Regulation of 25-hydroxyvitamin D3 1alpha-hydroxylase gene expression by parathyroid hormone and 1,25-dihydroxyvitamin D3.

Abstract:

:The conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) takes place mainly in the kidney and is catalyzed by the enzyme 1alpha-hydroxylase. Parathyroid hormone (PTH) and 1,25-(OH)2D3 are well-known regulators of this tightly controlled step, but the mechanisms by which they modulate 1alpha-hydroxylase activity have not been fully delineated. Northern analysis showed PTH and forskolin rapidly and transiently increase 1alpha-hydroxylase expression in AOK-B50 cells and HKC-8 cells. Actinomycin D treatment blocks the increase, but cycloheximide does not. No decrease of 1alpha-hydroxylase transcript by 1,25-(OH)2D3 was observed in either cell line, although 24-hydroxylase levels were strongly induced by 1,25-(OH)2D3 treatment. 1,25-(OH)2D3 suppressed the 1alpha-hydroxylase transcript in vivo both in the presence and absence of exogenously supplied PTH. These results suggest that the stimulatory action of PTH is directly on the 1alpha-hydroxylase gene, while the repressive action of 1,25-(OH)2D3 does not involve the parathyroid gland but is nevertheless indirect.

journal_name

Arch Biochem Biophys

authors

Brenza HL,DeLuca HF

doi

10.1006/abbi.2000.1970

subject

Has Abstract

pub_date

2000-09-01 00:00:00

pages

143-52

issue

1

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(00)91970-2

journal_volume

381

pub_type

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