5α-Dihydroprogesteroon (5α-DHP, allopregnandioon,of 5α-pregnaan-3,20-dion) is 'n endogene progestogeen en neurosteroïde wat uit progesteroon gesintetiseer word. Dit is ook 'n intermediêre in die sintese van allopregnanolone en isopregnanolone van progesteroon.
5α-DHP word gemetaboliseer deur die aldo-keto reduktase (AKR'e) 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)).It has also been found to act as a negative allosteric modulator of the GABAA-rho receptor.The steroid has been found to possess 82% of the affinity of progesterone for the progesterone receptor in rhesus monkey uterus.5α-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) (EC50 >10,000 μM), with approximately six-fold lower potency relative to its 5β-isomer, 5β-dihydroprogesterone.
Allopregnanolone is transformed back into 5α-DHP by 3α-hydroxysteroid oxidoreductase, and conversion of allopregnanonlone into 5α-DHP is responsible for the progestogenic activity of allopregnanonlone.5α-DHP, via the progesterone receptor, and allopregnanolone, via the GABAA receptor, tree saam op om lordose by diere te veroorsaak. 'n Studie het bevind dat 41% van allopregnanolone wat via inspuiting toegedien is, is in die rotbrein in 5α-DHP omskep.
