22-Oxa calcitriol is a less potent regulator of keratinocyte proliferation and differentiation due to decreased cellular uptake and enhanced catabolism.
22-oxa calcitriol (OCT) is a recently synthesized analog of calcitriol (1,25(OH)2D3) with potent biologic actions both in vivo and in vitro. Because it is considerably less hypercalcemic than 1,25(OH)2D3 when given in vivo, OCT is of potential use for the treatment of diseases, such as psoriasis, that respond to the antiproliferative, prodifferentiating actions of 1,25(OH)2D3. To determine the potential usefulness of OCT in hyperproliferative skin diseases, we compared the ability of OCT to that of 1,25(OH)2D3 with respect to regulation of keratinocyte proliferation and differentiation in vitro. These studies were performed in serum-free media to eliminate differences in potency secondary to differences in binding to the serum vitamin D-binding protein. We observed that OCT was considerably less effective than 1,25(OH)2D3 in inhibiting keratinocyte proliferation and stimulating differentiation. The decreased potency of OCT appeared to be due to decreased uptake and increased catabolism rather than decreased affinity for the vitamin D receptor. We conclude that under the conditions of our experiments OCT was less potent than 1,25(OH)2D3 because it failed to achieve comparable concentrations within the cell.
Bikle
D D
DD
Department of Medicine and Dermatology, Veterans Affairs Medical Center, San Francisco, California, USA.
Abe-Hashimoto
J
J
Su
M J
MJ
Felt
S
S
Gibson
D F
DF
Pillai
S
S
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007231:Infant, Newborn; D015603:Keratinocytes / Q000166:cytology*; D008297:Male; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D011498:Protein Precursors; D012333:RNA, Messenger; C032253:involucrin; D011503:Transglutaminases; D002117:Calcitriol; C051883:maxacalcitol