||Steroidogenic abnormalities in translocator protein knockout mice and significance in the aging male
Barron, Anna ,
Ji, Bin ,
Kito, Seiji ,
Suhara, TetsuyaHiguchi, Makoto
85 , 2017-11 , Published by Portland Press on behalf of the Biochemical Society
The translocator protein (TSPO) has been proposed to act as a key component in a complex important for mitochondrial cholesterol importation, which is the rate-limiting step in steroid hormone synthesis. However, TSPO function in steroidogenesis has recently been challenged by the development of TSPO knockout (TSPO-KO) mice, as they exhibit normal baseline gonadal testosterone and adrenal corticosteroid production. Here we demonstrate that despite normal androgen levels in young male TSPO-KO mice, TSPO deficiency alters steroidogenic flux and results in reduced total steroidogenic output. Specific reductions in levels of progesterone and corticosterone were observed in both young and aged male TSPO-KO mice, as well as age-dependent androgen deficiency. Collectively, these findings indicate that while TSPO is not critical for achieving baseline testicular and adrenal steroidogenesis, either indirect effects of TSPO on steroidogenic processes, or the presence of compensatory mechanisms and functional redundancy, lead to subtle steroidogenic abnormalities which become exacerbated with aging.