Enhanced expression of Cyp17a1 and production of DHEA-S in the liver of late-pregnant rats.

Abstract

Cytochrome P450 17A1 (CYP17A1) catalyzes two enzymatic reactions in the biosynthesis of dehydroepiandrosterone (DHEA) from pregnenolone. In pregnant humans, the adrenal gland is responsible for DHEA biosynthesis, which is then sulfated by SULT2A1 and released into the bloodstream. This sulfated DHEA is subsequently taken up by the placenta and deconjugated to serve as a precursor for estrogen biosynthesis. The expression of Cyp17a1 is regulated by methylation, typically showing marked interspecies differences, including repression of Cyp17a1 expression in the adrenal gland of rodents. This study focused on the liver, an extragonadal steroidogenic organ showing active sulfate conjugation, as a site for DHEA-sulfate (DHEA-S) biosynthesis during pregnancy in rodents, rather than the adrenal glands. Cyp17a1 expression in rat liver was significantly lower than in the testis, with no differences between sexes. However, Cyp17a1 expression increased significantly before parturition (gestational days [GD] 19-21) compared to late pregnancy (GD 15-18). The Sult2a family were expressed in the livers of both pregnant and non-pregnant rats. We also observed increased DHEA and DHEA-S levels in the liver of pregnant rats before parturition compared to non-pregnant rats, with DHEA-S concentrations being significantly higher at GD 19-21 than at days 15-18. These findings suggest that increased expression of Cyp17a1 in the last trimester enhances DHEA synthesis in the liver, and that DHEA is quickly conjugated by Sult2a. In rodents, the liver may be involved in DHEA-S biosynthesis before parturition, compensating for the repression of Cyp17a1 in the adrenal glands.