Adrenocorticotropin Secretion Rates Following Histamine Injection in Adult and Newborn Dogs

1975 ◽  
Vol 53 (4) ◽  
pp. 592-602 ◽  
Author(s):  
John S. Cowan

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.

1977 ◽  
Vol 55 (5) ◽  
pp. 1079-1083 ◽  
Author(s):  
Josée Lalonde ◽  
Maurice Normand

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.


1978 ◽  
Vol 235 (1) ◽  
pp. E74
Author(s):  
H A Schut ◽  
G J Pepe ◽  
J D Townsley

Serum concentrations of dehydroepiandrosterone (D) are greater and those of D sulfate (DS) are lower in female baboons than in women, suggesting interspecies differences in relative production and catabolism of these steroids. To examine this possibility, the metabolic clearance rate (MCR), interconversion (rho), and production of D and DS were determined in five adult female baboons by constant intravenous infusion of [3H]DS and [14C]D. MCR-D (mean +/- SE) was greater (407 +/- 72.8 1/day; 23.1 +/- 3.4 1/day.kg, P less than 0.01) than MCR-DS (44 +/- 5.7 1/day; 2.5 +/- 0.3 1/day.kg). rho-D leads to DS (mean % +/- SE) was greater (45.4 +/- 3.0, P less than 0.001) than rhoDS leads to D (3.8 +/- 0.6), indicating that the equilibrium favors DS formation. Calculated D production and secretion rates were similar (4.5 and 4.4 microgram/min, respectively), whereas DS production (4.1 microgram/min) was twice its secretion rate (2.1 microgram/min). The large difference between MCR-D and MCR-DS resembles that in human beings. However, when clearance is expressed per kilogram body weight, MCR-D is similar to that in man, but MCR-DS is approximately 15-fold greater in the baboon. It is concluded that compared to values in human beings, the greater MCR-DS in baboons maintains the lower serum DS concentration, whereas the higher serum D levels probably result from the relatively greater secretion rate of D baboons.


1974 ◽  
Vol 52 (1) ◽  
pp. 8-13 ◽  
Author(s):  
John S. Cowan ◽  
Allan E. Davis ◽  
Ross A. Layberry

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.


1982 ◽  
Vol 242 (2) ◽  
pp. E102-E108
Author(s):  
C. E. Wood ◽  
J. Shinsako ◽  
M. F. Dallman

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).


Life Sciences ◽  
1978 ◽  
Vol 23 (23) ◽  
pp. 2323-2330 ◽  
Author(s):  
Anthony S. Liotta ◽  
Choh Hao Li ◽  
George C. Schussler ◽  
Dorothy T. Krieger

2007 ◽  
Vol 61 (6) ◽  
pp. 681-686 ◽  
Author(s):  
Sithembiso C Velaphi ◽  
Kevin Despain ◽  
Timothy Roy ◽  
Charles R Rosenfeld

1987 ◽  
Vol 252 (3) ◽  
pp. E431-E438 ◽  
Author(s):  
J. M. Miles ◽  
M. G. Ellman ◽  
K. L. McClean ◽  
M. D. Jensen

The accuracy of tracer methods for estimating free fatty acid (FFA) rate of appearance (Ra), either under steady-state conditions or under non-steady-state conditions, has not been previously investigated. In the present study, endogenous lipolysis (traced with 14C palmitate) was suppressed in six mongrel dogs with a high-carbohydrate meal 10 h before the experiment, together with infusions of glucose, propranolol, and nicotinic acid during the experimental period. Both steady-state and non-steady-state equations were used to determine oleate Ra ([3H]oleate) before, during, and after a stepwise infusion of an oleic acid emulsion. Palmitate Ra did not change during the experiment. Steady-state equations gave the best estimates of oleate inflow approximately 93% of the known oleate infusion rate overall, while errors in tracer estimates of inflow were obtained when non-steady-state equations were used. The metabolic clearance rate of oleate was inversely related to plasma concentration (P less than 0.01). In conclusion, accurate estimates of FFA inflow were obtained when steady-state equations were used, even under conditions of abrupt and recent changes in Ra. Non-steady-state equations, in contrast, may provide erroneous estimates of inflow. The decrease in metabolic clearance rate during exogenous infusion of oleate suggests that FFA transport may follow second-order kinetics.


1987 ◽  
Vol 253 (2) ◽  
pp. G110-G115 ◽  
Author(s):  
E. Sikuler ◽  
J. Polio ◽  
R. J. Groszmann ◽  
R. Hendler

The role that portosystemic shunting plays in inducing the alterations of glucagon and insulin metabolism, which are observed in chronic liver disease, was studied in a rat model of prehepatic portal hypertension induced by portal vein constriction. Net splanchnic output of the hormones into the portal circulation was calculated from the difference between portal and systemic concentrations multiplied by portal plasma flow. Metabolic clearance rate was calculated as the ratio between output and systemic concentration. Portal blood flow was measured by the radioactive microsphere technique. Glucagon output in the portal vein-ligated rats was higher than in the sham-operated controls (5.9 +/- 1.5 vs. 2.0 +/- 0.2 ng/min, P less than 0.05). The metabolic clearance rate of glucagon was not significantly different between the two groups. Insulin output was not significantly different between the two groups; however, the metabolic clearance rate of insulin in the portal vein-ligated rats was reduced in comparison with the sham-operated group (9.5 +/- 1.5 vs. 18.4 +/- 3.3 ml/min, P less than 0.05). Our results indicate that portosystemic shunting per se is sufficient to cause an increased splanchnic output of glucagon into the portal system and a decreased metabolic clearance of insulin.


1984 ◽  
Vol 102 (3) ◽  
pp. 357-363 ◽  
Author(s):  
B. J. Waddell ◽  
N. W. Bruce

ABSTRACT Both production rate and metabolic clearance rate (MCR) of progesterone may vary rapidly and so effect short-term changes in blood concentration of the hormone. Here, a constant infusion and sampling technique was used to estimate these three characteristics of progesterone metabolism in seven conscious and ten anaesthetized rats on day 16 of pregnancy. After steady state was achieved, four samples were collected during a 1-h period from each rat. Mean values for production rate and MCR of progesterone in conscious rats were 14·0 ±1·4 μmol/day and 63·2 ± 6·2 litres/day respectively. Both values were substantially reduced in anaesthetized rats (8.6 ±0·8 μmol/ day and 39·4± 3·4 litres/day respectively) and so blood concentration was unchanged. The production rate was positively related to the total mass of luteal tissue (common correlation coefficient, r = 0·61, P <0·05). There were no consistent changes in the three characteristics with time but variation within rats was high. The estimated coefficients of variation for production rate, MCR and blood concentration within rats were 26, 18 and 17% in conscious and 27, 20 and 23% in anaesthetized rats respectively. Short-term changes in production rate and MCR generally were in the same direction (P <0·05). This reduced variation in blood concentration which would otherwise have occurred if production rate and MCR were unrelated. The pregnant rat is clearly capable of rapid shifts in production rate, MCR and blood concentration of progesterone and the positive relationship between production rate and MCR has a homeostatic effect on blood concentration. J. Endocr. (1984) 102, 357–363


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