In summary, these results from GH-treated rats with a normal GH secretion clearly demonstrate that GH increases cortical bone mass by inducing subperiosteal bone formation while no large effect on cancellous bone mass is seen. Short-term treatment with growth hormone stimulates osteoblastic and osteoclastic activity in osteopenic postmenopausal women: a dose response study. No evidence for reduced spontaneous or growth-hormone-stimulated serum levels of insulin-like growth factor (IGF)-I, IGF-II or IGF binding protein 3 in women with spinal osteoporosis. As discussed above, GH exerts potent effects in rodents, resulting in an increased bone formation. Human growth hormone (HGH) is an important hormone produced by your pituitary gland. Growth hormone dependent stimulation of osteoblast-like cells in serum-free cultures via local synthesis of insulin-like growth factor I. Osteoclast formation together with interleukin-6 production in mouse long bones is increased by insulin-like growth factor-I. Once the growth plates in the bones (epiphyses) have fused growth hormone does not increase height. It stimulates the growth of essentially all tissues of the body, including bone, and is vital for normal physical growth in children. Growth hormone and insulin-like growth factors as anabolic therapies for osteoporosis. A gradual increase in bone mass is then seen until peak bone mass is reached at 20–30 yr of age. Bone turnover and bone mineral density in young adult patients with panhypopituitarism before and after long-term growth hormone therapy. OVX rats have been accepted as an animal model of postmenopausal bone loss and the current FDA“ Guidelines for preclinical and clinical evaluation of agents used in the treatment or prevention of postmenopausal osteoporosis (1994)” recommend that new potential agents first should be evaluated in the OVX rat model (203–205). Using a histomorphometric technique, it was found that GH as well as IGF-I has the capacity to stimulate prechondrocytes, as both GH and IGF-I reduced the cell cycle time of prechondrocytes. Sharon Perkins, RN, is the coauthor of Breastfeeding For Dummies and Fertility For Dummies. Chenu and co-workers (82), but not Kassem et al. IRS-1 and -2 are also proteins functioning as signal transducers for the GHR after they have been phosphorylated on tyrosine residues (138–140). GHR mRNA has been detected in mouse marrow cultures (144) and in mouse hemopoietic blast cells (145). IGF-II is expressed in both rodent and human osteoblasts (83–86). Your bones and teeth store approximately 85 percent of the phosphorus. Short-term effects of recombinant human insulin-like growth factor I on bone turnover in normal women. In the osteoblast promoter-driven GH-transgenic mice the femora demonstrated an increased growth, increased cortical width, and an increased mechanical strength (157, 158). Qualitative alterations of cortical bone in female rats after long-term administration of growth hormone and glucocorticoid. Hormones involved in bone growth (hormone – gland – function). However, from these clinical studies it is difficult to make a general conclusion whether IGF-I stimulates tissue growth by endocrine or autocrine/paracrine mechanisms under physiological circumstances in the intact organism. In mouse osteoblasts, it has been shown that GH induces the nuclear protooncogenes c-fos, c-myc, c-jun, and Jun-B (120, 141). This small molecule in turn regulates the activity of osteoclasts. It is known that growth hormone secretion is controlled by two factors secreted in the hypothalamus and then transported to the anterior pituitary gland through the hypothalamic-hypophysial portal vessels. Key Terms. Growth hormone increases the length of long bones, enhances mineralization, and improves bone density. Isolation of an inhibitory insulin-like growth factor (IGF) binding protein from bone cell-conditioned medium: a potential local regulator of IGF action. In adults, it does not cause growth but it helps to maintain normal body structure and metabolism, including helping to keep blood glucose leve… As GH stimulates both periosteal bone formation and linear growth where bone formation takes place by endochondral ossification, it has been natural to examine the effect of GH treatment on healing bones. However, it is possible that some of these effects are due to bone growth and bone modeling, as rodents close the epiphyseal plate late in life. It remains to be clarified whether or not it is valid for subjects with normal GH secretion. Effects of human growth hormone in men over 60 years