I have browsed this forum and found no thorough explanation of Aromatase Inhibitors, otherwise known as an AI. Since I have been reading these forums I have seen many people neglect to use an AI on cycle, or be irresponsibly untimely with their dosing. If I leave anything out feel free to add, but the focus is to shed some light on the mechanism of action of an AI, not to regurgitate common knowledge.
What is Aromatase? Let us start with what Aromatase is. Pretty much anything in the world of science that ends with -ase is an enzyme. Other names for Aromatase are estrogen synthetase or the more common estrogen synthase. There may be exceptions to the -ase rule but I have not come across any yet.
So what is an enzyme? All enzymes are proteins but not all proteins are enzymes. This just means that an enzyme is yet another long chain of amino acids. What makes this chain different from other amino acid chains is that enzymes catalyze a reaction. In scientific terms they lower a reaction's activation energy, or the minimum energy required for a reaction to occur. By lowering activation energy in a particular reactant or group of reactants an enzyme is able to make the reaction occur much faster and easier than otherwise. It actually just offers an alternate pathway for a reaction to occur but we just say it lowers activation energy for simplicity's sake. In short, an enzyme speeds up reactions in our bodies and makes them occur more often. There have been some series of reactions that have been found to be over two billion times faster than they would have occurred with particular enzymes. Not all are that fast but most have no problem catalyzing thousands of reactions a minute.
Now that we know what an enzyme does let us focus on the specific reactions that Aromatase catalyzes. Aromatase is found in the endoplasmic reticulum of various cells in our bodies and primarily converts androgens to estrogens. This enzyme is found in many parts of our bodies to include skin, bone, blood vessels, brain, and even adipose tissues. It is found in many other places but the most important one you need to note here is the adipose tissue, aka body fat. The more body fat you have the more likely you are to have larger amounts of Aromatase in your body which in turn would increase your estrogen levels. Androgens and estrogens, for those of you new to this area, are sex hormones that regulate your sex specific functions and growth to put it simply. Hopefully you know this if you are looking at a cycle.
How does Aromatase work? Aromatase is controlled by a promoter gene, just like the other processes in your bodies. The promoter gene is in turn regulated by many other factors that aren't worth getting into here. When the promoter gene is on, which it usually always is, then Aromatase is busy at work converting androgens to estrogens. More specifically, it converts testosterone to estradiol and androstenedione to estrone. Both are estrogens and neither are great for the common bodybuilder and AAS user. Both estrone and estradiol contribute to the common negative effects that we see discussed on these forums in men such as gynocomastia and erectile dysfunction. It is also important to note that certain estrone molecules can also be converted into estradiol molecules, which is the most potent form of estrogen. Not that either aren't nasty for men in large amounts. To quote Zhou et al, "Aromatase, a cytochrome P450, synthesizes estrogens by catalyzing three consecutive hydroxylation reactions converting C19 androgens to aromatic C18 estrogenic steroids" (1996). What these guys are saying is that first cholesterol, yes nasty cholesterol (cholesterol is actually necessary for good health in moderation), gets converted into pregnenolone, reaction numero uno. Then pregnenolone is converted into progesterone, that would make number two. And lastly, progesterone is then converted through various other reactions to be eventually converted into androgens. Then Aromatase comes by and turns those androgens to estrogens mentioned above. This is again oversimplified as I am sure I have lost your interest by now.
So what are inhibitors? An inhibitor is a molecule that binds to a specific enzyme to slow down the rate of reactions in the body. This is usually regulated by your body through various negative feedback systems, but in our case is regulated also by our intake of inhibitors like arimidex. There are two ways an inhibitor can prevent an enzyme from doing its job. It can bind non-covalently to the enzyme's active site, or they can bond covalently to the enzyme's allosteric site. These have alternate names such as active and passive inhibition but I cannot think of the others at the moment. If a particular inhibitor binds to an enzyme's active site then the process is reversible, meaning the inhibitor can detach and the enzyme can resume normal function eventually. If the inhibitor binds to the allosteric site of the enzyme then the enzyme changes shape permanently and is disabled. Although there are many exceptions to this rule as is with all rules, nothing in life can be simple can it? Think of enzymes as puzzle pieces that are meant to fit only into the pieces of certain molecules. When you change the enzyme's shape then you render that particular function useless. Structure always equals function in biology. Keep in mind that there are also other molecules that can bind to enzymes to make them work better.
Putting it all together, Aromatase Inhibitors Anastrozole, my favorite AI, binds to the Aromatase's active site, which is reversible, via competitive inhibition. Competitive inhibition means that whoever gets there first wins in layman's terms. The more Anastrozole you flood your body with the higher the chances of it binding to the Aromatase before the androgens get there. Letrozole, which is the most powerful AI I have encountered to date, works in a similar fashion. Letro also inhibits competitively and reversibly. Yes, Exemestane works the same way as well. It is important to note that these commonly used AIs are binding to the active site reversibly because that tells us once we stop taking these particular AIs we will soon restart the process of synthesizing estrogen in greater amounts.
The theory of estrogen rebound comes from the idea that your body will detect low amounts of functioning Aromatase after it is no longer inhibited and will try to overcompensate by producing more enzymes to produce more estrogen. I find this is not something that is as serious as we might think because the same negative feedback systems will usually regulate our estrogen levels once they become too high under normal conditions. Just be careful with strong AIs like Letro or high doses.
So in short, take your AI on cycle religiously because more AAS usually means more androgen and therefore more estrogens in the presence of uninhibited Aromatase. If there has been any information I missed or am mistaken on feel free to add to it, it has been awhile since I have dealt with enzymes professionally and I do not do my best work at night. Below is my lonely reference, the list is short as most of this is common knowledge among biologists.
Identification of a Promoter That Controls Aromatase Expression in Human Breast Cancer and Adipose Stromal Cells
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Originally Posted by RangerDanger830
