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

1994 ◽  
Vol 143 (1) ◽  
pp. 183-190 ◽  
Author(s):  
B J Waddell ◽  
H C Atkinson
Keyword(s):  
Production Rate ◽  
Clearance Rate ◽  
Statistical Significance ◽  
Blood Levels ◽  
Additional Contribution ◽  
Metabolic Clearance ◽  
Maternal Weight ◽  
Metabolic Clearance Rate ◽  
Pregnant Rats ◽  
Conscious Rats

Abstract 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 μmol/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 1/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. Administration of ACTH (1–24) (3·5 nmol) increased the production rate of corticosterone at dioestrus and at day 16 of pregnancy, but this effect was less marked in the pregnant group (134% and 41% increase respectively). The MCR of corticosterone also rose (17%) following ACTH(1–24) administration in pregnant but not dioestrous rats. This difference in the MCR response is likely to reflect pregnancy-induced changes in the relative levels of corticosterone, progesterone and corticosteroid-binding globulin. In conclusion, this study shows that blood levels of corticosterone increase progressively during pregnancy in conscious rats. This increase apparently resulted from the net effects of increased production and decreased MCR, neither of which reached statistical significance. It would appear, however, that the trend toward increased production of corticosterone contributes more to the rise in blood corticosterone than does MCR, since the latter was more effectively maintained at pre-pregnancy levels. The demonstration of significant transuterine extraction of corticosterone at day 22 suggests that the maintenance of corticosterone clearance late in pregnancy is due, in part, to an additional contribution by the uterus and its contents. Journal of Endocrinology (1994) 143, 183–190

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

1984 ◽  
Vol 102 (3) ◽  
pp. 357-363 ◽  
Author(s):  
B. J. Waddell ◽  
N. W. Bruce
Keyword(s):  
Production Rate ◽  
Clearance Rate ◽  
Blood Concentration ◽  
Constant Infusion ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Short Term ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Anaesthetized Rats

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

ADRENAL FUNCTION IN BREAST CANCER: PRODUCTION AND METABOLIC CLEARANCE RATE OF CORTISOL IN PATIENTS WITH EARLY OR ADVANCED BREAST CANCER AND IN NORMAL WOMEN *

1968 ◽  
Vol 42 (3) ◽  
pp. 425-432 ◽  
Author(s):  
V. JENSEN ◽  
N. DESHPANDE ◽  
R. D. BULBROOK ◽  
T. W. DOOUSS
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Cancer Patients ◽  
Production Rate ◽  
Clearance Rate ◽  
Advanced Breast ◽  
Metabolic Clearance ◽  
Breast Cancer Patients ◽  
Metabolic Clearance Rate ◽  
Significant Difference

SUMMARY The production rate of cortisol in patients with early or advanced breast cancer was compared with that of controls of comparable age. The miscible pool of this hormone was raised in advanced breast-cancer patients due to a higher production rate. The plasma clearance of cortisol remained unaffected, resulting in a higher titre of cortisol (both total and unbound) in advanced breast-cancer patients. There was no significant difference in the production rate between the early breast-cancer cases and controls. The binding of cortisol to transcortin was studied in all cases. The amount of unbound cortisol was raised in advanced breast-cancer cases. There was a significant correlation between both total and unbound cortisol and the production rate of this hormone. The latter correlation suggests that there is no abnormality in the hepatic extraction of cortisol in these patients. The metabolic clearance rate was found to be of the order of the blood flow through the liver when unbound cortisol was used for its estimation, showing that it is the unbound cortisol which is removed by the liver.

