Parathyroid hormone (PTH) and PTH-related protein stimulate surfactant phospholipid synthesis in rat fetal lung, apparently by a mesenchymal-epithelial mechanism.
We examined the effects of parathyroid hormone (PTH) and PTH-related protein (PTHrP) on rat fetal lung fibroblast and pneumocyte cell signalling. We also studied the effects of PTH and PTHrP on surfactant phospholipid synthesis to determine whether these peptides can modulate pulmonary maturation. Exposure of fibroblasts (gestational days 18-21) to PTH(1-34) or PTHrP(1-34) produced time- and dose-dependent stimulations of cAMP and inositol phosphate accumulation. Maximal stimulation of cAMP accumulation occurred with 1 x 10(-8) M of either peptide. These effects upon cAMP accumulation were competitively inhibited by the PTH antagonist, [Nle8, Nle18, Tyr34]bPTH(3-34)amide. Maximal stimulation of fibroblast inositol phosphates was reached at 1 x 10(-7) M of either peptide. In contrast, PTH and PTHrP at these concentrations produced no changes in cAMP or inositol phosphate metabolism in isolated type II pneumocytes. When pneumocytes were exposed to PTH or PTHrP and pulse-labelled with [methyl-3H]choline chloride, no hormone-stimulated changes in saturated phosphatidylcholine (PC) synthesis were detected. However, PTH and PTHrP stimulated saturated PC synthesis in rat fetal lung explants (gestational day 19-20) by 46% and 106%, respectively. When fibroblasts and pneumocytes were co-cultured, PTH and PTHrP again stimulated saturated PC synthesis by 45% and 73%, respectively. Taken together, these findings suggest that PTH and PTHrP may be endocrine and/or paracrine regulators of fetal lung development.
Rubin
L P
LP
Department of Pediatrics, Women & Infants' Hospital, Brown University School of Medicine, Providence, RI 02905-2401.
Kifor
O
O
Hua
J
J
Brown
E M
EM
Torday
J S
JS
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000096:biosynthesis*; D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000187:drug effects; D004848:Epithelium / Q000378:metabolism; D005865:Gestational Age; D007295:Inositol Phosphates / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007295:Inositol Phosphates; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D015060:1,2-Dipalmitoylphosphatidylcholine; D000242:Cyclic AMP