in corticosterone secretion measured at 5 min after forced swimming. Fifteen minutes after forced swimming, plasma corticosterone concentrations were not different between groups. In the late-pregnant rats, the increases in plasma ACTH and corticosterone induced by forced swimming were significantly prolonged compared to virgins. The results show that endogenous opioid inhibition emerges in pregnancy to restrict the responses of oxytocin neurones to a stressor. In contrast, the endogenous opioid enhancement of mechanisms regulating HPA axis secretory responses in virgin rats is not evident during pregnancy.


2015 ◽  
Vol 228 (3) ◽  
pp. 135-147 ◽  
Author(s):  
Michaela D Wharfe ◽  
Peter J Mark ◽  
Caitlin S Wyrwoll ◽  
Jeremy T Smith ◽  
Cassandra Yap ◽  
...  

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.


2007 ◽  
Vol 92 (5) ◽  
pp. 1693-1696 ◽  
Author(s):  
Sunil Kumar Mishra ◽  
Nandita Gupta ◽  
Ravinder Goswami

Abstract Context: Although the production and metabolic clearance rate of cortisol is increased during thyrotoxic state, the net effect on adrenocortical reserves is not clear. Objective: We assessed circulating ACTH levels, cortisol binding globulin (CBG), and adrenocortical reserves in hyperthyroid patients (before and after carbimazole therapy) and healthy controls. Design and Setting: This was a case-control investigative study in a tertiary care setting. Patients and Methods: Plasma ACTH and free cortisol index (FCI; serum cortisol/CBG) were measured in 49 consecutive patients with hyperthyroidism and 50 controls. ACTH1–24 stimulation tests (250 and 1 μg) were carried out in the first 29 patients and 15 controls. Peak FCI less than the mean −3 sd of healthy controls was considered subnormal. ACTH1–24 stimulation tests were repeated in 24 patients in the euthyroid state. Results: The mean basal plasma ACTH and FCI were higher and CBG was lower in thyrotoxic patients in comparison with controls. The peak cortisol was less than 18 μg/dl in 10 of 29 and 14 of 29 on 250 and 1 μg ACTH1–24 stimulation. Peak FCI was subnormal only in three of 27 (11.1%) and two of 21 (7.4%) on 250 and 1 μg ACTH1–24 stimulation, respectively. The mean plasma ACTH, basal FCI, and subnormal peak FCI (two of the three) normalized after euthyroidism. Plasma ACTH and FCI did not correlate with severity of thyrotoxicosis. Conclusions: Up to 11% of thyrotoxics have subnormal peak FCI on ACTH1–24 stimulation. Such changes occur despite high basal plasma ACTH and FCI. Use of FCI, rather than total cortisol, is required for the interpretation of cortisol values in thyrotoxicosis due to the variation in CBG.


2019 ◽  
Vol 97 (11) ◽  
pp. 4464-4474
Author(s):  
Haipeng Shi ◽  
Qin Tong ◽  
Weichao Zheng ◽  
Jiang Tu ◽  
Baoming Li

Abstract Colony cages are commonly used in China for the natural mating of layer breeders. However, feather pecking (FP) is a major problem in this system, and feather damage mainly due to FP needs to be alleviated. The objective of this study was to investigate the effects of nest boxes provided in colony cages. Each colony cage confined 10 roosters and 90 laying hens. The use of nest boxes as it relates to age, feather damage, sexual behavior, fertility, and fearfulness was evaluated. Thyroid hormones, which are considered to be physiological indicators of various forms of stress in poultry and may be correlated with the quality of feather coverage, were also tested. The control group and the nest box group each had 12 replicates, totaling 24 identical cages. Analyses were conducted using the linear mixed models procedure of SPSS Statistics 22.0. The results showed that the control group had a significantly higher proportion of hens with feather damage to 4 specific body regions (back, rump, tail, and belly) compared to the nest box group (P < 0.05). Increasing the use of the nest boxes took place from weeks 41 to 47 and at 53 wk of age, as seen by the percentage of eggs and number of sitting events in the nests, number of hens using the nests, and frequency of visits. There were no significant differences in fertility, the occurrence of mounting, or full copulation behavior between the 2 groups. Hens in the control group showed a significantly longer duration of tonic immobility at 43, 49, and 55 wk of age (P < 0.05). No significant differences were found between groups for the concentration of triiodothyronine or thyroxine, but a significantly higher concentration of corticosterone was measured in the control group than in the nest box group (P < 0.05). In conclusion, hens with access to nest boxes during the laying period had a decreased FP frequency, fewer damaged feathers, lower plasma corticosterone secretion, and were less fearful. This information contributes to the understanding of the FP behavior and stress sensitivity of layer breeders, which will provide a basis for the development and optimization of the colony cage equipment.


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