Translocator protein/peripheral benzodiazepine receptor is not required for steroid hormone biosynthesis.
Kanako Morohaku,Susanne H. Pelton,Daniel J. Daugherty,W. Ronald Butler,Wenbin Deng,Vimal Selvaraj +5 more
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The results show that TSPO function is not essential for steroid hormone biosynthesis and challenge the prevailing dogma that claims an essential role for T SPO in steroid hormone synthesis and force reexamination of functional interpretations made for this protein.Abstract:
Molecular events that regulate cellular biosynthesis of steroid hormones have been a topic of intense research for more than half a century. It has been established that transport of cholesterol into the mitochondria forms the rate-limiting step in steroid hormone production. In current models, both the steroidogenic acute regulatory protein (StAR) and the translocator protein (TSPO) have been implicated to have a concerted and indispensable effort in this cholesterol transport. Deletion of StAR in mice resulted in a critical failure of steroid hormone production, but deletion of TSPO in mice was found to be embryonic lethal. As a result, the role of TSPO in cholesterol transport has been established only using pharmacologic and genetic tools in vitro. To allow us to explore in more detail the function of TSPO in cell type-specific experimental manipulations in vivo, we generated mice carrying TSPO floxed alleles (TSPOfl/fl). In this study we made conditional knockout mice (TSPOcΔ/Δ) with TSPO deletion in testicular Leydig cells by crossing with an anti-Mullerian hormone receptor type II cre/+ mouse line. Genetic ablation of TSPO in steroidogenic Leydig cells in mice did not affect testosterone production, gametogenesis, and reproduction. Expression of StAR, cytochrome P450 side chain cleavage enzyme, 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase type I, and TSPO2 in TSPOcΔ/Δ testis was unaffected. These results challenge the prevailing dogma that claims an essential role for TSPO in steroid hormone biosynthesis and force reexamination of functional interpretations made for this protein. This is the first study examining conditional TSPO gene deletion in mice. The results show that TSPO function is not essential for steroid hormone biosynthesis.read more
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References
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Linda Madisen,Theresa A. Zwingman,Susan M. Sunkin,Seung Wook Oh,Hatim A. Zariwala,Hong Gu,Lydia Ng,Richard D. Palmiter,Michael Hawrylycz,Allan R. Jones,Ed S. Lein,Hongkui Zeng +11 more
TL;DR: A set of Cre reporter mice with strong, ubiquitous expression of fluorescent proteins of different spectra is generated and enables direct visualization of fine dendritic structures and axonal projections of the labeled neurons, which is useful in mapping neuronal circuitry, imaging and tracking specific cell populations in vivo.
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Translocator protein (18kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function.
Vassilios Papadopoulos,Mario Baraldi,Tomás R. Guilarte,Thomas B. Knudsen,Jean Jacques Lacapère,Peter Lindemann,Michael D. Norenberg,David J. Nutt,Abraham Weizman,Ming Rong Zhang,Moshe Gavish +10 more
TL;DR: Translocator protein (18kDa) is proposed as a new name, regardless of the subcellular localization of the protein, to represent more accurately its sub cellular role (or roles) and putative tissue-specific function (or functions).
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Specific benzodiazepine receptors in rat brain characterized by high-affinity (3H)diazepam binding
TL;DR: Specific [3H]diazepam binding to membranes appears to be restricted to brain, where it is unevenly distributed: the density of diazepam receptors is about five times higher in cortex (the highest density) than in pons-meddula (lowest density).
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The purification, cloning, and expression of a novel luteinizing hormone-induced mitochondrial protein in MA-10 mouse Leydig tumor cells. Characterization of the steroidogenic acute regulatory protein (StAR).
TL;DR: It is demonstrated for the first time that expression of the protein in MA-10 cells in the absence of hormone stimulation is sufficient to induce steroid production and it is proposed that this protein is required in the acute regulation of steroidogenesis.