Accumulation of cyclic 3',5'-adenosine monophosphate in cultured neonatal human dermal fibroblasts exposed to parathyroid hormone and prostaglandin E2.
We sought to determine whether cultured human dermal fibroblasts respond to parathyroid hormone (PTH) with accumulation of cyclic 3',5'-adenosine monophosphate (cAMP) reproducibly enough for such cells to be useful in characterizing states of altered end-organ response to PTH. Thus, we cultured fibroblasts from 15 human neonatal foreskins and tested fibroblast cAMP responses to addition of synthetic human PTH-(1-34), bovine PTH-(1-34), and native bovine PTH-(1-84) at concentrations of 10(-6) to 10(-10) M. Accumulation of cAMP (cells plus medium) was significantly enhanced by PTH in only 10 of 37 experiments. In cells that had a significant cAMP response to PTH, the ratio of treated to control cAMP values ranged only from 1.27 to 2.18. No study showed a clear-cut dose-response relationship. In six of six experiments, the cells responded to prostaglandin E2 (1 microgram/ml) with markedly increased accumulation of cAMP (9.7 to 110.9-fold the basal value). We conclude that cultured human dermal fibroblast cAMP responses to PTH with use of the current methods are too small and inconsistent for that tissue to be useful in studies of reduced end-organ responsiveness to PTH such as pseudohypoparathyroidism. Nevertheless, states of hyperresponsiveness to PTH might still be detectable by this method.
M J
MJ
Fryer
S R
SR
Fritz
H
H
Heath
D015056:1-Methyl-3-isobutylxanthine; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000378:metabolism*
D010281:Parathyroid Hormone; D011458:Prostaglandins E; D000242:Cyclic AMP; D015232:Dinoprostone; D015056:1-Methyl-3-isobutylxanthine