Biomedical subjects

T T Andreassen

Publications and source records attributed to T T Andreassen.

At least 37 records · Page 2Linked to original sources

PubMed1999

Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats.

Ipamorelin is a new and potent synthetic pentapeptide which has distinct and specific growth hormone (GH)-releasing properties. With the objective of investigating the effects on longitudinal bone growth rate (LGR), body weight (BW), and GH release, ipamorelin in different doses (0, 18, 90 and 450 microg/day) was injected s.c. three times daily for 15 days to adult female rats. After intravital tetracycline labelling on days 0, 6, and 13, LGR was determined by measuring the distance between the respective fluorescent bands in the proximal tibia metaphysis. Ipamorelin dose-dependently increased LGR from 42 microm/day in the vehicle group to 44, 50, and 52 microm/day in the treatment groups (P<0.0001). There was also a pronounced and dose-dependent effect on BW gain. The treatment did not affect total IGF-I levels, IGFBPs, or serum markers of bone formation and resorption. The number of tartrate-resistant acid phosphatase-positive multinuclear cells in the metaphysis of the tibia did not change significantly with treatment. The responsiveness of the pituitary to a provocative i.v. dose of ipamorelin or GHRH showed that the plasma GH response was marginally reduced (P<0.03) after ipamorelin, but unchanged after GHRH. The pituitary GH content was unchanged by ipamorelin treatment. Whether ipamorelin or other GH secretagogues may have a place in the treatment of children with growth retardation requires demonstration in future clinical studies.

Animals↗

PubMed1999

Effect of experimental diabetes and growth hormone administration on the strength of colonic anastomoses in rats.

The influence of growth hormone (GH; 2 mg/kg/day) administration on the mechanical breaking strength of colonic anastomoses in diabetic rats has been investigated on the day of operation (suture binding capacity) and after 4 and 7 days of healing. In diabetic rats, the suture binding capacity was decreased by 26% in both ultimate load and relative failure energy. After 4 days of healing, no difference was observed between control and diabetic animals. After 7 days, relative failure energy in the diabetic animals was reduced by 33%. GH administration to diabetic animals did not alter strength during the first week of healing. We found an increased circumference (33%) and defatted dry weight (22%) of the colon in diabetic rats. In conclusion, diabetes impairs the suture-binding capacity of the colon in rats, while there is only little influence on healing in the following week. GH administration could not influence the strength of colonic anastomoses in diabetic animals.

Anastomosis, Surgical↗

PubMed1999

Growth hormone increases cortical and cancellous bone mass in young growing rats with glucocorticoid-induced osteopenia.

The effects of growth hormone (GH) on linear growth, bone formation, and bone mass have been examined in glucocorticoid (GC)-injected young growing rats. Two-month-old female Wistar rats were injected for 90 days with 1, 3, 6, or 9 mg of methylprednisolone alone or in combination with 5 mg of GH. Bone mass and bone formation parameters were examined in the femoral cortical bone and in cortical bone and cancellous bone of the lumbar vertebra. GC administration dose dependently decreased growth, longitudinal growth of the vertebra, as well as the modeling drift of the cortical bone of the vertebral body and femoral diaphysis. In the vertebral cancellous bone, GC also decreased the mineralizing surface and inhibited the growth-related increase in cancellous bone volume. GH increased growth, longitudinal growth of the vertebra, as well as the modeling drift of the vertebral body and the femoral diaphysis, resulting in an increased cortical bone mass. GH also increased cancellous bone volume and the mineralizing surface of the vertebral body. In GC-injected animals, GH normalized and further increased growth, longitudinal growth, and the modeling drift of both the femoral diaphysis and the vertebral body, resulting in an increased cortical bone mass at both locations. GH also increased cancellous bone volume of the vertebral body in GC-injected animals, but GH did not, however, reverse the decreased mineralizing surface of cancellous bone induced by GC injections. In conclusion, GC administration to growing rats retards normal growth, longitudinal growth, and cortical bone modeling drift. It also decreases the cancellous bone mineralizing surface and inhibits the normal age-related increase in cancellous bone volume of the vertebral body. In the growing rat skeleton, GH can counteract these GC-induced side effects, except for the GC-induced decrease in the mineralizing surface of cancellous bone of the vertebral body, which remained unaffected by GH administration.

