EFFECT OF DOSE AND ADMINISTRATION PERIOD OF GROWTH HORMONE ON LONGITUDINAL BONE GROWTH IN THE HYPOPHYSECTOMIZED RAT

1973 ◽  
Vol 74 (1) ◽  
pp. 1-23 ◽  
Author(s):  
K.-G. Thorngren ◽  
L. I. Hansson ◽  
K. Menander-Sellman ◽  
A. Stenström
Keyword(s):  
Growth Hormone ◽  
Growth Plate ◽  
Dose Response ◽  
Bone Growth ◽  
Growth Parameters ◽  
Growth Stimulation ◽  
The Body ◽  
Sprague Dawley ◽  
Longitudinal Bone Growth ◽  
Response Determination

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.

EFFECT OF THYROXINE AND GROWTH HORMONE ON LONGITUDINAL BONE GROWTH IN THE HYPOPHYSECTOMIZED RAT

1973 ◽  
Vol 74 (1) ◽  
pp. 24-40 ◽  
Author(s):  
K.-G. Thorngren ◽  
L. I. Hansson
Keyword(s):  
Growth Hormone ◽  
Growth Plate ◽  
Bone Growth ◽  
The Body ◽  
Heart Weight ◽  
Optimum Dose ◽  
Sprague Dawley ◽  
Promoting Effect ◽  
Longitudinal Bone Growth ◽  
Stimulation Of

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.

BIOASSAY OF GROWTH HORMONE

1974 ◽  
Vol 75 (4) ◽  
pp. 653-668 ◽  
Author(s):  
K.-G. Thorngren ◽  
L. I. Hansson
Keyword(s):  
Growth Hormone ◽  
Bone Growth ◽  
Control Period ◽  
Growth Parameter ◽  
The Body ◽  
Sprague Dawley ◽  
Longitudinal Bone Growth ◽  
Sprague Dawley Rats ◽  
Hypophysectomized Rats ◽  
Operative Control

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.

EFFECT OF WITHDRAWAL OF GROWTH HORMONE ADMINISTRATION ON LONGITUDINAL BONE GROWTH IN THE HYPOPHYSECTOMIZED RAT

1974 ◽  
Vol 75 (1) ◽  
pp. 11-23 ◽  
Author(s):  
K.-G. Thorngren ◽  
L. I. Hansson
Keyword(s):  
Growth Hormone ◽  
Growth Plate ◽  
Bone Growth ◽  
Proximal Tibia ◽  
Bovine Growth Hormone ◽  
Sprague Dawley ◽  
Cell Production ◽  
Longitudinal Bone Growth ◽  
Hormone Administration ◽  
Sprague Dawley Rats

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.

BIOASSAY OF GROWTH HORMONE

1974 ◽  
Vol 75 (4) ◽  
pp. 669-682 ◽  
Author(s):  
K.-G. Thorngren ◽  
L. I. Hansson
Keyword(s):  
Growth Hormone ◽  
Bone Growth ◽  
Control Period ◽  
Growth Stimulation ◽  
Sprague Dawley ◽  
Hormone Administration ◽  
Sprague Dawley Rats ◽  
Hypophysectomized Rats ◽  
Operative Control ◽  
Sensitivity Specificity

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.

CONDITIONS INFLUENCING THE DOSE-RESPONSE EFFECT OF GROWTH HORMONE ON LONGITUDINAL BONE GROWTH IN THE HYPOPHYSECTOMIZED RAT

1975 ◽  
Vol 80 (2) ◽  
pp. 284-296 ◽  
Author(s):  
K.-G. Thorngren ◽  
L. I. Hansson
Keyword(s):  
Growth Hormone ◽  
Dose Response ◽  
Growth Response ◽  
Bone Growth ◽  
Practical Importance ◽  
Longitudinal Bone Growth ◽  
Response Effect ◽  
Dependent Growth ◽  
Dose Response Effect ◽  
Dose Dependent

