7α‐Hydroxy‐Dehydroepiandrosterone and Immune Response

Abstract

A BSTRACT : In human and murine lymphoid organs, circulating 3 ␤ -hydroxysteroids, including pregnenolone (PREG), dehydroepiandrosterone (DHEA), and epiandrosterone (EPIA), are 7 ␣ -hydroxylated by a cytochrome P450 identified in the hippocampus as P4507B1. Mouse and human lymphoid organs produced different patterns of 3 ␤ -hydroxysteroid 7 ␣ -hydroxylation with the absence of pregnenolone and epiandrosterone hydroxylation in human and mouse, respectively. Both 7 ␣ -hydroxy-DHEA and 7 ␣ -hydroxy-EPIA triggered a significant increase of antitetanus toxoid and anti-Bordetella pertussis toxins IgGs production in cultures of activated B ؉ T cells derived from human tonsils, whereas both 7 ␣ -hydroxy-PREG and 7 ␣ -hydroxy-DHEA increased the immune response in mouse. Paracrine action of 7 ␣ -hydroxysteroids resulted from their production in cells of the lymphoid organs. Comparison of P4507B1 sequences in rat, human, and two mouse species showed that one amino acid change might explain important differences in K M for 7 ␣ -hydroxylation, and suggested that such differences might contribute to the extent of immune response.

CYP7B expression and activity in fibroblast‐like synoviocytes from patients with rheumatoid arthritis: Regulation by proinflammatory cytokines

“…Data from both in vitro and in vivo studies suggest that 7␣-OH-DHEA has immunostimulating activity (4,(8)(9)(10)(11). In this regard, it is of interest that 7␣-OH-DHEA appeared to be more active than DHEA in stimulating the production of antilysozyme antibodies (8) and enhancing the immune response to tetanus toxoid and Bordetella pertussis antigens (10,12). Moreover, it has been demonstrated that 7␣-OH-DHEA prevents the immunosuppressive effects of glucocorticoids in vitro (4,8).…”

The DHEA metabolite 7β-hydroxy-epiandrosterone exerts anti-estrogenic effects on breast cancer cell lines

“…Ces 20 dernières années, un certain nombre de travaux ont montré une activité biologique de ces stéroïdes 7-hydroxylés comme des effets anti-glucocorticoïdes (Muller et al, 2006a ;Hampl et al, 2000) ou immunomodulateurs (Sterzl et al, 2003 ;Morfin, 2002 ;Morfin et al, 2000).…”

The identification and simultaneous quantification of 7-hydroxylated metabolites of pregnenolone, dehydroepiandrosterone, 3β,17β-androstenediol, and testosterone in human serum using gas chromatography–mass spectrometry

“…These metabolites are further reduced at positions 7 and 17 to form their respective diols and triols that may be sulfated at the 3␤-position [22]. DHEA is converted to 7␣-hydroxy-DHEA by microsomal cytochromes of the liver or intestinal CYP3A family [23] or the ubiquitous CYP7b [1,[24][25][26]. 7␣-Hydroxy-DHEA can be further converted to a 7-oxo-derivative by 11␤-hydroxysteroid dehydrogenases (11 ␤-HSD) [23,27,28] that concurrently provide activation or deactivation of glucocorticoids.…”