Ethane dimethane sulfonate and NNN ' N '-tetrakis-(2-pyridylmethyl)ethylenediamine inhibit steroidogenic acute regulatory (StAR) protein expression in MA-10 Leydig cells and rat Sertoli cells

Apoptosis inhibits steroid biosynthesis, but it is not clear how the Steroi dogenic Acute Regulatory (StAR) protein, is affected. To characterize StAR expression during apoptosis, mouse MA-10 Leydig tumor cells were treated wi th ethane dimethane sulfonate (EDS), an inducer of apoptosis, and the metal ion chelator NNN'N'-tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN), an i nducer of cell death. Both chemicals induced cell death and similarly inhib ited dbcAMP-stimulated steroidogenesis and accumulation of the 30 kDa form of StAR. Utilizing the dye JC-1, it was found that TPEN and EDS also impair ed the mitochondrial electrochemical potential (Delta Psi). In Sertoli cell s, which also express StAR, EDS induced cell death and attenuated StAR expr ession. We conclude 1) steroidogenesis and accumulation of mature StAR prot ein are inhibited as a consequence of the induction of apoptosis; 2) reduce d levels of StAR may be partially attributed to inhibition of import becaus e of the loss of Delta Psi; 3) loss of steroidogenesis is probably due to l oss of StAR synthesis and disruption of Delta Psi.