Animals↗

PubMed1999

Intermittent parathyroid hormone (1-34) treatment increases callus formation and mechanical strength of healing rat fractures.

The influence of intermittent parathyroid hormone (PTH(1-34)) administration on callus formation and mechanical strength of tibial fractures in rats was investigated after 20 and 40 days of healing. A dose of 60 microg of PTH(1-34)/kg/day and 200 microg of PTH(1-34)/kg/day, respectively, was administered during the entire periods of healing, and control animals with fractures were given vehicle. The dose of 200 microg of PTH(1-34)/kg/day increased the ultimate load and the external callus volume of the fractures by 75% and 99%, respectively, after 20 days of healing and by 175% and 72%, respectively, after 40 days of healing. The dose of 60 microg of PTH(1-34)/kg/day did not influence either ultimate load or external callus volume of the fractures after 20 days of healing, but the ultimate load was increased by 132% and the external callus volume was increased by 42% after 40 days of healing. During the healing period, the callus bone mineral content (BMC) increased in all groups. After 40 days of healing, the callus BMC was increased by 108% in the 200 microg of PTH(1-34)/kg/day group and by 76% in the 60 microg of PTH(1-34)/kg/day group. Both doses of PTH(1-34) steadily augmented the contralateral intact tibia BMC (20 days and 40 days: 60 microg of PTH (1-34)/kg/day 9% and 19%, respectively; 200 microg of PTH (1-34)/kg/day 12% and 27%, respectively) and bone mineral density (20 days and 40 days: 60 microg of PTH(1-34)/kg/day 11% and 12%, respectively; 200 microg of PTH(1-34)/kg/day 11% and 15%, respectively).

Animals↗

PubMed1998

Bisphosphonate maintains parathyroid hormone (1-34)-induced cortical bone mass and mechanical strength in old rats.

This study was designed to determine the fate of new parathyroid hormone (PTH)-induced cortical bone after withdrawal of PTH treatment, and to evaluate whether subsequent treatment with a bisphosphonate would influence this. Six groups of 21-month-old rats were used: a baseline group killed at the beginning of the experiment, three groups injected with human PTH (1-34) (62 mug/kg) daily for 8 weeks (day 1-56), then one group was killed and the other two groups were injected for another 8 weeks (day 57-112) with either saline or bisphosphonate (risedronate 5 mug/kg twice a week). Two control groups were injected with vehicle for the first 8 weeks, then one group was killed and the other group injected with saline the next 8 weeks. All animals were labeled with tetracycline and calcein on day 35 and day 49 of the experiment, respectively. PTH increased periosteal (35%) and in particular endosteal mineralizing surfaces (188%), mineral appositional rates, and bone formation rates at the femur diaphysis, leading to an increase in cortical cross-sectional area of 31%. Withdrawal of PTH induced a fast and pronounced endosteal bone resorption whereas risedronate prevented this resorption. No differences were seen in apparent density of dry defatted bone and ash among the groups. PTH increased the mechanical strength of the femur diaphysis; ultimate load increased by 64% and ultimate stress by 25%. A pronounced decrease in mechanical strength and competence was found after withdrawal of PTH: ultimate load decreased by 31% and ultimate stress by 21%. Risedronate, however, prevented this decrease in mechanical strength and competence in these 2-year-old rats.

Animals↗

PubMed1998

Administration of a glucocorticoid with depot effect counteracts the stimulating effect of growth hormone on cancellous and cortical bone of the vertebral body in rats.

