Parathyroid hormone increases the expression of receptors for epidermal growth factor in UMR 106-01 cells.
PTH administration in vivo increases osteoblast number and activity, resulting in increased bone formation, and also increases osteoclast-mediated bone resorption. Studies in vitro, however, have shown that the actions of PTH on osteoblast-like cells are inhibitory and catabolic, as shown by decreases in growth rate and collagen synthesis and increases in collagenase production. The present studies were designed to investigate possible mechanisms for these observations by examining the effects of PTH on the response of osteoblast-like cells to the osteoblast growth factor, epidermal growth factor (EGF). Confluent cultures of UMR 106-01 cells were treated with rat PTH-(1-34) for periods up to 72 h, and EGF receptors were measured with [125I]EGF. PTH, in a dose- and time-dependent manner, increased the number of EGF receptors 2-fold. The half-maximal effect of PTH occurred at a concentration of 1 nM, the same PTH concentration that resulted in half-maximal increases in cAMP generation. The increase in EGF binding was associated with an enhanced biological effect, as shown by augmentation of EGF-stimulated diglyceride production. The effect of PTH could be reproduced by the addition of 8-bromo-cAMP, but not by the phorbol ester phorbol myristate acetate. In the presence of cyclohexamide, the effect of PTH on EGF binding was abolished, suggesting that new protein synthesis was required to increase the number of EGF receptors. Northern blots of total RNA, using a cDNA probe encoding the extracellular domain of the rat EGF receptor, revealed that PTH treatment resulted in a 2- to 3-fold increase in the level of EGF receptor mRNA. These data suggest that the proliferative effects of PTH on the osteoblast may be mediated indirectly by a PTH-induced increase in the number of EGF receptors.
Drake
M T
MT
Department of Internal Medicine, St. Louis University School of Medicine, Missouri 63110-0250.
Baldassare
J J
JJ
McConkey
C L
CL
Gonzalez
E A
EA
Martin
K J
KJ
D000818:Animals; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015290:Second Messenger Systems / Q000502:physiology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D010281:Parathyroid Hormone; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D003513:Cycloheximide; D000242:Cyclic AMP; D066246:ErbB Receptors; D011493:Protein Kinase C