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At least 19 recordsLinked to original sources
PubMed1984

Production rate, metabolic clearance rate and blood concentration of progesterone in conscious and anaesthetized pregnant rats.

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 mumol/day and 63.2 +/- 6.2 litres/day respectively. Both values were substantially reduced in anaesthetized rats (8.6 +/- 0.8 mumol/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 less than 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 less than 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.

Anesthesia, General↗
PubMed2000

[Primary study on characteristics of insulin secretion rate, metabolic clearance rate and sensitivity in non-insulin-dependent diabetic subjects from multiplex diabetic pedigrees].

OBJECTIVE: To investigate the characteristics of insulin secretion rate (ISR), metabolic clearance rate (MCR-I) and sensitivity and to explore their relationship with obesity in non-insulin-dependent diabetic subjects from multiplex diabetic pedigrees (MDP). METHODS: Fifteen subjects with normal glucose tolerance and 11 non-insulin-dependent diabetic patients from MDP were included in the study. Frequently sampled intravenous glucose tolerance test (FSIVGTT) was performed. Glucose, insulin (INS) and connecting-peptide (C-P) concentrations were measured. A computer procedure devised by our laboratory was used to calculate the value of ISR at each time point, then MCR-I was acquired. Insulin sensitivity index (SI) was calculated according to minimal model technique about glucose in FSIVGTT. RESULTS: The ISR curve in control group was biphasic, while in non-insulin. In non-insulin-dependent diabetic group, areas under the curves of C-P (AUCC) and ISR level (AUCS) measured during 0 approximately 16 min were 7.9 nmol.min(-1).L(-1) +/- 2.8 nmol.min(-1).L(-1), and 6.1 nmol +/- 2.2 nmol, respectively, which were significantly lower than those in control group 17.7 nmol.min(-1).L(-1) +/- 4.92 nmol.min(-1).L(-1) and 12.3 nmol +/- 3.9 nmol (P < 0.01). The two parameters were slightly higher than those in control group 155 nmol.min(-1).L(-1) +/- 44 nmol.min(-1).L(-1) vs 101 nmol.min(-1).L(-1) +/- 30 nmol.min(-1).L(-1) and 76 nmol +/- 26 nmol vs 54 nmol +/- 20.0 nmol (P < 0.05)measured during 16 approximately 180 min. There was no significant difference, between the two groups about the amount of insulin secretion during 3 hours (82 nmol +/- 28nmol vs 68 nmol +/- 21 nmol, P = 0.2). In control group, there were significant positive correlation, between AUCS, waist-hip ratio (WHR), and body surface area, (BSA) and significant negative correlation between MCR-I, SI and WHR, BSA (P < 0.01), and also between MCR-I and SI. In non-insulin-dependent diabetic group, AUCS were significantly correlated with body mass index (BMI) (P < 0.01), and MCR-I had significant negative correlation with AUCC (P < 0.01). CONCLUSIONS: There are obvious impaired first phase insulin secretion after glucose challenge in non-insulin-dependent diabetic subjects from MDP. Decrease in endogenous MCR-I might be an important factor to hyperinsulinemia and insulin resistance. Increased insulin secretion, decreased MCR-I and insulin sensitivity can be observed in abdominal obese subjects of control group.

Blood Glucose↗
PubMedDate not supplied

[Proceeding: Production rate, metabolic clearance rate and mean plasma concentration of cortisol in hyperthyroidism (author's transl)].

