HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: JOE-08-0128v1 199/1/113    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Nagayama, K. Articles by Nakamura, H. PubMed PubMed Citation Articles by Nagayama, K. Articles by Nakamura, H.

Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan¹ Ito Hospital, 4-3-6 Jingumae, Shibuya-ku, Tokyo, 150-8308, Japan

(Correspondence should be addressed to S Sasaki; Email: sasakis{at}hama-med.ac.jp)

Transcriptional repression of the TSH-specific β subunit (TSHβ) gene has been regarded to be specific to thyroid hormone (tri-iodothyronine, T₃) and its receptors (TRs) in physiological conditions. However, TSHβ mRNA levels in the pituitary were reported to decrease in the administration of pharmacologic doses of estrogen (17-β-estradiol, E₂) and increase in E₂ receptor (ER)- null mice. Here, we investigated the molecular mechanism of inhibition of the TSHβ gene expression by E₂-bound E₂-estrogen receptor 1 (E₂-ER). In kidney-derived CV1 cells, transcriptional activity of the TSHβ promoter was stimulated by GATA2 and suppressed by THRBs and ER in a ligand-dependent fashion. Overexpression of PIT1 diminished the E₂-ER-induced inhibition, suggesting that PIT1 may protect GATA2 from E₂-ER targeting by forming a stable complex with GATA2. Interacting surfaces between ER and GATA2 were mapped to the DNA-binding domain (DBD) of ER and the Zn finger domain of GATA2. E₂-dependent inhibition requires the ER amino-terminal domain but not the tertiary structure of the second Zn finger motif in E₂-ER-DBD. In the thyrotroph cell line, TT1, E₂ treatment reduced TSHβ mRNA levels measured by the reverse transcription PCR. In the human study, despite similar free thyroxine levels, the serum TSH level was small but significantly higher in post- than premenopausal women who possessed no anti-thyroid antibodies (1.90 µU/ml±0.13 S.E.M. vs 1.47 µU/ml±0.12 S.E.M., P<0.05). Our findings indicate redundancy between T₃-TR and E₂-ER signaling exists in negative regulation of the TSHβ gene.