Δ5-androstenediol: kinetics of metabolism and binding to plasma proteins in normal post-menopausal women

1982 ◽  
Vol 99 (2) ◽  
pp. 309-313 ◽  
Author(s):  
Charles E. Bird ◽  
John Tremblay ◽  
Valerie Masters ◽  
Albert F. Clark

Abstract. Δ5-androstenediol (Δ5-diol) while having minimal androgenic activity is of potential biological importance because it binds to oestrogen receptors and has oestrogenic activity in several systems. We have examined Δ5-diol metabolism in post-menopausal women utilizing the constant infusion technique. The metabolic clearance rate for 11 subjects was 763 ± 50 1/24 h or 467 ± 30 1/m2/24 h. Labelled dehydroepiandrosterone, testosterone, Δ4-androstenedione, androsterone and the sulphates of Δ5-diol, dehydroepiandrosterone and androsterone were found in the plasma. Of all the kinetic parameters only the conversion ratio for dehydroepiandrosterone sulphate was different from that for young women (4.958 ± 0.410 for young women vs 3.084 ± 0.220 for older women). The plasma concentration of Δ5-diol was 0.94 ± 0.19 ng/ml and the calculated blood production rate was 686 ± 80 μg/24 h. The per cent free plasma Δ5-diol was 4.6 ± 0.25. These values are slightly lower but not significantly different from those previously reported for normal young women.

Maturitas ◽  
1984 ◽  
Vol 5 (4) ◽  
pp. 251-257 ◽  
Author(s):  
M. Jasonni ◽  
C. Bulletti ◽  
F. Franceschetti ◽  
M. Bonavia ◽  
P. Ciotti ◽  
...  

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.


1985 ◽  
Vol 69 (3) ◽  
pp. 265-271 ◽  
Author(s):  
Peter L. Selby ◽  
Munro Peacock ◽  
Stuart A. Barkworth ◽  
Wendy B. Brown ◽  
Geoffrey A. Taylor

1. The early effects of sex steroid therapy were assessed in 28 normal post-menopausal women, 18 treated with ethinyloestradiol and 10 with norethisterone. 2. There was a reduction in the fasting urinary excretion of both calcium and hydroxyproline with both treatments, indicating reduced bone resorption. This was apparent after 1 week of therapy but became more marked after 3 weeks. 3. These changes were not accompanied by any changes in plasma levels of calcitonin or parathyroid hormone. 4. Patients receiving ethinyloestradiol showed a marked increase in plasma 1,25-dihydroxyvitamin D (1,25-(OH)2D) concentration but this was explicable entirely in terms of increased plasma levels of vitamin D binding protein. There was no change in the free plasma level of 1,25(OH)2D. Patients treated with norethisterone showed no increase in plasma concentrations of 1,25(OH)2D. 5. We conclude that both ethinyloestradiol and norethisterone have a rapid and similar effect in reducing bone resorption. This is not mediated via the plasma levels of the calcium regulating hormones.


1978 ◽  
Vol 235 (6) ◽  
pp. E591 ◽  
Author(s):  
R E Weitzman ◽  
D A Fisher

The plasma clearance rates (PCR) of arginine vasopressin (AVP), and iodinated AVP (125I-AVP) were determined after pulse injection in conscious water-loaded dogs. Both the PCR and the apparent initial volume of distribution were significantly greater for AVP than for the biologically inactive iodinated AVP 37.4 +/- 4.8 ml/kg per min vs. 6.7 +/- 0.8 ml/kg per min (P less than 0.001) and 12.7 +/- 0.9% body wt vs. 7.1 +/- 0.4% body wt (P less than 0.001). AVP clearance was then determined by the constant-infusion technique at doses that produced equilibrium AVP concentrations within and above the physiological range. AVP-PCR was 37.4 +/- 7.1 ml/kg per min at 34 microU/kg per min, which was comparable to that after pulse injection (P less than 0.9). AVP clearance fell progressively, and urine osmolality progressively increased with increasing AVP infusion rates to plateau values at 136 microU/kg per min; a strong negative correlation was observed between mean AVP-PCR and urine osmolality (r = -0.993). The data suggest a relationship between the biological activity of AVP and its clearance. It is proposed that plasma membrane receptors may mediate a portion of the metabolic clearance of AVP.


1984 ◽  
Vol 103 (2) ◽  
pp. 205-211 ◽  
Author(s):  
N. Hazon ◽  
I. W. Henderson

ABSTRACT Peripheral plasma concentrations, metabolic clearance rates (MCR) and blood production rates (BPR) of 1α-hydroxycorticosterone (1-OH-B) were determined in female dogfish (Scyliorhinus canicula) under varying environmental conditions. The constant-infusion technique, using high specific activity tritiated 1-OH-B, was applied to measure the MCR, and BPR were derived from the product of plasma concentration and MCR at equilibrium. Urea plasma clearances and apparent BPR were assessed in a similar manner. Fish were adapted stepwise to 140, 120, 90, 80, 70, 60 and 50% normal sea water (about 1000 mosmol/l). In all cases 1-OH-B was the major corticosteroid, cortisol and corticosterone were sought but never detected. In environments of reduced osmolarity, plasma osmolarity, sodium, chloride and urea concentrations all declined, alongside increases in plasma concentrations, MCR and BPR of 1-OH-B. In fish held in environments at concentrations greater than normal sea water, plasma osmolarity, sodium, chloride and urea concentrations all increased. Plasma clearance of urea increased in fish held in environments more dilute than sea water, while it decreased in the more hyperosmotic waters. It is tentatively concluded that homeostasis of plasma composition, with particular respect to urea, is in part regulated by 1-OH-B in the dogfish. J. Endocr. (1984) 103, 205–211


