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Based on observations that mutations of GATA-3 are responsible for the HDR-syndrome (hypoparathyroidism, deafness, renal defects) and that GATA-transcription factors have an important role to play in inner ear development, we hypothesized that these transcription factors may be involved in regulatory changes of prestin transcription. To prove this, we examined in parallel the expression of mRNA of prestin and Gata-3,-2 and Gata-1 in the organ of Corti during early postnatal development of rats and in organotypic cultures. Remarkable relations are observed between prestin and Gata-3,-2 expression in organ of Corti preparations in vivo and in vitro: (i) Gata-3,-2 expression display similar apical-basal gradients as prestin mRNA levels. (ii) The prestin expression increases between postnatal day two and postnatal day eight by a factor of about four in the apical and middle segments and by a factor of two in the basal part. Highly significant Pearson correlation coefficients were observed between Gata-3,-2 mRNA and prestin levels when the data were evaluated by regression analyses. (iii) Parallel changes of prestin mRNA and Gata-3,-2 mRNA levels were observed in response to thyroid hormone and to gemfibrozil application. These observations suggest a regulatory role played by the Gata-3,-2 transcription factors in prestin expression.
Animals Animals, Newborn/metabolism* Anion Transport Proteins/genetics Anion Transport Proteins/metabolism* Cells, Cultured GATA1 Transcription Factor/genetics GATA1 Transcription Factor/metabolism* GATA2 Transcription Factor/genetics GATA2 Transcription Factor/metabolism* GATA3 Transcription Factor/genetics GATA3 Transcription Factor/metabolism* Gemfibrozil/pharmacology Hypolipidemic Agents/pharmacology Lipid Metabolism/physiology Organ of Corti/cytology Organ of Corti/metabolism* RNA, Messenger/drug effects RNA, Messenger/metabolism* Rats Regression Analysis