BIOASSAY OF GROWTH HORMONE

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 (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 (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.


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.


1973 ◽  
Vol 74 (1) ◽  
pp. 24-40 ◽  
Author(s):  
K.-G. Thorngren ◽  
L. I. Hansson

ABSTRACT The effect of L-thyroxine and bovine growth hormone (NIH-GH-B16) on the growth in length from 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. Completeness of the hypophysectomy was determined microscopically. Daily sc injections of 5, 10, 20 or 40 μg/kg L-thyroxine alone, or in combination with 25 or 100 μg NIH-GH-B16, were given for 20 days, starting 15 days after hypophysectomy which was performed when the rats were 60 days of age. Thyroxine alone resulted in stimulation of the longitudinal bone growth with an optimum effect at 10–20 μg/kg. Further increase of the thyroxine dose did not increase the bone growth. Thyroxine given in association with growth hormone had a higher growing promoting effect than thyroxine or growth hormone alone. The growth stimulation of the two hormones was also significantly higher than the expected additive effect, indicating a potentiating synergism. When thyroxine and growth hormone were given in combination, the longitudinal bone growth reached an optimum for almost the same dose (20 μg/kg) of thyroxine as when it was given alone. At this optimum dose of thyroxine, the dose of growth hormone determined the longitudinal bone growth. The width of the growth plate was not influenced by thyroxine administration. The body weight decreased somewhat when thyroxine was given alone, and the combination with growth hormone seemed to compensate for this weight loss. The heart weight was found to increase with increasing doses of thyroxine both when given alone and in association with growth hormone.


1982 ◽  
Vol 99 (1) ◽  
pp. 24-30 ◽  
Author(s):  
John-Olov Jansson ◽  
Kerstin Albertsson-Wikland ◽  
Staffan Edén ◽  
Karl-Göran Thorngren ◽  
Olle Isaksson

Abstract. The effect of frequency of growth hormone (GH) administration on longitudinal bone growth and body weight was studied in hypophysectomized rats which were given replacement therapy with corticosteroids, thyroxine and GH with start of therapy on the day of surgery. Longitudinal bone growth, as determined by the tetracycline method, was measured during the last 5 days of the 9 day long period with replacement therapy. The daily replacement dose of GH (bGH-17:NIH) was 200 μg and was given on 1, 2, 4 or 8 occasions. Longitudinal bone growth was enhanced in the groups of animals receiving the hormone on two or more occasions per day. The most pronounced response was seen with an administration frequency of four times per day. Changes in body weight during the injection period showed similar changes. The results of the present study show that the administration frequency of growth hormone is important for the growth rate in hypophysectomized rats which have been given replacement therapy. The findings suggest that the secretory pattern of GH is an important factor for optimum growth.


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.


1986 ◽  
Vol 111 (1) ◽  
pp. 3-9
Author(s):  
Karl-Göran Thorngren ◽  
Bengt Hallengren

Abstract. Biological growth activity (bioassayable GH) was determined in blood from healthy individuals and from patients with acromegaly using the rate of longitudinal bone growth in hypophysectomized rats with tetracycline as intravital marker. Also radioimmunoassayable GH and somatomedin A activity were determined. In pooled plasma or serum from normal subjects no bioassayable growth activity was demonstrated. In the clinically active acromegalic patients as a group as well as in one individual patient there was a significant (P <0.05) bioassayable growth activity in serum as compared to serum from normal subjects. The bioassay determination of GH in plasma/serum from normal subjects and acromegalic patients was hampered by the toxicity and the problems connected with the administration of large volumes.


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

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.


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