BIOASSAY OF GROWTH HORMONE

1974 ◽  
Vol 75 (4) ◽  
pp. 669-682 ◽  
Author(s):  
K.-G. Thorngren ◽  
L. I. Hansson

ABSTRACT The growth stimulating effect of growth hormone was determined with tetracycline as intravital marker of the longitudinal bone growth of proximal tibia in female Sprague-Dawley rats hypophysectomized at 60 days of age. After a post-operative control period of 15 days growth hormone (NIH-GH-B16) was given daily for 5 or 10 days followed by a 10 day period after its withdrawal. L-thyroxine was given in association with the growth hormone administration to potentiate the growth stimulation. A linear log dose-response relation was found for the two administration models with a high precision. The thyroxine-treatment increased the sensitivity of the bioassay. An administration period of 5 days was found sufficient for the bioassay of growth hormone in thyroxine-treated hypophysectomized rats. Compared with the earlier bioassay methods for growth hormone, the present bioassay is more favourable when all the factors, such as precision, sensitivity, specificity, and administration period are considered.

1974 ◽  
Vol 75 (4) ◽  
pp. 653-668 ◽  
Author(s):  
K.-G. Thorngren ◽  
L. I. Hansson

ABSTRACT The longitudinal bone growth of proximal tibia determined by tetracycline in hypophysectomized rats was used for the bioassay of growth hormone. Female Sprague-Dawley rats were hypophysectomized at 60 days of age and after a post-operative control period of 15 days growth hormone (NIH-GH-B16) was given daily for 5 or 10 days followed by a 10 day period after its withdrawal. A linear log dose-response relation was found for the two administration models with high precision. In the present investigation the longitudinal bone growth was more favourable as a growth parameter for the bioassay of growth hormone than the body weight and the width of the proximal tibial growth plate.


1974 ◽  
Vol 75 (1) ◽  
pp. 11-23 ◽  
Author(s):  
K.-G. Thorngren ◽  
L. I. Hansson

ABSTRACT Bovine growth hormone was given daily for 10 days to female Sprague-Dawley rats hypophysectomized at the age of 60 days, beginning 15 days post-operatively. Longitudinal bone growth, studied in the proximal tibia, was reactivated and continued at an accelerating rate during the period of hormone administration and for a further 5 days after its withdrawal, but then ceased. The effect of withdrawal of growth hormone on the width of the growth plate of proximal tibia, the size of its degenerative cells, and the weight of body and heart was also studied. The cell production in the proximal growth plate of tibia was calculated. The changes in longitudinal bone growth were found to be due mainly to changes in cell production in the growth plate.


1977 ◽  
Vol 84 (3) ◽  
pp. 497-511 ◽  
Author(s):  
K.-G. Thorngren ◽  
L. I. Hansson

ABSTRACT The effect of the administration frequency of growth hormone on longitudinal bone growth was investigated with tetracycline as intravital marker of the bone growth of the proximal tibia in hypophysectomized rats. The total dose of growth hormone (NIH-GH-B16) and the administration period were the same in all compared experiments. It was possible to achieve an optimum growth response for a certain total dose of growth hormone by increasing the injection frequency. The period of hormone administration was 10 or 5 days followed by a 10 days withdrawal period. When the growth hormone was administered alone or in association with L-thyroxine for 10 days, the optimum injection frequency for growth hormone was found to be 1 inj./day in hypophysectomized rats and 2 inj./day in thyroxine-treated hypophysectomized rats. When the administration period was 5 days for growth hormone given in association with L-thyroxine, the growth stimulation induced by one daily growth hormone injection was the same as that induced by two or four daily injections of the same total dose. An increase in the administration frequency for a total daily dose of thyroxine from 1 to 2 inj./day did not increase the longitudinal bone growth either when thyroxine was given alone or in association with growth hormone.