ABSTRACT Various factors that might influence the dose-response effect of growth hormone on the longitudinal bone growth were investigated with tetracycline as intravital marker of the bone growth in hypophysectomized rats. These are of practical importance for the bioassay of growth hormone. The growth response was found to be almost the same for subcutaneous and intraperitoneal injection, whereas the intravenous route resulted in significantly lower growth response. The administration of growth hormone in various volumes subcutaneously did not significantly influence the dose-dependent growth response. Freezing of the dissolved growth hormone or addition of NaOH to the solution had no significant effect on the growth response. Cortisone acetate 0.5 mg/kg given at hypophysectomy increased the post-operative survival somewhat, without having any post-operative depressing influence on the growth hormone-induced longitudinal bone growth. The present investigation showed that in standardized conditions the dose-dependent growth response is constant.

scholarly journals Effect of Clodronate Administration on the Structure of the Primary Spongiosa derived from the Growth Cartilage in Growing Rats

2019 ◽  
Vol 2 (1) ◽  
pp. 27-35
Author(s):  
Helena Gil-Peña ◽  
Ángela Fernández-Iglesias ◽  
Rocío Fuente ◽  
Laura Alonso-Duran ◽  
Fernando Santos ◽  
...  
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Blue Staining ◽  
Growth Spurt ◽  
Alcian Blue Staining ◽  
Tartrate Resistant Acid Phosphatase ◽  
Sprague Dawley ◽  
Proliferating Cells ◽  
Longitudinal Bone Growth ◽  
Growth Plate Cartilage

The effect of the inhibition of the resorptive activity of osteoclastic cells induced by bisphosphonate treatment on the primary spongiosa derived from the calcified cartilage of the growth plate was studied. We focused our attention on the primary spongiosa because it is the initial trabecular bone network that is first formed directly from growth plate mineralized cartilaginous septa. The study was carried out in male Sprague-Dawley rats at the age of 35 days, coinciding with the prepubertal growth spurt, a stage characterized by the highest values for growth rate. Animals were classified in two groups, controls and rats treated with clodronate 60 mg/kg/day. Body weights and tibial length were measured. The rate of longitudinal bone growth was obtained by calceine labelling and the height of the growth plate cartilage was measured. Histochemical analysis included Alcian blue staining, detection of tartrate-resistant acid phosphatise (TRAP) activity, von Kossa staining for mineralization and immunolocalization of proliferating cells. Microscopic examination revealed numerous tartrate-resistant acid phosphatase (TRAP)-positive cells at the chondroosseous junction and associated with subchondral trabeculae in control rat and that clodronate treatment induced a marked reduction of these cells. Clodronate-treated rats presented thinner subchondral trabeculae that were more irregularly oriented and decreased cell proliferation in the primary spongiosa. Results obtained showed that changes induced by clodronate treatment has little effect on the activity of the growth plate cartilage, without a significant effect on longitudinal bone growth even at doses much higher than those used in clinical practice.

EFFECT OF ADMINISTRATION FREQUENCY OF GROWTH HORMONE ON LONGITUDINAL BONE GROWTH IN THE HYPOPHYSECTOMIZED RAT

1977 ◽  
Vol 84 (3) ◽  
pp. 497-511 ◽  
Author(s):  
K.-G. Thorngren ◽  
L. I. Hansson
Keyword(s):  
Growth Hormone ◽  
Total Dose ◽  
Bone Growth ◽  
Growth Stimulation ◽  
Total Daily Dose ◽  
Daily Growth ◽  
Longitudinal Bone Growth ◽  
Hormone Injection ◽  
Injection Frequency ◽  
Hypophysectomized Rats

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.

scholarly journals A Mixture of Humulus japonicus Increases Longitudinal Bone Growth Rate in Sprague Dawley Rats

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2625
Author(s):  
Ok-Kyung Kim ◽  
Jeong moon Yun ◽  
Minhee Lee ◽  
Soo-Jeung Park ◽  
Dakyung Kim ◽  
...  
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Tail Length ◽  
Janus Kinase ◽  
Sprague Dawley ◽  
Plate Height ◽  
Longitudinal Bone Growth ◽  
Sd Rats ◽  
Humulus Japonicus ◽  
Igfbp 3

