Constancy and Linearity of the Metabolic Clearance of Adrenocorticotropin in Dogs

1974 ◽  
Vol 52 (1) ◽  
pp. 8-13 ◽  
Author(s):  
John S. Cowan ◽  
Allan E. Davis ◽  
Ross A. Layberry
Keyword(s):  
Metabolic Clearance ◽  
Plasma Samples ◽  
Acth Level ◽  
Turnover Rates ◽  
Metabolic Clearance Rate ◽  
Plasma Acth ◽  
Acth Secretion ◽  
Adrenal Cells ◽  
Dose Dependent ◽  
Versus Concentration

The study of the turnover characteristics of adrenocorticotropin (ACTH) has been facilitated by (1) a sensitive bioassay for ACTH in plasma based upon the response of suspended adrenal cells to ACTH and (2) a technique for preserving the ACTH in small plasma samples. The metabolic clearance rate (MCR) of ACTH was determined by intravenous step infusions of ACTH into dogs lightly anesthetized with Nembutal, without blockade of ACTH secretion; in these dogs the endogenous plasma ACTH level was negligible. The infusion rates ranged from 0.25 to 3.0 mU/kg∙min, yielding plasma ACTH plateau concentrations of 1.8 to 37 mU/100 ml. In no dog did the MCR correlate significantly with plasma concentration, nor did the MCR differ significantly from dog to dog. The 34 successful plateaux yielded a mean MCR of 9.54 ± 0.24 ml/kg∙min. Linear regression of MCR versus concentration yielded a correlation coefficient of −0.00026. The findings showed that the disappearance of ACTH from blood is not dose-dependent and varies negligibly with time or among animals. Hence the measured MCR may be used to convert concentrations of ACTH in plasma into turnover rates.

Metabolic clearance rate of adrenocorticotropin in the rat

1977 ◽  
Vol 55 (5) ◽  
pp. 1079-1083 ◽  
Author(s):  
Josée Lalonde ◽  
Maurice Normand
Keyword(s):  
Body Weight ◽  
Steady State ◽  
Clearance Rate ◽  
Intravenous Infusion ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Plasma Acth ◽  
Adrenal Cells ◽  
Acth Concentration ◽  
Acth Release

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.

Adrenocorticotropin Secretion Rates Following Histamine Injection in Adult and Newborn Dogs

1975 ◽  
Vol 53 (4) ◽  
pp. 592-602 ◽  
Author(s):  
John S. Cowan
Keyword(s):  
Continuous Function ◽  
Clearance Rate ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Plasma Acth ◽  
Acth Secretion ◽  
Adrenal Cell ◽  
Continuous Curves ◽  
Secretion Rates ◽  
Nembutal Anesthesia

The metabolic clearance rate (MCR) for ACTH in adult dogs was previously shown not to vary significantly with varying plasma ACTH concentrations or among dogs. This is confirmed here for pups aged 1–7 days. Hence, ACTH secretion rates can be continuously calculated from a continuous function of plasma ACTH vs. time. Each of seven adult dogs under Nembutal anesthesia received two or three intravenous (i.v.) injections of histamine with increasing doses. The first injections in each dog ranged from 7 to 50 μg/kg, while the last dose was 62–108 μg/kg. A total of 16 injections were given. Twelve pups (two litters of six) aged 1–7 days each received one injection of histamine of 76–116 μg/kg (i.v.). ACTH concentrations in plasma were determined by an adrenal cell suspension bioassay before, and 6 times after each injection. Nine pups also underwent determinations of their MCR for ACTH, with plateau concentrations determined at three times during an ACTH infusion. Continuous curves of ACTH secretion rates were calculated for all 28 histamine injections, showing that all except the 1-day-old pups secrete considerable ACTH when stressed. Compared to adult dogs, the pups show lower secretion rate peaks and shorter periods of rapid secretion. Changes in plasma glucocorticoids also suggest that the adrenal cortex of newborn dogs can respond to ACTH by increased glucocorticoid secretion.