1982 ◽  
Vol 114 (2) ◽  
pp. 261-265 ◽  
Author(s):  
JOHN-OLOV JANSSON ◽  
KERSTIN ALBERTSSON-WIKLAND ◽  
STAFFAN EDÉN ◽  
KARL-GÖRAN THORNGREN ◽  
OLLE ISAKSSON

1973 ◽  
Vol 74 (1) ◽  
pp. 1-23 ◽  
Author(s):  
K.-G. Thorngren ◽  
L. I. Hansson ◽  
K. Menander-Sellman ◽  
A. Stenström

ABSTRACT The effect of bovine growth hormone (NIH-GH-B15) on the growth in length of the proximal growth plate of the tibia in hypophysectomized female Sprague-Dawley rats was studied by the tetracycline method. The width of the growth plate was also determined and the weight of the body and heart was registered. The completeness of the hypophysectomy was determined microscopically. The daily sc injection of 25 μg NIH-GH-B15 for 10, 20 or 30 days resulted in an increasing growth in length with increasing administration period. When various doses (5, 25, 100 or 400 μg) NIH-GH-B15 were administered daily for 20 days, the growth in length increased with the dose. A single injection of 45 mg/kg cortisone acetate given at hypophysectomy depressed the growth stimulation of growth hormone. The age at hypophysectomy also influenced the growth hormone-induced growth stimulation. Animals hypophysectomized at 40 days of age had a higher growth in length for the same doses and administration periods of growth hormone than those operated at 60 days of age. The width of the growth plate of the proximal tibia and the weight of the body and heart responded in a similar manner as the longitudinal bone growth to various doses and administration periods of growth hormone, but the changes were less obvious. The dose-response relation after the administration of various doses of growth hormone for 20 days was tested for different growth parameters by the index of precision (λ). Of the growth parameters in this investigation, the accumulated growth in length in animals hypophysectomized at 60 days of age without cortisone at operation was found to be most suitable for dose-response determination of growth hormone. The intention is to develop a bio-assay for growth hormone.


1977 ◽  
Vol 84 (3) ◽  
pp. 485-496 ◽  
Author(s):  
K.-G. Thorngren ◽  
L. I. Hansson

ABSTRACT The stimulating effect of different pituitary hormones on longitudinal bone growth was determined with tetracycline as intravital marker in hypophysectomized rats. Growth hormone was found to be the most effective growth stimulating pituitary hormone. At considerably higher doses, thyrotrophic hormone (TSH) and prolactin also showed growth stimulating activity. TSH exerts its effect via the production of thyroxine, whereas the growth stimulation by prolactin seems to be a direct effect of this hormone, similar to the effect of growth hormone. The LH, FSH, ACTH, MSH, vasopressin and oxytocin preparations did not stimulate longitudinal bone growth.


1989 ◽  
Vol 258 (2) ◽  
pp. 547-552 ◽  
Author(s):  
S Betley ◽  
K G M M Alberti ◽  
L Agius

The interactions of insulin, growth hormone (somatotropin) and tri-iodothyronine (T3) in the long-term (24 h) regulation of fatty acid and carbohydrate metabolism were studied in hepatocyte primary cultures isolated from normal or hypophysectomized Sprague-Dawley rats. Hepatocytes from hypophysectomized rats had similar rates of palmitate metabolism, but lower rates of ketogenesis, than hepatocytes from normal rats. They also had a lower endogenous triacylglycerol content and lower activities of NADP-linked dehydrogenases than did cells from normal rats. The inhibitions of ketogenesis and gluconeogenesis by insulin were more marked in hepatocytes from hypophysectomized than from normal rats. Insulin caused a 7-10-fold increase in cellular glycogen in hepatocytes from hypophysectomized rats, compared with a 2-3-fold increase in cells from normal rats, and it increased cellular triacylglycerol by 65% in cells from hypophysectomized rats, compared with 11% in cells from normal rats. In hepatocytes from hypophysectomized rats, growth hormone and T3 increased ketogenesis both separately and in combination (12% and 23% respectively; P less than 0.05), whereas in hepatocytes from normal rats only the combination of growth hormone and T3 caused a significant increase in ketogenesis. In cells from hypophysectomized rats, T3 and growth hormone had different effects on carbohydrate metabolism: T3, but not growth hormone, potentiated the anti-gluconeogenic and glycogenic effects of insulin. It is concluded that hypophysectomy increases the responsiveness of hepatocytes to insulin, growth hormone and T3, and that growth hormone and T3 regulate fatty acid and carbohydrate metabolism by different mechanisms.


