Anti-CYP26B1 monoclonal antibody, clone FQS24293

Retinoic acid ( RA), a principal metabolite of vitamin A ( retinol), is an essential endogenous regulator of gene transcription and an important therapeutic agent. The catabolism of RA must be well regulated to maintain physiological concentrations of RA. The cytochrome P450 ( CYP) gene family CYP26, which encodes RA- 4- hydroxylase activity, is strongly implicated in the oxidation of RA. Inflammation alters the expression of numerous genes; however, whether inflammation affects CYP26 expression is not well understood. We investigated the regulation of CYP26A1 and CYP26B1 mRNA levels by RA and LPS in the rat liver, as the liver is centrally involved in retinoid metabolism and the acute- phase response to LPS. Both CYP26A1 and CYP26B1 mRNA were induced in < 4 h by a single oral dose of all-trans-RA. RA- induced responses of both CYP26A1 and CYP26B1 were significantly attenuated in rats with LPS- induced inflammation whether LPS was given concurrently with RA or after the RA- induced increase in CYP26A1 and CYP26B1 mRNA levels. When RA and LPS were administered simultaneously ( 6- h study), LPS alone had little effect on either CYP26A1 or CP26B1 mRNA, but LPS reduced by 80% the RA- induced increase in CYP26A1 mRNA ( P < 0.02), with a similar trend for CYP26B1 mRNA. When LPS was administered 4 h after RA ( 16- h study), it abrogated the induction of CYP26A1 ( P < 0.02) and CYP26B1 ( P < 0.01). Overall, these results suggest that inflammation can potentially disrupt the balance of RA metabolism and maintenance of RA homeostasis, which may possibly affect the expression of other RA- regulated genes.

Subsequent to somatic gonadal sexual differentiation, germ cells enter meiosis or mitotic arrest in the ovary or testis, respectively. Among mice, these processes occur almost synchronically in fetal gonads and depend, among other factors, on the levels of retinoic acid (RA). In contrast to those in mice, rabbit germ cells enter meiosis or mitotic arrest after birth and coexist with proliferating germ cells. Here, we studied the somatic cell context in which germ cells enter meiosis or mitotic arrest in the rabbit. Using confocal immunofluorescence and real-time PCR, we studied the expression profiles of ALDH1A1 and ALDH1A2 and, comprising 2 genes required for RA synthesis, 2 meiosis markers STRA8 and SYCP3 as well as 2 genes involved in meiosis inhibition, CYP26B1 and NANOS2. We found that although both meiosis and mitotic arrest initiate after birth, these 2 processes are regulated in a way similar to the human fetal gonad. Current results reinforce the value of the neonatal rabbit gonad as an alternative experimental model for analyzing the direct effect of environmental factors during critical stages of germ cell establishment.