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

This Article Accepted manuscript (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 Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Nagayama, K. Articles by Nakamura, H. Search for Related Content PubMed PubMed Citation Articles by Nagayama, K. Articles by Nakamura, H.

K Nagayama, Department of Internal Medicine 2, Hamamatsu University School of Medicine, Hamamatsu, Japan
S Sasaki, Department of Internal Medicine 2, Hamamatsu University School of Medicine, Hamamatsu, 431-3192, Japan
A Matsushita, Department of Internal Medicine 2, Hamamatsu University School of Medicine, Hamamatsu, Japan
K Ohba, Department of Internal Medicine 2, Hamamatsu University School of Medicine, Hamamatsu, Japan
H Iwaki, Department of Internal Medicine 2, Hamamatsu University School of Medicine, Hamamatsu, Japan
H Matsunaga, Department of Internal Medicine 2, Hamamatsu University School of Medicine, Hamamatsu, Japan
S Suzuki, Department of Internal Medicine 2, Hamamatsu University School of Medicine, Hamamatsu, Japan
H Misawa, Department of Internal Medicine 2, Hamamatsu University School of Medicine, Hamamatsu, Japan
K Ishizuka, Department of Internal Medicine 2, Hamamatsu University School of Medicine, Hamamatsu, Japan
J Noh, Ito Hospital, Shibuya-ku, Japan
Y Oki, Department of Internal Medicine 2, Hamamatsu University School of Medicine, Hamamatsu, Japan
H Nakamura, Department of Internal Medicine 2, Hamamatsu University School of Medicine, Hamamatsu, Japan

Correspondence: Shigekazu Sasaki, Email: sasakis{at}hama-med.ac.jp

Abstract

Transcriptional repression of the thyrotropin (TSH) β gene has been regarded to be specific to thyroid hormone (T3) and its receptors (TRs) in physiological conditions. However, TSHβ mRNA levels in the pituitary were reported to decrease by the administration of pharmacologic doses of estrogen (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 ER (E2-ER ). In kidney-derived CV1 cells, transcriptional activity of the TSHβ promoter was stimulated by GATA2 and suppressed by TRβs 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 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-polymerase chain reaction. In the human study, despite of similar free T4 levels, the serum TSH level was small but significantly higher in post- than pre-menopausal women who possessed no anti-thyroid antibodies (1.90 +/- 1.07 vs 1.47 +/- 1.00 µU/ml, P<0.05). Our findings indicate redundancy between T3-TR and E2-ER signaling exists in negative regulation of the TSHβ gene.