2011 ◽  
Vol 300 (5) ◽  
pp. H1781-H1787 ◽  
Author(s):  
Sachin S. Kandlikar ◽  
Gregory D. Fink

Excess sympathetic nervous system activity (SNA) is linked to human essential and experimental hypertension. To test whether sympathetic activation is associated with a model of deoxycorticosterone acetate (DOCA)-salt hypertension featuring two kidneys and a moderate elevation of blood pressure, we measured whole body norepinephrine (NE) spillover as an index of global SNA. Studies were conducted in chronically catheterized male Sprague-Dawley rats drinking water containing 1% NaCl and 0.2% KCl. After a 7-day surgical recovery and a 3-day control period, a DOCA pellet (50 mg/kg) was implanted subcutaneously in one group of rats (DOCA), while the other group underwent sham implantation (Sham). NE spillover was measured on control day 2 and days 7 and 14 after DOCA administration or sham implantation. During the control period, mean arterial pressure (MAP) was similar in Sham and DOCA rats. MAP was significantly increased in the DOCA group compared with the Sham group after DOCA administration ( day 14: Sham = 109 ± 5.3, DOCA = 128 ± 3.6 mmHg). However, plasma NE concentration, clearance, and spillover were not different in the two groups at any time. To determine whether selective sympathetic activation to the kidneys contributes to hypertension development, additional studies were performed in renal denervated (RDX) and sham-denervated (Sham-DX) rats. MAP, measured by radiotelemetry, was similar in both groups during the control and DOCA treatment periods. In conclusion, global SNA is not increased during the development of mild DOCA-salt hypertension, and fully intact renal nerves are not essential for hypertension development in this model.


2002 ◽  
Vol 291 (3) ◽  
pp. 722-726 ◽  
Author(s):  
Stephen E. Borst ◽  
Harold G. Snellen ◽  
Henry Ross ◽  
Philip J. Scarpace ◽  
Yong-Woon Kim

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Casandra M Monzon ◽  
Jeffrey Garvin

About 50% of the Na reabsorbed in thick ascending limbs (TALs) traverses the paracellular pathway. The ionic selectivity of this route is regulated by claudins in the tight junctions. TALs express claudin-19 which has been reported to regulate TAL Na permeability. We showed that nitric oxide (NO) decreases Na/Cl permeability ratio (PNa/PCl) in TALs by increasing the absolute permeabilities of both ions though PCl increased more. However, whether NO affects paracellular permeability via claudin-19 is unknown. We hypothesize that NO regulates the paracellular permselectivity in TALs through this claudin. To test this we perfused TALs from Sprague Dawley rats and measured dilution potentials (a measure of permselectivity) with and without exogenously-added or endogenously-produced NO in the presence or absence of an antibody against an extracellular domain of claudin-19 or Tamm-Horsfall protein (control). Dilution potentials were generated by reducing bath NaCl from 141 to 32 mM. For the NO donor spermine NONOate (SPM): during the control period, the dilution potential was -9.3 ± 1.8 mV. After SPM (200 μM), it was -6.7 ± 1.6 mV (n = 6; p < 0.003). In the presence of the claudin-19 antibody, SPM had no significant effect on dilution potentials (claudin-19 antibody alone: -12.7 ± 2.1 mV vs claudin-19 antibody + SPM: -12.9 ± 2.4 mV; n = 6). The claudin-19 antibody alone had no effect on dilution potentials. In the presence of the Tamm-Horsfall protein, the effect of SPM was still present (Tamm-Horsfall protein antibody alone: -9.7 ± 1.0 mV; Tamm-Horsfall protein antibody + SPM: -6.3 ± 1.1 mV, p<0.006, n = 6). For experiments with endogenously-produced NO, L-arginine the substrate for NO synthase was added. During the control period, the dilution potential was -11.0 ± 1.1 mV. After L-arginine (500 μM) treatment, they were -9.0 ± 1.2 mV (n = 9; p < 0.05). In the presence of the claudin-19 antibody, L-arginine had no significant effect on dilution potentials (claudin-19 antibody alone: -10.1 ± 0.9 mV vs claudin-19 antibody + L-arginine: -10.1 ± 1.0 mV; n = 9). In the presence of the Tamm-Horsfall protein, the effect of L-arginine was still present. We conclude that the actions of NO on the paracellular permselectivity in thick ascending limbs are at least in part mediated by claudin-19.


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