ACTH and cortisol responses to hypotension in fetal sheep after a prior CRF injection

1992 ◽  
Vol 262 (3) ◽  
pp. E325-E329
Author(s):  
D. R. Kerr ◽  
M. I. Castro ◽  
N. K. Valego ◽  
N. M. Rawashdeh ◽  
J. C. Rose

To determine whether an ovine corticotropin-releasing factor (oCRF) injection modifies adrenocorticotropic hormone (ACTH) and cortisol responses to hypotension and whether the effect of any interactions between these stimuli changes across gestation, we studied chronically cannulated fetal lambs of 103-113 ("immature") and 133-139 days gestation ("mature"). Experimental groups received 500 ng/kg oCRF injections and 6 h later had arterial pressure reduced 20% for 10 min with nitroprusside. Blood samples were obtained before and after each manipulation. Controls received vehicle instead of oCRF. The oCRF increased plasma cortisol levels from 2.1 +/- 0.4 to 14.2 +/- 4.7 (SE) ng/ml in immature and 44.9 +/- 2.2 to 102.8 +/- 15 ng/ml in mature animals. In mature fetuses the oCRF did not alter plasma ACTH and cortisol increases due to hypotension. In immature animals ACTH increases were normal but cortisol increases were eliminated. This suggests that the CRF caused maximal stimulation of the adrenal gland. In older fetuses, it appears that the action of ACTH-releasing factors, secreted in response to arterial hypotension, can overcome the negative feedback effects of elevations in endogenous cortisol.

1983 ◽  
Vol 55 (5) ◽  
pp. 1441-1444 ◽  
Author(s):  
P. A. Farrell ◽  
T. L. Garthwaite ◽  
A. B. Gustafson

Adrenocorticotropic hormone (ACTH) levels were compared before and after submaximal and exhaustive isotonic exercise in six normally active college students (3 men and 3 women). Each subject participated in three experiments conducted at the same morning hour. Venous plasma was obtained before and immediately after 20-min runs at 65 and 80% of maximal O2 consumption (VO2 max) and after a run of gradually increasing work intensity which resulted in exhaustion (100% VO2 max) in 12.6 +/- 1.3 min. ACTH (mean +/- SE) was 48 +/- 15, 57 +/- 12, and 61 +/- 11 pg/ml before the 65, 80, and 100% VO2 max runs, and increased to 61 +/- 15 (NS), 128 +/- 18 (P less than 0.05), and 292 +/- 72 (P less than 0.05) pg/ml, respectively. Plasma glucose, growth hormone, cortisol, and lactic acid concentrations increased in a similar fashion. Cortisol and ACTH levels were significantly correlated at the higher levels of exertion: r = 0.18 (NS) for the 65% VO2 max run, r = 0.65 (P less than 0.05) for the 80% VO2 max run, and r = 0.64 (P less than 0.05) for the run to exhaustion. Both the change in ACTH with exercise and its postrun concentration were significantly related to the change in plasma lactic acid (r = 0.65, P less than 0.05) and the postrun plasma lactic acid (r = 0.64, P less than 0.05). We conclude that exercise-induced increases in plasma ACTH and their correlation with circulating cortisol depend on the intensity of isotonic exercise. Our observations also suggest that plasma lactic acid may influence ACTH release during exercise.


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 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.


1982 ◽  
Vol 242 (5) ◽  
pp. H790-H796
Author(s):  
H. O. Stinnett ◽  
F. J. Sepe ◽  
M. R. Magnusson

Reflex heart and mean arterial pressure (MAP) responses during unilateral and bilateral electrical stimulation of the central end of the cut aortic nerves were studied in 14 anesthetized closed-thorax rabbits. During control of carotid intrasinus pressure (ISP), with ISP = MAP, heart rate was 248 +/- 12 beats/min and fell -79 +/- 14, -61 +/- 16, and -117 +/- 16 beats/min during left (LAN), right (RAN), and bilateral (BAN) nerve stimulation. MAP was 79 +/- 5 mmHg and fell -57 +/- 4 (LAN), -46 +/- 6 (RAN), and -65 +/- 4 mmHg (BAN). Responses were also determined following blockade of cardiac vagal efferents (atropine) and then vagotomy (n = 4) or vagotomy alone (n = 10). Results indicated that cardiac parasympathetic effects of LAN and RAN stimulation were additive, whereas the respective summation of cardiac and arterial vascular sympathetic effects were mutually inhibitory. BAN stimulation at low (25 mmHg) and high (greater than or equal to 125 mmHg) ISP levels resulted in different magnitudes of MAP and heart rate responses before and after vagotomy and beta-receptor blockade. These results indicated that summation was mutually inhibitory for cardiac and vasomotor sympathetics when maximal stimulation of opposite influence was applied to aortic and carotid afferents. However, arterial baroreceptor afferents may summate differently at more normal blood pressure conditions.


