DARPP-32 and CREB are present in type 2 iodothyronine deiodinase-producingtanycytes: implications for the regulation of type 2 deiodinase activity

Type 2 iodothyronine deiodinase, an enzyme involved in the conversion of th yroxin to the biologically active 3,5,3'-triiodothyronine, is highly concen trated in a group of specialized ependymal cells, tanycytes, lining the wal l and floor of the third ventricle. As this distribution is highly reminisc ent of the distribution of cells containing the phosphatase inhibitor, DARP P-32, we raised the possibility that these two proteins may coexist in tany cytes and that DARPP-32 may modulate type 2 deiodinase activity by regulati ng the phosphorylation state of the cAMP regulatory factor, CREB. To addres s this question, double-labeling histochemical studies were performed for t ype 2 deiodinase mRNA and DARPP-32 immunoreactivity (IR), or DARPP-32- and CREB-IR in the same tissue sections. Type 2 deiodinase mRNA was found in th e cell bodies of all DARPP-32-immunolabeled tanycytes. Both type 2 deiodina se mRNA and DARPP-32-IR also extended into tanycyte processes that ramified in the arcuate nucleus and median eminence, in close association with bloo d vessels and portal capillaries. In contrast, type 2 deiodinase mRNA was n ot present in the same cells that contained DARPP-32-IR in the pituitary gl and. All tanycytes containing DARPP-32-IR also contained CREB-IR in their n ucleus. Since type 2 deiodinase activity can be induced by substances that increase cAMP, we hypothesize that DARPP-32 may regulate the activity of ty pe 2 deiodinase by prolonging the activation of CREB. Selectivity for the c olocalization of these factors to tanycytes but not the pituitary gland, ma y explain the heterogeneous response of type 2 deiodinase activity in these two loci in response to specific stimuli such as fasting. (C) 2000 Elsevie r Science B.V. All rights reserved.