DECREASED GROWTH-HORMONE RECEPTOR EXPRESSION IN LONG BONES FROM TOOTHLESS (OSTEOPETROTIC) RATS AND RESTORATION BY TREATMENT WITH COLONY-STIMULATING FACTOR-I

Growth hormone (GH) is known to regulate growth and development of ske letal tissues. This study examined the distribution of growth hormone receptor (GHR) expression in tibias from normal and osteopetrotic tl/t l rats. For normal 2 week-old rats, GHR expression was detected immuno cytochemically in cells of the articular and epiphyseal cartilage, pri mary and secondary ossification centres, zone of resting cartilage and bone marrow. Within the marrow, GHR immunopositive cells were concent rated in the central cone and largely excluded from the zone of immatu re progenitors at the periphery. For the marrow haemopoietic compartme nt, GHR expression was almost restricted to the nucleus in large monon uclear cells, adipocytes and megakaryocytes. A population of small lym phocyte-like cells in the marrow periphery expressed GHR on the plasma membrane. GHR was not detected in mature erythroid cells, macrophages , granulocytes, or osteoclasts. The expression of GHR was significantl y reduced in bone marrow cells of the tl/tl rat (p < 0.001) compared w ith normal animals. Injection of recombinant CSF-1 into tl/tl rats eve ry 48 hours for 2 weeks from birth restored GHR-positive cells to the central core of the marrow space. The most striking change was the app earance of substantial numbers of mononuclear cells expressing abundan t GHR on the cell surface. We infer that these cells are a novel subse t of CSF-1 responsive cells involved in bone resorption. The differenc es in relative expression of GHR by bone marrow cells in untreated and CSF-1-treated tl/tl rats suggests a CSF-1-dependent recruitment of ce lls bearing surface GHRs.