1982 ◽  
Vol 100 (4) ◽  
pp. 606-612 ◽  
Author(s):  
F. Elsaesser ◽  
K. Stickney ◽  
G. Foxcroft

Abstract. A continuous infusion technique of either [3H]oestradiol-17β (E2) or unlabelled E2 was used to investigate suggested differences in the metabolic clearance rate of oestradiol-17β (MCR-E2) in immature and peripubertal female pigs. Using the isotope infusion technique, the following values were obtained: 60 day old gilts; MCR-E2 = 2133 ± 274 ([unk] ± sem) ml/min, MCR-E2/kg BW = 116 ± 14.5 ml/min kg, and conversion ratio (CR) of E2 to oestrone (E1) = 31.6 ± 3.7%. The respective values for 160 day old gilts were: MCR-E2 = 3027 ± 340, MCR-E2/kg BW = 48.5 ± 4.82, and CR = 15.9 ± 2.12. Except for a significant difference in the weight related MCR-E2 data for the 60 day old group, similar values were found following infusion of unlabelled E2. The percentage of radioactivity extractable with ether from plasma was 22.6 ± 3.0% and 27.2 ± 2.0%. Fifty-seven and 66% of total radioactivity infused was recovered in the urine within 12 h in 60 and 160 day old gilts, respectively. There was no difference in the percentage binding of E2 to plasma proteins as determined by equilibrium dialysis (80%). It is concluded that in addition to an activation of ovarian steroidogenesis during puberty, a gradual maturational decrease in the MCR-E2/kg BW might play a role in raising plasma E2 concentrations and thus in constituting an effective oestrogen feedback signal, which results in the first pre-ovulatory LH-surge.


1976 ◽  
Vol 40 (3) ◽  
pp. 312-319 ◽  
Author(s):  
B. Issekutz ◽  
W. A. Shaw ◽  
A. C. Issekutz

The effect of treadmill run on the turnover rates of glucose ([2-3H]glucose) and lactate ([U-14C]lactate), on the rates of oxidation (ROX) of lactate, and its conversion to glucose (L LEADS TO G) were measured with the primed constant-infusion technique. Comparable lactate turnover rates were obtained at rest by infusing epinephrine, or Na-L(+)-lactate with or without norepinephrine. With increasing lactate levels (L) the rate of disappearance (RdL), ROX, and L leads to G increase in a linear manner. At the same lactate level, RdL, ROX, and L leads to G are significantly higher in the running dog. Exercise increased the metabolic clearance rate of lactate threefold. At rest ROX and L leads to G represented about 50% and 18–19% of RdL, respectively. The corresponding values in the running dogs were 55% and 25%, respectively. At rest about 9% of the hepatic glucose output arose from lactate while during exercise this varied from 7 to 26% depending on RdL. It is concluded that a) the working muscle produces and utilizes lactate at the same time, and b) “in vivo” the major factor which controls both ROX and gluconeogenesis is the substrate supply.


1992 ◽  
Vol 262 (6) ◽  
pp. E906-E910 ◽  
Author(s):  
L. Wada ◽  
R. Daly ◽  
D. Kern ◽  
B. Halloran

To determine whether postmaturational aging influences the kinetics of 1,25-dihydroxyvitamin D [1,25(OH)2D] metabolism in the rat, we measured the metabolic clearance (MCR) and production (PR) rates of 1,25(OH)2D in 6-, 12-, 18-, and 24-mo-old Fischer 344 rats using the constant infusion method. Plasma calcium, phosphorus, and parathyroid hormone (PTH), urinary calcium and phosphorus, and glomerular filtration rate (GFR) were also measured. MCR and PR increased 57 and 91%, respectively (when expressed per rat), and 32 and 39%, respectively (when expressed per kg body wt), between 6 and 24 mo of age, with the greatest increase occurring between 18 and 24 mo. The plasma concentration of 1,25(OH)2D remained unchanged. Plasma PTH, when compared with 6-mo-old animals, was significantly elevated at 18 mo (147%) and even higher at 24 mo (240%). GFR (51Cr-labeled EDTA clearance) remained unchanged through 18 mo but tended to be reduced at 24 mo. Plasma phosphorus tended to decrease with age, whereas plasma calcium, urinary calcium, and urinary phosphorus did not differ among the age groups. These data indicate that both clearance and production of 1,25(OH)2D increase with postmaturational aging in the rat. They also suggest that the early age-related rise in plasma PTH is neither a consequence of low plasma calcium nor of renal insufficiency.


1975 ◽  
Vol 80 (2) ◽  
pp. 275-283 ◽  
Author(s):  
Salvatore Raiti ◽  
Robert M. Blizzard ◽  
Robert Penny ◽  
Claude J. Migeon

ABSTRACT The urinary excretion method and the constant infusion technique were used to estimate hFSH production rates (PR) in three normal men (aged 25–40 years). Both studies were also done in a hypophysectomized nine year old boy. The PR of hFSH in the urinary excretion studies ranged from 20.0 to 45.7 IU/24 h, whereas the constant infusion studies yielded PR's of 68.7 to 107.8 IU/24 h. Possible reasons for the discrepancy of the results obtained by the two methods are discussed. In the hypophysectomized patient, the metabolic clearance rate (MCR) of infused hFSH was much lower (4.3 ml/min) than in the normal adults (7.8 to 12.0 ml/min) and was not affected by the dose of hFSH given.


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