We previously identified
androgen-dependent sex differences in the
mRNA expression of
drug metabolizing
enzymes (
DMEs), including CYPs,
sulfotransferases and
uridine 5'-diphospho-glucuronosyltransferases, and
drug transporters in the pig liver and kidney. To elucidate the mechanism for such sex differences in pigs, we herein focused on the key regulators cut-like homeobox 2 (Cux2),
B-cell lymphoma 6 (Bcl6), and
signal transducer and activator of transcription 5b (Stat5b), which are reported to be responsible for the sex-biased gene expression of Cyps in the mouse liver. We used real-time RT-PCR to examine
androgen-dependent sex differences in the
mRNA levels of these regulators in the liver and kidney basically using Meishan and Landrace pigs. Significant sex differences (male > female) in the level of CUX2
mRNA were detected in the liver of both breeds, and levels were significantly decreased in males by
castration and increased in castrated males and intact females by administering
testosterone propionate. No such clear
androgen-dependent sex differences in hepatic BCL6 or STAT5B
mRNA expression were observed in either breed. In the kidney,
androgen-dependent gene expression of these regulators was not observed. In the liver, CUX2
mRNA expression closely correlated with that of
DMEs and
drug transporters, which were previously shown to have
androgen-dependent expression. Together, these findings demonstrate that hepatic CUX2
mRNA is expressed in an
androgen-dependent manner, and strongly suggest that CUX2 plays a key role in the
androgen-dependent gene expression of hepatic
DMEs and
drug transporters.