Our earlier studies have shown that growth hormone administration could not counteract decreased longitudinal growth and cortical osteopenia of rat femora induced by a glucocorticoid with depot effect. In the present study we examined the effects of glucocorticoid on vertebral bone as well as the effect of growth hormone on vertebral bone in young growing animals also given glucocorticoid injections. Five groups of female rats (3 1/2 months) were treated for 80 days as follows: (1) saline, (2) prednisolone: Delcortol 5 mg/kg/day, (3) growth hormone: 5 mg/kg/day, (4) prednisolone and growth hormone, (5) food restriction. Vertebral dimensions, histomorphometry, and mechanical competence of the vertebral bone were examined. Growth hormone administration increased body weight, vertebral height, cross-sectional area, and volume. The compressive strength of the L4-corpus cylinder was also increased due to an increase in cancellous bone volume and an increase in the area of cortical bone surrounding the vertebral body. Glucocorticoid administration decreased body weight, height, and volume of the intact vertebrae. Histological examination revealed that glucocorticoid administration decreased the area of cortical bone surrounding the vertebral body but had no effect on the cancellous bone volume. No effect of glucocorticoid administration on mechanical strength of the L4 corpus cylinder could be detected. In agreement with our findings in cortical bone, we found no effect of growth hormone on vertebral bone when given to animals also receiving glucocorticoid injections. Growth hormone increases longitudinal growth, cortical and cancellous bone mass, and mechanical competence of the vertebral body. Glucocorticoid administration decreases longitudinal growth of the vertebrae and cortical bone mass without affecting cancellous bone mass of the vertebral body. Despite this, administration of a glucocorticoid with depot effect totally inhibits the effect of growth hormone on vertebral bone.

Aging↗

PubMed1998

Withdrawal of parathyroid hormone treatment causes rapid resorption of newly formed vertebral cancellous and endocortical bone in old rats.

When administered intermittently, parathyroid hormone (PTH) is a strong anabolic agent, increasing both bone mass and bone mechanical strength and competence. This study evaluates the fate of PTH-induced bone in vertebral bodies after withdrawal of PTH treatment in normal old rats. Sixty-seven 21-month-old male rats were treated with 62 microg/kg/day PTH(1-34) for 8 weeks, followed by saline or bisphosphonate (risedronate, 5 microg/kg twice a week) for another 8 weeks. The rats were scanned by dual-energy X-ray absorptiometry at intervals. The bone mineral content (BMC) of L2-5 increased by 33% during the PTH treatment. The BMC started decreasing shortly after withdrawal of PTH and continued to decline during the 8 weeks after withdrawal of PTH. Risedronate, however, prevented this decrease in BMC. All rats were labeled with tetracycline and calcein 3 weeks and 1 week before the cessation of PTH therapy. In the cancellous bone, PTH increased the mineralized surface: 32.9% +/- 2.8% (mean +/- standard error of the mean) vs. controls 12.0% +/- 1.5%, the mineral appositional rate (0.65 +/- 0.02 to 0.88 +/- 0.06 microm/day), and the cancellous bone volume (BV/TV: 14.5% +/- 0.7% to 27.5% +/- 1.7%). Withdrawal of PTH induced a fast and pronounced bone resorption, decreasing both the extent of the fluorochrome labels and the cancellous bone volume to control values. Risedronate prevented this resorption. In the cortical bone of the vertebral shell, PTH induced large increases in the endocortical mineralized surface, mineral appositional rate, and cortical area. The endocortical fluorochrome labels were, however, resorbed after withdrawal of PTH. Risedronate maintained both the fluorochrome labels and the cortical area. At the periosteum, the response to PTH was less evident, however, and hardly any labeling was seen at the periosteum facing the vertebral canal either in the controls or in the PTH-treated rats. The compressive strength of the vertebral body specimens increased with PTH treatment whether measured in newtons (317 +/- 23 to 623 +/- 54 N), normalized to cross-sectional area (23.0 +/- 1.4 to 44.7 +/- 2.5 N/mm2), or to ash content per millimeter height (58 +/- 2 to 76 +/- 2 N x mm/mg). Withdrawal of PTH decreased the compressive strength and competence to control values. Risedronate, however, maintained the PTH-induced mechanical strength and competence. The study discloses that even in very old rats withdrawal of PTH treatment causes a rapid and pronounced decline in the bone mass deposited during PTH treatment; treatment with risedronate can, however, maintain the PTH-induced bone properties in the axial skeleton of old rats.

Absorptiometry, Photon↗

PubMed1998

Thermal and mechanical stability of the lens capsule.

