Effect of human pregnancy on metabolic clearance rate of oxytocin

1990 ◽  
Vol 259 (1) ◽  
pp. R21-R24
Author(s):  
S. Thornton ◽  
J. M. Davison ◽  
P. H. Baylis

The metabolic clearance rate (MCR) of oxytocin (OT) was determined by use of constant infusion techniques to achieve low and high plasma OT concentrations in 10 women in late pregnancy and again 8-10 wk postpartum (mean plasma oxytocinase activity was 2.1 IU/ml plasma at term and less than 0.1 IU/ml plasma 8-10 wk postpartum). At the lower plasma OT concentrations (5.0 and 5.2 pg/ml, pregnant and postpartum, respectively) produced by infusion of 17.9 ng/min in pregnancy and 4.3 ng/min postpartum, mean MCR of OT was increased fourfold during pregnancy (5.7 +/- 0.6 and 1.3 +/- 0.1 l/min, pregnant and postpartum, respectively; P less than 0.001). At the higher plasma OT concentrations (8.0 and 8.0 pg/ml, pregnant and postpartum, respectively) produced by infusion of 35.7 ng/min in pregnancy and 8.5 ng/min postpartum, mean MCR of OT was likewise markedly increased during pregnancy compared with postpartum values (7.1 +/- 1.9 and 1.4 +/- 0.1 l/min, respectively; P less than 0.01). The MCR of OT was independent of plasma concentration (between 5 and 8 pg/ml) during pregnancy and in the postpartum period. It is concluded that the MCR of OT is increased markedly during human pregnancy. This may be due to concomitant increases in in vivo cystine aminopeptidase activity or other less specific pregnancy-associated metabolic changes.

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


1971 ◽  
Vol 111 (4) ◽  
pp. 555-563 ◽  
Author(s):  
Norman F. Gant ◽  
Harry T. Hutchinson ◽  
Pentti K. Siiteri ◽  
Paul C. MacDonald

1995 ◽  
Vol 79 (6) ◽  
pp. 1862-1869 ◽  
Author(s):  
S. M. Phillips ◽  
H. J. Green ◽  
M. A. Tarnopolsky ◽  
S. M. Grant

A short-term training model previously shown to result in a tighter metabolic control in working muscle in the absence of an increase in mitochondrial potential was used to examine changes in lactate turnover. Lactate flux was studied before and after 10 days of cycle training [2 h/day at 59% maximal oxygen consumption (VO2max)] in untrained men [VO2max = 45.5 +/- 2.4 (SE) ml.kg-1.min-1). A primed constant infusion of L-[1–13C]lactate was used to examine lactate kinetics during a prolonged exercise protocol (90 min at 59% VO2max). Rate of appearance of lactate increased with exercise (P < 0.01), both pretraining (rest = 30.3 +/- 4.9 ml.kg-1.min-1, exercise = 115 +/- 14 ml.kg-1.min-1) and posttraining (rest = 28.4 +/- 4.7 ml.kg-1.min-1, exercise = 112 +/- 13 ml.kg-1.min-1). Despite a lower blood lactate concentration (P < 0.05) during exercise after training, there was no difference in the rate of appearance of lactate. Training increased (P < 0.05) the metabolic clearance rate of lactate during exercise from 36.8 +/- 4.8 to 51.4 +/- 6.8 ml.kg-1.min-1. These findings indicate that at least part of the lower exercising blood lactate observed after training is due to an increase in metabolic clearance rate. In addition, the lower intramuscular lactate levels suggest a decreased recruitment of glycolysis particularly early in exercise.


1984 ◽  
Vol 247 (1) ◽  
pp. F168-F176 ◽  
Author(s):  
D. S. Emmanouel ◽  
E. Goldwasser ◽  
A. I. Katz

The metabolism of pure human erythropoietin (EPO) labeled with 125I was studied in the rat. Concentrations of the labeled hormone (125I-EPO) in plasma and urine were measured by both trichloroacetic acid precipitation and gel filtration. During steady-state conditions the metabolic clearance rate of 125I-EPO was slow, averaging 256 +/- 7 microliter. min-1 X kg-1 of which only 19 +/- 2 microliter X min-1 X kg-1 (or 7.4 +/- 0.8% of the metabolic clearance rate) could be accounted for by excretion of the labeled hormone in the urine. Urinary clearance of 125I-EPO amounted to less than 0.3% of the glomerular filtration rate, and there was no detectable arteriovenous concentration difference of 125I-EPO across the kidney. After both pulse injection and constant infusion to equilibrium, disappearance of 125I-EPO from the circulation could be approximated by a single exponential function: plasma half-life was 3.5 +/- 0.2 h in normal rats and was prolonged to 4.4 +/- 0.3 h (P less than 0.05) in animals with ligated renal pedicles. Although kidney homogenates degraded 125I-EPO in vitro (optimum pH 4.5), the hormone did not accumulate in the kidney when injected intravenously. We conclude that EPO metabolism is extremely sluggish compared with that of other polypeptide hormones. Whereas kidney tissue is capable of degrading EPO in vitro, the physicochemical characteristics of this glycoprotein (molecular size, shape, and charge) probably impede its access to degrading sites and therefore account for the limited contribution of renal extraction and excretion to the metabolic clearance of the hormone.


1995 ◽  
Vol 269 (1) ◽  
pp. H326-H331 ◽  
Author(s):  
R. R. Brandt ◽  
D. M. Heublein ◽  
L. L. Aarhus ◽  
J. A. Lewicki ◽  
J. C. Burnett

C-type natriuretic peptide (CNP) is a newly described 22-amino acid peptide of endothelial cell origin, which has selective cardiovascular actions and is structurally related to atrial natriuretic peptide (ANP). Recent in vitro studies have demonstrated that an important regulatory pathway for the clearance of natriuretic peptides involves binding to a common clearance receptor [natriuretic peptide C receptor (NPR-C)]. Although CNP has also been identified as a ligand for NPR-C in binding assays, no studies have defined the in vivo interaction of CNP with NPR-C. CNP (10 ng.kg-1.min-1) followed by C-ANP-(4-23), a specific ligand for NPR-C blockade, was infused intravenously in two groups (both n = 7) of anesthetized dogs at two different doses (0.1 or 1.0 micrograms.kg-1.min-1) to permit calculation of total metabolic clearance rate (TMCR). C-ANP-(4-23) increased circulating CNP and reduced TMCR in both groups. Pulmonary metabolic clearance rate was negative at baseline, suggesting a net secretion of CNP across the lung, which was increased during CNP infusion and was abolished with NPR-C blockade. Renal and femoral metabolic clearance rates were positive at baseline and increased with CNP infusion. A decrease in cardiac output and cardiac filling pressures in response to CNP administration was potentiated by NPR-C blockade. We conclude that 1) circulating CNP achieved by CNP infusion is regulated by NPR-C in vivo, 2) the pulmonary circulation is a possible site of CNP secretion, 3) the renal and peripheral circulations are sites of CNP clearance, and 4) NPR-C blockade potentiates the selective cardiovascular actions of CNP.


1973 ◽  
Vol 7 (5) ◽  
pp. 509-519 ◽  
Author(s):  
Inese Z Beitins ◽  
Francis Bayard ◽  
Isadore G Ances ◽  
Avinoam Kowarski ◽  
Claude J Migeon

Sign in / Sign up

Export Citation Format

Share Document