Endocrinology ◽  
2021 ◽  
Author(s):  
Arno Téblick ◽  
Lauren De Bruyn ◽  
Tim Van Oudenhove ◽  
Sarah Vander Perre ◽  
Lies Pauwels ◽  
...  

Abstract Purpose Sepsis is hallmarked by high plasma cortisol/corticosterone (CORT), low adrenocorticotropic hormone (ACTH) and high pro-opiomelanocortin (POMC). While corticotropin-releasing hormone-(CRH) and arginine-vasopressin-(AVP) driven pituitary POMC expression remains active, POMC processing into ACTH becomes impaired. Low ACTH is accompanied by loss of adrenocortical structure, although steroidogenic enzymes remain expressed. We hypothesized that treatment of sepsis with hydrocortisone (HC) aggravates this phenotype whereas CRH infusion safeguards ACTH-driven adrenocortical structure. Methods In a fluid-resuscitated, antibiotics-treated mouse model of prolonged sepsis, we compared the effects of HC and CRH infusion with placebo, on plasma ACTH, POMC and CORT and on markers of hypothalamic CRH and AVP signaling and pituitary POMC processing, and on the adrenocortical structure and markers of steroidogenesis. In adrenal explants, we studied the steroidogenic capacity of POMC. Results During sepsis, HC further suppressed plasma ACTH, but not POMC, predominantly by suppressing sepsis-activated CRH/AVP-signaling pathways. In contrast, in CRH-treated sepsis, plasma ACTH was normalized following restoration of pituitary POMC processing. The sepsis-induced rise in markers of adrenocortical steroidogenesis was unaltered by CRH and suppressed partially by HC which also increased adrenal markers of inflammation. Ex vivo stimulation of adrenal explants with POMC increased CORT as effectively as an equimolar dose of ACTH. Conclusions Treatment of sepsis with HC impaired integrity and function of the HPA axis at the level of the pituitary and the adrenal cortex while CRH restored pituitary POMC processing without affecting the adrenal cortex. Sepsis-induced high circulating POMC may be responsible for ongoing adrenocortical steroidogenesis despite low ACTH.


1992 ◽  
Vol 262 (3) ◽  
pp. E319-E324 ◽  
Author(s):  
D. R. Kerr ◽  
M. I. Castro ◽  
N. M. Rawashdeh ◽  
J. C. Rose

To determine whether an initial ovine corticotropin-releasing factor (oCRF) injection modifies adrenocorticotropic hormone (ACTH) and cortisol responses to a second injection and to establish whether the effect changes throughout gestation, we studied chronically cannulated fetal lambs of 103-113 and 133-137 days gestation. Experimental groups underwent an injection (500 ng/kg iv) of oCRF, arterial blood sampling for 6 h, then a similar oCRF injection followed by sampling. In control studies, vehicle was the initial injection. After the first oCRF injection, plasma cortisol levels went from 1.7 +/- 0.4 to 9.5 +/- 5.2 (SE) ng/ml ("immature") and from 22.3 +/- 4.9 to 52.5 +/- 5.8 ng/ml ("mature"), remaining elevated for 6 h. In immature fetuses, the first oCRF injection did not alter the ACTH response to a second injection. Cortisol increases were reduced. In mature animals, ACTH and cortisol response to oCRF were eliminated by prior oCRF. Thus a large increase in cortisol after oCRF in mature fetuses is associated with inhibition of the ACTH response to a second oCRF injection, whereas in immature animals a small increase in cortisol after the first oCRF injection is not.


1978 ◽  
Vol 06 (03) ◽  
pp. 241-245 ◽  
Author(s):  
H. L. WEN ◽  
W. K. K. HO ◽  
H. K. WONG ◽  
Z. D. MEHAL ◽  
Y. H. NG ◽  
...  

Plasma ACTH, cortisol, and cyclic-AMP levels of eleven heroin addicts were determined before and after treatment with a fast detoxification procedure using acupuncture and electrical stimulation (AES) together with the administration of limited doses of naloxone. At the end of the treatment period, the average plasma ACTH, cortisol, and cyclic-AMP level rose 130,83 and 24 percent, respectively. In view of the appearance of mild withdrawal signs during this method of treatment, the observed increases in ACTH and cortisol levels probably reflect the inability of AES to suppress withdrawal symptoms induced by naloxone completely. The mechanism underlying this new method of treatment is discussed in relation to AES's ability to stimulate the secretion of endorphisms.


