| 1. |
- Sjögren, Klara, 1970, et al.
(författare)
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Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice.
- 1999
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424. ; 96:12, s. 7088-92
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Tidskriftsartikel (refereegranskat)abstract
- The body growth of animals is regulated by growth hormone and IGF-I. The classical theory of this regulation is that most IGF-I in the blood originates in the liver and that body growth is controlled by the concentration of IGF-I in the blood. We have abolished IGF-I production in the livers of mice by using the Cre/loxP recombination system. These mice demonstrated complete inactivation of the IGF-I gene in the hepatocytes. Although the liver accounts for less than 5% of body mass, the concentration of IGF-I in the serum was reduced by 75%. This finding confirms that the liver is the principal source of IGF-I in the blood. However, the reduction in serum IGF-I concentration had no discernible effect on postnatal body growth. We conclude that postnatal body growth is preserved despite complete absence of IGF-I production by the hepatocytes.
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| 2. |
- Bentham, J, et al.
(författare)
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A double-staining technique for detection of growth hormone and insulin-like growth factor-I binding to rat tibial epiphyseal chondrocytes.
- 1993
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Ingår i: The Journal of endocrinology. - 0022-0795. ; 137:3, s. 361-7
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Tidskriftsartikel (refereegranskat)abstract
- In the present study a double-staining technique was developed to investigate simultaneous GH and insulin-like growth factor-I (IGF-I) binding to chondrocytes in a monolayer cell culture. Rat tibial epiphyseal chondrocytes were isolated by enzymatic digestion and cultured in monolayer. GH and IGF-I were labelled with biotin. The affinity of the biotin-labelled ligands was compared with unlabelled ligands in a radioreceptor assay. To study the distribution of GH and IGF-I binding in the monolayer, chondrocytes were incubated with biotinylated ligands with or without an excess of unlabelled ligands, followed by incubation with Vectastain ABC complex, which was then reacted with diaminobenzidine (DAB). Double staining was accomplished by carrying out the first reaction with DAB in the presence of nickel ammonium sulphate to give a black precipitate, followed by incubation with the second ligand, then ABC complex and finally DAB in the absence of nickel ammonium sulphate to give a brown stain. The presence of type-II collagen was demonstrated by immunohistochemistry and used as a marker for differentiated chondrocytes. Biotin-labelled GH and biotin-labelled IGF-I exhibited dose-dependent displacements of 125I-labelled GH and 125I-labelled IGF-I respectively from the chondrocytes in a radioreceptor assay. The displacement curves were identical to those of unlabelled ligands indicating that the affinity was unaltered. Binding of biotinylated GH to cells was seen throughout the culture in regions where there was little or no type-II collagen staining. IGF-I binding was predominantly localized to cells at high density; areas which also showed a high degree of staining for type-II collagen.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 3. |
- Bohlooly-Yeganeh, Mohammad, 1966, et al.
(författare)
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Enhanced spontaneous locomotor activity in bovine GH transgenic mice involves peripheral mechanisms
- 2001
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Ingår i: Endocrinology. ; 142:10, s. 4560-4567
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Tidskriftsartikel (refereegranskat)abstract
- Clinical and experimental studies indicate a role for GH in mechanisms related to anhedonia/hedonia, psychic energy, and reward. Recently we showed that transgenic mice with general overexpression of bovine GH display increased spontaneous locomotor activity. In the present study, we investigated whether this behavioral change is owing to a direct action of GH in the central nervous system or to peripheral GH actions. A transgenic construct, containing the glial fibrillary acidic protein promoter directing specific expression of bovine GH to the central nervous system, was designed. The central nervous system-specific expression of bovine GH in the glial fibrillary acidic protein-bovine GH transgenic mice was confirmed, but no effect on spontaneous locomotor activity was observed. Serum bovine GH levels were increased in glial fibrillary acidic protein-bovine GH transgenic mice but clearly lower than in transgenic mice with general overexpression of bovine GH. In contrast to the transgenic mice with general overexpression of bovine GH, glial fibrillary acidic protein-bovine GH mice did not display any difference in serum IGF-I levels. The levels of free T(3) and the conversion of the free T(4) to free T(3) were only increased in transgenic mice with general overexpression of bovine GH, but serum corticosterone levels were similarly increased in both transgenic models. These results suggest that free T(3) and/or IGF-I, affecting dopamine and serotonin systems in the central nervous system, may mediate the enhanced locomotor activity observed in transgenic mice with general overexpression of bovine GH.
