Connexin-32 acts as a downregulator of growth of thyroid gland.
Thyroid epithelial cells communicate through gap junctions formed from connexin (Cx)32, Cx43, and Cx26. We previously reported that reexpression of Cx32 in "gap junction-deficient" FRTL-5 and FRT thyroid cell lines induces a reduction of cell proliferation rate and an activation of expression of cell differentiation. The present study aimed at determining whether Cx32 could exert similar regulatory functions in vivo. We investigated morphological and functional characteristics of thyroid gland of Cx32-deficient mice (Cx32-KO), mice overexpressing Cx32 selectively in the thyroid (Cx32-T+), and Cx32-KO mice with a thyroid-selective Cx32 complementation obtained by crossing Cx32-KO and Cx32-T+ mice. In basal conditions, Cx32-KO mice did not present any detectable thyroid alteration, whereas Cx32-T+ mice showed a thyroid hypoplasia (20% reduction) associated with a slight increase in thyroid functional activity. Under thyrotropin stimulation (following sodium perchlorate treatment), Cx32-KO mice developed a larger goiter (< or =65% increase) than wild-type littermates, whereas Cx32-T+ mice exhibited the same thyroid hyperplasia as wild-type mice. Restoration of Cx32 expression in the thyroid of Cx32-KO mice abrogated the thyroid growth increase related to Cx32 deficiency. All together, these data show that Cx32 acts as a downregulator of growth of thyroid gland; an excess of Cx32 limits growth of thyroid cells in the basal state, whereas a lack of Cx32 confers an additional growth potential to TSH-stimulated thyroid cells.
Prost
Gaëlle
G
INSERM UMR 664, Faculté de Médecine Laennec, 7 rue Guillaume Paradin, Lyon Cedex 08, France.
Bernier-Valentin
Françoise
F
Munari-Silem
Yvonne
Y
Selmi-Ruby
Samia
S
Rousset
Bernard
B
D000818:Animals; D017630:Connexins / Q000235:genetics / Q000502:physiology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D015536:Down-Regulation / Q000502:physiology; D005838:Genotype; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009929:Organ Size / Q000502:physiology; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D012313:RNA / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013954:Thyroglobulin / Q000235:genetics; D013961:Thyroid Gland / Q000254:growth & development*; D013972:Thyrotropin / Q000097:blood / Q000494:pharmacology; D000097002:Gap Junction beta-1 Protein
D017630:Connexins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D049452:Green Fluorescent Proteins; D012313:RNA; D013954:Thyroglobulin; D013972:Thyrotropin; D000097002:Gap Junction beta-1 Protein; C034477:RNA primers