PURPOSE: Several procedures in cataract surgery carry the risk of high temperature increases in the capsular bag. The present study was undertaken to determine the shrinkage temperature of the human lens capsule and to investigate the effect of temperature on the mechanical behavior of the lens capsule. METHOD: Thermal-shrinkage characteristics of the lens capsule were determined during gradual heating of circular specimens (2 mm in diameter) prepared from anterior lens capsules from 25 human donors, ranging in age from 20 to 98 years. Uniaxial mechanical testing was carried out at 22 degrees C, 36 degrees C and 61 degrees C on ring-shaped test specimens prepared from anterior lens capsules from 5- to 6-month-old pigs. RESULTS: The mean shrinkage temperature (Ts) for the human lens capsule was 51.5 degrees C (range 49.3-54.3) and the mean shrinkage area in percent of the original area (AST) was 49% (36-66). Ts was significantly associated with the age of the donors and decreased 0.1 degree C per year until age 65 after which Ts was found to increase. AST showed no association with age. The mechanical effect of temperatures below the shrinkage temperature was modest. The capsule became slightly more extensible with increasing temperature. The effect of temperatures above the shrinkage temperature was an increased ultimate strain, a reduced ultimate stiffness and a slightly reduced ultimate stress. CONCLUSION: Thermal stability of the human lens capsule (type IV collagen) seems to be considerably lower than that of fibrous connective tissue (type I collagen). A potential risk of capsular shrinking has to be taken into account when the capsule is exposed to thermal stress during cataract surgery.

Adult↗

PubMed1998

Effect of freezing on lens capsule mechanical behavior.

Postmortem storage of lens capsules by freezing was found to increase capsular thickness slightly (5%). The effect on mechanical properties was minor. Ultimate tensile strength and ultimate stiffness were not changed by freezing. Ultimate strain was slightly increased (2%) and the elastic modulus calculated at 40% strain was decreased (20%). Frozen capsules were found to relax to a slightly lower value than fresh ones (2%). The results show that freezing tends to soften the tissue, possibly due to an increased hydration. In spite of this effect, which has to be kept in mind, postmortem freezing seems to be an acceptable storage method when collecting tissue for biomechanical research.

Animals↗

PubMed1998

Growth hormone and bone.

It is well known that GH is important in the regulation of longitudinal bone growth. Its role in the regulation of bone metabolism in man has not been understood until recently. Several in vivo and in vitro studies have demonstrated that GH is important in the regulation of both bone formation and bone resorption. In Figure 9 a simplified model for the cellular effects of GH in the regulation of bone remodeling is presented (Fig. 9). GH increases bone formation in two ways: via a direct interaction with GHRs on osteoblasts and via an induction of endocrine and autocrine/paracrine IGF-I. It is difficult to say how much of the GH effect is mediated by IGFs and how much is IGF-independent. GH treatment also results in increased bone resorption. It is still unknown whether osteoclasts express functional GHRs, but recent in vitro studies indicate that GH regulates osteoclast formation in bone marrow cultures. Possible modulations of the GH/IGF axis by glucocorticoids and estrogens are also included in Fig. 9. GH deficiency results in a decreased bone mass in both man and experimental animals. Long-term treatment (> 18 months) of GHD patients with GH results in an increased bone mass. GH treatment also increases bone mass and the total mechanical strength of bones in rats with a normal GH secretion. Recent clinical studies demonstrate that GH treatment of patients with normal GH secretion increases biochemical markers for both bone formation and bone resorption. Because of the short duration of GH treatment in man with normal GH secretion, the effect on bone mass is still inconclusive. Interestingly, GH treatment to GHD adults initially results in increased bone resorption with an increased number of bone-remodeling units and more newly produced unmineralized bone, resulting in an apparent low or unchanged bone mass. However, GH treatment for more than 18 months gives increased bone formation and bone mineralization of newly produced bone and a concomitant increase in bone mass as determined with DEXA. Thus, the action of GH on bone metabolism in GHD adults is 2-fold: it stimulates both bone resorption and bone formation. We therefore propose "the biphasic model" of GH action in bone remodeling (Fig. 10). According to this model, GH initially increases bone resorption with a concomitant bone loss that is followed by a phase of increased bone formation. After the moment when bone formation is stimulated more than bone resorption (transition point), bone mass is increased. However, a net gain of bone mass caused by GH may take some time as the initial decrease in bone mass must first be replaced (Fig. 10). When all clinical studies of GH treatment of GHD adults are taken into account, it appears that the "transition point" occurs after approximately 6 months and that a net increase of bone mass will be seen after 12-18 months of GH treatment. It should be emphasized that the biphasic model of GH action in bone remodeling is based on findings in GHD adults. It remains to be clarified whether or not it is valid for subjects with normal GH secretion. A treatment intended to increase the effects of GH/IGF-I axis on bone metabolism might include: 1) GH, 2) IGF, 3) other hormones/factors increasing the local IGF-I production in bone, and 4) GH-releasing factors. Other hormones/growth factors increasing local IGF may be important but are not discussed in this article. IGF-I has been shown to increase bone mass in animal models and biochemical markers in humans. However, no effect on bone mass has yet been presented in humans. Because the financial cost for GH treatment is high it has been suggested that GH-releasing factors might be used to stimulate the GH/IGF-I axis. The advantage of GH-releasing factors over GH is that some of them can be administered orally and that they may induce a more physiological GH secretion. (ABSTRACT TRUNCATED)

