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Update on biological actions of 1alpha,25(OH)2-vitamin D3 (rapid effects) and 24R,25(OH)2-vitamin D3.

Abstract：

:All biologic responses to vitamin D are now known to arise as a consequence of the metabolism of this seco-steroid into its two principal biologically active metabolites 1alpha,25(OH)(2)-vitamin D(3) (1ALPHA;,25(OH)(2)D(3)) and 24R,25(OH)(2)-vitamin D(3) (24R,25(OH)(2)D(3)). 1alpha,25(OH)(2)D(3) is the dominant metabolite and produces a wide array of biological responses via interacting both with the classical vitamin D nuclear receptor (VDR(nuc)) that regulates gene transcription in over 30 target organs and with a putative cell membrane receptor (VDR(mem1,25)) that mediates rapid (within seconds to minutes) biological responses. Ligand occupancy of VDR(mem1,25) is linked to signal transduction systems that can mediate the opening of Ca(2+) and chloride voltage gated channels as well as activation of MAP-kinase. MAP-kinase activation in some cells containing VDR(mem1,25)+VDR(nuc) then results in "cross-talk" from VDR(mem1,25) to VDR(nuc) which modulates transactivation of 1alpha,25(OH)(2)D(3) responsive gene promoters. The 24R,25(OH)(2)D(3) metabolite has been shown to be an essential hormone for the process of bone fracture healing. The activity of the enzyme responsible for the production of 24R,25(OH)(2)D(3), the renal 25(OH)D-24-hydroxylase, becomes elevated within 4-11 days after imposition of a tibial fracture, thereby increasing the blood concentrations of 24R,25(OH)(2)D(3) by threefold. The 24R,25(OH)(2)D(3) likely initiates its biological responses via binding to the ligand binding domain of a second cell membrane receptor, the VDR(mem24,25), which is stereospecific for 24R,25(OH)(2)D(3) in comparison with 24S,25(OH)(2)D(3) and 1alpha,25(OH)(2)D(3). This report summarizes the status of several current research frontiers in this arena of the vitamin D endocrine system.

journal_name

Mol Cell Endocrinol

journal_title

Molecular and cellular endocrinology

authors

Norman AW,Okamura WH,Bishop JE,Henry HL

doi

10.1016/s0303-7207(02)00273-3

keywords:

subject

Has Abstract

pub_date

2002-11-29 00:00:00

pages

1-13

issue

1-2

eissn

0303-7207

issn

1872-8057

pii

S0303720702002733

journal_volume

197

pub_type

杂志文章,评审

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Update on biological actions of 1alpha,25(OH)2-vitamin D3 (rapid effects) and 24R,25(OH)2-vitamin D3.