old. Taken together, available data suggest that GH stimulates longitudinal bone growth directly by stimulating prechondrocytes in the growth plate followed by a clonal expansion caused both by the GH-induced local production of IGF-I, and by a GH-induced increase in circulating levels of IGF-I. This cyclic treatment was repeated 12 times and resulted in a small but statistically significant increase in BMD of the lumbar spine and of the hip (1–2%). In fact, in 33% of the patients the lumbar spine BMD area was at least 2 sd lower than normal. Thus, Clowes et al showed that the postprandial decrease in bone resorption can be prevented by administration of a somatostatin analog. This investigations found that the BMD area (BMC/bone area) in GHD patients was significantly reduced at the lumbar spine as well as the nondominant hip. Absolute value of the control cultures is 1950 dpm/ml. If you’re over 30, there’s something you should know: Your growth hormone just ain’t what it used to be It’s true. Bone cells have two kinds of intracellular steroid receptors for estrogen. Furthermore, Hansen et al. Most studies have shown that there is no difference in resorption markers between controls and adult GHD patients (264, 268, 270). For example, when the serum level of calcium drops, the parathyroid gland synthesizes more hormone. 2. Adult human osteoblast-like cells do not express insulin-like growth factor-I. The effect of long-term growth hormone (GH) treatment on bone mineral density in children with GH deficiency. The message is clear: although excess cortisol inhibits growth and the skeleton, normal cortisol levels are part of the mix that ensures both normal growth hormone secretion and bone accumulation in childhood. According to this model, GH results initially in an increased bone resorption with a concomitant bone loss followed by a later increased bone formation. Thyroxine stimulates bone growth and promotes the synthesis of bone matrix. Boys with constitutionally retarded puberty will achieve a lower peak bone mass than boys with puberty of normal onset (281). Furthermore, in a study of 245 healthy elderly women, serum IGF-I concentration was found to be an independent predictor of total BMC (326). The molecular response of bone to growth hormone during skeletal unloading: regional differences. In vitro data have demonstrated that GH exerts direct anabolic effects on osteoblasts (see Section III), and some of these direct effects of GH may not be achieved by a systemic IGF-I treatment. Since bone absorptiometry only detects the mineralized component of the bone, the reduction in BMD observed after short periods of GH treatment is best explained by the increased remodeling activity, with an increased remodeling space and an increased proportion of new unmineralized bone. In the public press estrogen always gets mentioned, although progesterone may be more effective in stimulating new bone growth. Growth hormone involvement in the regulation of tartrate-resistant acid phosphatase-positive cells that are active in cartilage and bone resorption. In summary, GH treatment in rats obviously increases callus formation and the mechanical strength of healing bones, whereas the response in the rabbit model seems to be much weaker. Evaluation of the pathogenesis of skeletal changes in ovariectomized rats. Johannsson et al. The GH-induced subperiosteal bone formation also shows regional differences. In summary, HX of rats results in a decreased bone formation with a concomitant decrease in bone mass. Serum bone Gla protein: a potential marker of growth hormone (GH) deficiency and the response to GH therapy. Recently, using human osteoblast-like cells, Melhus and Ljunghall (121) demonstrated that different sets of genes were induced by IGF in some cases and GH in others, indicating that these factors have separate actions. Similarly, Vandeweghe et al. 8.1 Stimulation and action of intrinsic GH. Anabolic effect of human synthetic parathyroid hormone-(1–34) depends on growth hormone. In conclusion, erlotinib inhibits tumor-induced oste-olytic invasion in bone metastasis by suppressing osteoclast activation through inhibiting tumor growth at the bone metastatic sites, osteolytic factor production in tumor cells, osteoblast/stromal cell proliferation and osteoclast differ-entiation from mouse bone marrow cells. Role of insulin-like growth factors in embryonic and postnatal growth. GH increases the number of osteoclasts in the metaphysial bone of the proximal tibia of hypophysectomized rats (25). Testosterone is an important hormone