Loss of parathyroid hormone-stimulated 1,25-dihydroxyvitamin D3 production in aging does not involve protein kinase A or C pathways.
Intestinal calcium absorption declines with aging as a result of decreased renal 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] biosynthesis. At least part of the decline in 1,25-(OH)2D3 may be due to acquired resistance to parathyroid hormone (PTH) stimulation of renal 25-hydroxyvitamin D1-hydroxylase (1-OHase) activity. To test whether aging rats can increase 1,25-(OH)2D3 production in response to PTH, male rats of the same litter were fed a normal Ca diet and were sacrificed at 175-225 g (young rats) or 3 months later at 350-425 g (aging rats). At sacrifice, basal serum 1,25-(OH)2D3 levels (88 +/- 16 versus 49 +/- 8 pg/ml, P < 0.05) and in vitro renal proximal tubule 1-OHase activity (178 +/- 15 versus 77 +/- 5 pmol/mg protein/5 minutes, n = 6, P < 0.001) were lower in aging animals. rPTH-(1-34) (10(-11) or 10(-7) M) increased in vitro 1,25-(OH)2D3 secretion by perifused renal proximal tubules from young but not aging rats. For young and aging rats, rPTH-(1-34) (10(-7) M) increased proximal tubule cAMP-dependent protein kinase (PKA) activity, and lower concentrations (10(-11) M) stimulated translocation of protein kinase C (PKC) activity from cytosolic to soluble membrane proximal tubule cell fractions. The results of this study show that PTH activation of 1,25-(OH)2D3 production may involve both signaling pathways, with the PKC pathway responsive to lower concentrations of the hormone. The acquired resistance to PTH stimulation of 1,25-(OH)2D3 production in aging appears not to involve the hormonal activation of PKA or PKC.
Friedlander
J
J
Department of Medicine, University of Chicago Pritzker School of Medicine, Illinois.
Janulis
M
M
Tembe
V
V
Ro
H K
HK
Wong
M S
MS
Favus
M J
MJ
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002117:Calcitriol / Q000096:biosynthesis* / Q000097:blood; D053493:Cholestanetriol 26-Monooxygenase; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000201:enzymology*; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013250:Steroid Hydroxylases / Q000378:metabolism; D019379:Teriparatide
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D011994:Recombinant Proteins; D019379:Teriparatide; D013250:Steroid Hydroxylases; D053493:Cholestanetriol 26-Monooxygenase; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D002117:Calcitriol