Inhibition of stimulated and basal ACTH by cortisol during ovine pregnancy

1996 ◽  
Vol 271 (1) ◽  
pp. R130-R136 ◽  
Author(s):  
M. Keller-Wood

In pregnant ewes, as in pregnant women, plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations are increased. Inhibition of free cortisol concentrations by dexamethasone, a synthetic glucocorticoid, is reduced in pregnant women compared with nonpregnant women. These experiments were designed to test the hypothesis that basal and stimulated ACTH concentrations are less sensitive to negative feedback inhibition by cortisol in pregnant ewes than in nonpregnant ewes. Ewes were infused with vehicle and with cortisol at two different rates (1 and 2 micrograms.kg-1.min-1) for 1 h; plasma ACTH concentrations during and after the infusion and after subsequent stimulation by hypotension were measured. Basal plasma ACTH concentrations during a 2-h infusion of cortisol (2 micrograms.kg-1.min-1) were also measured in undisturbed ewes. Cortisol significantly inhibited both stimulated and basal ACTH. The degree of suppression of ACTH was not reduced in the pregnant ewes compared with the nonpregnant ewes. The results indicate that both basal and stimulated ACTH are sensitive to negative feedback inhibition by cortisol during ovine pregnancy.

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.


1992 ◽  
Vol 9 (3) ◽  
pp. 273-281 ◽  
Author(s):  
A. Stephanou ◽  
N. J. Sarlis ◽  
R. A. Knight ◽  
S. L. Lightman ◽  
H. S. Chowdrey

ABSTRACT Adjuvant arthritis (AA) in the rat leads to chronic stimulation of the hypothalamic-pituitary-adrenal (HPA) axis and the loss of its diurnal rhythmicity. We have investigated the effects of adrenalectomy (ADX) and different levels of corticosterone replacement upon plasma ACTH levels and anterior pituitary pro-opiomelanocortin (POMC), GH and prolactin mRNAs during the development of AA. In control ADX animals, we observed the negative feedback effects of exogenous corticosterone on plasma ACTH and anterior pituitary POMC mRNA. In the ADX animal with AA, however, the increased POMC mRNA which was observed was not reduced by exogenous corticosterone on day 7 of AA, although the negative feedback effect of corticosterone on plasma ACTH was intact. On day 14, however, even high dose corticosterone replacement failed to have a significant feedback effect on the raised levels of plasma ACTH. In control ADX animals, corticosterone replacement resulted in increased anterior pituitary GH mRNA and reduced prolactin mRNA. In contrast, in ADX animals with AA, GH mRNA was reduced and there was a further decrease in prolactin mRNA. In these animals, corticosterone replacement did not affect GH or prolactin mRNA expression. These data demonstrate a disruption of the normal mechanisms underlying feedback inhibition of the HPA axis by glucocorticoids during AA. Similarly, the glucocorticoid-dependent regulation of GH and prolactin mRNA expression is altered in AA.


1982 ◽  
Vol 92 (3) ◽  
pp. 443-448 ◽  
Author(s):  
S. C. J. READER ◽  
J. ALAGHBAND-ZADEH ◽  
J. R. DALY ◽  
W. R. ROBERTSON

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.


2010 ◽  
Vol 162 (1) ◽  
pp. 43-48 ◽  
Author(s):  
Massimo Scacchi ◽  
Leila Danesi ◽  
Agnese Cattaneo ◽  
Elena Valassi ◽  
Francesca Pecori Giraldi ◽  
...  

ObjectiveWe previously described in young thalassaemic patients an altered cortisol and ACTH responsiveness suggesting an impaired adrenocortical reserve. Owing to iron overload, a worsening of adrenal function should be expected in adult patients.DesignIn 124 adults with β-thalassaemia, urinary free cortisol (UFC) and plasma ACTH levels were determined and compared with those measured in 150 controls. In 45 patients, cortisol was measured in response to: i) tetracosactide 1 μg as an i.v. bolus (low-dose test, LDT) and ii) tetracosactide 250 μg infused i.v. over 8 h (high-dose test, HDT).ResultsUFC and serum cortisol were within the reference range in all patients. Conversely, basal plasma ACTH values were above the upper limit of the normal range in 19 patients. There were no statistically significant differences in the mean values of UFC, basal serum cortisol and plasma ACTH between patients and controls. A subnormal cortisol response to the LDT was registered in 18 out of 56 patients. Three of these patients also displayed a subnormal response to the HDT, together with elevated baseline plasma ACTH levels. In the LDT, a positive correlation was found between basal and peak cortisol values (P<0.0001). The latter were negatively correlated with basal ACTH values in both LDT (P<0.0001) and HDT (P<0.0001).ConclusionsAdult thalassaemic patients often present a subtle impairment of adrenocortical function. This may become clinically relevant in case of major stressful events. Thus, we recommend an assessment of adrenocortical function in all adult thalassaemic patients.


