Pregnancy alters cortisol feedback inhibition of stimulated ACTH: studies in adrenalectomized ewes

2001 ◽  
Vol 280 (6) ◽  
pp. R1790-R1798 ◽  
Author(s):  
Maureen Keller-Wood ◽  
Charles E. Wood
Keyword(s):  
Plasma Cortisol ◽  
Feedback Inhibition ◽  
Plasma Acth ◽  
Acth Secretion ◽  
Feedback Effects ◽  
Low Concentrations ◽  
Pregnancy And Postpartum ◽  
Cortisol Levels

These studies test the hypothesis that pregnancy alters the feedback effects of cortisol on stimulated ACTH secretion. Ewes were sham-operated (Sham), or adrenalectomized (ADX) at ∼108 days gestation and replaced with aldosterone (3 μg · kg−1· day−1) and with cortisol at either of two doses (ADX + 0.6 and ADX + 1 mg · kg−1· day−1); ewes were studied during pregnancy and postpartum. Mean cortisol levels produced in ADX ewes were similar to normal pregnant ewes (ADX+1) or nonpregnant ewes (ADX+0.6), respectively. Plasma ACTH concentrations in response to infusion of nitroprusside were significantly increased in the pregnant ADX+0.6 ewes (1,159 ± 258 pg/ml) relative to pregnant Sham ewes (461 ± 117 pg/ml) or the ADX+1 ewes (442 ± 215 pg/ml) or the same ewes postpartum (151 ± 69 pg/ml). Plasma ACTH concentrations were not significantly different among the groups postpartum. Increasing plasma cortisol to 20–30 ng/ml for 24 h before hypotension produced similar inhibition of ACTH in all groups. Pregnancy appears to decrease the effectiveness of low concentrations of cortisol to inhibit ACTH responses to hypotension.

NEGATIVE, RATE-SENSITIVE FEEDBACK EFFECTS ON ADRENOCORTICOTROPHIN SECRETION BY CORTISOL IN NORMAL SUBJECTS

1982 ◽  
Vol 92 (3) ◽  
pp. 443-448 ◽  
Author(s):  
S. C. J. READER ◽  
J. ALAGHBAND-ZADEH ◽  
J. R. DALY ◽  
W. R. ROBERTSON
Keyword(s):  
Negative Feedback ◽  
Feedback Inhibition ◽  
Fast Rate ◽  
Normal Subjects ◽  
Constant Infusion ◽  
Stress Tests ◽  
Nacl Solution ◽  
Plasma Acth ◽  
Acth Secretion ◽  
Feedback Effects

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.

Effect of naloxone on oxytocin-induced cortisol decrease in normal men

1985 ◽  
Vol 108 (2) ◽  
pp. 261-265 ◽  
Author(s):  
V. Coiro ◽  
P. Chiodera ◽  
G. Rossi ◽  
R. Volpi ◽  
M. Salvi ◽  
...  
Keyword(s):  
Inhibitory Control ◽  
Opioid Peptides ◽  
Plasma Cortisol ◽  
Inhibitory Action ◽  
Opioid Antagonist ◽  
Cortisol Secretion ◽  
Plasma Acth ◽  
Cortisol Levels ◽  
Normal Men ◽  
Cortisol Release

Abstract. iv administration of oxytocin decreases plasma ACTH-cortisol levels in normal men. In contrast, naloxone, a specific opioid antagonist, stimulates cortisol release, suggesting that opioid peptides exert an inhibitory control on ACTH-cortisol secretion. The present study was carried out in an attempt to determine whether an opioid pathway mediates oxytocin action; therefore, we evaluated the effect of naloxone on the decrease of cortisol induced by oxytocin. Six normal men were treated iv with oxytocin (2 IU as a bolus), naloxone (4 mg as a bolus plus 10 mg infused for 2 h) or a combination of the 2 drugs. Plasma cortisol levels were determined in samples taken before and 2 h after drug treatment. As expected, administration of oxytocin significantly decreased cortisol secretion, while naloxone had a stimulatory effect on plasma cortisol levels. When oxytocin injection was followed by administration of naloxone, cortisol levels remained unchanged; thus, naloxone abolished a cortisol decrement in response to oxytocin. These findings show that in man oxytocin requires an active opioid system in order to produce its inhibitory action on ACTH-cortisol secretion, suggesting that this effect of oxytocin could be mediated by an opioid pathway.