The adrenocortical function was studied in 23 patients with hyperthyroidism and compared with a group of 15 normal subjects. Parameters of adrenal function were determined with 1,2(3)H-cortisol. The half-life of cortisol is significantly shortened in hyperthyroidism, as compared to normal subjects (49,5 +/- 6,6 min vs 68,3 +/- 10,5 min) and metabolic clearance rate is increased (418,5 +/- 89,5 L/24 h vs 237,5 +/- 48,5 L/24 h, for normal subjects). The production rate of cortisol, calculated from specific and cumulate activities of THE and THF is increased in hyperthyroidism expressed as mg/24 h or mg/m2/24 h (respectively : 26,7 +/- 7,8 mg/24 h vs 15,7 +/- 3 mg/24 h and 16,9 +/- 4,6 mg/m2/24 h vs 9,5 +/- 1,8 mg/m2/24 h). The mean plasma concentration, calculated as the radio (see article) is not statiscally different in hyperthyroid and normal subjects (6,8 +/- 2,1 microg/100 ml vs 7,3 +/- 1,9 microg/100 ml). 7 patients were reinvestigated after treatment of thyrotoxicosis when they were clinically and biologically in euthyroid state. All the values were normalized, without statistically significant difference from control (T 1/2 = 65,4 +/- 18 min, Metb Cl. Rate : 255 +/- 64,5 L/24 h, production rate : 15,6 +/- 1,8 mg/24 h and 9 +/- 1,4 mg/m2/24 h. mean plasma concentration : 6,8 +/- 2,8 microg/100 ml). Shortened cortisol half life, increased metabolic clearance rate and production rate, and normal mean plasma concentration have been reported in hyperthyroidism (Peterson, Copinschi, Gallagher). These changes, secondary to thyroid hormone excess, are the consequences of increased hepatic catabolism of cortisol. The activity of 11 OH steroid deshydrogenase is increased, as demonstrated by increased ratio (see article) in normal subjects (0,001 less than p less than 0,005). There is a high proportion of 17 kéto metabolites (E, DHE, THE) whose feed-back effect is weak as compared to 17 OH metabolites (F, DHF, THF). The hypothalamo-hypophyso-adrenal system is stimulated to maintain a normal plasma concentration. The fact that the mean plasma concentration is normal despite the increased production rate suggest that changes are rather due to increased catabolism than to central effect of thyroid hormones.

Hydrocortisone↗
PubMed1994

Production rate, metabolic clearance rate and uterine extraction of corticosterone during rat pregnancy.

This study examined changes in the blood concentration of corticosterone with the onset and progression of pregnancy in the rat. To identify the source of variation in blood corticosterone, the metabolic clearance rate (MCR) and production rate of corticosterone were also determined. Measurements were made in conscious rats (n = 4-7 per group) in the morning of dioestrus and days 5, 10, 16 and 22 of pregnancy (term = day 23). Corticosterone levels were 713 +/- 38 nmol/l (mean +/- S.E.M.) in non-pregnant rats, remained unchanged to day 10 of pregnancy, then increased to 1036 +/- 52 nmol/l by day 16 and remained high at day 22. The production rate of corticosterone appeared to increase during pregnancy from 25.6 +/- 1.7 mumol/day on day 10 to reach 36.3 +/- 3.3 mol/day on day 22, but this did not reach statistical significance (one-way ANOVA). The MCR of corticosterone was similar among all groups (overall mean 34.6 +/- 2.5 l/day), although a slight but non-significant fall was apparent at day 16. When account was taken of changes in maternal weight, the MCR decreased progressively from 139 +/- 10 1/day per kg before pregnancy to reach a minimum of 88 +/- 7 1/day per kg on day 16. Transuterine extraction of corticosterone on day 22 of pregnancy was 19.2 +/- 3.1% and so, based on this and estimates of uterine blood flow, the uterus must account for around 15% of corticosterone clearance at this time. Because this uterine contribution is effectively additional clearance, it is likely that without it the MCR of corticosterone would have fallen during pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1975

Metabolic clearance rate, production rate, and mammary uptake and metabolism of progesterone in cows.

