title: Biologic activity of dihydroxylated 19-nor-(pre)vitamin D3.
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.
authors.affiliation: Laboratorium voor Experimentele Geneeskunde en Endocrinologie, Katholieke Universiteit Leuven, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Bouillon
authors.forename: L A
authors.initials: LA
authors.lastname: Sarandeses
authors.forename: K
authors.initials: K
authors.lastname: Allewaert
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.forename: J L
authors.initials: JL
authors.lastname: Mascareñas
authors.forename: A
authors.initials: A
authors.lastname: Mouriño
authors.forename: S
authors.initials: S
authors.lastname: Vrielynck
authors.forename: P
authors.initials: P
authors.lastname: de Clercq
authors.forename: M
authors.initials: M
authors.lastname: Vandewalle
mesh_terms: D000818:Animals; D064026:Calbindins; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000097:blood / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002645:Chickens; D002762:Cholecalciferol / Q000378:metabolism / Q000494:pharmacology*; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006900:Hydroxylation; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D015675:Osteocalcin / Q000097:blood / Q000378:metabolism; D012516:Osteosarcoma / Q000473:pathology; D018167:Receptors, Calcitriol / Q000378:metabolism*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013552:Swine; D014407:Tumor Cells, Cultured
chemical_list: D064026:Calbindins; D018167:Receptors, Calcitriol; D064030:S100 Calcium Binding Protein G; D015675:Osteocalcin; C083610:1,25-dihydroxy-19-norvitamin D3; C083611:1,25-dihydroxy-19-norprevitamin D3; D002762:Cholecalciferol; D002117:Calcitriol; D002118:Calcium