A novel assay for retinoic acid catabolic enzymes shows high expression in the developing hindbrain.
We have employed a novel technique that determines the relative capacity of tissues to catabolize all-trans retinoic acid (RA) to a metabolite incapable of activating a RA reporter cell line. This assay uses the microsomal fraction of tissues from the developing mouse and detects a pathway which requires NADPH and is inhibitable by ketoconazole, suggesting that a cytochrome P450-dependent enzyme may be required. High catabolic activity was detected transiently in the developing cerebellum which peaked at postnatal day 2. The medulla oblongata was the only other CNS region with high catabolic capacity, its earlier expression peak, between embryonic days 16 and 17, likely reflecting its earlier maturation. In the CNS, the hindbrain is exceptional in its high expression of RA catabolic enzymes, suggesting a unique function for regulated RA levels in this region.
Yamamoto
M
M
E. Kennedy Shriver Center, Waltham, MA 02254, USA.
Dräger
U C
UC
McCaffery
P
P
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism* / Q000502:physiology; D005314:Embryonic and Fetal Development / Q000502:physiology; D004798:Enzymes / Q000378:metabolism*; D007654:Ketoconazole / Q000494:pharmacology; D008722:Methods; D051379:Mice; D009249:NADP / Q000494:pharmacology; D018168:Receptors, Retinoic Acid / Q000502:physiology; D011994:Recombinant Proteins; D012249:Rhombencephalon / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism*
D004798:Enzymes; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins; C082927:retinoic acid binding protein I, cellular; D009249:NADP; D014212:Tretinoin; D007654:Ketoconazole