Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

Tertiary Hypothyroidism and Hyperglycemia in Mice with Targeted Disruption of the Thyrotropin-Releasing Hormone Gene

Masanobu Yamada, Yumiko Saga, Nobuyuki Shibusawa, Jyunko Hirato, Masami Murakami, Toshiharu Iwasaki, Koshi Hashimoto, Teturou Satoh, Katsumi Wakabayashi, Makoto M. Taketo and Masatomo Mori
Proceedings of the National Academy of Sciences of the United States of America
Vol. 94, No. 20 (Sep. 30, 1997), pp. 10862-10867
Stable URL: http://www.jstor.org/stable/43430
Page Count: 6
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Tertiary Hypothyroidism and Hyperglycemia in Mice with Targeted Disruption of the Thyrotropin-Releasing Hormone Gene
Preview not available

Abstract

Thyrotropin-releasing hormone (TRH) is a brain hypothalamic hormone that regulates thyrotropin (TSH) secretion from the anterior pituitary and is ubiquitously distributed throughout the brain and other tissues including pancreas. To facilitate studies into the role of endogenous TRH, we have used homologous recombination to generate mice that lack TRH. These TRH-/- mice are viable, fertile, and exhibit normal development. However, they showed obvious hypothyroidism with characteristic elevation of serum TSH level and diminished TSH biological activity. Their anterior pituitaries exhibited an apparent decrease in TSH immunopositive cells that was not due to hypothyroidism. Furthermore, this decrease could be reversed by TRH, but not thyroid hormone replacement, suggesting a direct involvement of TRH in the regulation of thyrotrophs. The TRH-/- mice also exhibited hyperglycemia, which was accompanied by impaired insulin secretion in response to glucose. These findings indicate that TRH-/- mice provide a model of exploiting tertiary hypothyroidism, and that TRH gene abnormalities cause disturbance of insulin secretion resulting in marked hyperglycemia.

Page Thumbnails

  • Thumbnail: Page 
10862
    10862
  • Thumbnail: Page 
10863
    10863
  • Thumbnail: Page 
10864
    10864
  • Thumbnail: Page 
10865
    10865
  • Thumbnail: Page 
10866
    10866
  • Thumbnail: Page 
10867
    10867