Endocrine Abstracts

Thyroid hormone (TH) regulation of hypothalamic function has been extensively investigated. It is driven, in part, by the presence of deiodinase enzymes in tanycytes surrounding the third ventricle converting T₄ to active T₃. Retinoic acid (RA), the transcriptionally active form of Vitamin A, has not previously been considered to be an important part of hypothalamic regulation. Data presented here highlights novel parallels between the TH and RA synthetic pathways in the hypothalamus implying that RA also acts to regulate hypothalamic gene expression and function.

Using immunohistochemistry the RA synthesizing enzyme retinaldehyde dehydrogenase (RALDH) was localised to the tanycytes surrounding the third ventricles of the mouse and rat. This provides the machinery to convert CSF derived retinol to RA for use by the hypothalamus and parallels the capacity of these cells to synthesize T₃ from CSF derived T₄. Changes in photoperiod can modify the RALDH expression in rat tanycytes, demonstrating external regulation of RA availability to the hypothalamus. Hypothalamic cells responding to RA synthesized by tanycytes express retinoic acid receptors and retinoid X receptors and are predominantly localized to the arcuate nucleus. The cellular pattern of these receptors was changed by photoperiod. Other cells located in the hypothalamus express retinoic acid cellular binding protein-1 a negative intracellular regulator of available RA that can be manipulated by photoperiod. Overall, alteration in length of light exposure indicated that RA signalling was enhanced when the photoperiod was extended. To mimic this RA was added to organotypic hypothalamic slice cultures, which produced an increase in hypothalamic ACTH production demonstrating the potential for RA to alter hypothalamic neuroendocrine peptides.

This work presents the new concept of controlled RA synthesis by hypothalamic tanycytes and gives rise to the possible involvement of this system in endocrine, and possibly vitamin A, homeostasis.