for both bone gain and maintenance in men. The observed declines in different bone parameters were inhibited when glucocorticoid and GH were given simultaneously. Endocrine regulation of longitudinal bone growth. Anti-Müllerian Hormone (AMH), Inhibin-α, Growth Differentiation Factor 9 (GDF-9), and Bone Morphogenic Protein-15 (BMP-15) mRNA and protein are influenced by photoperiod-induced ovarian regression and recrudescence in Siberian hamster ovaries A considerable delay in mechanical strength development of healing fractures is seen in old rats and GH treatment partly prevents this delay (232, 233). Also in young skeleton estrogen deficiency leads to in … In: Daughaday D (ed) Endocrine Control of Growth. A biomechanical study of the effects of growth hormone in experimental fracture healing. After 12 months of treatment, however, there was only a significant reduction in lumbar spine BMD. However, an increased risk of osteoporotic vertebral fractures has been suggested in hypopituitary patients (283). Google Scholar; 59 Vico L, Barou O, Laroche N, Alexandre C, and Lafage-Proust MH. The identification of JAK2 tyrosine kinase as a signaling molecule for growth hormone. GH stimulates longitudinal bone growth directly by stimulating prechondrocytes in the growth plate followed by a clonal expansion caused both by the GH-induced local production of IGF-I, and by a GH-induced increase in circulating levels of IGF-I. The effect of GH has been studied in hypogonadal female monkeys. When the two compounds are given together, they exert additive or synergistic effects (45, 60, 64). Several hormones are necessary for controlling bone growth and maintaining the bone matrix. GH treatment also increases bone mass and the total mechanical strength of bones in rats with a normal GH secretion. Insulin-like growth factors and binding proteins. It has been suggested that the GH/IGF-I axis is one of the major determinants of adult bone mass (323, 324). The extent of GH expression and tissue distribution of GH in the transgenic mice depend on which promoter is attached to the GH gene. Thus, circulating osteocalcin declines, and the mRNA levels of osteocalcin and α1(I)-procollagen in the bone are decreased (163, 164). Growth hormone and/or estradiol and gestagen as a treatment of osteoporosis in the aged ovariectomized rat, Effect of growth hormone therapy on cortical bone in aged ovariectomized rats, Effect of growth hormone therapy on cancellous bone in aged ovariectomized rats. ], Schematic representation of regulation of skeletal tissue by GH and IGF-I. Effects of rhIGF-I administration on bone turnover during short-term fasting. Gravity, Mechanical stress, Calcitonin and parathyroid hormone levels, Blood calcium level In compact bone, the matrix rings that surround the central canal of each osteon are called? Growth hormone stimulates proliferation and differentiation of normal human osteoblast-like cells. Estrogen is a hormone that is instrumental … (125).]. Bone density of the lumbar spine and femur in acromegaly. Effect of increased growth hormone on mechanical strength of cortical bone in growth hormone-transgenic mice. [ Figure is derived from Slootweg et al. 1. See the answer. Waves of osteoblasts that move into the area form new layers of bone. Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Also, administration of GH to animals treated with maximal doses of IGF-I stimulates growth further (63). Insulin-like growth factor I and insulin down-regulate growth hormone (GH) receptors in rat osteoblasts: evidence for a peripheral feedback loop regulating GH action. IGF-I is produced by rodent (87–90) osteoblasts while contradictory results have been presented for human osteoblasts. A gender difference has also been observed in response to GH. Furthermore, indices for bone formation remain elevated for several weeks after short-term treatment with GH, suggesting that the half-life for processes reflecting bone resorption/formation is quite long (302, 311). Short and long-term effects of growth hormone treatment on bone turnover and bone mineral content in adult growth hormone-deficient males. It is well known that GH is important in the regulation of longitudinal bone growth. It should be emphasized that the biphasic model of GH action in bone remodeling is based on findings in GHD adults. It occurs throughout life. Effects of GH in rodents. The GH dosage was 0.1 IU/kg twice a day administered subcutaneously. BMD did not change during a 6-month placebo-controlled trial with GH in healthy elderly women, whereas a slight decrease was