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 microM 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 microM all-trans-RA and 9-cis-RA producing half-maximal effect). Retinol was effective at physiological concentrations (1 and 10 microM). The 48 h effects of 5 microM 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 microM all-trans-RA did not alter the induction by all-trans-RA, whereas 0.1 microM TPA in the same conditions produced an additive effect with all-trans-RA. All-trans-RA (5 microM) had little or no effect on type II deiodinase, the enzyme which catalyzes the activation of thyroxine to 3,5,3'-triiodothyronine.(ABSTRACT TRUNCATED AT 250 WORDS)
Esfandiari
A
A
U. 96 INSERM, Unité de Recherche sur la Glande Thyroîde et la Régulation Hormonale, Le Kremlin-Bicêtre, France.
Gagelin
C
C
Gavaret
J M
JM
Pavelka
S
S
Lennon
A M
AM
Pierre
M
M
Courtin
F
F
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D007150:Immunohistochemistry; D007453:Iodide Peroxidase / Q000096:biosynthesis*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012176:Retinoids / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013963:Thyroid Hormones / Q000494:pharmacology
D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D012176:Retinoids; D013963:Thyroid Hormones; D016220:Fibroblast Growth Factor 1; D000242:Cyclic AMP; D007453:Iodide Peroxidase; D013755:Tetradecanoylphorbol Acetate