JOE
HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Journal of Endocrinology (2008) 199, 113-125       DOI: 10.1677/JOE-08-0128
© 2008 Society for Endocrinology
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
JOE-08-0128v1
199/1/113    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nagayama, K.
Right arrow Articles by Nakamura, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nagayama, K.
Right arrow Articles by Nakamura, H.

Inhibition of GATA2-dependent transactivation of the TSHβ gene by ligand-bound estrogen receptor {alpha}

 Koji Nagayama, Shigekazu Sasaki, Akio Matsushita, Kenji Ohba, Hiroyuki Iwaki, Hideyuki Matsunaga, Shingo Suzuki, Hiroko Misawa, Keiko Ishizuka, Yutaka Oki, Jaeduk Yoshimura Noh1 and Hirotoshi Nakamura

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)-{alpha} null mice. Here, we investigated the molecular mechanism of inhibition of the TSHβ gene expression by E2-bound E2-estrogen receptor 1 (E2-ER{alpha}). In kidney-derived CV1 cells, transcriptional activity of the TSHβ promoter was stimulated by GATA2 and suppressed by THRBs and ER{alpha} in a ligand-dependent fashion. Overexpression of PIT1 diminished the E2-ER{alpha}-induced inhibition, suggesting that PIT1 may protect GATA2 from E2-ER{alpha} targeting by forming a stable complex with GATA2. Interacting surfaces between ER{alpha} and GATA2 were mapped to the DNA-binding domain (DBD) of ER{alpha} and the Zn finger domain of GATA2. E2-dependent inhibition requires the ER{alpha} amino-terminal domain but not the tertiary structure of the second Zn finger motif in E2-ER{alpha}-DBD. In the thyrotroph cell line, T{alpha}T1, 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{alpha} signaling exists in negative regulation of the TSHβ gene.






HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2008 by the Society for Endocrinology.