Dihydrotestosterone (DHT)
April 8, 2008
The main androgen secreted by the testes is of course testosterone. However, in most of the body, the androgenic signal is not carried through by testosterone. In these tissues, which include the brain (CNS), skin, genitals – practically everything but muscle – the active androgen is actually DHT. Testosterone in this case simply acts as a prohormone that is converted to the active androgen DHT by the action of the enzyme 5alpha reductase (5-AR).
5-AR is concentrated heavily in practically every androgen dependent area of the body except for skeletal muscle. This results in very little testosterone actually getting through to these parts of the body to bind to androgen receptors. Instead, it is quickly transformed into DHT, which then interacts with receptors.
This transformation serves a very important biological function in these tissues. You see, DHT is a much stronger androgen than testosterone – it binds about 3-5 times more strongly to the androgen receptor. If you took away 5-AR from these tissues and blocked the formation of DHT, then you would see some dramatic changes in physiology.
A good case in point is demonstrated in male pseudohermaphroditism due to congenital 5-AR deficiency. This is a relatively rare disorder, however it is actually quite common in the Dominican Republic. In this disorder, males are born with little or no 5-AR enzyme. They have ambiguous genitalia and are often raised as girls. When puberty occurs, their testosterone levels elevate normally although their DHT levels remain very low. Their musculature develops normally like that of other adults, however, they end up with little or no pubic / body hair and underdeveloped prostate and penis. Their libido and sexual function is often disrupted also.
Anti – Estrogen effects of DHT
One important function of DHT in the body that does not get much discussion is its antagonism of estrogen. Some men that take Proscar learn this the hard way – by developing a case of gynecomastia. By reducing DHT’s protection against estrogen in the body, these men have fallen victim to its most dreaded ramification – bitch tits!
How does DHT protect against estrogen? There are at least three ways that this likely occurs. First of all, DHT directly inhibits estrogens activity on tissues. It either does this by acting as a competitive antagonist to the estrogen receptor or by decreasing estrogen-induced RNA transcription at a point subsequent to estrogen receptor binding.
Second of all, DHT and its metabolites have been shown to directly block the production of estrogens from androgens by inhibiting the activity of the aromatase enzyme. The studies done in breast tissue showed that DHT, androsterone, and 5alpha-androstandione are potent inhibitors of the formation of estrone from androstenedione. 5alpha-androstandione was shown to be the most potent, while androsterone was the least.
Lastly, DHT acts on the hypothalamus / pituitary to decrease the secretion of gonadotropins. By decreasing the secretion of gonadotropins you decrease the production of the raw materials for estrogen production – testosterone and androstenedione (DHT itself cannot aromatize into estrogens).
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