Tracer kinetic techniques have been used to measure the production rate, metabolic clearance rate and mammary uptake of progesterone in six experiments on two Jersey cowsmthe cows were surgically prepared so that the carotid artery, jugular vein and mammary vein concentrations of progesterone, and udder blood flow, could be determined in conscious animals without anaesthesia or stress. The mean production rate of progesterone was 173 +/- 23-3 (S.ET) mug/min, with values ranging from 80 to 276 mug/min in pregnancy. The metabolic clearance rate was 22-5 +/- 2-0 1/min, or 0-21 +/- 0-025 1/min/kg metabolic body weight. The mammary uptake of progesterone was low, 3-1 +/- mug/min, and udder uptake accounted for about 3% of progesterone production rate. During [3H]A1progesterone infusion, radioactivity was transferred from blood to milk, probably by diffusion down a concentration gradient. Progesterone accounted for more than 88% of the ether-soluble radioactivity recovered from milk.

Animals↗
PubMed1971

A decreased metabolic clearance rate of aldosterone in benign essential hypertension.

Aldosterone secretion rate, metabolic clearance rate, and/or plasma concentration were determined in 16 patients with benign, uncomplicated essential hypertension and compared with those of control subjects. The mean metabolic clearance rate of aldosterone in 10 patients was significantly (P < 0.001) lower (mean 867 liters of plasma/day per m(2) +/-270 SD) than in a group of 7 healthy subjects (mean 1480 liters/day per m(2) +/-265 SD). Secretion rates in 13 patients (including the 10 already mentioned) tended to be low (83 +/-43 vs. 109 +/-54 mug/day) and plasma concentrations tended to be high (13.6 +/-4.6 vs. 7.5 +/-4.8 ng/100 ml), but neither of these differences was statistically significant. The lower metabolic clearance rate could account for elevated plasma concentrations of aldosterone even when the secretion rate is normal or low. Measurement of secretion rate or urinary excretion only is therefore insufficient to establish the presence and/or mode of evolution of hyperaldosteronism. Failure of the aldosterone secretion to adapt fully to a decreased aldosterone metabolic clearance rate (MCR) could explain the state of relative hyperaldosteronism in patients with benign essential hypertension, even when the secretion rate and the urinary excretion rate are in the normal range.

Adaptation, Physiological↗
PubMed1969

Production rates and metabolic clearance rates of human follicle-stimulating hormone in premenopausal and postmenopausal women.

The production rates (PR) and the metabolic clearance rates (MCR) of human follicle-stimulating hormone (HFSH) were determined in six pre- and five postmenopausal women. Human FSH (PER-780) labeled with (131)I to specific activities of 50-150 muc/mug was used as a tracer. Both double antibody and trichloroacetic acid (TCA) precipitation techniques were used to determine HFSH-(131)I levels in infusate and plasma. In four of the subjects MCRs measured by both constant infusion and single injection techniques were the same. By constant infusion, plasma HFSH-(131)I levels reached equilibrium between 4-5 hr.MCRs in six premenopausal women were 14.2+/-1.1 (mean +/-SE) ml/min. MCRs in five postmenopausal women were 12.6 +/-1.1 ml/min. Simultaneous HFSH and human luteinizing hormone (HLH) MCRs were determined in a single patient using HFSH-(125)I and HLH-(131)I as tracers by both constant infusion and single injection methods. These studies showed that the MCR of HFSH was 10.8-11.1 ml/min, and the MCR of HLH was 18.5-19.4 ml/min. From these data and previous MCR and PR studies of HLH from this laboratory, it appears that the MCR of HFSH is about one-half that of HLH. Endogenous HFSH and HLH levels were measured by radioimmunoassay. The PRs of HFSH, calculated by the product of endogenous level and MCR, were 146 +/-27mU/min in the premenopausal women and 2141 +/-264 mM/min in the postmenopausal women. 24-hr PRs, based on these results, compared with reports of 24-hr urinary excretions of biologically active HFSH indicate that 3-5% of production is found in urine in biologically active form. After our single injections of HFSH-(131)I, 8-29% was recovered in urine over 24 hr.

Adult↗
PubMed1979

Secretion rate and metabolic clearance rate of prolactin in the rat during mid- and late lactation.

