Androgen backdoor pathway (English Wikipedia)

Analysis of information sources in references of the Wikipedia article "Androgen backdoor pathway" in English language version.

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de Hora M, Heather N, Webster D, Albert B, Hofman P (2023). "The use of liquid chromatography-tandem mass spectrometry in newborn screening for congenital adrenal hyperplasia: improvements and future perspectives". secondary. Frontiers in Endocrinology. 14: 1226284. doi:10.3389/fendo.2023.1226284. PMC 10578435. PMID 37850096. In 2004, a "backdoor" pathway was described with a metabolic route from 17OHP to DHT that does not involve A4 or T. In CAH, accumulating 17OHP is 5α- and 3α- reduced before being converted to androsterone by CYP17A1 with subsequent reduction and oxidation steps yielding DHT (44). Urinary steroid profiles in babies with CAH revealed that this pathway is active in CAH in the newborn period (45). The backdoor pathway may also make further contributions to the total androgen pool in CAH in the newborn period. In vitro studies have demonstrated that 11-hydroxylated corticosteroids such as 21DF, 21-deoxycortisone (21DE) and 11β-hydroxyprogesterone (11βOHP) can be converted by backdoor pathway enzymes to yield 11-ketodihydrotestosterone (11KDHT) (46), an androgen with a similar potency to DHT ( Figure 1 ). Almost 60 years ago, Jailer and colleagues demonstrated that 21DF and not 17OHP dosing resulted in increased 11-hydroxyandrosterone (11OHAST) excretion, an indication that 21DF is an androgen precursor (47). Whether the route is via the backdoor pathway or by the direct conversion of 21DF to 11OHA4 via CYP17A1, 21DF may be an important contributor to the androgen pool in CAH.
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Barnard L, Gent R, van Rooyen D, Swart AC (November 2017). "Adrenal C11-oxy C
₂₁ steroids contribute to the C11-oxy C
₁₉ steroid pool via the backdoor pathway in the biosynthesis and metabolism of 21-deoxycortisol and 21-deoxycortisone". secondary. The Journal of Steroid Biochemistry and Molecular Biology. 174: 86–95. doi:10.1016/j.jsbmb.2017.07.034. PMID 28774496. S2CID 24071400. The downstream metabolism of 21dF and 21dE by the enzymes in the backdoor pathway, SRD5A and AKR1C2, was investigated and the resulting novel C11‐oxy C21 steroids, 5α‐pregnan-3α,11β,17-triol-20-one (11OHPdiol) and 5α-pregnan-3α,17-diol-11,20-dione (11KPdiol), were shown to be suitable substrates for the lyase activity of CYP17A1, resulting in the production of C11-oxy C19 steroid metabolites 11β‐hydroxyandrosterone (11OHAST) and 11‐ketoandrosterone (11KAST) [...] The interconversion of 21dF and 21dE by 11βHSD yielded two C11-oxy C21 steroids which our in vitro assays showed are metabolised by steroidogenic enzymes in the backdoor pathway to yield C11-oxy C19 androgens. [...] the backdoor pathway may include the 5α-reduction of 21dF and 21dE in these patients and, as a consequence, the production of potent androgens, 11OHDHT and 11KDHT.
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