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7α‐Hydroxy‐Dehydroepiandrosterone and Immune Response
Author(s) -
MORFIN R.,
LAFAYE P.,
COTILLON A. C.,
NATO F.,
CHMIELEWSKI V.,
POMPON D.
Publication year - 2000
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2000.tb05464.x
Subject(s) - pregnenolone , dehydroepiandrosterone , immune system , alpha (finance) , biology , endocrinology , medicine , hydroxylation , paracrine signalling , immunology , biochemistry , receptor , androgen , steroid , enzyme , hormone , construct validity , nursing , patient satisfaction
A bstract : In human and murine lymphoid organs, circulating 3β‐hydroxysteroids, including pregnenolone (PREG), dehydroepiandrosterone (DHEA), and epiandrosterone (EPIA), are 7α‐hydroxylated by a cytochrome P450 identified in the hippocampus as P4507B1. Mouse and human lymphoid organs produced different patterns of 3β‐hydroxysteroid 7α‐hydroxylation with the absence of pregnenolone and epiandrosterone hydroxylation in human and mouse, respectively. Both 7α‐hydroxy‐DHEA and 7α‐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 7α‐hydroxy‐PREG and 7α‐hydroxy‐DHEA increased the immune response in mouse. Paracrine action of 7α‐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 7α‐hydroxylation, and suggested that such differences might contribute to the extent of immune response.