The prolactin concentration in the plasma of lactating rats rose less rapidly and attained a significantly lower plateau level in response to suckling on day 20--21 of lactation than it did on day 13--14 of lactation. Neither differences in suckling stimulation of the older pups nor a higher metabolic clearance rate (MCR) of prolactin were implicated in the reduced prolactin concentration seen in the late-lactating rats. The MCR was, in fact, slightly reduced in both conscious and late-lactating rats anaesthetized with urethane when compared with those in mid-lactation. The MCR of prolactin was not significantly altered by urethane anaesthesia in rats on either day of lactation. However, the secretion rate of prolactin, computed from the MCR multiplied by the equilibrium concentration of prolactin during suckling, was considerably reduced (665 to 392 ng/min) from mid- to late lactation. We conclude from these data that the reduced plasma concentration of prolactin in response to suckling in late lactation is the result of an impairment within the prolactin secretory mechanism.

Anesthesia, General↗
PubMed1978

The metabolic clearance rate and uterine metabolism and retention of progesterone and 20alpha-hydroxypregn-4-en-3-one during the secretion of uteroglobin in ovariectomized, steroid-treated rabbits.

The metabolic clearance rate (MCR) and in vivo uterine metabolism and retention of progesterone (P) and 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OHP) during the uterine synthesis of uteroglobin in the rabbit have been studied. Oophorectomized rabbits with the uteri ligated received daily im injections of oil vehicle (C), 2 mg P/kg BW, or 2 microgram estradiol/kg BW. The MCR of [14C]P and [3H]20 alpha-OHP did not differ among treatment groups and was 260 +/- 30 and 270 +/- 33(SE) liters/day, respectively. Although the uterine tissue to arterial blood ratio of [14C]P differed between groups (E greater than C greater than P), the tissue to blood ratio of 20 alpha-OHP was the same for the three groups and was about 1. The uterine extraction of P was 32 +/- 6.2(SE)% and was the same for the three treatment groups. The uterine extraction of 20 alpha-OHP was significantly increased by estrogen treatment [33.4 +/- 6.0(SE)%] compared to the control [14.8 +/- 3.3(SE%)] or P[16.9 +/- 4.5(SE)%] groups. These studies indicate that the ability of exogenous 20alpha-OHP to stimulate uteroglobin secretion is probably mediated by its peripheral conversion to P. These studies also indicate the value of continuous infusion of radioactive steroids to evaluate tissue retention and metabolism in vivo.

20-alpha-Dihydroprogesterone↗
PubMed1980

Epinephrine plasma metabolic clearance rates and physiologic thresholds for metabolic and hemodynamic actions in man.

To determine the plasma epinephrine thresholds for its metabolic and hemodynamic actions and plasma epinephrine metabolic clearance rates, 60-min intravenous epinephrine infusions at nominal rates of 0.1, 0.5, 1.0, 2.5, and 5.0 microgram/min were performed in each of six normal human subjects. These 30 infusions resulted in steady-state plasma epinephrine concentrations ranging from 24 to 1,020 pg/ml. Plasma epinephrine thresholds were 50-100 pg/ml for increments in heart rate, 75-125 pg/ml for increments in blood glycerol and systolic blood pressure, 150-200 pg/ml for increments in plasma glucose (the resultant of increments in glucose production and decrements in glucose clearance), blood lactate, blood beta-hydroxybutyrate, and diastolic blood pressure, and greater than 400 pg/ml for early decrements in plasma insulin. Changes in blood alanine, plasma glucagon, plasma growth hormone, and plasma cortisol were not detected. At steady-state plasma epinephrine concentrations of 24-74 pg/ml, values overlapping the basal normal range, the mean (+/-SE) plasma metabolic clearance rate of epinephrine was 52 +/- 4 ml x min-1 x kg-1; this value rose to 89 +/- 6 ml x min-1 x kg-1 (P less than 0.01) at steady-state epinephrine concentrations of 90-1,020 pg/ml. We conclude that in human subjects: (a) the plasma epinephrine thresholds for its hemodynamic and metabolic actions lie within the physiologic range, (b) epinephrine and norepinephrine accelerate their own metabolic clearance, and (c) epinephrine is 10 times more potent than norepinephrine.

