5α-Dihydroprogesterone (5α-DHP, allopregnanedione,or 5α-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.
5α-DHP is metabolized by the aldo-keto reductases (AKRs) AKR1C1, AKR1C2, and AKR1C4 with high catalytic efficiency.AKR1C1 preferentially forms 20α-hydroxy-5α-pregnane-3-one while AKR1C2 preferentially forms allopregnanolone.Similarly AKR1C1 reduces and consequently inactivates allopregnanolone into 5α-pregnane-3α,20α-diol.In contrast to the other AKRs, AKR1C3 has low catalytic efficiency for reduction of 5α-DHP.These AKRs are highly expressed in the human liver and mammary gland but have relatively modest expression in the human brain and uterus.
5α-DHP is an agonist of the progesterone receptor and a positive allosteric modulator of the GABAA receptor (albeit with an affinity for this receptor that is regarded as relatively low (in comparison to 3α-hydroxylated progesterone metabolites such as allopregnanolone and pregnanolone)).Ugotovljeno je bilo tudi, da deluje kot negativni alosterični modulator receptorja GABAA-rho. Ugotovljeno je bilo, da ima steroid 82% afinitete progesterona za progesteronski receptor v maternici opice rezus. Rečeno je, da ima 5α-dihidroprogesteron približno 33% relativne progestogene moči progesterona.Poleg tega, je šibek agonist receptorja pregnane X (PXR) (EC50 >10,000 μM), s približno šestkrat manjšo močjo glede na njegov 5β-izomer, 5β-dihidroprogesteron.
Alopregnanolon se pretvori nazaj v 5α-DHP s 3α-hidroksisteroid oksidoreduktazo, in pretvorba alopregnanonlona v 5α-DHP je odgovorna za progestogeno aktivnost alopregnanonlona.5α-DHP, preko progesteronskega receptorja, in alopregnanolon, preko receptorja MARKET, delujejo skupaj, da povzročijo lordozo pri živalih. Študija je pokazala, da 41% alopregnanolona, ki je bil dan z injekcijo, se je v možganih podgan spremenil v 5α-DHP.
