Abstract

Cytochrome P450 (P450) monooxygenases play a role in target tissue metabolic activation of xenobiotics and/or endogenous compounds, such as vasoactive molecules or hormones. Indeed, tissue-specific metabolism of steroids is important in a variety of organs, including thymus, and may alter tissue-specific functions. Steroids have been shown to regulate thymus growth and function, but surprisingly little is known about expression of the responsible enzyme systems in thymus tissue, nor is the thymus-specific biotransformation of testosterone known. We therefore investigated gene and protein expression, total protein content, and enzyme activity of major P450 isoforms and other key steroid-metabolizing enzymes in thymus tissue of adult and fetal rats. We detected 6β-hydroxytestosterone (HT), 7α-HT, 16α-HT, 2α-HT, and androstenedione to be major testosterone metabolites in the adult thymus. The high production of 7α-HT and 16α-HT correlated well with the gene and protein expression of CYP2A1/2 and CYP2B1/2 in thymus of adult animals. When compared with fetal thymic tissue, CYP2A1/2, 17β-hydroxysteroid dehydrogenase isoform 1 (17β-HSDH1) and the androgen receptor were 8-, 3-, and 3-fold more highly expressed in adult rats, whereas 17β-HSDH2, 17β-HSDH3, and 5α-reductase were reduced to 12%, 0%, and 32% of those in fetal thymus. In conclusion, we demonstrated that rat thymus expresses a variety of cytochrome P450 monooxygenases and other steroid-metabolizing enzymes, and it successfully metabolizes testosterone. Changes of the underlying steroid-metabolizing enzyme systems may aid in understanding the role of androgens in altering biological functions of the thymus.