TGF-beta inhibits CYP17 transcription in H295R cells acting via activin receptor-like kinase 5

Abstract

Objective: Transforming growth factor beta (TGF-beta) is a potent inhibitor of 17alpha-hydroxylase/17,20 lyase activity and CYP17 gene expression. We investigated the mechanism how CYP17 is inhibited by TGF-beta in adrenocortical cells.

Methods: H295R cells were culture and incubated with TGF-beta, transcription inhibitor (DRB), activin receptor-like kinase 5 ALK5 (TbetaRII) inhibitor (SB431542), mitogen activated kinases inhibitors (PD98059 and SB203580), subsequently using reverse transcription and quantitative PCR (RT-qPCR) we determined CYP17 expression.

Results: TGF-beta significantly decreased the level of cytochrome P450c17 mRNA and this inhibitory effect of TGF-beta on CYP17 expression required activin receptor-like kinase 5 (ALK5) and on-going transcription. Mitogen activated kinases MEK1 and p38 MAPK are not involved it the inhibitory effect of TGF-beta on CYP17 expression.

Conclusion: We concluded that the TGF-beta-dependent decrease of 17alpha-hydroxylase/17,20 lyase activity in the H295R cells is caused by inhibition of CYP17 transcription and is mediated by the ALK5 receptor.