These observations were further translated into increasingly physiological models of bone growth. Foetal mouse metatarsal organ explants, where the three dimensional structure and cell connections of the growing bone remain intact, again demonstrated that Dex and IGF-I had opposite effects on bone growth. The length of the metatarsals at day 10 from harvesting day length in the control, Dex and IGF-I bones was 50% ± 3, 42% ± 2, xv (p<0.05) 99.3% ± 5(p<0.05) respectively. In contrast to Dex the effects of IGF-I were immediate. Most importantly, it was demonstrated for the first time in vitro that IGF-I increased the size of the hypertrophic zone, as occurs in vivo, and this accounted for most of the increase in metatarsal length

The ATDC5 chondrocyte cell line was fully characterised, which allowed a unique opportunity to study GC effects on a homogeneous population of chondrocytes at the chondrogenesis and terminal differentiation phases. The GCs caused a reduction in cell number, cell proliferation and proteoglycan content whilst stimulating chondrocyte differentiation. These effects were dose dependent and only observed during the chondrogenesis phase when the cells are rapidly dividing. Furthermore these negative effects could be partially reversed with the use of a GC receptor antagonist and completely reversed with IGF-I.

This thesis consists of four major types of studies each utilising different models of growth and chondrocyte biology, which in combination strengthens the understanding of the effects of GC and growth factors on the growing skeleton. The initial in vivo study showed that in children treated with Dexamethasone (Dex) or Prednisolone (Pred) for Acute Lymphoblastic Leukaemia, the effects of Dex on body composition were more apparent in that it was up to 18 times more potent at reducing short term linear growth than Pred.

Glucocorticoids (GCs) regulate many physiological systems in the body and have potent immunosuppressive and anti-inflammatory properties. In children prolonged administration causes a reduction in growth, which is in part due to the direct effects they have on the growth plate. This effect is dependent on the dose, duration and type of GCs used.

Prenatal administration of Dex caused a reduction in birth weight and length and this difference was greater in the female mice. The growth restriction was associated with elevated IGF-I and IGFBP-2 levels raising the possibility of a state of IGF-I insensitivity, which may explain subsequent growth failure.

In conclusion, this thesis translated the clinical observation that Dex is more potent than Pred at inhibiting linear growth and these effects are dependent on the dose and duration of the GC exposure as well as the chondrocyte phenotype. These negative effects of GC can be reversed by IGF-I administration.