Evidence for reset of regulated cortisol in pregnancy: studies in adrenalectomized ewes

1998 ◽  
Vol 274 (1) ◽  
pp. R145-R151 ◽  
Author(s):  
Maureen Keller-Wood

These studies test the hypothesis that the increased adrenocorticotropic hormone (ACTH) and cortisol in pregnancy reflect a reset of regulated plasma cortisol concentrations. Ewes were sham operated (Sham) or adrenalectomized (ADX) at ∼108 days gestation. Adrenalectomized ewes were replaced with aldosterone (3 μg ⋅ kg−1 ⋅ day−1) and with cortisol at either of two doses (ADX + 0.6 and ADX + 1.0 mg ⋅ kg−1 ⋅ day−1); the ewes were also studied postpartum. Plasma cortisol concentrations in ADX + 0.6 ewes (5.3 ± 1.3 ng/ml) were similar to the Sham ewes postpartum (5.5 ± 0.6 ng/ml), whereas ADX + 1.0 concentrations (8.9 ± 1.0 ng/ml) were similar to pregnant Sham ewes (9.5 ± 1.9 ng/ml). Plasma ACTH concentrations were significantly increased in the pregnant ADX + 0.6 ewes (273 ± 44 pg/ml) relative to pregnant Sham ewes (84 ± 9 pg/ml) or the same ewes postpartum (42 ± 9 pg/ml). Plasma ACTH concentrations were not different among the groups postpartum. Acute increases in plasma cortisol to 15–25 ng/ml produced similar inhibition in all groups. These results suggest that pregnancy resets the basal cortisol concentration required for normalization of basal ACTH concentration.

1992 ◽  
Vol 263 (4) ◽  
pp. R762-R769 ◽  
Author(s):  
V. L. Brooks ◽  
L. C. Keil

Angiotensin II (ANG II) and vasopressin participate in baroreflex regulation of adrenocorticotropic hormone (ACTH), glucocorticoid, and renin secretion. The purpose of this study was to determine whether this participation is enhanced in water-deprived dogs, with chronically elevated plasma ANG II and vasopressin levels, compared with water-replete dogs. The baroreflex was assessed by infusing increasing doses of nitroprusside (0.3, 0.6, 1.5, and 3.0 micrograms.kg-1.min-1) in both groups of animals. To quantitate the participation of ANG II and vasopressin, the dogs were untreated or pretreated with the competitive ANG II antagonist saralasin, a V1-vasopressin antagonist, or combined V1/V2-vasopressin antagonist, either alone or in combination. The findings were as follows. 1) Larger reflex increases in ANG II, vasopressin, and glucocorticoids, but not ACTH, were produced in water-deprived dogs compared with water-replete dogs. 2) ANG II blockade blunted the glucocorticoid and ACTH responses to hypotension in water-deprived dogs, but not water-replete dogs. In contrast, vasopressin blockade reduced the ACTH response only in water-replete dogs. 3) Vasopressin or combined vasopressin and ANG II blockade reduced the plasma level of glucocorticoids related either to the fall in arterial pressure or to the increase in plasma ACTH concentration in water-replete dogs, and this effect was enhanced in water-deprived dogs. 4) In both water-deprived and water-replete animals, saralasin and/or a V1-antagonist increased the renin response to hypotension, but a combined V1/V2-antagonist did not. These results reemphasize the importance of endogenous ANG II and vasopressin in the regulation of ACTH, glucocorticoid, and renin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)


2019 ◽  
Vol 31 (4) ◽  
pp. 585-587 ◽  
Author(s):  
Kayla N. Shepard ◽  
John C. Haffner ◽  
Dwana L. Neal ◽  
Steven T. Grubbs ◽  
Greg L. Pearce

