An Estimate of the Endogenous Secretion Rate of Calcitonin in Man

1982 ◽  
Vol 63 (2) ◽  
pp. 145-152 ◽  
Author(s):  
J. A. Kanis ◽  
G. Heynen ◽  
T. Cundy ◽  
F. Cornet ◽  
A. Paterson ◽  
...  

1. The metabolic clearance rate (MCR) of human calcitonin was measured in 12 normal subjects and four patients with Paget's disease by the infusion of synthetic human calcitonin (15–40 μg/h for 2–24 h), and in 10 additional patients with Paget's disease from the disappearance rate of immunoreactive calcitonin from plasma after the intravenous injection of large doses of synthetic human calcitonin (0·5–1·0 mg). 2. The estimated MCR during the infusion studies (range 531–1224 litres/day) was similar to that calculated from the disappearance of large doses of synthetic human calcitonin injected intravenously in patients with Paget's disease (mean = 1035 litres/day; range = 593–1408 litres/day). 3. An eightfold range in the basal values of plasma immunoreactive calcitonin, in spite of the presence of a relatively constant MCR, suggests that the variation in basal plasma calcitonin was due principally to variation in the endogenous secretion rate for calcitonin. 4. The results suggest that the endogenous secretion rate for calcitonin is low in normal subjects (mean 124 ± sem 24 μg/day), and give a basis for selecting the doses of calcitonin which can be considered physiological.

1981 ◽  
Vol 96 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Kazumasa Chikamori ◽  
Fumie Suehiro ◽  
Toshiki Ogawa ◽  
Kei Sato ◽  
Hiroyoshi Mori ◽  
...  

Abstract. Synthetic LRH was infused into normal women and women with obesity and anorexia nervosa to determine the distribution volume (DV), metabolic clearance rate (MCR) and half disappearance time (t½) of plasma LRH. In normal women, the DV of LRH was 12.1 ± 0.9 (mean ± se) l, the MCR was 1478.9 ± 39.8 ml/min (28.5 ± 1.2 ml/min/kg body weight) and the initial t½ was 5.6 ± 0.4 min. In obese patients the DV (20.6 ± 1.5 l) was significantly higher than that in normal subjects (P < 0.005), but the MCR and t½ were not significantly different from those in normal subjects. In patients with anorexia nervosa the DV and MCR were 6.5 ± 1.1 l and 621.8 ± 110.5 ml/min (17.9 ± 2.4 ml/ min/kg body weight), respectively, which were both significantly lower than those in normal subjects (P < 0.02), while the t½ (7.3 ± 0.1 min) was longer than in normal subjects (P < 0.02). These data suggest that 1) the abnormal responses of some hormones to provocation tests observed in obese patients and patients with anorexia nervosa should be evaluated in consideration of changes in the DV and metabolic clearance of hormones in these conditions, and 2) in patients with anorexia nervosa changes in MCR and t½ may reflect low metabolism of LRH.


BMJ ◽  
1972 ◽  
Vol 4 (5835) ◽  
pp. 267-269 ◽  
Author(s):  
N. J. Y. Woodhouse ◽  
M. T. Fisher ◽  
G. Sigurdsson ◽  
G. F. Joplin ◽  
I. MacIntyre

1973 ◽  
Vol 45 (5) ◽  
pp. 633-654 ◽  
Author(s):  
P. H. Sönksen ◽  
Christine V. Tompkins ◽  
M. C. Srivastava ◽  
J. D. N. Nabarro

1. The metabolism of unlabelled monocomponent human insulin and porcine proinsulin was studied in ten normal subjects (five males and five females) by using a priming dose-constant-infusion technique. In each subject, the metabolic clearance rate (MCR) was measured at four separate steady-state hormone concentrations averaging 16–216 μunits/ml (insulin) and 4·2–42·8 ng/ml (proinsulin). 2. For insulin the MCR fell progressively from 34 ml kg−1 min−1 at a mean fasting insulin concentration of 3·8 μunits/ml to 11·4 ml kg−1 min−1 at the highest concentration achieved (280 μunits/ml); for proinsulin MCR averaged 3·7 ml kg−1 min−1 at a mean plasma concentration of 4·2 ng/ml and fell to 2·71 ml kg−1 min−1 at 10·7 ng/ml, remaining constant thereafter at concentrations up to 71 ng/ml. 3. The half-disappearance time (T½) from the plasma, after the end of the infusion, averaged 4·3 min for insulin and 25·6 min for proinsulin. 4. The apparent distribution space (DS) was similar for both hormones (83 ml/kg of insulin and 98·9 ml/kg of proinsulin). 5. There was a direct correlation between T½ and DS for both hormones. 6. Although the higher MCR of insulin was reflected in its shorter T½ there was, for each hormone, no relationship between MCR and T½. 7. The biological potency of porcine proinsulin, as judged by its effect on plasma glucose, was approximately 5% of that of insulin. 8. The responses of serum growth hormone and Cortisol were shown to be directly related to the degree of hypoglycaemia induced.