Fate of circulating renin in conscious rats

1987 ◽  
Vol 252 (1) ◽  
pp. E136-E146 ◽  
Author(s):  
S. Kim ◽  
H. Iwao ◽  
N. Nakamura ◽  
F. Ikemoto ◽  
K. Yamamoto
Keyword(s):  
Clearance Rate ◽  
Half Life ◽  
High Performance ◽  
Slow Component ◽  
High Performance Liquid Chromatographic ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Conscious Rats ◽  
Liver And Kidney ◽  
Liquid Chromatographic

Highly purified 125I-labeled rat renal renin (125I-renin) was given intravenously to conscious rats to study the fate of circulating renin. Specific antirat renin antiserum was used to identify the labeled renin molecules. In sham-operated rats, the disappearance of 125I-renin from the plasma showed two exponential components with a half-life of 6.7 +/- 0.4 min for the rapid component and 65.1 +/- 5.7 min for the slow component. The metabolic clearance rate was 11.4 +/- 1.0 ml X min-1 X kg-1. In bilaterally nephrectomized rats, the metabolic clearance rate of 125I-renin was reduced by 55%, but the half-life of the slow component remained unchanged. Seventy percent hepatectomy caused a 54% decrement in the metabolic clearance and prolonged the half-life of the slow component. Five minutes after injection of 125I-renin, approximately 59 and 11% of the administered 125I-renin had accumulated in the liver and the kidneys, respectively, and at later time points the 125I-renin was highly concentrated in these organs. High-performance liquid chromatographic analysis of the liver and kidney extracts demonstrated that 125I-renin was catabolized by these organs. Biliary excretion of 125I-renin was negligible. Urinary excretion of 125I-renin up to 120 min was approximately 2% of the injected dose. We conclude that both the liver and the kidney are responsible for the clearance of circulating renin, with participation of the liver being predominant.

A primed-infusion technique for rapid estimation of the metabolic clearance rate of 1,25(OH)2D3

1987 ◽  
Vol 253 (3) ◽  
pp. E246-E250
Author(s):  
R. Eastell ◽  
B. L. Riggs ◽  
R. Kumar
Keyword(s):  
Production Rate ◽  
Clearance Rate ◽  
Human Subjects ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Study Interval ◽  
Normal Women ◽  
Infusion Technique

We have developed a rapid primed-infusion technique for the measurement of the metabolic clearance and production rate of 1,25-dihydroxyvitamin D3 in normal human subjects and experimental animals. With this method, an estimate of the metabolic clearance rate of 1,25-dihydroxyvitamin D3 can generally be made within 3 to 4 h. Initial studies in five dogs using 1,25-[3H]-dihydroxyvitamin D3 (180 Ci/mmol) allowed us to determine the optimal ratio of loading dose to infusion rate that resulted in the most rapid attainment of steady-state levels of plasma radioactivity. By use of this technique we found that the metabolic clearance rate of 1,25-dihydroxyvitamin D3 in dogs was 6.3 +/- 1.2 ml/min (mean +/- SD); the production rate of the hormone was 0.40 +/- 0.25 microgram/day (20.4 +/- 14.4 ng . kg-1 . day-1). In eight normal women, aged 28-51 yr, the metabolic clearance rate for 1,25-dihydroxyvitamin D3 was 25.9 +/- 4.7 ml/min; the production rate was 1.38 +/- 0.45 microgram/day (20.7 ng . kg-1 . day-1). The advantages of this method relative to ones used in the past are that it can be performed quickly (generally within 3-4 h) with the use of only tracer amounts of this hormone (equivalent to 1.1% of the production rate). With this method, no assumptions about the most appropriate model to which to fit the data need to be made. Because of its rapidity, no metabolites of the injected 1,25-dihydroxyvitamin D3 are formed during the study interval.

scholarly journals Metabolic clearance rate and production rate of calcitriol in uremia

1989 ◽  
Vol 35 (3) ◽  
pp. 860-864 ◽  
Author(s):  
Adriana Dusso ◽  
Silvia Lopez-Hilker ◽  
Jane Lewis-Finch ◽  
Patricia Grooms ◽  
Alex Brown ◽  
...  
Keyword(s):  
Production Rate ◽  
Clearance Rate ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate

Testosterone Metabolic Clearance Rate and Production Rate in the Male Infant Rhesus Monkey

1985 ◽  
Vol 17 (02) ◽  
pp. 110-111
Author(s):  
J. Booth ◽  
J. Bacher ◽  
D. Loriaux ◽  
F. Cassorla
Keyword(s):  
Rhesus Monkey ◽  
Production Rate ◽  
Clearance Rate ◽  
Male Infant ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Infant Rhesus

