Parathyroid Hormone Down-Regulates the Epidermal Growth Factor Receptors in Clonal Osteoblastic Mouse Calvarial Cells, MC3T3-E1: Possible Mediation by Adenosine 3',5'-Cyclic Monophosphate

The effects of PTH on the binding and mitogenic activity of epidermal growth factor (EGF) were studied in clonal, PTH- and EGF-responsive mouse osteoblastic cell line, MC3T3-E1. Treatment of cells with synthetic rat PTH-(l-34) at 10-10-10-8 M resulted in a dose-related decrease (maximally 30% relative to the control value) in the specific binding of a biologically active, 125I-iodolabeled derivative of recombinant human EGF ([125I]iodo-EGF). The PTH-induced decrease in EGF binding was time dependent, requiring at least 4 h of PTH treatment at 37 C for a maximal effect, completely reversible after cessation of PTH exposure and specific only to biologically active PTH. Scatchard analysis of saturation binding data revealed that the PTH-induced reduction of EGF binding was accounted for by a proportional decrease in the available EGF-binding sites without an alteration in binding affinity (Kd = 0.7- 0.8 nM). PTH treatment resulted in a concomitant decrease in mitotic responsiveness to EGF (maximally 40-50% o...