title: Depletion of the p43 mitochondrial T3 receptor increases Sertoli cell proliferation in mice.
abstract: Among T3 receptors, TRα1 is ubiquitous and its deletion or a specific expression of a dominant-negative TRα1 isoform in Sertoli cell leads to an increase in testis weight and sperm production. The identification of a 43-kDa truncated form of the nuclear receptor TRα1 (p43) in the mitochondrial matrix led us to test the hypothesis that this mitochondrial transcription factor could regulate Sertoli cell proliferation. Here we report that p43 depletion in mice increases testis weight and sperm reserve. In addition, we found that p43 deletion increases Sertoli cell proliferation in postnatal testis at 3 days of development. Electron microscopy studies evidence an alteration of mitochondrial morphology observed specifically in Sertoli cells of p43-/- mice. Moreover, gene expression studies indicate that the lack of p43 in testis induced an alteration of the mitochondrial-nuclear cross-talk. In particular, the up-regulation of Cdk4 and c-myc pathway in p43-/- probably explain the extended proliferation recorded in Sertoli cells of these mice. Our finding suggests that T3 limits post-natal Sertoli cell proliferation mainly through its mitochondrial T3 receptor p43.
authors.affiliation: INRA, UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly, France ; CNRS, UMR7247 Physiologie de la Reproduction et des Comportements, Nouzilly, France ; Université François Rabelais de Tours, Tours, France ; IFCE, Nouzilly, France.
authors.forename: Betty
authors.initials: B
authors.lastname: Fumel
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Roy
authors.forename: Sophie
authors.initials: S
authors.lastname: Fouchécourt
authors.forename: Gabriel
authors.initials: G
authors.lastname: Livera
authors.forename: Anne-Simone
authors.initials: AS
authors.lastname: Parent
authors.forename: François
authors.initials: F
authors.lastname: Casas
authors.forename: Florian
authors.initials: F
authors.lastname: Guillou
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D049109:Cell Proliferation; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D009929:Organ Size; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D012708:Sertoli Cells / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D013737:Testis / Q000378:metabolism / Q000473:pathology; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics* / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D037021:Thyroid Hormone Receptors alpha
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