THE PERSISTENCE OF PROGESTERONE SECRETION IN PREGNANT RATS AFTER HYPOPHYSECTOMY AND HYSTERECTOMY: A COMPARISON WITH PSEUDOPREGNANT, DECIDUOMATABEARING PSEUDOPREGNANT, AND LACTATING RATS

1973 ◽  
Vol 57 (1) ◽  
pp. 63-74 ◽  
Author(s):  
I. ROTHCHILD ◽  
R. B. BILLIAR ◽  
I. T. KLINE ◽  
G. PEPE
Keyword(s):  
Luteinizing Hormone ◽  
Clearance Rate ◽  
Progesterone Level ◽  
Corpora Lutea ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Serum Progesterone ◽  
Pregnant Rats ◽  
Oestrogen Treatment ◽  
Progesterone Secretion

SUMMARY To test the hypothesis of Raj & Moudgal (1970) that luteinizing hormone (LH) is the essential luteotrophin during pregnancy in the rat, pregnant rats were hypophysectomized and hysterectomized on either day 12 or day 15 of pregnancy, and the changes in peripheral serum progesterone level measured. The serum progesterone level remained at approximately the day-12 value for 3 days after hypophysectomy and hysterectomy on day 12, but fell drastically and remained low after the same operation on day 15, or in pseudopregnant rats operated on on day 12, or after removal of the ovaries from pregnant rats on day 12. Oestrogen treatment increased the serum progesterone level slightly in the pregnant rats after hypophysectomy and hysterectomy, but not after ovariectomy; it had no effect in the pseudopregnant rats, with or without deciduomata, or in lactating rats nursing litters of seven to nine pups. The corpora lutea stopped growing or slowly regressed soon after hypophysectomy—hysterectomy in all except the pregnant rats operated on on day 12 and treated with oestrogen, and in these growth was very slight. The luteal content of progesterone did not change for 3 days after hypophysectomy—hysterectomy on day 12 of pregnancy, and fell slightly thereafter. The metabolic clearance rate of progesterone was not significantly changed by hypophysectomy—hysterectomy. It thus appears that true secretion of progesterone continues in pregnant rats for about 3 days after day 12 in the absence of the pituitary and placentas, but at a much lower rate than that found in intact, or in day-12 hypophysectomized pregnant rats (Pepe & Rothchild, 1972a). The placental luteotrophin thus seems to increase the rate of progesterone secretion in the absence of LH. The results do not seem to fit with the hypothesis that LH is essential for progesterone secretion.

Pharmacokinetics of norethindrone acetate in women after the insertion of a single subdermal implant releasing norethindrone acetate

1982 ◽  
Vol 99 (2) ◽  
pp. 302-308 ◽  
Author(s):  
Harbans Singh ◽  
J P Uniyal ◽  
P Jha ◽  
D Takker ◽  
K Murguesan ◽  
...  
Keyword(s):  
Production Rate ◽  
Clearance Rate ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Significant Change ◽  
Continuous Presence ◽  
Norethindrone Acetate ◽  
Subdermal Implant

Abstract. The metabolic clearance rate (MCR) of norethindrone acetate1 (NETA) and norethindrone (NET) levels in plasma were studied after an iv injection of [3H]NETA in three women before and at 1 week, 1, 2 and 6 months following the insertion of a single silastic subdermal implant releasing microquantities of NETA. No significant change in the MCR of NETA was observed at 1 week (459 ± 72 1/day), 1 month (489 ± 113 1/day) and 2 months (522 ± 144 1/day) compared with that of control (525 ± 108 1/day). However, MCR of NETA showed significant increase in women exposed to continuous presence of NETA for a period of 6 months (608 ± 121 1/day; P < 0.025). NETA was rapidly and extensively metabolized into NET. At 1 week, 1, 2 and 6 months of study, NET was observed to be present in higher amounts compared with NETA. The production rate (PR) of progesterone decreased significantly at 2 and 6 months of NETA implant insertion compared with the PR before the insertion of implant.

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