A Fast-Acting Pathway

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Science  09 Jul 2004:
Vol. 305, Issue 5681, pp. 151
DOI: 10.1126/science.305.5681.151b

In vertebrates, thyroid hormone is needed for normal physiology and development. Although thyroid hormone is known to regulate transcription via thyroid hormone receptors, there is a puzzling temporal aspect of hormone effects. Signaling to the nucleus has been shown to operate on the order of days; however, with exposure to thyroid hormone, rapid effects have been seen in vivo.

Scanlan et al. have synthesized several thyroid hormone analogs and examined their potencies. One of the thyronamine derivatives, T1AM, occurs naturally in the brains of vertebrates. When injected intraperitoneally, it caused hypothermia and inactivity in mice. Cardiovascular performance was also affected: In an ex vivo heart model, injection of T1AM produced a rapid reduction in cardiac output. In contrast to prior understanding of thyroid hormone function through regulation of expression, these results support a model in which thyroid hormone response is mediated on a much shorter time scale by differential processing of thyroid hormone and by signal transduction via G protein- coupled receptors. — BAP

Nature Med. 10, 638 (2004).

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