5ñ-Dihydroprogesterone (5ñ-DHP, allopregnanedione, or 5ñ-pregnane-3,20-dione) is an endogenous progestogen and neurosteroid that is synthesized from progesterone. It is also an intermediate in the synthesis of allopregnanolone and isopregnanolone from progesterone.
5ñ-DHP is metabolized by the aldo-keto reductases (AKRs) AKR1C1, AKR1C2, and AKR1C4 with high catalytic efficiency. AKR1C1 preferentially forms 20ñ-hydroxy-5ñ-pregnane-3-one while AKR1C2 preferentially forms allopregnanolone. Similarly AKR1C1 reduces and consequently inactivates allopregnanolone into 5ñ-pregnane-3ñ,20ñ-diol. In contrast to the other AKRs, AKR1C3 has low catalytic efficiency for reduction of 5ñ-DHP. These AKRs are highly expressed in the human liver and mammary gland but have relatively modest expression in the human brain and uterus.
5ñ-DHP is an agonist of the progesterone receptor and a positive allosteric modulator of the GABA<sub>A</sub> receptor (albeit with an affinity for this receptor that is regarded as relatively low (in comparison to 3ñ-hydroxylated progesterone metabolites such as allopregnanolone and pregnanolone)). It has also been found to act as a negative allosteric modulator of the GABA<sub>A</sub>-rho receptor. The steroid has been found to possess 82% of the affinity of progesterone for the progesterone receptor in rhesus monkey uterus. 5ñ-Dihydroprogesterone has been said to possess about 33% of the relative progestogenic potency of progesterone. In addition, it is a weak agonist of the pregnane X receptor (PXR) (EC<sub>50</sub> >10,000 üM), with approximately six-fold lower potency relative to its 5ò-isomer, 5ò-dihydroprogesterone.
Allopregnanolone is transformed back into 5ñ-DHP by 3ñ-hydroxysteroid oxidoreductase, and conversion of allopregnanolone into 5ñ-DHP is responsible for the progestogenic activity of allopregnanolone. 5ñ-DHP, via the progesterone receptor, and allopregnanolone, via the GABA<sub>A</sub> receptor, act together to induce lordosis in animals. A study found that 41% of allopregnanolone that was administered via injection was transformed into 5ñ-DHP in the rat brain.
Levels of 5ñ-DHP have been quantified.