Loss of parathyroid hormone‐stimulated 1,25‐dihydroxyvitamin D3production in aging does not involve protein kinase A or C pathways

Jason Friedlander, Mark Janulis, Vrishali Tembe, Heung Kyu Ro, Man Sau Wong, Murray J. Favus

Research output: Journal article publicationJournal articleAcademic researchpeer-review

21 Citations (Scopus)

Abstract

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)2D3may 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)2D3production 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)2D3levels (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) (10−11or 10−11M) increased in vitro 1,25‐(OH)2D3secretion by perifused renal proximal tubules from young but not aging rats. For young and aging rats, rPTH‐(1–34) (10−7M) increased proximal tubule cAMP‐dependent protein kinase (PKA) activity, and lower concentrations (10−11M) 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)2D3production 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)2D3production in aging appears not to involve the hormonal activation of PKA or PKC.
Original languageEnglish
Pages (from-to)339-345
Number of pages7
JournalJournal of Bone and Mineral Research
Volume9
Issue number3
DOIs
Publication statusPublished - 1 Jan 1994
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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