Plasma adrenocorticotropic hormone (ACTH) concentration is used in the diagnosis of pituitary pars intermedia dysfunction (PPID) in horses. We enrolled 10 horses, 5 PPID-positive and 5 PPID-negative, in our study, September 20–22, 2016. On day 0, 5 mL of whole blood was collected into each of 6 EDTA tubes and immediately placed in a refrigerator at 7°C. One tube was centrifuged within 15 min of collection, followed by centrifugation of one tube from each horse at 4, 8, 12, 24, and 36 h following collection. At each time, centrifuged plasma was pipetted into 1.5-mL polypropylene tubes and stored at −80°C. None of the plasma samples were turbid, hemolyzed, or icteric. Plasma was shipped frozen with cold packs overnight to the Animal Health Diagnostic Center of Cornell University (Ithaca, NY) for analysis. The percent change from baseline (PCFB) was reported to standardize the data given that baseline values differed. The mean PCFB was 2.8 (95% confidence interval: –2.9%, 7.0%). Neither refrigeration of whole blood for up to 36 h prior to centrifugation nor freezing affected plasma ACTH concentrations significantly.


2006 ◽  
Vol 190 (3) ◽  
pp. 601-609 ◽  
Author(s):  
J M Hanson ◽  
H S Kooistra ◽  
J A Mol ◽  
E Teske ◽  
B P Meij

The 6-h plasma profiles of adrenocorticotropic hormone (ACTH), cortisol, α-melanocyte-stimulating hormone (α-MSH), and GH were studied in 17 dogs with pituitary-dependent hyperadrenocorticism (PDH) before and after hypophysectomy. The aim of the study was to investigate the relation between the hormone profile characteristics and recurrence of PDH after surgery. The hormones were secreted in a pulsatile fashion. The basal plasma cortisol concentration and area under the curve (AUC) for cortisol were significantly higher in the PDH cases than in eight controls. The characteristics of the plasma profiles of ACTH and α-MSH were not significantly different between the PDH cases and the controls. In the PDH cases, less GH was secreted in pulses than in the controls, but the difference was not significant. The basal plasma cortisol concentration, the AUC for ACTH and cortisol, and the pulse frequency of ACTH and cortisol decreased significantly after hypophysectomy for the group of PDH cases. The basal plasma concentrations of ACTH and α-MSH, the AUC for α-MSH, and the characteristics of the plasma GH profiles of the PDH cases remained unchanged after hypophysectomy. No pulses of α-MSH were observed after hypophysectomy. The co-occurrence between the ACTH and cortisol pulses decreased significantly with hypophysectomy. The postoperative pulse frequency of ACTH was the only characteristic with predictive value for the recurrence of PDH after hypophysectomy. The results of this study demonstrate that ACTH, cortisol, α-MSH, and GH are secreted in a pulsatile fashion in dogs with PDH. Hypophysectomy effectively reduces the secretion of ACTH and cortisol. The presence of ACTH pulses after hypophysectomy is a risk factor for the recurrence of hyperadrenocorticism.


1997 ◽  
Vol 65 (3) ◽  
pp. 465-472 ◽  
Author(s):  
S. Jarvis ◽  
A. B. Lawrence ◽  
K. A. McLean ◽  
L. A. Deans ◽  
J. Chirnside ◽  
...  

AbstractThis study examined the temporal relationships between behavioural activity and hormones associated with stress in gilts farrowing in two environments. Thirty-one Large White × Landrace gilts with indwelling jugular catheters were blood sampled daily (08.00 and 16.00 h) from 10 days before their expected parturition date (EPD). Five days before EPD they were moved to either a farrowing crate (C) with no bedding, or a pen (P) (2·5 m × 3·0 m) with straw provided and were blood sampled daily at 08.00, 12.00 and 16.00 h. Around 12 h before the onset of farrowing an extension was fitted to the catheter and blood samples were taken remotely at 30-min intervals. The posture of the gilts was recorded using 5-min scan samples over the 24 h pre-farrowing. The proportion of scans standing (an index of activity) was strongly affected by time (P < 0·001) with peak levels at approximately 8 h pre-farrowing in both treatments, and by treatment (0·25 v. 0·33 (s.e.d. 0·03) for C and P gilts respectively; P < 0·05). Plasma cortisol concentrations also increased before farrowing (P < 0·001) reaching a peak at 12 to 6 h pre-farrowing. Crated gilts had higher cortisol concentrations than, penned gilts (overall mean 41·5 v. 30·7 (s.e.d. 3·8) [μg/l for C and P gilts respectively; P < 0·05) at 24 to 12 (P < 0·05), 12 to 6 (P < 0·01) and 6 to 2 (P < 0·05) h pre-farrowing. Plasma ACTH concentration showed a similar pattern to cortisol over the pre-parturient period, peaking at 12 h pre-farrowing in both treatments (time: P < 0·001); crated gilts had significantly higher concentrations of ACTH at 6h pre-farrowing only (P < 0·05). Plasma β-endorphin concentrations also showed a gradual rise (P < 0·001) towards parturition; however no treatment differences were seen. These results suggest that the pituitary-adrenal (PA) axis is stimulated during pre-farrowing activity irrespective of farrowing environment. Crates, without bedding, further stimulate the PA axis over the pre-farrowing period perhaps by preventing nest-building. The rise in Q-endorphin may be involved in an endogenous defence against parturition pain.


