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• W2523366914 abstract "16α-hydroxyprogesterone (16OHP4) is not well characterised in terms of metabolism and receptor interaction. We therefore investigated its metabolism by adrenal CYP11B and peripheral steroidogenic enzymes, SRD5A and AKR1C2. UHPLC-MS/MS analyses identified novel steroids: the biosynthesis of 4-pregnen-11β,16α-diol-3,20-dione catalysed by CYP11B2; the 5α-reduction of the latter and 16OHP4 catalysed by SRD5A yielding 5α-pregnan-11β,16α-diol-3,20-diovne and 5α-pregnan-16α-ol-3,20-dione (16OH-DHP4); and 16OH-DHP4 converted by AKR1C2 to 5α-pregnan-3α,16α-diol-20-one. Receptor studies showed 16OHP4, 16OH-DHP4, progesterone and dihydroprogesterone (DHP4) were weak partial AR agonists; 16OHP4, 16OH-DHP4 and DHP4 exhibited weak partial agonist activity towards PR-B with DHP4 also exhibiting partial agonist activity towards PR-A. Data showed that while the 5α-reduction of P4 decreased PR activation significantly, 16OHP4 and 16OH-DHP4 exhibited comparable receptor activation. Although the clinical relevance of 16OHP4 remains unclear the elevated 16OHP4 levels characteristic of 21OHD, CAH, PCOS, prostate cancer, testicular feminization syndrome and cryptorchidism likely contribute towards these clinical conditions, inducing receptor-activated target genes." @default.
• W2523366914 created "2016-09-30" @default.
• W2523366914 creator A5022369864 @default.
• W2523366914 creator A5058540463 @default.
• W2523366914 creator A5069314289 @default.
• W2523366914 creator A5081188726 @default.
• W2523366914 creator A5088503838 @default.
• W2523366914 creator A5090028838 @default.
• W2523366914 date "2017-02-01" @default.
• W2523366914 modified "2023-10-07" @default.
• W2523366914 title "The metabolic fate and receptor interaction of 16α-hydroxyprogesterone and its 5α-reduced metabolite, 16α-hydroxy-dihydroprogesterone" @default.
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• W2523366914 doi "https://doi.org/10.1016/j.mce.2016.09.025" @default.
• W2523366914 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27664517" @default.
• W2523366914 hasPublicationYear "2017" @default.
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