Dehydroepiandrosterone Sulfate Stimulates Expression of Blood-Testis-Barrier Proteins Claudin-3 and -5 and Tight Junction Formation via a Gnα11-Coupled Receptor in Sertoli Cells

摘要: Dehydroepiandrosterone sulfate (DHEAS) is a circulating sulfated steroid considered to be pro-androgen in mammalian physiology. Here we show that at physiological concentration (1 μM), DHEAS induces the phosphorylation of kinase Erk1/2 and transcription factors CREB ATF-1 murine Sertoli cell line TM4. This signaling cascade stimulates expression tight junction (TJ) proteins claudin-3 claudin-5. As consequence increased expression, connections between neighboring cells are augmented, as demonstrated by measurements transepithelial resistance. Phosphorylation Erk1/2, CREB, or not affected presence sulfatase inhibitor STX64. was observed when dehydroepiandrosterone (DHEA) used instead DHEAS. Abrogation androgen receptor (AR) siRNA did affect DHEAS-stimulated phosphorylation, nor it change DHEAS-induced stimulation claudin-5 expression. All above indicate desulfation conversion into different hormone required trigger cascade. activating effects DHEAS, however, abolished G-protein Gnα11 suppressed siRNA, including -5 TJ formation indicated reduced Taken together, these results consistent with being mediated through membrane-bound G-protein-coupled interacting pathway resembles non-classical pathways hormones. Considering fact produced reproductive organs, findings also suggest acting an autonomous influencing dynamics blood-testis barrier, might play crucial role for regulation maintenance male fertility.