1988 ◽  
Vol 255 (4) ◽  
pp. R665-R671
Author(s):  
V. L. Brooks ◽  
L. J. Blakemore ◽  
L. C. Keil

Vasopressin infusion increases arterial and atrial pressures, which could stimulate arterial and cardiac baroreceptors to inhibit adrenocorticotropin (ACTH) secretion. Therefore, the current experiments were performed to test the hypothesis that vasopressin infusion decreases plasma ACTH concentration in conscious dogs. Vasopressin was infused for 90 min in three doses (0.5, 1.0, and 2.0 ng.kg-1.min-1) that produced increases in plasma levels within the physiological range. Only the highest dose of vasopressin increased mean arterial pressure, but left atrial pressure increased with all doses, and right atrial pressure increased with the two highest doses. A bradycardia was produced with all doses of vasopressin. Plasma ACTH concentration decreased from 44 +/- 12 to 25 +/- 7 (P less than 0.01), from 50 +/- 11 to 26 +/- 9 (P less than 0.001), and from 70 +/- 15 to 28 +/- 4 pg/ml (P less than 0.001) with infusion of 0.5, 1.0, and 2.0 ng.kg-1.min-1 vasopressin, respectively. In contrast, plasma cortisol concentration first increased (P less than 0.05) with each vasopressin dose, but after 15-30 min it decreased back to control levels. These results demonstrate that intravenous infusion of vasopressin decreases plasma ACTH concentration. Because the inhibition is associated with increases in atrial pressure and decreases in heart rate, it may be mediated via activation of the baroreceptor reflex.


2019 ◽  
Vol 31 (6) ◽  
pp. 856-858
Author(s):  
John C. Haffner ◽  
Dwana L. Neal ◽  
Rhonda M. Hoffman ◽  
Steven T. Grubbs

We investigated the stability of adrenocorticotropic hormone (ACTH) in plasma after freezing for different lengths of time. The plasma ACTH concentrations of 12 horses were measured on day 0 (baseline) and over time, after stimulation with thyrotropin-releasing hormone. Samples were stored at −80°C for 3, 7, 30, 60, and 90 d, or at −20°C for 3, 7, 30, and 60 d, or between ice packs at −20°C for 3 and 7 d prior to determination of ACTH concentration. ACTH concentrations were compared to baseline (non-frozen day 0 plasma) for each storage method using a mixed model with repeated measures in which each horse served as its own control and day was the repeated effect. Statistical significance was set at p ≤ 0.05, and 0.05 < p < 0.10 was considered a trend. Plasma ACTH frozen at −20°C or at −80°C resulted in degradation of ACTH compared to baseline samples at 60 and 90 d respectively. There was no degradation of ACTH after 7 d when stored between ice packs, or before 30 d at −20°C, or before 60 d at −80°C.


