INDUCTION OF TYPE III-DEIODINASE ACTIVITY IN ASTROGLIAL CELLS BY RETINOIDS

Thyroid hormones and retinoic acid (RA) are important modulators of growth, development, and differentiation. Type III deiodinase (D-III), which catalyzes thyroid hormones degradation in the brain and in cultured astroglial cells, is induced in astroglial cells by multiple pathways, including cAMP, 12.0-tetradecanoylphorbol-13-acetate (TPA), fibroblast growth factors, and thyroid hormones themselves. In the present study, the effects of retinoids on D-III activity were examined in astroglial cells cultures in a chemically defined medium devoid of hormones and growth factors. Incubation of astroglial cells with 5 mu M all-trans-RA caused up to 200-fold increase in D-III activity, which reached a plateau after 48 h. The retinoid-induced increase in D-III activity was concentration dependent (0.5 mu M all-trans-RA and 9-cis-RA producing half-maximal effect). Retinol was effective at physiological concentrations (1 and 10 mu M). The 48 h effects of 5 mu M all-trans-RA and 10 nM thyroid hormones on D-III activity were at least additive. Addition of 2 nM acidic fibroblast growth factor or 1 mM 8-bromo-cAMP for the last 8 h of a 48 h incubation with 5 mu M all-trans-PA did not alter the induction by all-trans-RA, whereas 0.1 mu M TPA in the same conditions produced an additive effect with all-trans-RA. All-trans-RA, (5 mu M) had little or no effect on type II deiodinase, the enzyme which catalyzes the activation of thyroxine to 3,5,3'-triiodothyronine. The potent action of retinoids on the enzyme responsible for thyroid hormones degradation in the brain may protect the brain from the effects of 3,5,3'-triiodothyronine in regions influenced by retinoids. (C) 1994 Wiley-Liss, Inc.