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| 4. |
- Bohlooly-Yeganeh, Mohammad, 1966, et al.
(författare)
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Growth hormone overexpression in the central nervous system results in hyperphagia-induced obesity associated with insulin resistance and dyslipidemia.
- 2005
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Ingår i: Diabetes. - 0012-1797 .- 1939-327X. ; 54:1, s. 51-62
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Tidskriftsartikel (refereegranskat)abstract
- It is well known that peripherally administered growth hormone (GH) results in decreased body fat mass. However, GH-deficient patients increase their food intake when substituted with GH, suggesting that GH also has an appetite stimulating effect. Transgenic mice with an overexpression of bovine GH in the central nervous system (CNS) were created to investigate the role of GH in CNS. This study shows that overexpression of GH in the CNS differentiates the effect of GH on body fat mass from that on appetite. The transgenic mice were not GH-deficient but were obese and showed increased food intake as well as increased hypothalamic expression of agouti-related protein and neuropeptide Y. GH also had an acute effect on food intake following intracerebroventricular injection of C57BL/6 mice. The transgenic mice were severely hyperinsulinemic and showed a marked hyperplasia of the islets of Langerhans. In addition, the transgenic mice displayed alterations in serum lipid and lipoprotein levels and hepatic gene expression. In conclusion, GH overexpression in the CNS results in hyperphagia-induced obesity indicating a dual effect of GH with a central stimulation of appetite and a peripheral lipolytic effect.
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| 5. |
- Bollano, Entela, 1970, et al.
(författare)
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Impairment of cardiac function and bioenergetics in adult transgenic mice overexpressing the bovine growth hormone gene.
- 2000
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Ingår i: Endocrinology. - 0013-7227. ; 141:6, s. 2229-35
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular abnormalities represent the major cause of death in patients with acromegaly. We evaluated cardiac structure, function, and energy status in adult transgenic mice overexpressing bovine GH (bGH) gene. Female transgenic mice expressing bGH gene (n = 11) 8 months old and aged matched controls (n = 11) were used. They were studied with two-dimensional guided M-mode and Doppler echocardiography. The animals (n = 6) for each group were examined with 31P magnetic resonance spectroscopy to determine the cardiac energy status. Transgenic mice had a significantly higher body weight (BW), 53.2+/-2.4 vs. 34.6+/-3.7 g (P < 0.0001) and hypertrophy of left ventricle (LV) compared with normal controls: LV mass/BW 5.6+/-1.6 vs. 2.7+/-0.2 mg/g, P < 0.01. Several indexes of systolic function were depressed in transgenic animals compared with controls mice such as shortening fraction 25+/-3.0% vs. 39.9+/-3.1%; ejection fraction, 57+/-9 vs. 77+/-5; mean velocity of circumferential shortening, 4.5+/-0.8 vs. 7.0+/-1.1 circ/sec, p < 0.01. Creatine phosphate-to-ATP ratio was significantly lower in bGH overexpressing mice (1.3+/-0.08 vs. 2.1+/-0.23 in controls, P < 0.05). Ultrastructural examination of the hearts from transgenic mice revealed substantial changes of mitochondria. This study provides new insight into possible mechanisms behind the deteriorating effects of long exposure to high level of GH on heart function.
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| 6. |
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| 7. |
- Brittberg, Mats, 1953, et al.
(författare)
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Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation.
- 1994
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Ingår i: The New England journal of medicine. - 0028-4793. ; 331:14, s. 889-95
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Full-thickness defects of articular cartilage in the knee have a poor capacity for repair. They may progress to osteoarthritis and require total knee replacement. We performed autologous chondrocyte transplantation in 23 people with deep cartilage defects in the knee. METHODS. The patients ranged in age from 14 to 48 years and had full-thickness cartilage defects that ranged in size from 1.6 to 6.5 cm2. Healthy chondrocytes obtained from an uninvolved area of the injured knee during arthroscopy were isolated and cultured in the laboratory for 14 to 21 days. The cultured chondrocytes were then injected into the area of the defect. The defect was covered with a sutured periosteal flap taken from the proximal medial tibia. Evaluation included clinical examination according to explicit criteria and arthroscopic examination with a biopsy of the transplantation site. RESULTS. Patients were followed for 16 to 66 months (mean, 39). Initially, the transplants eliminated knee locking and reduced pain and swelling in all patients. After three months, arthroscopy showed that the transplants were level with the surrounding tissue and spongy when probed, with visible borders. A second arthroscopic examination showed that in many instances the transplants had the same macroscopic appearance as they had earlier but were firmer when probed and similar in appearance to the surrounding cartilage. Two years after transplantation, 14 of the 16 patients with femoral condylar transplants had good-to-excellent results. Two patients required a second operation because of severe central wear in the transplants, with locking and pain. A mean of 36 months after transplantation, the results were excellent or good in two of the seven patients with patellar transplants, fair in three, and poor in two; two patients required a second operation because of severe chondromalacia. Biopsies showed that 11 of the 15 femoral transplants and 1 of the 7 patellar transplants had the appearance of hyaline cartilage. CONCLUSION. Cultured autologous chondrocytes can be used to repair deep cartilage defects in the femorotibial articular surface of the knee joint.