Animals↗

PubMed1998

Growth hormone and mild exercise in combination markedly enhance cortical bone formation and strength in old rats.

The effects of a combination of mild exercise and GH injections on bone were studied in old female rats. Biosynthetic human GH, 2.7 mg/kg/day, was injected s.c. for 73 days. Exercised rats ran 8 m/min on a treadmill for 1 h/day. All rats (age 21 months old) were labeled with a tetracycline injection 56 days and a calcein injection 11 days before killing. The GH injections resulted in an 11-fold increase in femoral middiaphyseal bone formation rate and a 12% increase in cross-sectional area compared with the saline-injected group. The mild exercise doubled the mineralizing surface but did not influence the bone formation rate significantly. The combination of GH injections plus exercise, however, resulted in a further increase of 39% in bone formation rate, primarily at the anterolateral aspects, and an increase of 5% in cross-sectional area compared with the group injected with GH only. The femur ultimate breaking load was increased by 37% and the stiffness by 42% in the group injected with GH compared with the saline-injected group. Exercise alone did not influence the femur mechanical properties. The combination of GH injections plus exercise induced a 4% further increase in ultimate breaking load and 7% further increase in stiffness compared with the group injected with GH alone. The GH injections induced a 117% increase in serum insulin-like growth factor I. The GH-insulin-like growth factor I axis stimulates recruitment of osteoblast precursor cells, resulting in increased bone formation at the periosteal surface. GH injections and mild excercise in combination modulate and increase further the formation and strength of cortical bone in old female rats.

Aging↗

PubMed1997

Biomechanical characteristics of the human anterior lens capsule in relation to age.

PURPOSE: The purpose of the study was to investigate the influence of age on the biomechanical properties of the human anterior lens capsule. METHODS: The material comprised 67 lens capsules obtained from human donors ranging in age from 7 months to 98 years. Test specimens were prepared from the anterior lens capsule as tissue rings by means of excimer laser technique using a metal ring (mask) to shape the laser output (outer diameter = 3.2 mm, width = 100 microns). Capsular thickness was measured under microscope as the difference in focus between microspherules placed on the outer and inner surfaces of the capsule. The rings were slipped over two pins connected to a motorized micropositioner and a force transducer, respectively, and stretched at constant speed until rupture, with continuous recording of load and elongation. RESULTS: Capsular thickness was associated significantly with age of the donors and increased gradually (1.2% per year) until age 75, after which a slight decrease was observed. The elastic response curves showed a high degree of nonlinearity and were influenced markedly by age. Ultimate strain decreased 0.5% per year (range, 108% to 40%). Ultimate tensile strength decreased 1% per year (range, 17.5 N/mm2 to 1.5 N/mm2), and ultimate elastic stiffness (tangent modulus) decreased 0.9% per year (range, 44.8 N/mm2 to 4.4 N/mm2), whereas elastic stiffness corresponding to a specific strain level (30%) increased until age 35, after which a slight decrease was observed. CONCLUSIONS: Aging of the human anterior lens capsule is associated with a progressive loss of mechanical strength. The young capsule is strong, tough, and highly extensible, whereas the older, thicker capsule is less extensible and much more brittle, and it has a markedly reduced breaking strength.

Adolescent↗

PubMed1996

The influence of growth hormone on cancellous and cortical bone of the vertebral body in aged rats.

