Metabolic clearance rate and plasma half life of alpha-human atrial natriuretic peptide in man

The disappearance and metabolic clearance rate (MCR) of alpha human atrial natriuretic peptide (alpha h-ANP) has been studied in normal man by radioimmunoassay of the atrial peptide in plasma and plasma extracts. After an intravenous (iv) bolus injection of 100 micrograms alpha h-ANP, levels of immunoreactive alpha h-ANP (IR-alpha hANP) in unextracted plasma fell rapidly and exponentially during the first 10 min (t1/2 = 2.5 min), after which levels declined more slowly to reach basal values 30 min after injection. Venous plasma extracts, purified by Sep Pak cartridges, were used to calculate the MCR of IR-alpha hANP under steady state conditions of constant iv infusion (200 micrograms over 60 min) in healthy volunteers. Calculated MCR from venous samples was 2.4 L/min and volume of distribution 10.7 L. After cessation of infusions, the disappearance rate (rapid phase) of IR-alpha hANP was 3.1 min. These studies show that alpha h-ANP is rapidly metabolized at rates similar to other vasoactive hormones such as angiotensin II and vasopressin.     

Metabolic clearance rate of adrenocorticotropin in the rat.

The metabolic clearance rate (MCR) of adrenocorticotropin (ACTH) was estimated after the intravenous infusion of graded rates of the hormone (40-2560 muU/min per 100 g body weight) in rats pretreated with chlorpromazine, morphine, and Nembutal, a preparation which proved effective in blocking endogenous ACTH release. The hormone was infused over a period of 45 min, at which time the plasma ACTH concentration had reached a steady state. A specific and sensitive bioassay, based on the corticosterone production of dispersed adrenal cells, was used to measure the plasma ACTH concentration. With increasing infusion rates of ACTH, a threefold decrease in the MCR of ACTH was observed. Previous studies of our group have shown that the MCR of corticosterone increases as a function of the infusion rate of the steroid. It appears, therefore, that the metabolism of these two hormonal links of the hypothalamo-pituitary-adrenocortical axis vary in opposite fashions as a function of the secretion rate of the hormone.     

Metabolic clearance rate of rat prolactin in preweanling rat pups

The metabolic clearance rate (MCR) of immunoreactive rat prolactin (rPRL) was determined in urethane-anaesthetized 14 to 16-day-old rat pups using the constant infusion to equilibrium method. Two different doses of rPRL were used, 329 and 472 ng/min each at a volume of 0.0025 ml/min for 30 min. The MCR was 0.216 ml/min following infusion of 329 ng PRL/min dose and 0.337 ml/min following infusion of the 472-ng/min dose. When calculated on the basis of metabolic body weight the MCR of rPRL in rat pups was comparable to that of adult rats.     

Bispecific-Ab-based immunoassay of thyroid-stimulating hormone

 A bispecific F(ab′)₂ fragment recognizing both human thyroid-stimulating hormone (TSH) and alkaline phosphatase (AP) was prepared by disulfide bond exchange between F(ab′)₂ fragments of IgG1 mAb against TSH and AP. AP was polymerized by glutaraldehyde, and a sandwich enzyme-linked immunosorbent assay for TSH was developed by using the AP polymers and the bispecific F(ab′)₂ fragment. In this assay, the preparation of covalently linked AP-mAb conjugates was not needed, and the interaction of mAb with non-specific proteins was greatly reduced. The sensitivity for TSH increased in proportion to the degree of AP polymerization, and the lower detection limit obtained with the AP trimer was 0.5 μU/ml. The use of the bispecific F(ab′)₂ fragment allows us to use monomers and polymers of AP and thereby regulates the sensitivity of the assay. Accepted: 14 October 1997     

Testosterone metabolic clearance rate and production rate in the male infant rhesus monkey

The male infant rhesus monkey (Macaca mulatta) undergoes a period of testicular activation similar to that seen in the human infant. Plasma testosterone (T) concentrations rise after birth, reaching levels of about 500 ng/dl at 1-3 mo of age and then fall to approximately 50 ng/dl at 60 mo. The plasma T metabolic clearance rates (MCRT) and production rates (PRT) were measured in two rhesus infants at 1 and 6 mo of age to determine the mechanism of the observed increase in plasma T. While there was little change in the MCRT between 1 and 6 mo, PRT was much higher at 1 mo than at 60 mo of age. These observations are consistent with the hypothesis that the increased plasma testosterone levels in infant rhesus monkeys reflect an increased production of testosterone rather than an altered metabolic disposition of the hormone.     

The production of active human thyroid-stimulating hormone from alpha and beta mRNAs in Xenopus laevis oocytes

Active human thyroid-stimulating hormone (hTSH) was produced by Xenopus laevis oocytes following injection of an mRNA mixture of hTSH beta and alpha subunits synthesized by T3 RNA polymerase. Some of the hTSH molecules were secreted into the medium, while others remained in the cells. The active molecules consisted of alpha and beta subunits and were in highly glycosylated form. The Xenopus laevis oocyte-produced hTSH stimulated the rat thyroid cell line FRTL-5 to produce and secrete the cyclic AMP as does authentic hTSH.     

