Allopregnanolone

Allopregnanolone, also known as 3α-hydroxy-5α-pregnan-20-one, is an endogenous neurosteroid that acts as a positive allosteric modulator of the GABAA receptor, exhibiting anxiolytic effects in animals 1. It is biosynthesized by 3α-hydroxysteroid dehydrogenase from progesterone 1. Allopregnanolone has been found to inhibit the secretion of follicle-stimulating hormone (FSH) from the rat pituitary gland, demonstrating possible antigonadotropic properties 1. Unlike the case of most other inhibitory neurosteroids, 3α-DHP production is not blocked by 5α-reductase inhibitors like finasteride 1.

Allopregnanolone can be purchased openly from many chemical companies in the US, and it is used as a lab product 2. It is described as being as active as allopregnanolone in regard to its action on the GABAA receptor 1. Allopregnanolone has also been found to agonize the bile acid receptor TGR5, which increases energy expenditure, mostly via increasing T4 to T3 conversion 4.

The first commercial antidepressant of the SSRI class, fluoxetine (Prozac), was found to increase the activity and expression of an enzyme called 3α-hydroxysteroid dehydrogenase (3α-HSD), which is one of the major steps in synthesizing allopregnanolone from progesterone 2. Since levels of allopregnanolone have been consistently found to increase after fluoxetine administration, and allopregnanolone levels were found to be universally low in people with depression 6.

While allopregnanolone has been extensively studied, 3α-DHP, a closely-related neurosteroid, has not been as extensively studied, but it can be described as an allopregnanolone mimetic, with similar pharmacological profile and strength 8. Some of the more unique and interesting properties of 3α-DHP include its anti-cancer effects demonstrated in animal studies, with the notable finding that those anti-cancer effects are NOT shared by neither allopregnanolone nor its precursor neurosteroid 5α-dihydroprogesterone (5α-DHP) 8.