Adult↗
PubMed1990

Effect of human pregnancy on metabolic clearance rate of oxytocin.

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.

Adult↗
PubMed1992

Metabolic clearance rate of arginine vasopressin in patients with cirrhosis.

Metabolic clearance rate and half-time of arginine vasopressin were measured in 43 cirrhotic patients and 10 control subjects. Synthetic arginine vasopressin was infused intravenously at a rate of 500 pg/min/kg of body weight for 75 min. The metabolic clearance rate was significantly reduced, and the half-time of arginine vasopressin after stopping the infusion was significantly increased in patients with cirrhosis, particularly in those with ascites and in those with moderate or severe liver dysfunction. Changes in metabolic clearance rate and half-time of arginine vasopressin correlated with the score of the liver dysfunction, prothrombin activity and levels of serum albumin and bilirubin but not with parameters of kidney function (serum creatinine levels and clearance of creatinine). We conclude that reduced metabolic clearance rate and prolonged half-time of vasopressin in plasma are frequent findings in cirrhotic patients with poor liver function. This impaired catabolism of antidiuretic hormone may contribute to maintaining elevated plasma levels of this hormone in these patients and may be an additional factor leading to fluid retention and to dilutional hyponatremia.

Adult↗
PubMed1982

Metabolic clearance rate of immunoreactive vasopressin in man.

Metabolic clearance of synthetic arginine vasopressin (AVP) has been measured in sixteen healthy subjects and ten uraemic patients on maintenance haemodialysis. Plasma AVP was measured using a specific radioimmunoassay at different intervals after a single injection of 2 micrograms AVP. The theoretical curve which fitted best with the disappearance curve was the sum of two exponentials in twenty-two subjects and of three exponentials in the other four. Metabolic clearance rate and the volume of fast initial distribution were 287.1 ml min-1 (m2)-1 and 219.3 ml/kg b.w., respectively, in normal subjects. Metabolic clearance rate was considerably lower in the uraemic group. This emphasizes the role of kidneys in the degradation of AVP and may account, at least in part, for the higher basal plasma value of this hormone observed in uraemic patients.

Adult↗
PubMed1984

Catecholamine physiology in ovine fetus. II. Metabolic clearance rate of epinephrine.

This study measured the metabolic clearance rate (MCR) of epinephrine (E) in 13 chronically catheterized fetal lambs between 120 and 145 days gestation. The E-MCR was determined by a constant infusion method at an E infusion rate of 0.1 microgram/kg estimated fetal wt. Fetal and maternal arterial blood samples were taken for measurements of catecholamine levels, pH, blood gases, and glucose. There was a significant positive correlation between gestational age and E-MCR (r = 0.87, P less than 0.001). The E production rate in fetuses less than 132 days (n = 6) (1,234 +/- 301 pg/min) was not significantly different from fetuses greater than or equal to 132 days (n = 7) (1,195 +/- 242). Catecholamine infusion resulted in a decrease in pH from a control value of 7.37 +/- 0.01 to 7.31 +/- 0.01 by 15 min of infusion, but there were no significant changes in fetal heart rate or blood pressure. The mean fetal plasma glucose concentration increased 45% above base line at 15 and 20 min and 65% above base line by 30 min of catecholamine infusion. After 60 min of infusion plasma norepinephrine (NE) increased from 380 +/- 60 to 520 +/- 75 pg/ml and plasma dopamine from 100 +/- 20 to 240 +/- 50 pg/ml (both P less than 0.05). These results indicate that E-MCR increases with maturation in the absence of a change in basal E production.

Animals↗