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Physiological regulation of hypothalamic TRH transcription in vivo is T 3 receptor isoform specific
Author(s) -
Guissouma Hajer,
Ghorbel Mohamed T.,
Seugnet Isabelle,
Ouatas Taoufik,
Demeneix Barbara A.
Publication year - 1998
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.12.15.1755
Subject(s) - transcription (linguistics) , medicine , luciferase , transcription factor , gene isoform , thyrotropin releasing hormone , endocrinology , thyroid hormone receptor , biology , receptor , in vivo , hypothalamus , response element , transcriptional regulation , microbiology and biotechnology , hormone , gene expression , chemistry , gene , transfection , promoter , biochemistry , genetics , philosophy , linguistics
Thyroid hormone (tri‐iodo‐thyronine, T 3 ) exerts transcriptional effects on target genes in responsive cells. These effects are determined by DNA/protein interactions governed by the type of T 3 receptors (TRs) in the cell. As TRs show tissue and developmental variations, regulation is best addressed in an integrated in vivo model. We examined TR subtype effects on thyrotropin‐releasing hormone (TRH) transcription and on the pituitary/thyroid axis end point: thyroid hormone secretion. Polyethylenimine served to transfect a TRH‐luciferase construct containing 554 bp of the rat TRH promoter into the hypothalami of newborn mice. Transcription from the TRH promoter was regulated in a physiologically faithful manner, being significantly increased in hypothyroidism and decreased in T 3 ‐treated animals. Moreover, when various ligand binding forms of mouse or chicken TRβ and TRα were expressed with TRH‐luciferase, all forms of TRβ gave T 3 ‐dependent regulation of TRH transcription, whereas transcription was T 3 insensitive with each TRα tested. Moreover, chicken TR α increased TRH transcription sixfold, whereas mouse TR α decreased transcription. These transcriptional effects had correlated physiological consequences: expression of the chicken TR α in the hypothalamus of newborn mice raised circulating T 4 levels by fourfold, whereas mouse TR α had opposite effects. Thus, TR subtypes have distinct, physiologically relevant effects on TRH transcription.—Guissouma, H., Ghorbel, M. T., Seugnet, I., Ouatas, T., Demeneix, B. A. Physiological regulation of hypothalamic TRH transcription in vivo is T3 receptor isoform specific. FASEB J. 12, 1755–1764 (1998)