METABOLIC CLEARANCE RATES OF PREGNENOLONE, 17-ACETOXYPREGNENOLONE AND THEIR SULPHATE ESTERS IN MAN AND IN RABBIT

1967 ◽  
Vol 39 (3) ◽  
pp. 395-403 ◽  
Author(s):  
D. Y. WANG ◽  
R. D. BULBROOK ◽  
F. ELLIS ◽  
M. M. COOMBS

SUMMARY The metabolic clearance rates, distribution volumes and half-lives of pregnenolone, 17-acetoxypregnenolone and their sulphate esters were determined in man and in the rabbit. Pregnenolone was cleared about three times more quickly than pregnenolone sulphate in both species. The metabolic clearance rate of 17-acetoxypregnenolone sulphate is greater in the rabbit than in man, whether expressed in absolute terms or in relation to the metabolic clearance rate of the free steroid. The slow clearance rate of 17-acetoxypregnenolone sulphate in man is similar to that of testosterone sulphate, dehydroepiandrosterone sulphate and cholesterol sulphate; but is unlike that of pregnenolone sulphate, which is cleared approximately ten times as quickly.

1973 ◽  
Vol 56 (2) ◽  
pp. 285-294 ◽  
Author(s):  
B. A. PANARETTO ◽  
J. Y. F. PATERSON ◽  
F. HILLS

SUMMARY The uptake of cortisol by organs in the splanchnic area of conscious, undisturbed sheep was estimated before and during the administration of adrenocorticotrophic hormone (ACTH) by measuring cortisol concentration differences in portal and hepatic venous plasma and estimating hepatic plasma flow rates. Metabolic clearance rates (MCR) of plasma cortisol were measured simultaneously. The total splanchnic clearance of cortisol was 61% of MCR in the animal, 48% being accounted for by the liver. When ACTH was given there were increases in MCR and these were accompanied by proportional increases in hepatic plasma flow rates. When ACTH was infused the total splanchnic clearance rate was 65% of MCR, 52–59% being accounted for by the liver. In other experiments the renal clearance rate of cortisol was studied. Under control conditions, and when ACTH was given, the renal clearance was 11% of MCR. The relationship of the sum of individual clearances to MCR is compared and discussed.


1967 ◽  
Vol 38 (3) ◽  
pp. 307-318 ◽  
Author(s):  
D. Y. WANG ◽  
R. D. BULBROOK ◽  
A. SNEDDON ◽  
T. HAMILTON

SUMMARY The disappearance of isotopically labelled dehydroepiandrosterone, testosterone and their sulphates from the peripheral circulation of man, rabbit and rat has been investigated. Metabolic clearance rates, distribution volumes and half-lives have been determined for these compounds in the above species. In man, the steroid sulphates have a much lower metabolic clearance rate than the corresponding free steroids. This large difference stems from longer half-lives and lower distribution volumes of the former. In the rabbit or rat the steroid sulphates and the appropriate free steroids do not show such marked differences in their metabolic clearance rates: the half-lives and distribution volumes are comparable.


1976 ◽  
Vol 156 (2) ◽  
pp. 233-238 ◽  
Author(s):  
R N Barton

1. Rats starved for 30h were injected with trace amounts of [3-14C]acetoacetate and β-hydroxy[3-14C]butyrate 1h after ischaemic limb injury in a 20 °C environment, and the concentrations and radioactivities of blood ketone bodies were determined at intervals. 2. Starvation alone raised the rates of production and utilization of β-hydroxybutyrate plus acetoacetate about 3.7-fold, but lowered their metabolic clearance rates by about 50%. In the starved rat ketone-body oxidation could account for up to 30% of whole body O2 consumption. 3. Injury in starved rats lowered the rates of production and utilization of both β-hydroxybutyrate and acetoacetate, the combined fall of about 37% slightly exceeding the concomitant fall in whole-body O2 consumption. The concentration of β-hydroxybutyrate decreased after injury, but its metabolic clearance rate was unaltered; the concentration of acetoacetate rose slightly and its metabolic clearance rate fell.


1993 ◽  
Vol 5 (2) ◽  
pp. 181 ◽  
Author(s):  
DJ Phillips ◽  
NL Hudson ◽  
S Lun ◽  
LA Condell ◽  
KP McNatty

Five pituitary preparations of follicle stimulating hormone (FSH), namely NIDDK-oFSH-17, Bioscan oFSH, Ovagen, Folltropin-V and F.S.H.-P., were examined for biological activity in terms of their potency in an in vitro bioassay, receptor assay and heterologous radioimmunoassay and in terms of their metabolic clearance rates. In the three assays, Bioscan oFSH was the most potent (P < 0.05) (3- to 5-fold the potency of NIDDK-oFSH-17), with Ovagen being 25-50% the potency of the NIDDK standard (P < 0.05). Folltropin-V and F.S.H.-P. had the lowest potencies in all three assays. For each preparation, the ratio of activities between the assays was not consistent, suggesting that the preparations behaved differently in each assay. In 9 of 10 cases, potency estimates in the heterologous radioimmunoassay were greater than those in the in vitro bioassay or receptor assay. Polyacrylamide gel electrophoresis of the preparations showed banding consistent with the molecular weight of FSH, but also indicated that the preparations were contaminated with other proteins to varying extents. The half-lives of these preparations when injected into the bloodstream of mature female mice were 28.0, 8.6, 13.4, 11.6 and 17.4 min for NIDDK-oFSH-17, Bioscan oFSH, Ovagen, Folltropin-V and F.S.H.-P. respectively. The slopes of the decay rates were significantly different from each other (P < 0.05) except between Ovagen and Folltropin-V. The results of these studies show that a number of widely available FSH preparations have differing biopotencies. Moreover, the biopotency of a preparation in vitro is not related to its metabolic clearance rate, and not all FSH preparations behave identically in different assays. Measures of biopotency in vitro combined with those of metabolic clearance rate may provide useful information on the properties of FSH preparations used for research purposes and for superovulation of farmed livestock.


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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