1990 ◽  
Vol 124 (1) ◽  
pp. 27-35 ◽  
Author(s):  
A. N. Brooks ◽  
A. White

ABSTRACT In sheep, birth is preceded by an increase in fetal plasma concentrations of ACTH and cortisol. Activation of the fetal pituitary-adrenal axis is pivotal to the onset of parturition in this species and may be regulated, at least in part, by corticotrophin-releasing factor (CRF). Pulsed administration of CRF has been shown to activate the fetal pituitary-adrenal axis in immature fetal sheep. However, pituitary ACTH responsiveness declined after continued administration of CRF, as a result of increasing negative feedback effects of increased concentrations of endogenous cortisol. To test the hypothesis that arginine vasopressin (AVP) is required, in addition to CRF, to produce the necessary trophic stimulus to the pituitary-adrenal axis, we administered saline, CRF (1 μg), AVP (200 ng) or CRF plus AVP as pulses every 4 h for 7 days to fetal sheep beginning at days 117–120 of pregnancy (term =145 days). Pituitary-adrenal responses were assessed by measuring plasma concentrations of immunoreactive (ir) ACTH and cortisol in response to one of the pulses on each of the 7 days of treatment. On day 1, CRF and AVP significantly increased plasma concentrations of ir-ACTH and there was a synergistic interaction when the two peptides were given together (P<0·05). However, as pulsed treatment continued there was a decline in the pituitary ir-ACTH response to all treatments (P<0·05). This decline in pituitary response occurred over a much longer period of time when CRF and AVP were given together when compared with the two peptides given separately. In contrast, the cortisol response to endogenously released ir-ACTH after administration of CRF, AVP or CRF plus AVP was small on day 1 but gradually increased as treatment progressed. This was particularly apparent when the two peptides were given together. A significant inverse correlation (r = 0·781, P<0·01) between basal cortisol concentrations and the ir-ACTH response to CRF plus AVP was observed over the 7 days of treatment. Premature delivery was not induced by any of the treatments despite significant increases in fetal adrenal weight. Furthermore, there were no changes in the circulating maternal plasma concentrations of progesterone or oestrone during the 7 days of the experiment. We conclude that combination of CRF and AVP administered as pulses to immature fetal sheep results in a greater degree of pituitary-adrenal activation when compared with the two peptides given independently. However, even after this combined treatment regimen pituitary responsiveness eventually declines, an effect which may be due to increased negative feedback effects of increased endogenous cortisol. Journal of Endocrinology (1990) 124, 27–35


1999 ◽  
Vol 181 (2) ◽  
pp. 498-502 ◽  
Author(s):  
William A. Block ◽  
Michael L. Draper ◽  
James C. Rose ◽  
Jeffrey Schwartz

2000 ◽  
pp. 227-234 ◽  
Author(s):  
P Colombo ◽  
C Dall'Asta ◽  
L Barbetta ◽  
T Re ◽  
E Passini ◽  
...  

OBJECTIVE: To evaluate the plasma ACTH and serum cortisol responses to desmopressin in patients with Cushing's disease either before or after pituitary adenomectomy during long-term follow-up, and to compare the results with those obtained after corticotrophin-releasing hormone (CRH) testing. DESIGN: Plasma ACTH and serum cortisol concentrations were evaluated after the administration of desmopressin (10 microg i.v.) or CRH (1 microg/kg i. v.) in 34 patients with Cushing's disease. Twenty-four patients with active Cushing's disease were evaluated both before and after transsphenoidal pituitary surgery (TSS); these patients were followed up for 1-36 months. Ten patients were studied only after a long-term period (1-19 years, median 4 years) after TSS (six patients), TSS plus external pituitary irradiation (three patients) and TSS plus radiosurgery (one patient). RESULTS: In 24 patients with active Cushing's disease a significant ACTH/cortisol response (P<0.001) was induced by either desmopressin (ACTH from a baseline of 15.3+/-2.7 pmol/l to a peak of 40.9+/-7.3 pmol/l; cortisol from 673+/-59 nmol/l to 1171+/-90 nmol/l) or CRH (ACTH from a basal of 14. 2+/-2.5 pmol/l to a peak of 47.2+/-7.7 pmol/l; cortisol from 672+/-50 nmol/l to 1192+/- 80 nmol/l). In all patients a positive cortisol response to desmopressin was found. After pituitary adenomectomy the 14 'cured' patients were followed up for 1-36 months; desmopressin administration never induced ACTH or cortisol responsiveness in any patient. In contrast, a progressive recovery of ACTH and cortisol responses after CRH was observed at different intervals of time in all patients but one. Five patients, in whom the cortisol concentration only normalized after surgery, showed a persistent responsiveness to desmopressin, and two of them relapsed 12 and 24 months later. In five patients who were not cured, the hormonal responsiveness to either CRH or desmopressin was similar before and after operation. Of 10 patients studied only after long-term follow-up, six were cured and a normal response to CRH was present, whereas no changes in ACTH/cortisol concentrations were induced by desmopressin. The other four unsuccessfully operated patients underwent pituitary irradiation and showed different and equivocal hormonal responses to desmopressin and to CRH. CONCLUSIONS: During the postoperative follow-up of patients with Cushing's disease, the maintenance or the disappearance of the hormonal response may be related to the persistence or the complete removal of adenomatous corticotrophs, respectively. It is suggested that desmopressin test should be performed in the preoperative evaluation and follow-up of patients with ACTH-dependent Cushing's syndrome.


Sign in / Sign up

Export Citation Format

Share Document