Delineation of responsive AVP-containing neurons to running stress in the hypothalamus

2004 ◽  
Vol 286 (3) ◽  
pp. R484-R490 ◽  
Author(s):  
Tsuyoshi Saito ◽  
Hideaki Soya
Keyword(s):  
Lactate Threshold ◽  
Supraoptic Nucleus ◽  
Dominant Role ◽  
Plasma Osmolality ◽  
Regulation Mechanism ◽  
Stress Model ◽  
Plasma Samples ◽  
Acth Level ◽  
Plasma Acth ◽  
Acth Release

Running becomes a stress, termed running stress, if it persists above the lactate threshold (LT) and results in enhanced plasma ACTH level in humans. Although the exact underlying regulation mechanism is still uncertain, hypothalamic AVP has been shown to play a dominant role in running-induced ACTH release. It is still not known, however, whether running stress activates the hypothalamic AVP-containing neurons that are involved in the activation of the ACTH response. For this reason, we applied our rat running stress model, in which both plasma ACTH and osmolality levels increase just above LT running (supra-LT running), to delineate which hypothalamic AVP neurons were responsive to running stress. Rats were previously habituated to running and then subjected to a 30-min run either just below or above the LT. Plasma samples were collected from these animals to determine ACTH and osmolality levels. Brains were prepared for immunocytochemistry for both AVP/Fos in the hypothalamus and enzyme immunoassay for the stalk median eminence (SME) AVP content. Only supra-LT running resulted in an increase in the number of Fos/AVP-immunoreactive neurons in both the parvocellular paraventricular nucleus (pPVN) and the magnocellular supraoptic nucleus (SON) accompanied by increased ACTH and plasma osmolality levels. Similarly, running reduced the SME content of the AVP. We thus found that AVP-containing neurons located in both the pPVN and SON are responsive to running stress just above the LT.

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.

Urinary clearance of atrial natriuretic peptide in Pekin ducks

1995 ◽  
Vol 147 (2) ◽  
pp. 211-215 ◽  
Author(s):  
D A Gray
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Plasma Concentrations ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Pekin Ducks ◽  
Important Means ◽  
Excretion Rates ◽  
Dose Dependent ◽  
Atrial Natriuretic

Abstract To quantify the renal excretion of atrial natriuretic peptide (ANP) in birds, synthetic ANP was infused intravenously into conscious Pekin ducks at rates of 10, 30 and 90 ng/kg per min for 30 min and the relationships between plasma and urine ANP concentrations were monitored by RIA. The infusions of ANP produced dose-dependent elevations in the plasma concentrations of the hormone; however, urinary concentrations and excretion rates did not change significantly from the basal values of 142·2 ±21·5 pg/ml and 26·4 ± 4·5 pg/min per kg respectively. The metabolic clearance rate of ANP remained constant at each infusion dose (approximately 200 ml/min per kg). The urinary clearance rates (<0·3 ml/min per kg) indicated that the fraction of ANP cleared from the blood via the urine was less than 0·2%. Clearly, excretion of intact ANP via this route is not a quantitatively important means of elimination for this hormone in birds. Journal of Endocrinology (1995) 147, 211–215

Comparison of canine corticosteroid responses to mean and phasic increases in ACTH

1982 ◽  
Vol 242 (2) ◽  
pp. E102-E108
Author(s):  
C. E. Wood ◽  
J. Shinsako ◽  
M. F. Dallman
Keyword(s):  
Clearance Rate ◽  
Volume Of Distribution ◽  
Conscious Dogs ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Plasma Acth ◽  
Apparent Paradox ◽  
Control Value ◽  
Disappearance Time ◽  
Arterial Plasma

To determine the dynamics and magnitudes of adrenal corticosteroid responses to ACTH, we measured arterial plasma ACTH and corticosteroid concentrations in conscious dogs during infusions of ACTH or saline. Synthetic alpha 1-24-ACTH was infused at rates of 300,900, or 4,500 ng/30 min either as constant infusions or as three equal short infusions at 10-min intervals. In dogs infused with saline, plasma ACTH fluctuated, whereas corticosteroids did not, suggesting that ACTH is secreted episodically in dogs as in man. The magnitudes of the plasma corticosteroid responses to ACTH infusions were linearly related to the logarithm of the total amount of ACTH infused in 30 min and not to the pattern of administration. In all ACTH infusion experiments, the lag between an increase in arterial ACTH and corticosteroids was not less than 3 min. Mean ACTH half-disappearance time, metabolic clearance rate, and volume of distribution estimated from the different experiments ranged between 1.8 and 2.1 min, 24 and 38 ml . kg-1 . min-1, and 95 and 114 ml/kg, respectively. Collectively, these results explain the apparent paradox that corticosteroid responses to ACTH-releasing stimuli can be initiated before a detectable increase in ACTH above the highest control value (Wood et al. Apparent dissociation of ACTH and corticosteroid responses to ml/kg hemorrhage in conscious dogs. Endocrinology In press).

