title: 11β-hydroxyandrostenedione returns to the steroid arena: biosynthesis, metabolism and function.
abstract: The biological significance of 11β-hydroxyandrostenedione (11OHA4) has eluded researchers for the past six decades. It is now known that 11OHA4 is biosynthesized in the androgen arm of the adrenal steroidogenesis pathway and subsequently metabolized by steroidogenic enzymes in vitro, serving as precursor to recognized and novel androgenic steroids. These in vitro findings extend beyond the adrenal, suggesting that 11OHA4 could be metabolized in steroid-responsive peripheral tissues, as is the case for androgen precursor metabolites of adrenal origin. The significance thereof becomes apparent when considering that the metabolism of 11OHA4 in LNCaP androgen dependent prostate cancer cells yields androgenic steroid metabolites. It is thus possible that 11OHA4 may be metabolized to yield ligands for steroid receptors in not only the prostate but also in other steroid-responsive tissues. Future investigations of 11OHA4 may therefore characterize it as a vital steroid with far-reaching physiological consequences. An overview of the research on 11OHA4 since its identification in 1953 will be presented, with specific focus on the most recent works that have advanced our understanding of its biological role, thereby underscoring its relevance in health and disease.
authors.affiliation: Department of Biochemistry, Stellenbosch University, Private Bag X1, Matieland 7602, South Africa. storbeck@sun.ac.za.
authors.forename: Liezl M
authors.initials: LM
authors.lastname: Bloem
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Storbeck
authors.forename: Lindie
authors.initials: L
authors.lastname: Schloms
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Swart
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D000735:Androstenedione / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism; D013252:Steroid 11-beta-Hydroxylase / Q000378:metabolism
chemical_list: D013196:Dihydrotestosterone; D000735:Androstenedione; C003582:11-hydroxyandrostenedione; D006913:Hydroxysteroid Dehydrogenases; D013252:Steroid 11-beta-Hydroxylase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase