Like it or not (and I'm sure T-mag readers really like it), Testosterone is the hormone of the decade. The granddaddy of the male hormones has gotten more media attention over the last few years than any other hormone around. Heck, I even heard a rumor that some crazy bodybuilding media guys were thinking of naming a magazine after it. Can you imagine that?
While Testosterone (the hormone, of course) has been the target of much bad press, I think that if you asked this big dog of hormones what he thought of all of this, he would bark out something to the effect of "What of it? I must be doing something right if they keep talking about me! Now can't you see I'm trying to work this shaved little poodle over here?"
Although the popular media has made Testosterone out to be a destructive bad guy, researchers have been slowly but surely embracing its use. Clinical trials have been conducted in diverse groups of individuals from HIV wasting patients and burn victims to people with compromised immunity, along with older men whose "Testosterone" hasn't been up in years. There have even been a number of recent trials investigating the use of Testosterone in healthy weight trained men. So where do I sign up?
The results of these investigations have shown that Testosterone is not the demon the medical community once thought it to be and that it actually can be of great benefit to certain individuals and, in certain patients, possesses very few risks.
I'm pretty positive though, that the use of Testosterone will never be condoned for use in healthy weight trained males. To this end, us law abiding citizens have to do the best we can with what we've got to work with. So let's talk about how our own body provides us with the big T and what we can do, both naturally and with dietary supplements, to maximize our T levels.
When most people think of steroids, they tend only to think of Testosterone. This, my friends, is yet another fact which tends to make me believe that T is the hormone of the decade. Testosterone, however, is only one member of the steroid family. Some of the other steroids in this family include cholesterol, progesterone, the estrogens, cortisol, and aldosterone.
Although these molecules are part of the same family and have strikingly similar structures, their functions differ like night and day. This is important to recognize because although the steroids tend to act very differently, they are subject to similar rules with respect to biochemistry and metabolism.
For a simplified view of steroid metabolism in the body, you can assume that all steroid hormones begin with cholesterol. From cholesterol, steroid metabolites are formed in various tissues of the body. For example, enzymes in the adrenal glands are responsible for converting cholesterol into cortisol, while enzymes in the gonads are responsible for converting cholesterol to Testosterone.
With this simplified view, it's easy to make the mistake of thinking that by simply providing the body with more cholesterol (make that two large fries, please), we can make more Testosterone. This is a mistake because the body has regulatory mechanisms that control hormone production. These regulatory mechanisms, not your bedtime prayers to the iron gods, are what determine which steroid metabolites will ultimately be formed.
So the next important questions are, what magic does it take to make Testosterone out of cholesterol (now don't get too excited, you can't do this in your bath tub), what regulates this conversion, and ultimately, what regulates Testosterone production? In order to get the gonads to produce T, the body has a chain of command that must be dealt with just like any smooth running business.
In business, the action plan comes down from the CEO to upper management, the plan is solidified and delegated to the production team, and the production team gets the job done. Well, in the body, a portion of the brain called the hypothalamus is the CEO, the pituitary gland is the upper management, and the testes are the production team members.
As in business, the buck stops with the CEO/hypothalamus, which is known as a "pulse generator," because during the day it sends out pulses of hormones that are designed to stimulate other organs. With respect to T, the hypothalamus sends out numerous daily pulses of GNRH (gonadotropin releasing hormone) through the blood stream. These pulses are designed to stimulate the pituitary gland to get to work.
The pituitary gland then senses the pulses of GNRH and sends out a work order of its own, consisting of LH (leutinizing hormone) pulses. The LH message travels down to the leydig cells of the testis to stimulate the enzymatic conversion of cholesterol to Testosterone.
Cholesterol conversion to T is no easy process and I'm not going to go into all of the details (partly because no one really knows them all). One fact that you should understand, though, is that there's a high level of complexity to this pathway and that there are many enzymes and intermediates that cholesterol has to encounter before forming T.
Some of these intermediates include pregnenolone, DHEA, androstenedione, and other well-known androgens. So, although the hypothalamus might be functioning well, the pituitary might be doing the right thing, and the testis are getting the "ball" in motion, ultimately the enzymes in the leydig cells determine whether you're pumping out loads of muscle building T or simply forming other intermediates at the expense of the top dog.
As a result of the process I mentioned above, T levels fluctuate wildly. If you were to measure your Testosterone levels throughout the day, you'd likely be amazed. One minute you have the hormonal profile of a hyper-muscular bull ready to "fertilize" an entire herd of cattle and the next minute your blood profile is that of a fully menstruating Martha Stewart intent on color coordinating your powder room.
