Page 73 - Slipped Capital Femoral Epiphysis Pathogenetic and Clinical aspects

oestrogens stimulate the local production of IGF-1 and other growth factors. Indirectly, low concentrations of oestrogens stimulate GH secretion, thereby, increasing circulating IGF-1 levels that, in turn, stimulate chondrocyte growth in the proliferation zone and may also potentiate clonal expansion. Oestrogens also seem to have a biphasic effect on the physis. Low concentrations of oestrogen augment skeletal growth, whereas continued high levels of oestrogens lead to epiphyseal fusion. High doses of oestrogen inhibit clonal expansion and cell proliferation in the hypertrophic zone. Furthermore, high concentrations of oestrogen induce apoptosis of hypertrophic chondrocytes and stimulate osteoblast invasion in the physis [12, 18, 20, 26].
The current understanding of how oestrogens affect growth may suggest separate
roles for the different estrogen receptors (ERs). Two ERs exist: ER-α and ER-β. Juul et 4 al. [20] found that ER-α is localized in all zones of the physis and ER-β is expressed
in hypertrophic chondrocytes exclusively. Nilsson et al. [29] demonstrated that
both receptors are present in all zones of the physis, but in a greater frequency in
the resting and proliferative zones. The androgen receptor (AR) was found to be
more abundant in the resting and hypertrophic zones.
Also, a new membrane-bound ER G-protein-coupled receptor 30 (GPR30)
was discovered. The highest level of this receptor was found in hypertrophic chondrocytes. The receptor revealed a weak immunostaining in the resting zone.
During puberty, a decline was found in the expression of this receptor in both
boys and girls. This new receptor could play an important role for the cessation of
growth in puberty [30].
Testosterone has, not only after aromatisation, an effect on growth but also
directly on the physis by the stimulation of proliferation and differentiation in chondrocytes. This direct effect on the human physis is not necessary for the
pubertal growth acceleration or for the cessation of growth. ARs have been found
in hypertrophic chondrocytes in the human physis and cartilage. Some organs are
capable of synthesizing sex steroids from sulphated precursors which are present
in high amounts in the circulation. The term ‘intracrinology’ was introduced,
suggesting that sex steroids can be synthesized locally and act in the same cell
without being released, indicating that a more complicated mechanism may be
available in the physis [12, 13, 18, 29].
Delayed sexual maturation is often present in patients with SCFE, which might
suggest a delay in closure of the physis. This creates a prolonged phase of weakness
that makes the physis vulnerable for the effects of increasing load, mainly in the
Slipped Capital Femoral Epiphysis
71