ABSTRACT

Both human and murine species carry out the 7 -hydroxylation of dehydroepiandrosterone (DHEA) and produce 7 -hydroxy-DHEA mainly in liver and brain (Stárka and Kutova, 1962; Šulcová et al., 1968; Doostzadeh and Morfin, 1996) and to a lesser extent in other tissues and organs (Šulcová and Stárka, 1963; Faredin et al., 1969; Couch et al., 1977; Akwa et al., 1992; Morfin and Courchay, 1994). The cytochrome P450 (P450) responsible for 7 -hydroxylation of DHEA appeared as a key to this process (Warner et al., 1989; Akwa et al., 1992; Morfin and Courchay, 1994; Doostzadeh and Morfin, 1996). Recent discovery of this P450 from rat, mouse and human, identified it as CYP7B1 from its cDNA sequence (Stapleton et al., 1995; Nelson et al., 1996; Wu et al., 1999). Demonstration of its DHEA 7 -hydroxylating potencies when expressed in HepG2 and HeLa cells (Rose et al., 1997; Wu et al., 1999) provided valuable tools for studies of the relationships between cDNA sequences and activity of the resulting CYP 7B1. Production in lymphoid organs and immunoactivating potencies of the 7 -hydroxy-DHEA were demonstrated in mouse (Morfin and Courchay, 1994; Doostzadeh and Morfin, 1996) and led to the concept of a native steroid counteracting the glucocorticoid-mediated immunosuppressive effects (Stárka et al., 1998; Chmielewski et al., 2000; Morfin et al., 2000). Very few data are available on the effects triggered by the 7 -hydroxy-DHEA produced in the brain, but all of the effects described in other tissues and the new data shown in this review imply that brain production of 7 -hyroxy-DHEA may be a key process for the maintenance and the protection of neuronal and nervous structures.