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| 8. |
- Carlsson, Björn, 1958, et al.
(författare)
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Expression and physiological significance of growth hormone receptors and growth hormone binding proteins in rat and man.
- 1991
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Ingår i: Acta paediatrica Scandinavica. Supplement. - 0300-8843. ; 379
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Tidskriftsartikel (refereegranskat)abstract
- The molecular structure of the GH receptor has recently been characterized and the receptor identified as a member of a new receptor superfamily that includes the prolactin receptor and several cytokine receptors. No obvious signal transducing domain has been identified on any of these related receptors. One possible signalling mechanism involves receptor interaction with other membrane-associated proteins that function as mediators of signal transduction. Whether such a mechanism is involved in signal transduction of the GH receptor is not known. Another common feature of these receptors is the presence of soluble forms such as the GHBP. The functions of these proteins in the circulation and at the level of the target cell remain to be resolved.
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| 9. |
- Fu, Michael, 1963, et al.
(författare)
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Myocardial hypertrophy in transgenic mice overexpressing the bovine growth hormone (bGH) gene.
- 2000
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Ingår i: Journal of internal medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 247:5, s. 546-52
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The main purpose of the present study was to characterize cardiac muscle hypertrophy using both qualitative and quantitative microscopy in mice overexpressing the bovine growth hormone. RESULTS: Measurements of 30 fibres from each group revealed that fibre diameter in transgenic hearts was significantly larger than in control hearts. There was a significant decrease in interfibrillar space in transgenic hearts as compared with control hearts. The enlarged transgenic hearts displayed unchanged organelles such as normal myofibrils and mitochondria in a normal pattern, suggesting balanced growth. Myelin structures were occasionally observed between normal myofibrils. Moreover, myocardial beta-adrenergic receptors and muscarinic receptors in the hearts of transgenic mice overproducing GH were studied to see whether they are involved in the hypertrophic process. It was shown that the density of muscarinic receptors had decreased and the super-high affinity of muscarinic receptors was lost, without any significant changes in either the density or the affinity of beta-adrenergic receptors, as compared with controls. CONCLUSIONS: These results demonstrate that a GH excess was able to induce significant myocardial hypertrophy and that there was a downregulation of muscarinic receptors.
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| 10. |
- Isaksson, Olle, 1943, et al.
(författare)
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GH and bone--experimental and clinical studies.
- 2000
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Ingår i: Endocrine journal. - 0918-8959. ; 47 Suppl
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Tidskriftsartikel (refereegranskat)abstract
- GH increases bone formation both via a direct interaction with GH receptors on osteoblasts and via locally produced IGF-I (autocrine/paracrine action). GH deficiency results in decreased bone mass in both man and laboratory animals and treatment of GHD patients with GH for several months results in increased bone mass. GH treatment also increases bone mass and the total mechanical strength of bones in rats with normal GH secretion. Because of the short duration of GH-treatment in man with normal GH secretion, the effect on bone mass is still inconclusive. The action of GH on bone metabolism in GHD adults is twofold: It stimulates both bone resorption and bone formation. A "Biphasic model" of GH action in bone remodeling has recently been proposed [1] (Fig. 2). According to this model the net effect of GH first results in a loss of bone mass, followed by a net increase in bone mass. The transition point occurs when bone formation proceeds at a higher rate than bone resorption. Taking all clinical studies of GH-treatment of GHD adults into account, it appears that the "transition point" occurs after approximately six months and that a net increase in bone mass usually is seen after 12-18 months of GH treatment. It should be emphasized that the "Biphasic model" of GH action in bone remodeling is proposed based on findings in GHD adults, and it remains to be clarified whether or not it is valid for subjects with normal GH secretion.
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