Biologic activity of dihydroxylated 19-nor-(pre)vitamin D3.
J Bone Miner Res
; 8(8): 1009-15, 1993 Aug.
Article
en En
| MEDLINE
| ID: mdl-8213251
ABSTRACT
Vitamin D3 and its hydroxylated metabolites are normally in thermal equilibrium with their previtamin D isomers. To evaluate the biologic activity of 1 alpha, 25-dihydroxyprevitamin D3, we synthesized 19-nor analogs of 1 alpha, 25-dihydroxy(pre)vitamin D3 because the absence of a C19 methylene group prevents the isomerization of these analogs. The affinity of 1 alpha, 25-(OH)2D3-19-nor-D3 for the intestinal vitamin D receptor and plasma vitamin D binding protein was mildly decreased [30 and 20% of the affinity of 1 alpha, 25-(OH)2D3, respectively], but the affinity of 1 alpha, 25-(OH)2-19-nor-previtamin D3 was only 1 and 6% of that of 1 alpha, 25-(OH)2D3 for the receptor and DBP, respectively. The in vitro effects on human promyeloid leukemia (HL-60 cell) differentiation and osteocalcin secretion by human osteosarcoma (MG-63) cells by 1 alpha, 25-(OH)2-19-nor-D3 were nearly identical to those of 1 alpha-25-(OH)2D3, whereas 19-nor-previtamin D3 showed poor activity (2%). The in vivo calcemic effects of both analogs, studied in vitamin D-deficient chicks treated for 10 consecutive days with the analogs, showed no activity of the previtamin D3 analog and reduced calcemic effects (< or = 10%) of 1 alpha, 25-(OH)2-19-nor-D3. We conclude that the previtamin D form of 1 alpha, 25-(OH)2D3 has lost most of its biologic activity in vitro and in vivo.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Calcitriol
/
Calcio
/
Receptores de Calcitriol
/
Colecalciferol
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Bone Miner Res
Asunto de la revista:
METABOLISMO
/
ORTOPEDIA
Año:
1993
Tipo del documento:
Article
País de afiliación:
Bélgica