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.


Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 520 ◽  
Author(s):  
Katiuska Satué ◽  
Esterina Fazio ◽  
Ana Muñoz ◽  
Pietro Medica

In cycling females, the periovulatory period is characterized by stimulation of the hypothalamic pituitary adrenal (HPA) axis. The aim of present study was to analyze the pattern and interrelationships among adrenocorticotropic hormone (ACTH), cortisol (CORT), aldosterone (ALD) and electrolytes (sodium—Na+, potassium—K+ and chloride—Cl−) during periovulatory period in cycling mares. Venous blood samples were obtained daily from a total of 23 Purebred Spanish broodmares, aged 7.09 ± 2.5 years, from day −5 to day +5 of estrous cycle, considering day 0, the day of ovulation. Plasma ACTH was measured by a fluorescent immunoassay kit, serum CORT and ALD by means of a competitive ELISA immunoassay, and plasma Na+, K+ and Cl− were quantified by an analyzer with selective electrodes for the three ions. ACTH showed higher concentrations at day 0 compared to days −5 to −1 and +1 to +3 (p < 0.05). CORT showed higher concentrations at day 0 compared to days −5 to −2 and +1 to +5 (p < 0.05). ALD showed higher concentrations at day 0 compared to days −5 to −2 (p < 0.05) and +2 (p < 0.05). Na+ and Cl− showed higher concentrations at day 0, compared to day −5 and +5. K+ showed lower concentrations at day 0 compared to day +1 (p < 0.05). The significant correlations obtained between ACTH and CORT (r = 0.20) and between ACTH and ALD (r = 0.32) suggest that although ACTH may have an effect both on CORT and ALD, there are other very important determinants that could be considered. Hence, it is possible to presume that the pituitary adrenocortical response and ALD may be involved in the ovulatory mechanisms without a direct relation with electrolyte pattern.


1988 ◽  
Vol 254 (6) ◽  
pp. G802-G807 ◽  
Author(s):  
M. Gue ◽  
C. Honde ◽  
X. Pascaud ◽  
J. L. Junien ◽  
M. Alvinerie ◽  
...  

The influence of the kappa-opioid substances dynorphin-(1-13), ethylketocyclazocine (EKC), and U 50488 and mu-opioid substance [D-Ala2-N-Me, p-nitro-Phe4-Gly5-ol]enkephalin (DAGO) on gastric motor inhibition induced by acoustic stress (AS) was investigated in fasted dogs with strain-gauge transducers chronically implanted on the antrum and proximal jejunum. AS induced by 1 h of music (80-90 dB) was delivered through earphones. Starting 40-50 min after the last migrating motor complex (MMC), AS delayed by 114% the occurrence of the next gastric MMC, whereas intestinal motility was unaffected. During AS plasma cortisol increased (P less than 0.05) by 215%, 15 min after the beginning of noise and reached a peak at 30 min. When administered intracerebroventricularly at doses higher than 20 ng/kg, dynorphin abolished the AS-induced lengthening of the gastric MMC cycle. Similar blockade was observed for EKC and U 50488 at doses of 10 and/or 20 ng/kg, but DAGO was unable to affect the AS-induced gastric inhibition at any dosage tested (20-200 ng/kg icv). At doses effective against AS-induced hypomotility, both dynorphin-(1-13) and EKC reduced significantly (P less than or equal to 0.05) the associated maximal increase in plasma cortisol level. Plasma cortisol was unmodified by intracerebroventricular administration of DAGO. None of the agonists affected basal plasma cortisol levels or the increase (0-90 min) in response to intravenous adrenocorticotropic hormone (ACTH, 5 IU). Both EKC (50 ng/kg) and U 50488 (20 ng/kg) were unable to antagonize the inhibitory effect of ovine corticotropin-releasing factor (CRF, 100 ng/kg icv).(ABSTRACT TRUNCATED AT 250 WORDS)


Author(s):  
Jakub Wach ◽  
Marian Bubak ◽  
Piotr Nowakowski ◽  
Irena Roterman ◽  
Leszek Konieczny ◽  
...  

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