5α-Pregnane-3α,11β-diol-20-one explained

5α-Pregnane-3α,11β-diol-20-one, abbreviated as 3,11diOH-DHP4,^[1] also known as 3α,11β-dihydroxy-5α-pregnan-20-one, is an endogenous steroid.^{[2] [3] [4]}

The steroid 5α-pregnan-3α,11β-diol-20-one (3,11diOH-DHP4) plays a role in the 11-oxygenated steroid backdoor pathway to androgens as a metabolic intermediate. This pathway involves the metabolism of C₂₁ steroids (pregnanes) via enzymes such as steroid 11β-hydroxylase (CYP11B1), steroid 5α-reductase (SRD5A1), 17α-hydroxylase/17,20-lyase (CYP17A1), resulting in the production of androgen precursors.^[1] Docking studies have shown that the C11-oxy group of 3,11diOH-DHP4 and alfaxalone does not significantly affect their binding to CYP17A1. Furthermore, it has been observed that the lyase activity of CYP17A1 is impaired by the C11-hydroxyl (-OH) and keto- (=O) moieties present in these steroids. The lyase activity of CYP17A1 converts intermediates like 3,11diOH-DHP4 to potent androgens such as 5α-pregnan-3α,11β,17α-triol-20-one (11OH-Pdiol). These findings indicate that CYP17A1 plays a role in the metabolism of this steroid through both hydroxylation and lyase reactions in the 11-oxygenated steroid backdoor pathway to androgens.^[1] This pathway is important for regulating adrenal and gonadal steroid hormone biosynthesis and can contribute to elevated levels of androgens in certain conditions.^{[1] [5] [6]}

Notes and References

1. van Rooyen D, Yadav R, Scott EE, Swart AC . CYP17A1 exhibits 17αhydroxylase/17,20-lyase activity towards 11β-hydroxyprogesterone and 11-ketoprogesterone metabolites in the C11-oxy backdoor pathway . J Steroid Biochem Mol Biol . 199 . 105614 . May 2020 . 32007561 . 10.1016/j.jsbmb.2020.105614 . 210955834 .
2. Ebner MJ, Corol DI, Havlíková H, Honour JW, Fry JP . Identification of neuroactive steroids and their precursors and metabolites in adult male rat brain . Endocrinology . 147 . 1 . 179–90 . January 2006 . 16223859 . 10.1210/en.2005-1065 .
3. Yamada A, Yamada M, Fujita Y, Nishigami T, Nakasho K, Uematsu K . Self-augmentation effect of male-specific products on sexually differentiated progesterone metabolism in adult male rat liver microsomes . J Biol Chem . 276 . 7 . 4604–10 . February 2001 . 10995741 . 10.1074/jbc.M003355200 . free .
4. free. Ali HI, Yamada M, Fujita Y, Maeda M, Akaho E . Studies on 16α-Hydroxylation of Steroid Molecules and Regioselective Binding Mode in Homology-Modeled Cytochrome P450-2C11 . Int J Med Chem . 2011 . 918168 . 2011 . 27516905 . 4970648 . 10.1155/2011/918168 .
5. 10.15347/WJM/2023.003 . free . Alternative androgen pathways . 3 April 2023 . Masiutin MM, Yadav MK . WikiJournal of Medicine . 10 . 29 . 257943362 .
6. Slavíková B, Bujons J, Matyáš L, Vidal M, Babot Z, Krištofíková Z, Suñol C, Kasal A . Allopregnanolone and pregnanolone analogues modified in the C ring: synthesis and activity . J Med Chem . 56 . 6 . 2323–36 . March 2013 . 23421641 . 10.1021/jm3016365 . 10261/89237 . free .