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Endocrinology, Vol 124, 2419-2426, Copyright © 1989 by Endocrine Society


ARTICLES

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

S Ohta, C Shigeno, I Yamamoto, H Okumura, K Lee, S Uneno, J Konishi and T Yamamuro
Department of Orthopedic Surgery, Kyoto University School of Medicine, Japan.

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-(1-34) 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 ina concomitant decrease in mitotic responsiveness to EGF (maximally 40-50% of control). Both of these down-regulatory effects of PTH were closely mimicked by forskolin, cholera toxin, or (Bu)2cAMP. Addition of either colchicine or cytochalasin-B during PTH treatment completely abolished the PTH-induced reduction of EGF binding. These data indicate that PTH down-regulates EGF receptors and reduces the mitotic responsiveness to EGF, probably via a cAMP-dependent cytoskeleton-mediated mechanism(s) in osteoblastic MC3T3-E1 cells.


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T. Onishi and K. Hruska
Expression of p27Kip1 in Osteoblast-Like Cells during Differentiation with Parathyroid Hormone
Endocrinology, May 1, 1997; 138(5): 1995 - 2004.
[Abstract] [Full Text] [PDF]




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