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| Names | |
|---|---|
| IUPAC name 5α-Pregnane-3,20-dione | |
| Systematic IUPAC name (1S,3aS,3bR,5aS,9aS,9bS,11aS)-1-Acetyl-9a,11a-dimethylhexadecahydro-7H-cyclopenta[a]phenanthren-7-one | |
| Other names Allopregnanedione | |
| Identifiers | |
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3D model (JSmol) | |
| ChEBI | |
| ChemSpider | |
| ECHA InfoCard | 100.008.453 |
| UNII | |
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| Properties | |
| C21H32O2 | |
| Molar mass | 316.485 g·mol−1 |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
5α-Dihydroprogesterone (5α-DHP,allopregnanedione,[1] or5α-pregnane-3,20-dione) is anendogenousprogestogen andneurosteroid that issynthesized fromprogesterone.[2][3] It is also anintermediate in the synthesis ofallopregnanolone andisopregnanolone from progesterone.
5α-DHP is metabolized by thealdo-keto reductases (AKRs)AKR1C1,AKR1C2, andAKR1C4 with high catalytic efficiency.[4] AKR1C1 preferentially forms 20α-hydroxy-5α-pregnane-3-one while AKR1C2 preferentially forms allopregnanolone.[4] Similarly AKR1C1 reduces and consequently inactivates allopregnanolone into5α-pregnane-3α,20α-diol.[4] In contrast to the other AKRs,AKR1C3 has low catalytic efficiency for reduction of 5α-DHP.[4] These AKRs are highly expressed in the humanliver andmammary gland but have relatively modest expression in the humanbrain anduterus.[5]
5α-DHP is anagonist of theprogesterone receptor and apositive allosteric modulator of theGABAA receptor (albeit with anaffinity for thisreceptor that is regarded as relatively low (in comparison to 3α-hydroxylated progesteronemetabolites such as allopregnanolone andpregnanolone)).[2][3][6][7] It has also been found to act as anegative allosteric modulator of theGABAA-rho receptor.[8] The steroid has been found to possess 82% of the affinity of progesterone for the progesterone receptor inrhesus monkeyuterus.[9] 5α-Dihydroprogesterone has been said to possess about 33% of the relativeprogestogenicpotency of progesterone.[10] In addition, it is a weak agonist of thepregnane X receptor (PXR) (EC50 >10,000 μM), with approximately six-fold lower potency relative to its 5β-isomer,5β-dihydroprogesterone.[11]
Allopregnanolone is transformed back into 5α-DHP by3α-hydroxysteroid oxidoreductase, and conversion of allopregnanolone into 5α-DHP is responsible for the progestogenic activity of allopregnanolone.[6][12][13] 5α-DHP, via the progesterone receptor, and allopregnanolone, via theGABAA receptor, act together to inducelordosis in animals.[12][13] A study found that 41% of allopregnanolone that was administered via injection was transformed into 5α-DHP in the rat brain.[12]
Levels of 5α-DHP have been quantified.[14]
