The interaction of glucocorticoids with the growth hormone-insulin-like growth factor axis and its effects on growth plate chondrocytes and bone cells.
Glucocorticosteroids interfere with the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis at different levels, and while low-dose corticosteroids may have permissive effects, high-dose, long-term treatment with corticosteroids may lead to growth disturbance. The mechanism involved is not clearly understood. The Janus kinase (JAK)-2/signal transducers and activators of transcription (STAT)-5 pathway is the means by which the corticosteroid interacts with the target-cell GH receptors. The production of local IGF-I is lowered by the corticosteroid via IGF-I transcription inhibition, and the rate of apoptosis is also increased, both in growth plate chondrocytes and osteoblast cell lines. GH in vitro and in vivo can partly counterbalance the negative effects of glucocorticoids on growth. GH has been seen to normalize growth rates in corticosteroid-treated rats as well as in children receiving glucocorticoids for immunosuppression following kidney transplantation.
Mehls
O
O
Division of Pediatric Nephrology, University Children 's Hospital of Heidelberg, Germany. Otto_Mehls@med.uni-heidelberg.de
Himmele
R
R
Hömme
M
M
Kiepe
D
D
Klaus
G
G
D000818:Animals; D001842:Bone and Bones / Q000737:chemistry / Q000502:physiology*; D019902:Chondrocytes / Q000502:physiology*; D005938:Glucocorticoids / Q000502:physiology*; D013006:Growth Hormone / Q000502:physiology* / Q000627:therapeutic use; D006132:Growth Plate / Q000166:cytology / Q000502:physiology*; D006801:Humans; D013002:Somatomedins / Q000502:physiology*
D005938:Glucocorticoids; D013002:Somatomedins; D013006:Growth Hormone