1979 ◽  
Author(s):  
N. Ardaillou ◽  
J. Yvart ◽  
M.J. Larrieu

The in vivo catabolism of purified 131-I-fragment D (Fg D) was studied in comparison with that of 125-I-Fibrinogen (Fg) simultaneously injected in 6 controls and 8 patients with liver cirrhosis. Fg D, M.W. 85,000, was obtained following prolonged (24 hours) plasmin digestion of human Fg. Labelling was performed using the chloramine T method. Linlabelled and labelled Fg and Fg D were characterized hy immunoelectrophoresis and SDS Polyacrylamide gel electrophoresis. Radioactivity was measured in thrombin-clottable (Fg) and TCA-precipitable (Fg D) proteins from plasma. Labelled Fg D present in plasma samples 1, 6 and 12 hours following injection eluted from Sephadex G 2D0 at the same position as native Fg D. A two compartment system was derived from the corresponding plasma disappearance curves for both Fg and Fg D in controls and patients. In controls, the first component of Fg D disappearance curve represented 54.1±13.4% of the total clearance with T 1/2 of 2.5±0.9 hours. The T 1/2 of the second component was 3.9±1.0 hours, Fg D disappeared more rapidly from plasma than Fg, and the ratio of Fg D to Fg was 0.11-0,02. In patients with liver cirrhosis, there was a significant (p<0.005) increase of T 1/2 of the second component (13.6±2.6 hours), whereas the in vivo survival of Fg was normal (4 cases) or decreased (2 cases). These results suggest that the liver interfers with the metabolic clearance rate of Fg D.


2009 ◽  
Vol 23 (9) ◽  
pp. 1445-1454 ◽  
Author(s):  
Kumaran Sundaram ◽  
Joseph Senn ◽  
Sambandam Yuvaraj ◽  
D. Sudhaker Rao ◽  
Sakamuri V. Reddy

Abstract Receptor activator for nuclear factor-κB ligand (RANKL), a critical osteoclastogenic factor expressed in marrow stromal/preosteoblast cells is up-regulated in Paget’s disease of bone (PDB). We previously demonstrated that heat-shock factor-2 (HSF-2) is a downstream target of fibroblast growth factor-2 (FGF-2) signaling to induce RANKL expression in bone marrow stromal/preosteoblast cells. In this study, we identified a 2.5-fold increase in serum FGF-2 levels in patients (n = 8) with PDB compared with normal subjects (n = 10). We showed that HSF-2 co-immunoprecipitates with heat-shock protein-27 (HSP-27) and that FGF-2 stimulation significantly increased phospho-HSP-27 levels in marrow stromal cells. Confocal microscopy revealed HSF-2 colocalization with HSP-27 in unstimulated cells and HSF-2 nuclear translocation upon FGF-2 stimulation. We further show that FGF-2 stimulation significantly increased the levels of phosphorylated signal transducers and activators of the transcription (p-STAT-1) in these cells. Western blot analysis confirmed that small interfering RNA suppression of STAT-1 significantly decreased (3.2-fold) RANKL expression and promoter activity in FGF-2-stimulated cells. Chromatin immunoprecipitation assay revealed STAT-1 binding to a putative motif located far upstream (−8 kb) in the hRANKL gene promoter region. These results suggest STAT-1 is a downstream effector of FGF-2 signaling and that elevated levels of FGF-2 stimulates RANKL expression in PDB.


Life Sciences ◽  
1983 ◽  
Vol 33 (26) ◽  
pp. 2599-2608 ◽  
Author(s):  
Chao-Lin Lu ◽  
John S.D. Chan ◽  
André De Léan ◽  
Andrew Chen ◽  
Nabil G. Seidah ◽  
...  

1969 ◽  
Vol 26 (7) ◽  
pp. 1789-1799 ◽  
Author(s):  
Edward M. Donaldson ◽  
Ulf H. M. Fagerlund

Gonadectomized female sockeye salmon (Oncorhynchus nerka) were injected intramuscularly with cortisol, estradiol, estradiol cypionate, or peanut oil for 8 weeks. The metabolic clearance rate of cortisol was determined by the single injection technique and calculated from the formula for a two pool system. The cortisol secretion rate was determined from the metabolic clearance rate and the plasma cortisol concentration.The volume of distribution of cortisol in the inner compartment (V1) and the outer compartment (V2), the metabolic clearance rate (MCR), the resting secretion rate (S), and the resting plasma cortisol concentration were all significantly higher in the estradiol-injected group than in the peanut oil-injected control group, and the plasma cortisol concentration at the end of the experiment was lower. V1, MCR, and S were also significantly higher in the estradiol cypionate-injected group. There were no significant differences between the cortisol-injected group and the peanut oil-injected control group or in the biological half life of cortisol between any groups.There were no significant changes in the red colour of the flesh or in body weight during the experiment. However, the cortisol-injected group did show the largest weight loss.


1990 ◽  
Vol 89 (2) ◽  
pp. 181-184 ◽  
Author(s):  
Roman Muff ◽  
Maximilian A. Dambacher ◽  
Alain Perrenoud ◽  
Christa Simon ◽  
Jan A. Fischer

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