Monday, October 26, 2009

Does being stressed stunt growth?

The effect of acute and chronic stress on growth.

"Impaired bone growth is observed in many children exposed to stress. The growth plate is specifically targeted by stress through many different mechanisms, including increased serum concentrations of proinflammatory cytokines and cortisol, as well as impaired actions of the growth hormone (GH)-insulin-like growth factor-1 (IGF-1) axis. Both glucocorticoids, such as cortisol, and proinflammatory cytokines adversely affect several aspects of chondrogenesis in the growth plate, and these effects can be ameliorated[improved] by raising local IGF-1 concentrations. However, this intervention does not completely normalize growth. In children with stress related to chronic inflammation, the cornerstone of improving stress-impaired growth remains the judicious use of glucocorticoids while ensuring effective control of the disease process. Specific immunomodulatory therapy that targets the actions of tumor necrosis factor-α (TNFα) is at least partially effective at rescuing linear growth in many children with juvenile idiopathic arthritis (JIA). Patients who do not respond to anti-TNF treatment may be candidates for therapeutic agents that target other proinflammatory cytokines and for GH intervention. Although GH treatment rescues linear growth in some patients with JIA, it is unknown whether GH can rescue growth in those patients who do not respond to anticytokine therapy."

"Acute and chronic stress may influence many mechanisms involved in the regulation of bone growth. Many of the effects can be linked to increased serum concentrations of the proinflammatory cytokines tumor necrosis factor–α (TNFα), interleukin-1β (IL-1β), and IL-6. These cytokines affect the production of many hormones, such as leutenizing hormone (LH), follicle stimulating hormone (FSH), sex steroids, GH, IGF-1, insulin-like growth factor binding proteins (IGFBPs), and glucocorticoids "

" receptors for both IL-1 (IL-1R1) and TNF (TNF-R1) are widely expressed in the growth plate, verifying that these cytokines have the potential to act directly on growth plate chondrocytes. When fetal rat metatarsal bones were cultured with either IL-1β or TNFα, alone, longitudinal bone growth was unaffected. In contrast, the combination of IL-1β and TNFα markedly inhibited bone growth, confirming that these cytokines act synergistically on the growth plate"

"combined treatment with IL-1β and TNFα induces massive chondrocyte apoptosis in cultured fetal rat metatarsal bones. Growth plate chondrocytes are effectively rescued from undergoing apoptosis when IGF-1 is added to the bones exposed to IL-1β and TNFα"<-IGF-1 activates Akt which protects cells from apoptosis.

"Anakinra (Kineret) is an IL-1 receptor antagonist (IL-1Ra), and etanercept (Enbrel) is a soluble TNF receptor."

"we measured femur growth in young male and female rabbits treated with glucocorticoid eye drops for 8 weeks. These experiments demonstrated that animals that received eye drops containing the synthetic glucocorticoid dexamethasone (Dexam) had significantly impaired femur growth when compared to vehicle-treated controls. These animal data show that glucocorticoids have the potential to impair longitudinal bone growth even when locally administered in the eye."

"no catch-up growth occurs after dexamethasone injections are discontinued."

"dexamethasone induces cell death throughout the growth plate. Furthermore, the abundance of the proapoptotic protein caspase 3 increased, whereas the abundance of the antiapoptotic protein Bcl-2 decreased in growth plates from dexamethasone-treated rats."

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