Patterns of CYP26 expression in human prenatal cephalic and hepatic tissues indicate an important role during early brain development

CYP26 (P450RAI) catalyzes catabolic retinoic acid (RA) hydroxylation and th ereby appears to play a critical role in retinoid signaling pathways during development. In this study, a quantitative competitive reverse transcripta se-polymerase chain reaction (RT-PCR) assay was developed for evaluation of CYP26 message levels in human prenatal tissues. Statistical analyses of tr anscription levels in 12 prenatal human brains and six prenatal human liver s demonstrated good sensitivity and reproducibility. Quantitative profiles of CYP26 gene expression in early (gestational days 57-110) prenatal cephal ic and hepatic tissues and comparisons with adult counterparts are reported for the first time. Prenatal cephalic tissues at days 57-67 exhibited valu es of 1950 +/- 420 (CYP26 molecules/10(6) GAPDH molecules) whereas prenatal cephalic tissues at days 105-110 exhibited values of 22300 +/- 4450 (CYP26 molecules/10(6) GAPDH molecules), indicating a sharp developmental increas e (approximately 11-fold). Levels in human adult cephalic tissues were slig htly less than the prenatal cephalic levels measured during the earliest st ages of gestation and were approximately 3-fold lower than those measured i n adult human hepatic tissues. Levels in human prenatal hepatic tissues at days 63-110 gestation were less than 800 (CYP26 molecules/10(6) GAPDH molec ules) and did not exhibit developmental increases. Considered together, the data have strong implications for the importance of CYP26 in early develop ment of the human brain. (C) 2000 Elsevier Science B.V. All rights reserved .