Characterization of the vitamin D endocrine system in human sebocytes in vitro.
Sebocytes are sebum-producing cells that form the sebaceous glands. We investigated the role of sebocytes as target cells for vitamin D metabolites and the existence of an enzymatic machinery for the local synthesis and metabolism of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3), calcitriol], the biologically active vitamin D metabolite, in these cell types. Expression of vitamin D receptor (VDR), vitamin D-25-hydroxylase (25 OHase), 25-hydroxyvitamin D-1alpha-hydroxylase (1 alphaOHase), and 1,25-dihydroxyvitamin D-24-hydroxylase (24 OHase) was detected in SZ95 sebocytes in vitro using real time quantitative polymerase chain reaction. Splice variants of 1alphaOHase were identified by nested touchdown polymerase chain reaction. We demonstrated that incubation of SZ95 sebocytes with 1,25(OH)(2)D(3) resulted in a cell culture condition-, time-, and dose-dependent modulation of cell proliferation, cell cycle regulation, lipid content and interleukin-6/interleukin-8 secretion in vitro. RNA expression of VDR and 24 OHase was upregulated along with vitamin D analogue treatment. Although several other splice variants of 1alphaOHase were detected, our findings indicate that the full length product represents the major 1 alphaOHase gene product in SZ95 cells. In conclusion, SZ95 sebocytes express VDR and the enzymatic machinery to synthesize and metabolize biologically active vitamin D analogues. Sebocytes represent target cells for biologically active metabolites. Our findings indicate that the vitamin D endocrine system is of high importance for sebocyte function and physiology. We conclude that sebaceous glands represent potential targets for therapy with vitamin D analogues or for pharmacological modulation of 1,25(OH)(2)D(3) synthesis/metabolism.
Krämer
Christina
C
Department of Dermatology, The Saarland University Hospital, 66421 Homburg/Saar, Germany.
Seltmann
Holger
H
Seifert
Markus
M
Tilgen
Wolfgang
W
Zouboulis
Christos C
CC
Reichrath
Jörg
J
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D017398:Alternative Splicing / Q000187:drug effects; D015153:Blotting, Western; D002112:Calcifediol / Q000494:pharmacology; D002117:Calcitriol / Q000031:analogs & derivatives / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004703:Endocrine System / Q000187:drug effects / Q000378:metabolism*; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D018167:Receptors, Calcitriol / Q000378:metabolism; D012627:Sebaceous Glands / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology
D015850:Interleukin-6; D016209:Interleukin-8; D018167:Receptors, Calcitriol; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol; D002112:Calcifediol; C078903:seocalcitol