Cyclic Cushing's syndrome combined with cortisol suppressible, dexamethasone non-suppressible ACTH secretion: a new variant of Cushing's syndrome

1985 ◽  
Vol 110 (3) ◽  
pp. 289-295 ◽  
Author(s):  
Hans-Udo Schweikert ◽  
Horst Lorenz Fehm ◽  
Rudolf Fahlbusch ◽  
Rainer Martin ◽  
Rainer Kolloch ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Normal Tissue ◽  
Plasma Cortisol ◽  
Cushing's Syndrome ◽  
Cortisol Secretion ◽  
Plasma Acth ◽  
Acth Secretion ◽  
Normal Response ◽  
New Variant ◽  
Marked Suppression

Abstract. A 55 year old woman with an unusual form of Cushing's disease was studied. During several periods (periods lasting up to 84 days) evidence of cortisol hypersecretion with cycles occurring every 6 days was found. Suppression of plasma cortisol through orally administered dexamethasone (up to 32 mg per day) could not be achieved either during periods of cyclic cortisol hypersecretion or during apparent remission with normal cortisol secretion. Marked suppression of plasma ACTH was measured in response to an iv infusion of 50 mg cortisol over a period of 55 min whereas a similar test with 2 mg dexamethasone (iv bolus) did not suppress ACTH secretion. Transsphenoidal exploration of the sella revealed a tumour surrounding the anterior pituitary. Examination of the pituitary showed a few tiny tumour structures embedded in normal tissue which could not be removed, when the tumour was resected selectively under preservation of normal appearing tissue. Post-operatively, clinical and chemical remission (normal response to 1 mg dexamethasone) was observed for about 4 months. Thereafter, cortisol hypersecretion occurred again necessitating bilateral adrenalectomy. Our results are compatible with the assumption that normal hypothalamic-pituitary-adrenal suppressibility with cortisol, but not with dexamethasone, was caused by the loss of feedback receptors for dexamethasone in the presence of cortisol receptors in the cells which secrete ACTH or CRF. The combination of cyclic hypercortisolism with dexamethasone non-suppressible Cushing's syndrome has not been reported before and thus represents a new variant of Cushing's syndrome.

ACTH responses to hypotension and feedback inhibition of ACTH increased by chronic progesterone treatment

1998 ◽  
Vol 274 (1) ◽  
pp. R81-R87
Author(s):  
Maureen Keller-Wood
Keyword(s):  
Arterial Pressure ◽  
Acute Treatment ◽  
Adrenocorticotropic Hormone ◽  
Feedback Inhibition ◽  
Acth Secretion ◽  
Baroreceptor Sensitivity ◽  
Feedback Effects ◽  
Plasma Progesterone ◽  
Progesterone Treatment ◽  
Simple Effect

During pregnancy, arterial pressure, baroreceptor sensitivity, and adrenocorticotropic hormone (ACTH) responses to hypotension are decreased. Basal ACTH and cortisol are increased in pregnancy, suggesting a reduction in cortisol feedback inhibition of ACTH. Acute treatment with progesterone decreases arterial pressure, baroreflex-mediated responses, and corticosteroid feedback effects on ACTH. These experiments test the hypothesis that chronic increases in progesterone produce changes in arterial pressure, ACTH responses to stress, and feedback inhibition of ACTH similar to pregnancy. Ewes were treated with progesterone for 60–80 days. This increase in plasma progesterone (to 7.6 ± 0.4 ng/ml) did not alter basal ACTH, cortisol, arterial pressure, or heart rate. However, ACTH and AVP responses to hypotension were augmented in progesterone-treated ewes compared with untreated ewes. Chronic progesterone treatment resulted in greater inhibition of ACTH by cortisol. Because chronic progesterone treatment did not decrease the ACTH response to hypotension or attenuate the feedback control of ACTH secretion, these results suggest that the changes in pituitary-adrenal control during pregnancy do not reflect a simple effect of progesterone alone.