The influence of growth hormone administration on cancellous and cortical bone of the vertebral body in 2-year-old male rats has been investigated. All rats were injected for 80 days, then killed. Controls were given saline, and three recombinant human growth hormone (rhGH) injected groups were given either rhGH (2.7 mg/kg/day) for the first 20 or 40 days, followed by saline injection, or rhGH for all 80 days. Tetracycline labeling was performed on days 41 and 69. In all groups given rhGH, an increase in the cortical bone volume was found. In the rhGH 40-day group, single labeling corresponding to injection on day 41 was seen all around the anterior surface of the vertebral body wall (toward the abdominal cavity). In the rhGH 80-day group, double labeling was seen all around the anterior surface of the vertebral body, and a substantial increase in the mineralizing surface/total surface, mineral apposition rate, and mineralized bone formation rate was found. In the cortical bone of the anterior wall, cavities had developed in the rhGH 40- and 80-day groups. In the cancellous bone, no differences in bone volume, bone volume/total volume, or bone surface/bone volume were seen, but in the middle part of the vertebral body a decrease in the mineralizing surface/total surface was found in the rhGH 80-day group. The height of the vertebral body was not influenced by rhGH administration, whereas the transversal and midsaggital diameters were increased in the rhGH 80-day group. The compressive mechanical strength of the vertebral body specimens was increased in the rhGH 80-day group, and this increase most likely could be explained by formation and deposition of cortical bone.

Aging↗

PubMed1996

Biomechanical measurements of the porcine lens capsule.

Biomechanical measurements were carried out on capsular rings prepared from the anterior lens capsule by means of photoablation technique (excimer laser). The outer diameter of the metal ring used to shape the laser output was 3.2 mm and the width (wall thickness) was 100 microns. Thickness of the lens capsule (depth of the tissue ring) was measured with a microscope coupled to an electronic length gauge as the difference in focus between latex spherules placed on the upper and lower surfaces of the capsular rings. For mechanical measurements the capsular rings were mounted around two pins connected to a motorized micropositioner and a force transducer, respectively, and stretched at a constant rate until rupture. Estimates of the precision of the test method were based on differences between measurements of paired eyes from 15 6-month-old pigs. Thickness of the lens capsules was 59 microns (50-66) (median, range). Repeatability of a single measurement was +/- 2 microns for a probability of 95%. Maximum strain as a percentage of the initial length was 78% [68-89] with a repeatability of +/- 6%. Maximum stiffness (elastic modulus) was 23.0 N mm-2 [10.0-31.5] with a repeatability of +/- 4.3 N mm-2, and maximum stress was 4.4 N mm-2 [2.8-7.7] with a repeatability of ./:1.27 N mm-2. There were no significant differences between paired eyes, but a significant variance component between individuals. The experimental set-up described in this paper seems reliable and useful for biomechanical measurements of the lens capsule, in the physiological as well as the surgical function range.

Animals↗

PubMed1996

Collagen deposition and mechanical strength of colon anastomoses and skin incisional wounds of rats.

The mechanical strength development of healing wounds depends on the formation of collagen fibrils bridging the wound cleft. A considerable deposition, degradation, and remodeling of these fibrils takes place influencing the mechanical strength of the healing wounds. A method for studies of wound collagen metabolism in vivo is delineated, enabling determination of collagen deposition per hour in rat colon anastomoses and skin incisional wounds. Labeled proline was incorporated into wound collagen with a flooding dose of unlabeled proline, reducing errors introduced by proline recycling and proline de novo synthesis. The mechanical strength was determined by a materials testing machine. In both colon anastomoses and skin wounds a substantial increase in collagen deposition was observed at Day 2, reached a maximum at Day 6, and was still relatively high at Day 12 during the remodeling of collagen fibers in the wound cleft. The collagen deposition in colon anastomoses at Day 6, however, was 10-fold higher compared with that of the skin incisional wounds. The time course of the collagen deposition was much alike in colon anastomoses and skin incisional wounds reaching a maximum at Day 6. The mechanical strength of these two rather different types of wounds was increased correspondingly and to the same level during the 1st week of healing. The measurements of collagen deposition, collagen content, and biomechanical strength indicated a substantial turnover of newly synthesized and deposited collagen during the early phases of wound healing. On the basis of this, it seems obvious that even small disturbances to the balance between collagen synthesis, deposition, collagen cross-linking, and collagen degradation/remodeling may result in defective wound healing.

Anastomosis, Surgical↗

PubMed1995

Growth hormone stimulates bone formation and strength of cortical bone in aged rats.

