Growth Hormone and IGF-I Stimulate Cell Function in Distinct Zones of the Rat Epiphyseal Growth Plate

Proliferation and maturation of growth plate chondrocytes are primarily responsible for linear bone elongation, although the exact mechanisms involved have not been fully characterized. We have used discrete chondrocyte populations to address the mode of growth hormone (GH) action on the growth plate. Low doses of GH, and insulin-like growth factor-I (IGF-I) preferentially enhanced cell proliferation in proliferative zone chondrocytes; the mitogenic response of immature proliferative and resting zone cells was minimal. Proliferation was not enhanced by combining the effects of GH and IGF-I. Exposure to IGF-I increased IGF-I mRNA in resting zone cells. Both GH and IGF-I stimulated the accumulation of IGF-I receptor mRNA in the most immature proliferative zone cells but did not alter the accumulation of IGF-binding protein 4 mRNA in any fraction. These results confirm a direct effect of GH on growth plate chondrocytes and suggest that GH preferentially acts on the actively proliferating chondrocytes.