The comparative analysis of the results of clinical and hormonal investigations in the patients presenting with ACTH-producing neuroendocrine tumours

2013 ◽  
Vol 59 (4) ◽  
pp. 11-17
Author(s):  
E I Marova ◽  
S D Arapova ◽  
G S Kolesnikova ◽  
I I Sitkin ◽  
N P Goncharov
Keyword(s):  
Comparative Analysis ◽  
Clinical Picture ◽  
Neuroendocrine Tumours ◽  
Pituitary Tumour ◽  
Overwhelming Majority ◽  
Acth Level ◽  
Plasma Acth ◽  
Acth Secretion ◽  
Free Cortisol ◽  
Cortisol Levels

This study included the patients presenting with neuroendocrine tumours (NET) and the clinical picture of hypercoticism caused by excessive ACTH secretion from the tumour. The overwhelming majority of the patients (85%) suffered Cushing's disease (CD) associated with a pituitary tumour. The remaining 15% of the patients presented with ACTH-ectopic syndrome (ACTH-ES). The clinical picture of CD and ACTH-ES was very similar. The latter condition was associated with the higher plasma ACTH and cortisol levels as well as the free cortisol content in 24 hour urine and saliva samples collected in the evening compared with CD even though the differences were insignificant due to data scattering. Decompressin administration and catheterization of inferior petrosal sinuses caused a much greater enhancement of the ACTH level in the patients with CS in comparison with those suffering ASTH-ES.

EFFECT OF ACTH AND DEXAMETHASONE ON THE DIURNAL RHYTHM OF UNCONJUGATED OESTRIOL IN PREGNANCY

1978 ◽  
Vol 87 (4) ◽  
pp. 820-827 ◽  
Author(s):  
G. Reck ◽  
H. Nowostawskyj ◽  
M. Breckwoldt
Keyword(s):  
Pregnant Women ◽  
Negative Correlation ◽  
Diurnal Rhythm ◽  
Plasma Cortisol ◽  
Total Plasma ◽  
Acth Secretion ◽  
Back Action ◽  
Cortisol Levels ◽  
In Pregnancy

ABSTRACT The present study is concerned with the role of maternal cortisol in regulating diurnal rhythm of unconjugated oestriol in 9 pregnant women. Blood was drawn at 30 min intervals between 5 p. m. and 3 a. m. In 5 patients endogenous ACTH-secretion was simultaneously suppressed by 12 mg dexamethasone over 48 h. Between 8 p. m. and 2 a. m., 0.25 mg ACTH1-24 (Synacthen®) was infused into the subjects. Free oestriol was measured by radioimmunoassay, and the total plasma cortisol by the protein binding method. Patients without dexamethasone demonstrated high oestriol levels (21.5 ± 9 ng/ml) and episodic secretion between 5 p. m. and 8 p. m. At the same time cortisol concentrations were relatively low (274.1 ± 66 ng/ml). Ninety min after starting ACTH-infusion, plasma oestriol decreased in negative correlation to rising cortisol (r = −0.916, P < 0.001). Between 11 p. m. and 2 a. m. oestriol levels were significantly below the control values (12.9 ± 3 ng/ml, P < 0.001) and were associated with high cortisol levels (887 ± 312 ng/ml). Episodic oestriol production did not occur during the period of elevated cortisol levels. Under dexamethasone both oestriol (2.1 ± 1.2 ng/ml) and cortisol values (36.5 ± 24 ng/ml) were markedly suppressed. Only cortisol production could be stimulated during ACTH-infusion (374 ± 80 ng/ml), whereas oestriol concentration remained in the range of the controls (1.91 ± 0.5 ng/ml). These results suggest that diurnal rhythm of unconjugated oestriol is predominantly regulated by feed-back action of maternal cortisol on the foetal hypothalamus.

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.

Effect of ovine corticotrophin releasing factor, bromocriptine, and dopamine on release of ACTH and β-endorphin in a patient with Cushing's disease

1985 ◽  
Vol 109 (1) ◽  
pp. 7-12 ◽  
Author(s):  
Hiroko Nakashima ◽  
Yukio Hirata ◽  
Masahito Uchihashi ◽  
Masahiro Tomita ◽  
Takuo Fujita
Keyword(s):  
Pituitary Adenoma ◽  
Cushing’S Disease ◽  
Plasma Cortisol ◽  
Cushing's Disease ◽  
Intermediate Lobe ◽  
Plasma Acth ◽  
Corticotrophin Releasing Factor ◽  
Predominant Component ◽  
Cortisol Levels