These odd fluctuations occur as a result of the pulsatile nature of hormone secretion. Again, this begins with the hypothalamic pulse generator's release of GNRH. Incidentally, researchers now believe that it is this physiologic pulsatility of Testosterone that makes it anabolic. So if you can mimic this pattern of hormone release, you can stimulate muscle growth.
With this hormonal cascade in mind, it's important to realize that each step in the pathway has a regulation point designed to either stimulate or inhibit pulse release. In this respect, the body is a bit of a control freak as it tends to like many control points rather than just one.
In this particular case there are three main control points; the hypothalamus, the pituitary, and the testis. With this type of control, the body can maintain the Testosterone homeostasis (a sort of hormonal status quo) and prevent us from any abnormal changes in muscle development and strength. For example, if our Testosterone levels go way up, the body senses this and the hypothalamus and the pituitary produce less GNRH and LH in order to slow down T production. This, of course, is the famous negative feedback. Damn that homeostasis!
Now that I'm certain you're all experts in Testosterone production (and there will be a test at the end — I'm serious!), I'd like to address one more important issue that will come up later in the article with regard to Testosterone in the body. When Testosterone is converted from cholesterol in the leydig cells of the testis, it's released into the blood stream where it embarks on an anabolic adventure.
However, when in the blood, 60% of the big T released from the boys down below is bound up by a protein known as SHBG, or sex-hormone binding globulin. SHBG is produced and released by the liver. The important point is that the Testosterone bound to SHBG is biologically inactive and this is why there's an important distinction between total T and bioavailable T.
Total T represents all the Testosterone in the blood, while bioavailable T represents the non SHBG bound Testosterone. There are other proteins in the blood that bind Testosterone, too, but their binding is rather weak, so this T is bioavailable and these proteins can still enter the cells to produce and effect all the things we're interested in.
As I said, bioavailable T represents the Testosterone that is not SHBG bound, while free T represents the Testosterone that's not bound to any blood proteins at all. It's tricky, I know, but I hope that it's now evident that although only about 2% of the T in blood is technically considered free T, there is a larger percentage of T (about 40% or so) that is bioavailable because it's only weakly bound to non SHBG blood proteins.
I'm taking you through this complex path for good reason. When trying to increase T levels in the body, one must attempt to not only increase total T. More importantly, one must attempt to increase bioavailable T. If you increase total T, but you increase SHBG to a larger extent, they you will actually have less bioavailable T for muscle building purposes!
A great example of this is the use of both thyroid drugs and tamoxifen (nolvadex). Both may increase total T levels in the body, but both also increase SHBG to a large extent. Although you may get a bit of a T surge with each (hurray!), the increase in SHBG may bind up any extra, and actually decrease your bioavailable T (boo!).
Well, now that the class is up to speed with our physiology and endocrinology (will someone please wake up Mr. Luoma! — he's always falling asleep during my physiology lectures), we can dive, full force, into how lifestyle factors including things like diet, training, recreational drugs, over the counter medications, altitude, and how psychological mood states influence T levels. There's an abundance of Testosterone literature out there and some of it is applicable for us while some is not, but to a science geek like me who both likes facts and likes being big and lean, it's all interesting nevertheless.
Oh wait, I almost forgot! Before we go on, I promised a test didn't I? Settle down! Although there are no actual grades on this test, I hope that you take away a few fundamental things from this article. If you can answer these questions, you're ready to take on next week's article in which I'll review a number of environmental and lifestyle factors that can influence your levels of free T, total T, and bioavailable T.
Rest easy, next week's article ties in all that you learned this week and makes some recommendations about how to up the T levels. And next week there won't be a test!
Question #1 — True or False
John Berardi is the most intelligent man on the face of the earth.
(I thought I'd start off with an easy one — And the answer of course is "True")
Question #2 — Short Answer
What are the three main organs/glands that regulate T production and what are the big three hormones they release?
Question #3 — True or False
Testosterone is synthesized directly from cholesterol.
Question #4 — Short answer
What are the cells that actually produce T and where are they located?
Question #5 — Short answer
All the Testosterone in the body, bound and unbound is referred to as what?
Question #6 — Short answer
All the Testosterone that is not bound to SHBG is referred to as what?
Question #7 — Short answer
All the Testosterone not bound to any blood protein is known as what?
Question #8 — True or False
If you are interested in the anabolic effects of Testosterone, the optimal situation is to increase total T levels and decrease SHBG.
This concludes Part 1 of "The Big T". Next week, John will conclude the article with a review of both interesting and applicable Testosterone research.