title: Culture serum-induced conversion from agonist to antagonist of a Vitamin D analog, TEI-9647.
abstract: The nuclear receptor for Vitamin D (VDR) mediates many of the effects of Vitamin D in target tissues by regulating gene expression. The transactivation function of ligand-bound VDR in target tissues is thought to depend on the tissue-type and the cellular-environment, but the molecular basis for these differences has not been fully understood. In this study, during characterization of TEI-9647 as a synthetic ligand for the VDR, we found that depletion of serum from the culture medium converted TEI-9647 from an antagonist to an agonist of VDR-mediated transactivation, whereas it retained antagonistic activity in the presence of serum. Consistent with these results, using a mammalian two-hybrid system, we found that TEI-9647 recruited different coactivators to the VDR in the presence and absence of serum. These findings suggest that an unknown serum factor modulates the transactivation function of the VDR.
authors.affiliation: Exploratory Research for Advanced Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Yamaoka
authors.forename: Mi-sun
authors.initials: MS
authors.lastname: Kim
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takada
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Takeyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Kamimura
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kato
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D003470:Culture Media / Q000737:chemistry*; D016895:Culture Media, Serum-Free; D004247:DNA / Q000378:metabolism; D006801:Humans; D008024:Ligands; D051381:Rats; D018167:Receptors, Calcitriol / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047490:Retinoid X Receptor alpha / Q000378:metabolism; D013237:Stereoisomerism; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D003470:Culture Media; D016895:Culture Media, Serum-Free; D008024:Ligands; D018167:Receptors, Calcitriol; D047490:Retinoid X Receptor alpha; C400545:TEI 9647; D014807:Vitamin D; D004247:DNA; D002117:Calcitriol