17α-hydroxylase/C17-20 lyase cytochrome P450 mRNA expressions and enzyme activities during the development of arthritis in collagen-induced arthritis mice

Abstract

In our previous study, we have investigated the serum levels of dehydroepiandrosterone (DHEA) in type II collagen (CII)-induced arthritis (CIA) mice. During the study, we found that in normal control mice, serum levels of DHEA in the latter half of the experimental period (13 - 16 weeks old) were significantly lower than those at the beginning of the experiment (10 weeks old). However, in CIA mice, such decreases were not observed by CII treatment. To examine the cause of the retention of DHEA during the development of arthritis in CIA mice in this study, 17α-hydroxylase/C17-20 lyase P450 (CYP17) mRNA expressions were measured by real time RT-PCR and the CYP17 enzyme activities were investigated in the liver and testis on days 6, 13, 28 and 48 after CII treatment in DBA/1J mice. There were no significant differences of CYP17 expressions in the liver between control and CIA mice at each experimental day, while a significant increase of expression in the testis of CIA mice was observed on day 48. On the other hand, CYP17 enzyme activities on days 28 and 48 in testis microsome (Mc) from the CIA mice were significantly higher than those of the control on the same day, while no significant differences of activities in liver Mc were observed between the CIA and control mice. These findings suggested that the cause of the retention of DHEA on days 28 and 48 after CII treatment may be the increase of CYP17 expression and the enzyme activities in the testis. © 2004 Pharmaceutical Society of Japan.