17beta-hydroxysteroid dehydrogenase (17bHSD)


Where a steroid that has a keto group in the 17th position, this particular enzyme can convert it to one with a hydroxy group in that position, and vice versa - working in both directions. For example, this initial conversion is the case when androstenedione is being converted into testosterone.


3beta hydroxysteroid dehydrogenase (3bHSD)


There are very few bodybuilders who have heard of the 3bHSD enzyme, despite those who are actually very knowledgeable on the subject of anabolic androgenic steroids. Now, very similar to the Esterases enzyme, this too can work in two directions. Essentially this enzyme can convert a steroid with a keto group on position 3 of the steroid molecule, to one with a hydroxy group in the same positionor vice versa. Similar also to that of the 17bHSD enzyme. Looking at the names you will notice one works at the 3r position, and one at the 17th position. You will see this interaction working when androdiol is being converted into testosterone by the 3bHSD enzyme. The reverse action is seen when DHT is converted to androstanediol (different from androstenediol) in muscle tissue and of course this is the reason why DHT is not an effective anabolic in muscle tissue. Note that Proviron also undergoes this very transformation and is deactivated in muscle tissue.


Where the conversion of DHT to androstanediol occurs in muscle tissue, it is also present and occuring in scalp tissue, and there is evidence to support that androsanediol is of some relevance in the development of male-pattern baldness.


Because this enzyme works in two directions, it cannot convert a keto steroid entirely into the hydroxy form, or vice versa, as logically, some fo what is converted will simply be acted upon immediately once again to convert it right back into its original state. For this reason, there will always be a mixture of the two compounds at one time, and in some instances the mixture may favour one side of the balance over the other.


3bHSD is widely distributed in the body.


3-oxosteroid-4,5-isomerase


This enzyme is of no interest unless one is concerned with the conversion of DHEA or one of the 5-andro products to testosterone, where the enzyme is required to change the double bond from the 5 position to the 4 position of testosterone. Since DHEA has since been banned, this information is of little interest to most people.


UDP-glucuronysyltransferase (UDPGT)


Here is an interesting and lesser heard of enzyme present within the body that will take effect and act upon steroid molecules in quite a dramatic manner. Now this enzyme attaches a sugar molecule to an -OH group of a steroid, which will render it inactive and making it far more water soluble, which as discussed, causes the steroid to become more easily excreted.


It is possible to a small degree, to reverse this effect in the body, by the presence of glycosidase enzymes. This reversal process is called entherohepatic recycling, and this does have a significant effect. What happens in this process is the deactivated, glucuronidated steroids are excreted in the bile into the intestine, where bacteria then cleave the glucuronide, thus restoring the steroid intact and active. Much of this steroid will then be reabsorbed back into the body. The result is, just because a steroid is excreted once, never means that it will not work once it has come back for another turn.


We see this as being such a very important aspect of birth control, and is the very reason why antibiotics can have an interference with the contraceptive pill. What happens, is the physical amount of gut bacteria present in the body is greatly reduced by the antibiotics, which thus in turn reduces the chances of enterohepatic recycling, and in turn reduces estrogen levels. Very similar, this is also the case for the androgen user. Any dose of antibiotics will reduce the response of enterohepatic recycling, affecting the reabsorption of any steroid, and thus lessening the overall effectiveness of the administered anabolic.


It has been shown that men have about twice as much UDPGT activity on steroids as women do and there is also a great deal of variation between individuals.


Sulfotransferases (various types, including DHEA-ST)


The Sulfotransferases enzymes convert a -OH group of a steroid to the totally inactive sulfate form. However this process is indeed reversible. What happens here is the sulfated form of steroid provides a depot of temporarily inactivated steroid, which may be converted back into the active parent steroid at a later time. This is of particular relevance with DHEA. With DHEA you have a very large percentage of the compound already in the sulfated form at any one given moment. This is/was true also with other banned pro-hormone products such as the diol prohormones, which may also be sulfated, and therefore deactivated at the 3-OH position.


The process of sulfation is a significant one in the metabolism of testosterone, although somewhat slower occuring that that of glucuronidation, whereby conversion is in the liver to the sulfate, inactivating the drug, and rendering it to be more easily excreted in the bile, allowing eventual enterohepatic recycling to occur naturally.