The aim of this study was to investigate the effects of administration of a mixture of Humulus japonicus (MH) on longitudinal bone growth in normal Sprague Dawley (SD) rats. We measured the femur and tibia length, growth plate area, proliferation of chondrocytes, and expression of insulin-like growth factor-1 (IGF-I) and IGF binding protein-3 (IGFBP-3), and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) phosphorylation after dietary administration of MH in SD rats for four weeks. The nose–tail length gain and length of femur and tibia increased significantly in the group that received MH for a period of four weeks. We performed H&E staining and Bromodeoxyuridine/5-Bromo-2′-Deoxyuridine (BrdU) staining to examine the effect of dietary administration of MH on the growth plate and the proliferation of chondrocytes and found that MH stimulated the proliferation of chondrocytes and contributed to increased growth plate height during the process of longitudinal bone growth. In addition, serum levels of IGF-1 and IGFBP-3 and expression of IGF-1 and IGFBP-3 mRNAs in the liver and bone were increased, and phosphorylation of JAK2/STAT5 in the liver was increased in the MH groups. Based on these results, we suggest that the effect of MH on longitudinal bone growth is mediated by increased JAK2/STAT5-induced IGF-1 production.

scholarly journals Evidence supporting dual, IGF-I-independent and IGF-I-dependent, roles for GH in promoting longitudinal bone growth

2004 ◽  
Vol 180 (2) ◽  
pp. 247-255 ◽  
Author(s):  
J Wang ◽  
J Zhou ◽  
CM Cheng ◽  
JJ Kopchick ◽  
CA Bondy
Keyword(s):  
Growth Hormone ◽  
Growth Plate ◽  
Bone Growth ◽  
Long Bone ◽  
Null Mouse ◽  
Chondrocyte Proliferation ◽  
Chondrocyte Hypertrophy ◽  
Longitudinal Bone Growth ◽  
Germinal Zone ◽  
Igf I

The possibility that growth hormone (GH) has effects on long bone growth independent of insulin-like growth factor-I (IGF-I) has long been debated. If this is true, then long bone growth should be more profoundly affected by the absence of GH (since both GH and GH-stimulated IGF-I effects are absent) than by the absence of IGF-I alone (since GH is still present and actually elevated). To test this hypothesis, we compared long bone growth in mice with targeted deletions of Igf1 vs growth hormone receptor (Ghr). Tibial linear growth rate was reduced by approximately 35% in Igf1 null mice and by about 65% in Ghr null mice between postnatal days 20 and 40, a time of peak GH effect during normal longitudinal growth. The Igf1 null mouse growth plate demonstrated significant enlargement of the germinal zone; chondrocyte proliferation and numbers were normal but chondrocyte hypertrophy was significantly reduced. In contrast, the Ghr null mouse germinal zone was hypoplastic, chondrocyte proliferation and numbers were significantly reduced, and chondrocyte hypertrophy was also reduced. We have previously demonstrated that IGF-II is highly expressed in growth plate germinal and proliferative zones, so we considered the possibility that GH-stimulated IGF-II production might promote germinal zone expansion and maintain normal proliferation in the Igf1 null mouse growth plate. Supporting this view, IGF-II mRNA was increased in the Igf1 null mouse and decreased in the Ghr null mouse growth plate.Thus, in the complete absence of IGF-I but in the presence of elevated GH in the Igf1 null mouse, reduction in chondrocyte hypertrophy appears to be the major defect in longitudinal bone growth. In the complete absence of a GH effect in the Ghr null mouse, however, both chondrocyte generation and hypertrophy are compromised, leading to a compound deficit in long bone growth. These observations support dual roles for GH in promoting longitudinal bone growth: an IGF-I-independent role in growth plate chondrocyte generation and an IGF-I-dependent role in promoting chondrocyte hypertrophy. The question of whether GH has direct effects on chondrocyte generation is still not settled, however, since it now appears that IGF-II may medicate some of these effects on the growth plate.

Sign in / Sign up

Export Citation Format

Share Document