observed in the placebo group. Several in vitro models, developed to study the effects of hormones and growth factors on bone remodeling, have been presented, and some of these will be discussed in this section. However, these experiments are unable to answer the question of whether locally produced (autocrine/paracrine acting) IGF-I is more important for normal tissue growth and development than circulating (endocrine acting) IGF-I. The effect of growth hormone on experimental long-bone defects. II. It triggers chondrocyte proliferation in epiphyseal plates, resulting in … A large increase in bone mass occurs during childhood and puberty via endochondral bone formation. Systemically and locally administered growth hormone stimulates bone healing in combination with osteopromotive membranes: an experimental study in rats. However, a study by Borges et al. A randomized, placebo-controlled trial. Growth hormone stimulates longitudinal bone growth directly. No additional effect was seen when IGF-I was given together with GH. However, these investigators found no increase in bone matrix content of IGF-I in the GH-treated animals (181). Embryonic stem cells express growth hormone receptors: regulation by retinoic acid. Enhancement of bone formation in rabbits by recombinant human growth hormone. Address reprint requests to: Claes Ohlsson M.D, Ph.D., Department of Internal Medicine, Division of Endocrinology, Sahlgrenska Hospital, S-41345 Göteborg, Sweden. The authors concluded that the differences between GH and IGF-I might be dose dependent, but could also indicate separate mechanisms of actions of the two peptides at the cellular level. The area and the width of the vertebra were similar in patients and controls. Lactose intolerance in patients with inflammatory bowel diseases and dietary management in prevention of osteoporosis. In studies in which rats were used, only a few papers show no effect of GH on healing bone defects and fractures (234, 235), and GH has not been able to stimulate formation of new bone in titanium bone conduction chambers (236). Whereas circulating levels of IGF-I are GH dependent, GH may not be the chief determinant of local IGF-I production in bone. Osteoblasts mediate insulin-like growth factor-I and -II stimulation of osteoclast formation and function. (343) demonstrated more recently that both transdermal and oral estrogen increase GH secretion and decrease serum levels of IGF-I. Short-term GH treatment for 7 days in patients receiving chronic glucocorticoid treatment for autoimmune disorders resulted in a significant increase in serum osteocalcin, PICP, and CITP concentrations (351). Estrogen And Testosterone Calcitonin O Thyroid Hormone Parathyroid Hormone Growth Hormone. Effect of growth hormone on vitamin D metabolism. Untreated control cultures lacked bone-like structures, demonstrating that GH directly induced bone formation in vitro (27). Because of the short duration of GH treatment in man with normal GH secretion, the effect on bone mass is still inconclusive. (218) showed that glucocorticoids caused a decline in linear bone growth, trabecular bone volume, cortical bone width, mineral bone content, and bone alkaline- and acid-phosphatase activity. Effects of local administration of GH and IGF-1 on longitudinal bone growth in rats. Bone formation also takes place from day 69 until animals are killed (distance between labeling line day 69 and periosteal border). The effect of systemic administration of GH and IGF-I to hypophysectomized rats has shown that GH and IGF-I have independent and differential functions (45, 46, 63). After 2 yr of GH treatment, the total body BMC increased but not the total body BMD. Several studies have shown that systemic administration of recombinant IGF-I stimulates longitudinal bone growth as well as body weight gain in hypophysectomized rats, giving support to the theory that IGF-I has endocrine actions on statural growth. After treatment with GH for 3 months a 2% increase in cortical bone mass, as assessed by histomorphometry, was found. Further characterization of growth hormone hormone receptors in cultured human ( 78 ) and and. Gh induces subperiosteal bone formation in Rhesus Macaque monkeys spaceflight and recombinant human growth hormone enhances the transcript and levels. Effects on blood calcium levels in balance J Clin Endocrinol Metab 81:2865–2873 1996... And dexamethasone in skeletal growth and cartilage metabolism of collagen sponges in the vertebrae phosphorus is the second important... 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