Tanycytes line the wall of the third ventricle sitting at the boundary between the cerebral spinal fluid (CSF) and the hypothalamus. Tanycytes actively take up substances from the CSF using their villi-like apical projections that extend into the third ventricle. Retinol is one such compound and can be oxidized by these cells to retinoic acid, which can be released to regulate transcription in the hypothalamus via specific nuclear receptors. Two retinal dehydrogenases (RALDHs) required to catalyze this reaction, RALDH1 and RALDH2, are present in tanycyte processes that infiltrate the hypothalamus. However, when mRNA from rat hypothalamic tissue is quantified for these enzymes only RALDH1 is present in tissue but both proteins are clearly present.
The possible absence of RALDH2 mRNA transcript in tanycytes suggests that the enzyme may be derived from an alternative source. Western blotting of CSF identified that RALDH2 is present in CSF and may, hypothetically, be taken up by tanycytes. Thus CSF may potentially provide both retinol and the enzyme required to convert retinol to retinoic acid. One possible source of RALDH2 for the CSF is the choroid plexus, which produces the CSF including the proteins transthyretin and retinol binding protein that transport retinol. RALDH2 protein and transcript were detected in the choroid plexus by immunohistochemistry and in-situ hybridization respectively. Interestingly, a second source of RALDH2 for the CSF is the meninges which, in the lateral ventricles, borders the hippocampus and is in direct contact with the CSF. RALDH2 transcript was detected in the meninges by in-situ hybridization while protein was detected immunohistochemically in cytoplasmic vesicles. Other hypotheses for the source of RALDH2 are presently being tested.
The unique origins and tanycyte subtype expression patterns of RALDH1 and RALDH2 in the hypothalamus suggest that retinoic acid generated by these two enzymes is required to regulate differing events.