Vasopressin and ANG II in the control of ACTH secretion and arterial and atrial pressures

1989 ◽  
Vol 256 (2) ◽  
pp. R339-R347 ◽  
Author(s):  
V. L. Brooks
Keyword(s):  
Arterial Pressure ◽  
Right Atrial ◽  
Ang Ii ◽  
Plasma Acth ◽  
Acth Secretion ◽  
Arterial Blood ◽  
Acth Concentration ◽  
Left And Right ◽  
Dose Dependent

Hypotension stimulates the secretion of adrenocorticotropin (ACTH) and vasopressin (AVP) and increases plasma levels of angiotensin II (ANG II). Because AVP and ANG II increase ACTH secretion, the present experiments were performed to evaluate the role of these peptides in the increases in plasma ACTH and glucocorticoid concentrations produced by hypotension in conscious dogs. This was accomplished by determining whether administration of receptor antagonists to vasopressin, [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)tyrosine]Arg8-vasopressin, and ANG II (saralasin), reduced the ACTH and glucocorticoid responses to infusion of four doses of the vasodilator nitroprusside. Nitroprusside (NP) infusion produced dose-dependent decreases in mean arterial pressure. Larger decreases in arterial pressure were produced in dogs pretreated with the AVP antagonist or with both saralasin and the vasopressin antagonist. Left and right atrial pressures also fell with NP infusion, and larger decreases in atrial pressures were found in dogs pretreated with the AVP antagonist. Finally, NP infusion increased plasma glucocorticoid concentration and plasma ACTH concentration. Both the glucocorticoid and the ACTH responses to hypotension were reduced in dogs given the AVP antagonist and in dogs given both saralasin and the AVP antagonist, but there was no difference in the effect of AVP blockade alone vs. the effect of combined AVP and ANG II blockade. These data suggest that AVP, but not ANG II, is required for normal glucocorticoid and ACTH responses to hypotension. They also suggest that AVP is necessary for normal maintenance of arterial blood pressure and atrial pressures during NP infusion.

ADRENERGIC CONTROL MECHANISM FOR ACTH SECRETION IN MAN

1973 ◽  
Vol 74 (2) ◽  
pp. 263-270 ◽  
Author(s):  
Yoshikatsu Nakai ◽  
Hiroo Imura ◽  
Teruya Yoshimi ◽  
Shigeru Matsukura
Keyword(s):  
Intravenous Infusion ◽  
Human Subjects ◽  
Blocking Agent ◽  
Inhibitory Effect ◽  
Plasma Acth ◽  
Acth Secretion ◽  
Glucose Levels ◽  
Alpha Receptors ◽  
Normal Human ◽  
Adrenergic Blocking

ABSTRACT In order to determine if an adrenergic mechanism is involved in the secretion of corticotrophin (ACTH), the effect of adrenergic-blocking or -stimulating agent on plasma ACTH, cortisol and glucose levels was studied in normal human subjects. The intravenous infusion of methoxamine, an alpha adrenergic-stimulating agent, caused a rise in plasma ACTH and cortisol. This increase in plasma ACTH and cortisol was significantly inhibited by the simultaneous administration of phentolamine, an alpha adrenergic-blocking agent, in combination with methoxamine. The intravenous infusion of propranolol, a beta adrenergic-blocking agent, caused no significant change in plasma ACTH and cortisol, although it enhanced the plasma ACTH response to insulin-induced hypoglycaemia. On the other hand, alpha adrenergicblockade by intravenous infusion of phentolamine significantly suppressed the plasma ACTH response to insulin-induced hypoglycaemia. These studies suggest a stimulatory effect of alpha receptors and a possible inhibitory effect of beta receptors on ACTH secretion in man.

Comparative metabolic clearance rate, volume of distribution and plasma half-life of human β-lipotropin and acth

Life Sciences ◽  
1978 ◽  
Vol 23 (23) ◽  
pp. 2323-2330 ◽  
Author(s):  
Anthony S. Liotta ◽  
Choh Hao Li ◽  
George C. Schussler ◽  
Dorothy T. Krieger
Keyword(s):  
Clearance Rate ◽  
Half Life ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Plasma Half Life
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