Steindler lecture. Binding sites in fetal and growth plate cartilage.

Abstract

In addition to genetic and nutritional factors, linear growth during the prenatal and postnatal periods is controlled by peptide, steroid, and thyroid hormones interacting with the receptors present on the membrane or in the cytosol and nuclei of growth plate cartilage. Using standard procedures, insulin and "nonsuppressible insulin-like activity" (a somatomedin) showed significant binding in 600, 15,000, and 105,000 g membrane fractions of epiphyseal cartilage of immature animals. The binding of growth hormone and prolactin was small and probably not significant. Specific uptake of glucocorticoid was demonstrated in viable canine chondrocytes, but not of androgen, estrogen, or vitamin D3 metabolite. A triiodothyronine receptor was present in nuclei from dog epiphyseal cartilage. Hormones that lack binding may affect cartilage only indirectly. Hormone receptors were studied in those portions of fetal growth cartilage that will later evolve into an ossification center, articular cartilage, and epiphyseal cartilage. Cytosol fractions contained a receptor for glucocorticoid but not for androgen or estrogen. Zonal analysis showed a higher level in the peripheral and central sections than in the palisade section. Triiodothyronine binding was also detected in nuclei prepared from whole fetal cartilage. Heterogeneity of cell function was obvious in fetal cartilage. Cell division was high in the central and peripheral zones as well as the upper half of the palisade zone, but low in the lower palisade section. Proline and sulfate incorporation predominated in the palisade section compared with the central and peripheral sections. Disease states with changes of metabolic activities in the cartilage may perhaps be better understood with a clearer knowledge of receptor levels and interactions.