In vivo activation of the constitutive androstane receptor beta (CARbeta) by treatment with dehydroepiandrosterone (DHEA) or DHEA sulfate (DHEA-S).
We investigated whether dehydroepiandrosterone (DHEA) or DHEA-sulfate (S) affected the activities of nuclear receptors, with special reference to constitutive androstane receptor beta (CARbeta). Administration of DHEA or DHEA-S enhanced the DNA binding of hepatic nuclear extracts to responsive elements for the retinoic acid receptor, the retinoic acid receptor beta 2 and the peroxisome proliferator activated receptor. The bound complexes were shown to be the CARbeta-RXR heterodimer by antibody-supershift assays. The expression of a target gene of CARbeta, Cyp2b10, was increased in liver by DHEA or DHEA-S treatment, suggesting that DHEA or DHEA-S actually activated CARbeta in vivo. It was suggested that the metabolic conversion of DHEA, DHEA-S to CARbeta ligands could occur in vivo and the metabolites could regulate the expression of CARbeta target gene expression. Our results provide new insights into the in vivo relationship between DHEA/DHEA-S and CARbeta activation.
Fujita
Atsushi
A
Aino Institute for Aging Research, 3-9-25, Ohta, Ibaraki, 567-0018, Osaka, Japan.
Furutama
Daisuke
D
Tanaka
Toshifumi
T
Sakai
Reiko
R
Koyama
Akio
A
Hanafusa
Toshiaki
T
Mitsuhashi
Tomoaki
T
Ohsawa
Nakaaki
N
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D000090702:Constitutive Androstane Receptor; D003687:Dehydroepiandrosterone / Q000097:blood / Q000494:pharmacology*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D008024:Ligands; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D000090702:Constitutive Androstane Receptor; D008024:Ligands; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D014157:Transcription Factors; C082925:retinoic acid receptor beta; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate