In What Tissues Is DHT Primarily Synthesized?

[Nicolas Noyola]

"DHT is synthesized irreversibly from testosterone by the enzyme 5α-reductase.[8][13] This occurs in various tissues including the genitals (penis, scrotum, clitoris, labia majora),[53] prostate gland, skin, hair follicles, liver, and brain.[8] Around 5 to 7% of testosterone undergoes 5α-reduction into DHT,[54][55] and approximately 200 to 300 μg of DHT is synthesized in the body per day. Most DHT is produced in peripheral tissues like the skin and liver, whereas most circulating DHT originates specifically from the liver. The testes and prostate gland contribute relatively little to concentrations of DHT in circulation.[8]"

I know that testosterone is primarily produced by the testicles (>95% according to wikipedia). On the other hand DHT is not a classical hormone, it is paracrine/autocrine in nature, and its synthesis occurs in peripheral tissues, as the text above elucidates. My question then, is what tissues are primarily responsible for DHT synthesis? Mr. Peat has spoken at length regarding the importance of tissue levels vs. blood levels of hormones, does this then relegate the liver's role in DHT synthesis to irrelelvance, given that it mostly synthesizes circulating DHT? Where does the majority of DHT originate? I'm sorry if this is too many questions, I am just curious and would appreciate some hardcore clarification from any of the forum's more credentialed members. An actual quantification would be wonderful, i.e. 50% of DHT from here, 50% from there, etc.

 

[Wagner83]

@haidut have a look at the daily amount they talk about.

 

[haidut]

"DHT is synthesized irreversibly from testosterone by the enzyme 5α-reductase.[8][13] This occurs in various tissues including the genitals (penis, scrotum, clitoris, labia majora),[53] prostate gland, skin, hair follicles, liver, and brain.[8] Around 5 to 7% of testosterone undergoes 5α-reduction into DHT,[54][55] and approximately 200 to 300 μg of DHT is synthesized in the body per day. Most DHT is produced in peripheral tissues like the skin and liver, whereas most circulating DHT originates specifically from the liver. The testes and prostate gland contribute relatively little to concentrations of DHT in circulation.[8]"

I know that testosterone is primarily produced by the testicles (>95% according to wikipedia). On the other hand DHT is not a classical hormone, it is paracrine/autocrine in nature, and its synthesis occurs in peripheral tissues, as the text above elucidates. My question then, is what tissues are primarily responsible for DHT synthesis? Mr. Peat has spoken at length regarding the importance of tissue levels vs. blood levels of hormones, does this then relegate the liver's role in DHT synthesis to irrelelvance, given that it mostly synthesizes circulating DHT? Where does the majority of DHT originate? I'm sorry if this is too many questions, I am just curious and would appreciate some hardcore clarification from any of the forum's more credentialed members. An actual quantification would be wonderful, i.e. 50% of DHT from here, 50% from there, etc.

@Wagner83
As Nicolas mentioned, DHT is a paracrine hormone and is produced in tissues where it is needed. I don't think the total amount is just 0.3mg/day. Given that androsterone production can exceed 15mg daily and most of androsterone is derived from DHT, the total body production of DHT is in the range of milligrams. But the problem is that DHT is not the true end of the pathway so talking of just DHT production is misleading. DHT is a bidirectional hormone and at any given time it can exist in the organism as androsterone, androstanediol, androstanedione, and DHT. These 4 types interconvert into each other and each of them can be synthesized from various precursors like T, androstenedione and androstenediol. So, in a sense when one talks about daily DHT synthesis, one has to consider ALL of these steroids into account as they are all in effect DHT with small variations and can easily become DHT when needed. Actually, one has to take into account ALL steroids derived from the 5-AR pathway, even inlcuding progestins like 5a-DHP, allopregnanolone, etc since those have also been shown to convert into DHT through the so-called "alternative" or "backdoor" pathway.
So, the total pool of 5-AR steroids that can serve as reservoirs/sources of DHT is probably on the order of 15mg-20mg daily. Same with T, which is interconvertible with androstenedione and 4-androstenediol - i.e. the amount of those steroids has to be taken into account as well since they easily interchange with T. Admittedly, T synthesis is more location-specific than DHT and occurs mostly in the gonads and skin (and maybe liver).
I hope that makes sense.

 

[Nicolas Noyola]

@Wagner83
As Nicolas mentioned, DHT is a paracrine hormone and is produced in tissues where it is needed. I don't think the total amount is just 0.3mg/day. Given that androsterone production can exceed 15mg daily and most of androsterone is derived from DHT, the total body production of DHT is in the range of milligrams. But the problem is that DHT is not the true end of the pathway so talking of just DHT production is misleading. DHT is a bidirectional hormone and at any given time it can exist in the organism as androsterone, androstanediol, androstanedione, and DHT. These 4 types interconvert into each other and each of them can be synthesized from various precursors like T, androstenedione and androstenediol. So, in a sense when one talks about daily DHT synthesis, one has to consider ALL of these steroids into account as they are all in effect DHT with small variations and can easily become DHT when needed. Actually, one has to take into account ALL steroids derived from the 5-AR pathway, even inlcuding progestins like 5a-DHP, allopregnanolone, etc since those have also been shown to convert into DHT through the so-called "alternative" or "backdoor" pathway.
So, the total pool of 5-AR steroids that can serve as reservoirs/sources of DHT is probably on the order of 15mg-20mg daily. Same with T, which is interconvertible with androstenedione and 4-androstenediol - i.e. the amount of those steroids has to be taken into account as well since they easily interchange with T. Admittedly, T synthesis is more location-specific than DHT and occurs mostly in the gonads and skin (and maybe liver).
I hope that makes sense.

Hmmm thank you haidut. that does help.