Abstract. Release of immunoreactive ACTH and β-endorphin (β-EP) in response to corticotrophin-releasing factor (CRF) and dopaminergic agents was studied in vivo and in vitro in a patient with Cushing's disease. Iv administration of synthetic ovine (o) CRF significantly stimulated plasma ACTH release, accompanied by increase of plasma cortisol levels. Oral administration of bromocriptine significantly suppressed plasma cortisol levels. Although reduced responses of plasma ACTH and cortisol to o-CRF was observed 1 month after removal of the pituitary adenoma, these normalized 6 months after operation. In vitro perifusion of the pituitary adenoma obtained by surgery revealed that o-CRF also stimulated ACTH and β-EP release in a dose-responsive manner (10−9m–10−5 m) and that dopamine suppressed their basal secretion. Gel exclusion chromatography of the perfusates showed that the predominant component of ACTH and β-EP before and after o-CRF stimulation coeluted with standard ACTH and β-EP, respectively. The present data suggest that o-CRF is a potent secretagogue for ACTH and β-EP release from the human pituitary adenoma causing Cushing's disease and that ACTH secretion from certain adenomas, possibly originating from the intermediate lobe of the pituitary gland, is partly regulated by a dopaminergic mechanism.

Negative-feedback inhibition of fetal ACTH secretion by maternal cortisol

1987 ◽  
Vol 252 (4) ◽  
pp. R743-R748 ◽  
Author(s):  
C. E. Wood
Keyword(s):  
Plasma Cortisol ◽  
Feedback Inhibition ◽  
Plasma Renin ◽  
Maternal Plasma ◽  
Cortisol Concentration ◽  
Acth Secretion ◽  
Fetal Plasma ◽  
Plasma Cortisol Concentration ◽  
Subsequent Period ◽  
Arteries And Veins

Previous studies in this laboratory have shown that small increases in fetal cortisol (F) decreased basal fetal plasma renin activity (PRA) and completely inhibited the fetal adrenocorticotropin hormone (ACTH) response to hypotension. The present study was designed to quantitate suppression of fetal ACTH and renin secretion by maternal F. Fetal and maternal femoral arteries and veins were chronically catheterized (11 fetuses, 118-129 days gestation). Maternal intravenous infusion of 0, 0.5, 1.0, and 2.0 micrograms F X kg-1 X min-1 (n = 5-6) increased mean maternal and fetal cortisol and suppressed fetal ACTH responses to a subsequent period of hypotension in a dose-related manner. Increases in fetal plasma cortisol to 8.3 ng/ml completely suppressed the fetal ACTH response to hypotension. The results indicate that increases in maternal plasma cortisol concentration sufficient to produce modest increases in fetal plasma cortisol inhibit fetal ACTH secretion.

Ageing and the sensitivity of the adrenal gland to physiological doses of ACTH in man

1990 ◽  
Vol 126 (3) ◽  
pp. 507-513 ◽  
Author(s):  
N. A. Roberts ◽  
R. N. Barton ◽  
M. A. Horan
Keyword(s):  
Plasma Cortisol ◽  
Response Curve ◽  
Elderly Women ◽  
The Elderly ◽  
Cortisol Concentration ◽  
Elderly Subjects ◽  
Elderly Men ◽  
Plasma Acth ◽  
Acth Secretion ◽  
Cortisol Responses

ABSTRACT Healthy men and women aged 19–38 or 67–83, in whom endogenous ACTH secretion was suppressed with dexamethasone, were given successive injections of 60 ng, 150 ng and 250 μg ACTH(1–24) at hourly intervals, and blood samples for measurement of plasma cortisol were taken every 10 min. The response to each injection was taken as the increase in cortisol concentration 20 min later, when there was a peak with the lower doses, with allowance for disappearance of cortisol produced after the previous injection. On average, the responses to 60 and 150 ng ACTH were about 0·4 and 0·7 respectively of the response to 250 μg. There were no consistent effects of age or sex on any index of adrenocortical sensitivity or responsiveness, but some groups showed isolated differences from both their age- and sex-matched counterparts: the response to 60 ng ACTH was low in young men, maximal responsiveness was low in elderly men and the slope of the dose–response curve was high in elderly women. In most of the elderly subjects, plasma ACTH was determined separately under normal conditions. It was negatively correlated with the cortisol responses to 60 and 150 ng ACTH, suggesting that differences in adrenal sensitivity between subjects contribute to the variability of plasma ACTH. Journal of Endocrinology (1990) 126, 507–513

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