TY - JOUR
T1 - lα,25-dihydroxyvitamin D3 receptor
T2 - competitive binding of vitamin D analogs
AU - Brumbaugh, Peter F.
AU - Haussler, Mark R.
N1 - Funding Information:
an efficient (but not naturally occurring) precursor of 1(x,25-(OH)2-D3 rather than en ideal analog of the hormone . We propose that this analog is rapidly 25-hydro~lated and acts by metabolic transformation to 1a,25-(OH)2-D3. The phenomenon of 25-hydroxylation, in yivo, probably also is applicable to dihydrotachyaterol2, which does not bind effectively to the hormone receptor (Fig . 2), but is biologically active at high dose levels . In addition to providing possible explanations of the previous data on the biological activity of vitamin D and its analogs, extension of these studies may be of value in designing analogs of the vitamin to correct renal oateodyetropby, vitamin D-resistant rickets, and possibly osteoporo-sis. Flarthexmore, the specificity and high affinity of this receptor for 1,25-(OH)2-D3 suggest that it could be utilized in the development of a competitive protein binding assay for the hormone . Ackno~le da~ents - This research was supported in part by USPHS Grant AM15781, USPHS Training Grant GM01982 funds from the Arizona Heart Association. Rote Added In Proof - Recently and Norman reported that a 250 fold excess of 25-OH-D3 50~ reduction of ~3iL~11Y,25-(OH)2-D3 bind- ing to thin receptor
PY - 1973/12/16
Y1 - 1973/12/16
N2 - The intestinal nuclear receptor for lα,25-dihydroxyvitamin D3 has been utilized to determine the ability of vitamin D-active sterols to compete with this hormone at the molecular level. 25-Hydroxyvitamin D3 and lα-hydroxyvitamin D3 must be present in 150 and 450 times the concentration respectively of lα,25-dihydroxyvitamin D3, in vitro, to displace the physiologic hormone. These data indicate that: i) superphysiologic levels of 25-hydroxyvitamin D3 may simulate lα,25-dihydroxyvitamin D3 and act directly on isolated target organs and ii) the biologic potency observed for low doses of lα-hydroxyvitamin D3, in vivo, is probably the result of 25-hidroxylation of the lα-derivative to form lα,25-dihydroxyvitamin D3.
AB - The intestinal nuclear receptor for lα,25-dihydroxyvitamin D3 has been utilized to determine the ability of vitamin D-active sterols to compete with this hormone at the molecular level. 25-Hydroxyvitamin D3 and lα-hydroxyvitamin D3 must be present in 150 and 450 times the concentration respectively of lα,25-dihydroxyvitamin D3, in vitro, to displace the physiologic hormone. These data indicate that: i) superphysiologic levels of 25-hydroxyvitamin D3 may simulate lα,25-dihydroxyvitamin D3 and act directly on isolated target organs and ii) the biologic potency observed for low doses of lα-hydroxyvitamin D3, in vivo, is probably the result of 25-hidroxylation of the lα-derivative to form lα,25-dihydroxyvitamin D3.
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U2 - 10.1016/0024-3205(73)90120-3
DO - 10.1016/0024-3205(73)90120-3
M3 - Article
C2 - 4777332
AN - SCOPUS:0015691733
SN - 0024-3205
VL - 13
SP - 1737
EP - 1746
JO - Life Sciences
JF - Life Sciences
IS - 12
ER -