Low 3aDiolG as a result of an inborn deficiency of 3aHSD

[Oscar]

3α-hydroxysteroid dehydrogenase (3aHSD) deactivates DHT to form 3aDiol, it regulates access of DHT to the AR. As a result 3aDiolG is a related to intracellular DHT activity and therefore is used as a marker of 5aR. It could just as easily be a marker for 3aHSD.

3aHSD deactivates 5a/5b reduced androgens, but activates 5a/5b reduced neurosteroids. You might expect a person with an inborn deficiency of 3aHSD to have high androgenicity due to less DHT being deactivated, such a person would be prone to baldness and high libido. Due to low levels of active neurosteroids such a person may be prone to depression and anxiety. Although other factors will also influence these things that does sound like a good description of most guys on this forum.

I did list other reasons for low 3aDiolG - viewtopic.php?f=27&t=4695&start=80 decreased 5aR or increased Sulfunation of hormones. But I did not consider this.

I therefore looked into 3aHSD in a bit more detail to determine if such a deficiency could lead to low levels of 3aDiolG too. Unfortunately I was not able to reach any conclusions because I am not a cellular biologist, but I did find some useful info which I will share below.

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There are four 3aHSD isoforms (AKR1C1, AKR1C2, AKR1C3 and AKR1C4). Here is their relative distribution in the human body (unfortunately skin and nerves are not listed - although 3aHSD’s are also to be found in both);

In the liver, 3a-HSDs work in concert with 5a-reductase and 5b-reductase to convert 5a/5b-dihydrosteroids into 5a/5b tetrahydrosteroids. In this manner they catalyse the second step in the metabolism of all steroid hormones that contain a Delta-3-ketosteroid functionality and serve to protect against circulating steroid hormone excess.

The 5a/5b urine analysis do not show a reduction of all 3a-reduced metabolites viewtopic.php?f=4&t=4674. This may be due to a deficiency of a particular 3aHSD, or that no deficiency exists.

In steroid target tissues, the production of 5a/5b-tetrahydrosteroids catalysed by 3a-HSD is not without consequence. In the human prostate, 3a-HSD can regulate the occupancy of the androgen receptor. It catalyses the reduction of 5a-dihydrotestosterone, a potent androgen to 3a-androstanediol a weak androgen and is positioned to regulate normal and abnormal androgen-dependent growth of this gland.

it was apparent that all isoforms could reduce 5a-DHT to 3a-androstanediol

The physiological role of the isoforms is influenced by their tissue distribution - each has slightly different abilities: AKR1C2 is the poorest steroid substrate but the 3aHSD that can convert 3aDiol back into 5aDHT. AKR1C3, the 3aHSD found highest in the prostate, can also make testosterone from androstenedione. AKR1C4 is the most catalytically efficient and reduced 5a-DHT 15-30 times better than the other isoforms and is thought to be the major isoform responsible for hormone metabolism in concert with 5a/5b reductases. Each also has other abilities.

see;

Human 3a-hydroxysteroid dehydrogenase isoforms (AKR1C1–AKR1C4) of
the aldo-keto reductase superfamily : functional plasticity and tissue
distribution reveals roles in the inactivation and formation of male and
female sex hormones ncbi.nlm.nih.gov/pmc/articles/PMC1221336/