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Updated: Aug 1, 2026
A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
Published on: July 14, 2016
Steroidogenic abnormalities in translocator protein knockout mice and significance in the aging male
Anna M Barron1,2, Bin Ji3, Seiji Kito1
1National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
Abstract:
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 the levels of progesterone and corticosterone as well as age-dependent androgen deficiency were observed in both young and aged male TSPO-KO mice. 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 compensatory mechanisms and functional redundancy, lead to subtle steroidogenic abnormalities which become exacerbated with aging.
Insights
Translocator protein (TSPO) deficiency causes subtle steroidogenic abnormalities, including reduced progesterone and corticosterone, with age-dependent androgen decline in mice.
Area of Science:
- Endocrinology
- Molecular Biology
- Mitochondrial Biology
Background:
- The translocator protein (TSPO) is implicated in mitochondrial cholesterol transport, a critical step in steroid hormone synthesis.
- TSPO knockout mice initially presented normal baseline steroid production, challenging its essential role in steroidogenesis.
- Investigating TSPO's precise function in steroid production remains crucial.
Purpose of the Study:
- To investigate the impact of TSPO deficiency on steroidogenic flux and hormone production in mice.
- To determine if TSPO plays a role beyond baseline steroidogenesis, particularly concerning aging.
Main Methods:
- Utilized TSPO knockout (TSPO-KO) mouse models.
- Analyzed baseline and age-dependent levels of key steroid hormones (testosterone, corticosterone, progesterone).
- Assessed overall steroidogenic output and flux.
Main Results:
- TSPO-KO mice exhibited normal baseline androgen levels in youth but showed altered steroidogenic flux.
- Specific reductions in progesterone and corticosterone were observed in TSPO-KO mice.
- Age-dependent androgen deficiency became apparent in TSPO-KO mice, indicating exacerbated effects with aging.
Conclusions:
- TSPO is not essential for maintaining normal baseline testicular and adrenal steroidogenesis.
- TSPO deficiency leads to subtle steroidogenic abnormalities, potentially through indirect effects or compensatory mechanisms.
- These abnormalities are exacerbated with aging, highlighting a more complex role for TSPO in steroid hormone synthesis over time.
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