Regulation of 25-hydroxyvitamin D3 1alpha-hydroxylase gene expression by parathyroid hormone and 1,25-dihydroxyvitamin D3.
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.
Brenza
H L
HL
Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin-Madison 53706, USA.
DeLuca
H F
HF
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002117:Calcitriol / Q000494:pharmacology*; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D026541:Heymann Nephritis Antigenic Complex; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D010281:Parathyroid Hormone / Q000494:pharmacology*; D016105:Parathyroidectomy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone / Q000235:genetics; D013552:Swine; D013965:Thyroidectomy
D017931:DNA Primers; D026541:Heymann Nephritis Antigenic Complex; D008562:Membrane Glycoproteins; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol