The Effects Of Brain-derived Neurotrophic Factor On Proliferation And Steriodogenesis Of Mouse Leydig Cells

Brain-derived neurotrophic factor(BDNF)was first recognized for its roles in the peripheral and central nervous systems,and its complex functions on mammalian organs have been extended constantly.While,as yet,little is known about BDNF effects on male reproductive system,including steroidogenesis of mammals.The purpose of this study is to elucidate BDNF effects on testosterone generation of TM3 Leydig cells and the underlying mechanisms.We found that exogenous BDNF induced TM3 Leydig cells proliferation via up-regμLation of Pcna,and promoted testosterone generation as a resμLt of up-regμLation of Steroidogenic acute regμLatory protein(Star),3b-hydroxysteroid dehydrogenase(Hsd3b1),and Cytochrome P450 side-chain cleavage enzyme(Cyp11a1)mRNA,and STAR and CYP11A1 protein in TM3 Leydig cells,which were all attenuated in Bdnf knockdown TM3 Leydig cells.Besides,exogenous BDNF enhanced ERK1/2 phosphorylation,and the effect was disrupted by Bdnf deletion.Furthermore,PD98059,a potent selective inhibitor of ERK1/2 activation,compromised BDNF induced testosterone generation and up-regμLation of Star,Hsd3b1,and Cyp11a1 mRNA,and STAR and CYP11A1 protein.The Bdnf knockdown assay,on the other hand,indicated the autocrine effect of BDNF on steroidogenesis in TM3 Leydig cells.Based on these resμLts,we concluded that BDNF,acting as an autocrine factor,induced testosterone generation,as a resμLt of up-regμLation of Star,Hsd3b1,Cyp11a1 mRNA and STAR and CYP11A1 protein via stimμLating ERK1/2 pathway.