Neonatal thyroid-stimulating hormone level and perchlorate in drinking water

BACKGROUND: The effect of perchlorate in drinking water on neonatal blood thyroid-stimulating hormone (thyrotropin; TSH) levels was examined for Las Vegas and Reno, Nevada. METHODS: The neonatal blood TSH levels in Las Vegas (with up to 15 microg/L (ppb) perchlorate in drinking water) and in Reno (with no perchlorate detected in the drinking water) from December 1998 to October 1999 were analyzed and compared. The study samples were from newborns in their first month of life (excluding the first day of life) with birth weights of 2, 500-4,500 g. A multivariate analysis of logarithmically transformed TSH levels was used to compare the mean TSH levels between Las Vegas and Reno newborns, with age and sex being controlled as potential confounders. RESULTS: This study of neonatal TSH levels in the first month of life found no effect from living in the areas with environmental perchlorate exposures of 相似文献   

Effect of pentagastrin on adrenocorticotropin hormone and thyroid-stimulating hormone release in normal subjects

The possible role of gastrin on TSH, ACTH and cortisol secretion was evaluated by intravenous administration of pentagastrin, the carboxyl-terminal tetrapeptide of gastrin (0.5 microgram/kg b.w.) into 12 healthy subjects. Pentagastrin produced a significant rise in plasma ACTH and cortisol levels but did not alter TSH basal release. These preliminary results suggest that gastrin can influence basal activity of ACTH-cortisol axis. However, further investigation is required to determine its physiological role and mechanisms of action.     

Fluorophotometric enzyme immunoassay of thyroid-stimulating hormone.

A method for enzyme immunoassay of thyroid-stimulating hormone (TSH) is described, TSH was conjugated with horseradish peroxidase according to periodate oxidation method. Separation of the bound and free was obtained by double-antibody solid-phase technique using Sepharose 4B-anti-rabbit immunogiobulin G (IgG)-geat IgG. The fluorescence reaction using tyramine and hydrogen peroxide as substrates was used for the determination of enzyme activity in order to increase the sensitivity of enzyme immunoassay. The standard curve for serum TSH was satisfactory to recognize TSH concentrations as 0.06 μU/tube. TSH values obtained by this method correlated well with those obtained by radioimmunoassay (r, 0.96). The coefficients of variation were 1.8 to 5.3% (within assay) and 5.1 to 10.5% (between assay). The method is about equal to radioimmunoassay with respect to sensitivity. Since it requires minimal equipment and is less expensive than radioimmunoassay, it is possible to perform routine assays even in laboratories with limited facilities.     

Metabolic clearance and production rates of oestradiol and progesterone during pubertal and postpubertal development in gilts

The crossbred gilts studied were aged 80 days (prepubertal), 180 days (prepubertal or postpubertal) and 260 days (postpubertal or pregnant). Estimates of metabolic clearance rate (MCR) of oestradiol and progesterone were consistently less (21 and 27%) in plasma than in blood, and these differences were not influenced by age of gilt. The MCR (1/day per kg body weight) for oestradiol and progesterone in plasma was greater (P less than 0.05) for 80-day-old prepubertal gilts than for older gilts. The MCR values of oestradiol and progesterone were similar in 180-day-old and 260-day-old gilts independent of reproductive state. Production rate (PR) of oestradiol and progesterone increased with age (80-180 days), and age and reproductive state differences were much more pronounced for PR of progesterone than of oestradiol. These results support the hypothesis that a reduction in the MCR and an increase in PR of oestradiol and progesterone in the gilt are associated with the process of pubertal development, and changes in gonadal steroid concentrations appear not to alter the MCR of oestradiol and progesterone.     

Metabolic clearance rate and half-time disappearance rate of human N-terminal and adrenocorticotropin of pro-opiomelanocortin in the rat: a comparative study

In metabolic clearance rate (MCR) and plasma half-time disappearance rate (t 1/2) of human N-terminal (1-76) and adrenocorticotropin(hACTH 1-39) of pro-opiomelanocortin were compared after intravenous bolus injection of both peptides simultaneously into rat. The level of immunoreactive (IR) hNT and IR-ACTH in plasma and urine samples were measured by specific and homologous radioimmunoassays (RIAs). The MCR and hNT and hACTH were 3.01 +/- 0.20 ml/min (M +/- S.D., N = 4) and 2.04 +/- 0.06 ml/min, respectively (p less than 0.05), The curve for the disappearance rate of IR-hNT was triphasic (rapid t 1/2 = 0.96 +/- 0.39 min, intermediate t 1/2 = 6.7 +/- 2.25 min, and slow t 1/2 = 74 +/- 15.8 min), while that of IR-ACTH was biphasic (rapid t 1/2 = 3.3 +/- 0.68 min, and slow t 1/2 = 41.5 +/- 3.03 min) as analyzed by the non-linear least-squares methods. Statistically significant difference (p less than 0.01) was found between IR-hNT and IR-hACTH in the rapid t 1/2 and in the slow t 1/2. Subsequent analysis of pooled plasma sample (30 min post-injection) by molecular sieve chromatography on Sephadex G-50 superfine column revealed that the majority of IR-hNT (90-95%) and IR-ACTH (60-70%) are co-chromatographed with [125I]iodo hNT and [125I]iodo ACTH respectively. Similarly, gel filtration of pooled urine sample (120 min post-injection) on Sephadex G-50 superfine revealed that 80-90% of IR-hNT and less than 50% of IR-ACTH co-eluted with [125I]iodo hNT and [125I]iodo ACTH, respectively. Smaller molecular forms of IR-hNT and IR-ACTH were definitely apparent in the urine sample. In conclusion, hNT has a larger MCR and a longer half-time disappearance rate (t 1/2) than IR-hACTH in rat plasma and it appears that hNT is more resistant to degradation by plasma and by kidney than hACTH.