First Author | Liere P | Year | 2023 |
Journal | Int J Mol Sci | Volume | 24 |
Issue | 3 | PubMed ID | 36768796 |
Mgi Jnum | J:336280 | Mgi Id | MGI:7436430 |
Doi | 10.3390/ijms24032474 | Citation | Liere P, et al. (2023) The Comprehensive Steroidome in Complete TSPO/PBR Knockout Mice under Basal Conditions. Int J Mol Sci 24(3) |
abstractText | The 18 kDa translocator protein (TSPO/PBR) is a multifunctional evolutionary highly conserved outer mitochondrial membrane protein. Decades of research has reported an obligatory role of TSPO/PBR in both mitochondrial cholesterol transport and, thus, steroid production. However, the strict dependency of steroidogenesis on TSPO/PBR has remained controversial. The aim of this study was to provide insight into the steroid profile in complete C57BL/6-(Tspotm1GuWu(GuwiyangWurra))-knockout male mice (TSPO-KO) under basal conditions. The steroidome in the brain, adrenal glands, testes and plasma was measured by gas chromatography coupled to tandem mass spectrometry (GC-MS/MS). We found that steroids present in wild-type (WT) mice were also detected in TSPO-KO mice, including pregnenolone (PREG), progestogens, mineralo-glucocorticosteroids and androgens. The concentrations of PREG and most metabolites were similar between genotypes, except a significant decrease in the levels of the 5alpha-reduced metabolites of progesterone (PROG) in adrenal glands and plasma and of the 5alpha-reduced metabolites of corticosterone (B) in plasma in TSPO-KO compared to WT animals, suggesting other regulatory functions for the TSPO/PBR. The expression levels of the voltage-dependent anion-selective channel (VDAC-1), CYP11A1 and 5alpha-reductase were not significantly different between both groups. Thus, the complete deletion of the tspo gene in male mice does not impair de novo steroidogenesis in vivo. |