The influence of growth hormone on bone formation, mechanical strength, and composition has been investigated in femur middiaphyseal cortical bone from 2-year-old male rats. The rats were given biosynthetic human growth hormone (bhGH) at 2.7 mg/kg/day in two daily injections for 20, 40, or 80 days, and all animals were killed 80 days after the start of bhGH administration. Control animals were given saline. All animals were labeled with tetracycline on days 41 and 69. Only in the bhGH-80-day group was subperiosteal tetracycline double labeling seen all around the femur diaphysis, and this pattern was found in all animals of the group. Double labeling subperiosteally at the posteromedial aspect was found in all animals of the experiment, but compared with the control group, a 400% and an 800% increase in mineral apposition rate was seen in the bhGH-40-day and bhGH-80-day groups, respectively. Light microscopy and polarization microscopy showed that this newly deposited bone was organized in the same concentric lammellae and had the same direction of the collagen fibers when compared with the surrounding bone formed before the start of bhGH injections. The cortical bone cross-sectional area was increased in the bhGH-40-day and bhGH-80-day groups. At the endosteum, scattered labeling was found in animals from all groups, and no differences in medullary cross-sectional areas were seen. The mechanical analysis revealed an increased mechanical strength of the whole diaphyseal bone after bhGH administration. When the data were corrected for dimensions of the diaphyseal bone, no differences in intrinsic mechanical properties of the bone tissue were found. No differences in apparent density of dry defatted bone, ash, and collagen were seen, whereas apparent density of dry defatted bone minus ash was decreased in all groups given bhGH. Correspondingly, a slight increase in ash concentrations of the bhGH-injected animals was seen. bhGH administration also increased the body weight, muscle mass, and total serum IGF-I and thyroxine concentrations.

Aging↗

PubMed1995

Dose-response study of the effect of growth hormone on mechanical properties of skin graft wounds.

The aim of the study was to investigate the effect of growth hormone on compromised wound healing in a model without exogenously applied metabolic disturbances, e.g., diabetes mellitus. Female Wistar rats were injected with biosynthetic human growth hormone (b-hGH) at 2.0, 4.0, 8.0, and 16.0 mg/kg/day from 7 days before operation to 7 days after. Controls were given saline. On the left side of the dorsal skin a 35 x 20-mm full-thickness skin graft was raised and replaced in situ. After 7 days of healing the wound between the graft and the skin was tested mechanically. The maximum load and maximum stiffness showed a positive correlation with dose of b-hGH, being increased by 40 and 47% in the 8.0 mg group and 34 and 48% in the 16.0 mg group compared with the saline group. During the 7 days of injection before operation serum insulin-like growth factor I (IGF-I) decreased in the saline group, was unchanged in the group given 2.0 and 4.0 mg b-hGH, and was increased in the groups given 8.0 and 16.0 mg b-hGH. Postoperatively, no changes in se-IGF-I were seen in any of the groups when compared to the values at operation. Blood glucose was unaffected by b-hGH treatment. Postoperatively the saline-treated rats showed an 8% weight loss and the 2.0 mg b-hGH group a 3% weight loss, whereas no significant changes were seen postoperatively in the 4.0, 8.0, and 16.0 mg b-hGH groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

PubMed1995

Growth hormone normalizes vertebral strength in ovariectomized rats.

Ten-month-old lactating breeders were ovariectomized and kept on a low calcium diet. One month after ovariectomy, the rats were dosed once daily for 6 months with either a low dose of growth hormone (GH) (0.05 mg), a high dose of GH (1 mg), estrogen plus gestagen (E-G) [17 beta-estradiol (0.1 mg); norethisterone-acetate (0.05 mg)], or a combination of GH and E-G. Mechanical competence, apparent dry density, apparent ash density and ash concentration were measured in the fourth lumbar vertebral body. The reduced mechanical strength, ash density and ash concentration found in the vertebral body of ovariectomized animals were prevented by the high dose of GH alone, or in combination with E-G. E-G alone partly prevented the decline in ash density and ash concentration, but did not affect the reduced mechanical strength seen after ovariectomy. Only minor effects were observed after treatment with the low dose of GH, alone or in combination with E-G. In conclusion this study shows that GH administration prevents the decline in mechanical strength and bone mineral density seen in rats after ovariectomy.

Animals↗