1988 ◽  
Vol 255 (3) ◽  
pp. R412-R417 ◽  
Author(s):  
C. E. Wood

Previous studies from this laboratory have demonstrated that intravenous infusions of hydrocortisone (cortisol) into fetal sheep at rates that produce plasma concentrations achieved during fetal stress inhibit fetal adrenocorticotropic hormone (ACTH) and renin secretion. The present study was designed to test for inhibition of fetal renin and ACTH after maternal adrenal secretion of cortisol. ACTH-(1-24) or saline infusion into 12 pregnant ewes (120-132 days gestation) at rates of 0, 1, 5, or 20 ng ACTH.kg-1.min-1 for 5 h produced dose-related increases in maternal plasma ACTH and cortisol concentrations and fetal plasma cortisol concentration. In the 20-ng.kg-1.min-1 group, increases in fetal plasma cortisol of 8.0 ng/ml (to 24.3 +/- 3.7 ng/ml) did not suppress basal fetal plasma renin activity. One hour after the end of the maternal vehicle or ACTH infusion, fetal ACTH secretion was stimulated by fetal intravenous infusion of sodium nitroprusside. In the 0-, 1-, and 5-ng.kg-1.min-1 groups, fetal ACTH responses to nitroprusside were suppressed in animals infused with ACTH. Together, these results indicate that the maternal adrenal secretion of cortisol inhibits stimulated secretion of ACTH but not renin in 120- to 132-day-gestation fetal sheep.


1979 ◽  
Vol 91 (2) ◽  
pp. 319-328 ◽  
Author(s):  
Koichiro Yoshida ◽  
Hiroshi Satowa ◽  
Akio Sato ◽  
Yoichi Ichikawa ◽  
Jacob Kream ◽  
...  

ABSTRACT Plasma cortisol profiles were studied by the frequent sampling method in 5 patients with Cushing's disease (CD), 7 patients with Cushing's syndrome due to adrenocortical adenoma (AA), and one patient with bronchogenic carcinoma. Plasma ACTH was measured by radioimmunoassay at 10 min intervals in 2 of the subjects. In CD, there was distinct episodic secretion of cortisol and ACTH; the coefficients of variation about the mean plasma cortisol concentration ranged from 24 to 27 %; plasma ACTH ranged from zero to 455 pg/ml with a mean of 94 pg/ml. In AA, the tumour secreted cortisol at a constant rate with little fluctuation; the coefficients of variation of plasma cortisol concentration ranged from 8 to 14%; plasma concentrations of ACTH were always near zero. In the patient with bronchogenic carcinoma, the coefficient of variation of cortisol was 14 %. These results were apparent even in profiles of plasma cortisol concentrations measured over only a 6 h period. It is concluded that characteristics of plasma cortisol and ACTH secretory patterns are helpful in differentiating Cushing's syndrome of differing aetiology.


2003 ◽  
pp. 535-541 ◽  
Author(s):  
K Borm ◽  
M Slawik ◽  
L Seiler ◽  
F Flohr ◽  
M Petrick ◽  
...  

OBJECTIVE: The insulin tolerance test (ITT) is an established standardized test for the evaluation of the hypothalamic-pituitary-adrenal axis. While a peak cortisol value of >18 microg/dl is usually interpreted as a sufficient response to the ITT, the plasma ACTH response has not yet been standardized. METHODS: We evaluated retrospectively the peak plasma ACTH concentrations during 140 ITTs in 125 patients with suspected pituitary insufficiency and prospectively in 15 healthy subjects. RESULTS: All healthy subjects had a peak cortisol concentration >/=18 microg/dl; 32 of 125 tests in the patients showed an insufficient cortisol response (peak cortisol concentration <18 microg/dl). The peak stimulated ACTH concentration in patients with secondary adrenal insufficiency (SAI) was 49.2+/-37.2 pg/ml (mean+/-s.d.) vs 130.9+/-89.3 pg/ml in patients without SAI, and 110.9+/-55.4 pg/ml in normal subjects (P<0.001). There was a weak, but significantly positive correlation between the peak ACTH and peak cortisol concentrations (rho=0.446, P<0.001), but there was also a very wide spread of the values. Defining a cut-off value for the peak plasma ACTH concentration with a sufficient sensitivity and specificity to identify patients with an impaired hypothalamic-pituitary-adrenal (HPA) axis was not possible. A peak plasma ACTH <20 pg/ml as a cut-off value had a sensitivity of 25% and a specificity of 98% for SAI. A cut-off value of a peak plasma ACTH <140 pg/ml had a sensitivity of 97% but a low specificity of 39%. CONCLUSIONS: Although there is a significant positive correlation between the peak ACTH and the peak cortisol concentrations, we conclude that there is no additional benefit in determining the ACTH concentrations during an ITT. Because of the strong variations of the values, the peak ACTH concentration is a poor parameter for the evaluation of the HPA axis.


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