Skin-derived fibroblasts respond to human parathyroid hormone-like adenylate cyclase-stimulating proteins.
Human tumors and keratinocyte-conditioned medium contain PTH-like adenylate cyclase-stimulating proteins. Human dermal fibroblasts have receptors that recognize PTH and a factor associated with humoral hypercalcemia of malignancy in rats. We examined 10 human dermal fibroblast lines for an adenylate cyclase response to PTH. Six of 10 lines tested displayed a definite response (2.4- to 3.8-fold over basal) to 10(-6) M bovine PTH-(1-34). This response was inhibited by the PTH analog and antagonist Nle8,18,Tyr34-bPTH-(3-34). We also examined whether human dermal fibroblasts are capable of responding to either a human PTH-like tumor-derived factor or the PTH-like factor contained in human keratinocyte-conditioned medium. Both human humoral hypercalcemia of malignancy-associated tumor extract (2.5 X 10(-10) M) and keratinocyte-conditioned medium (8 X 10(-10) M) stimulated human dermal fibroblast adenylate cyclase. These concentrations are markedly lower than those required for PTH-induced adenylate cyclase stimulation. This activity was also inhibited by the PTH analog. The high prevalence of PTH-responsive adenylate cyclase in dermal fibroblast lines and the apparent potency of tumor-derived and keratinocyte-derived PTH-like factors in dermal fibroblasts suggest that these factors may play a role in normal dermal physiology.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D007231:Infant, Newborn; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009363:Neoplasm Proteins / Q000494:pharmacology*; D010281:Parathyroid Hormone / Q000494:pharmacology; D011506:Proteins / Q000494:pharmacology*; D012867:Skin / Q000201:enzymology*
D009363:Neoplasm Proteins; D010281:Parathyroid Hormone; D011506:Proteins; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol