yes / Thyroid hormone (TH) is essential for adult brain function and its actions include several key roles in the hypothalamus.
Although TH controls gene expression via specific TH receptors of the nuclear receptor class, surprisingly few genes have
been demonstrated to be directly regulated by TH in the hypothalamus, or the adult brain as a whole. This study explored
the rapid induction by TH of retinaldehyde dehydrogenase 1 (Raldh1), encoding a retinoic acid (RA)-synthesizing enzyme, as a
gene specifically expressed in hypothalamic tanycytes, cells that mediate a number of actions of TH in the hypothalamus. The
resulting increase in RA may then regulate gene expression via the RA receptors, also of the nuclear receptor class. In vivo
exposure of the rat to TH led to a significant and rapid increase in hypothalamic Raldh1 within 4 hours. That this may lead to
an in vivo increase in RA is suggested by the later induction by TH of the RA-responsive gene Cyp26b1. To explore the
actions of RA in the hypothalamus as a potential mediator of TH control of gene regulation, an ex vivo hypothalamic rat slice
culture method was developed in which the Raldh1-expressing tanycytes were maintained. These slice cultures confirmed that
TH did not act on genes regulating energy balance but could induce Raldh1. RA has the potential to upregulate expression
of genes involved in growth and appetite, Ghrh and Agrp. This regulation is acutely sensitive to epigenetic changes, as has
been shown for TH action in vivo. These results indicate that sequential triggering of two nuclear receptor signalling systems
has the capability to mediate some of the functions of TH in the hypothalamus.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/10838 |
| Date | 03 November 2015 |
| Creators | Stoney, P.N., Helfer, Gisela, Rodrigues, D., Morgan, P.J., McCaffery, P.J. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, Published version |
| Rights | © 2016 The Authors. Glia Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,provided the original work is properly cited. |
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