Increases in CYP3A Expression and Glucocorticoid‐Inducibility in Liver of Rats Fed Soy Protein Isolate (SPI) Involves Post‐Transcriptional Effects on mRNA Processing.

We analyzed a time course of dexamethasone (DEX)‐induction at PND25 and PND60 in male and female rats fed soy protein isolate (SPI) or casein (CAS) based AIN93G diets throughout development to examine molecular mechanisms underlying increased CYP3A expression and inducibility after SPI‐feeding. At PND25, SPI‐feeding increased CYP3A1 and CYP3A2 mRNA expression (p < 0.05) only in male liver but increased CYP3A expression (p < 0.05) in both sexes at PND60. After 50 mg/kg DEX, CYP3A1 mRNA expression was induced >200‐fold in SPI‐fed males and females peaking 17 h post‐injection but only 100–150‐fold in CAS‐fed animals (p < 0.05). A similar increase in DEX‐inducibility was observed in CYP3A1 at PND60. CYP3A2 mRNA was also induced more in SPI‐fed rats, but DEX‐induction was only 2–4‐fold. Measurement of steady‐state HnRNA for CYP3A1 using RT‐PCR with intron‐specific primers showed no difference with diet and only 3–4‐fold induction peaking at 8 h post‐DEX. Quantitation of newly synthesized CYP3A1 RNA transcripts by nuclear run‐on analysis using biotinylated nucleotides followed by avidin‐bead precipitation and real‐time RT‐PCR demonstrated dramatic induction 8 h post‐DEX, but no effects of diet on constitutive or induced levels of transcription. These data suggest that primary transcripts of CYP3A have a short half life relative to its mature mRNA and that while DEX increases transcription, increased mRNA expression and inducibility following SPI‐feeding involves post‐transcriptional effects on RNA processing. Supported in part by ARS CRIS#6251‐51000‐003‐065.