How Sex Hormone-Binding Globulin (SHBG) really works?
My friend Dr. George Touliatos, from Greece, posted these great questions on Facebook, about how Sex Hormone Binding Globulin (SHBG) really works, within our biological system. Please click on the very helpful photo for my responses:
Is aromatisation and beta estradiol elevation, a matter of TT or FT?
If we manage to elevate FT, by lowering SHBG, the higher FT will lead to higher E2?
Or it is also a matter of TT elevation?
As we now TT/FT are not obligatory proportional high/low.
FT interacts with SHBG/E2, thus a high TT is not always followed by high FT (and sex drive).
Commentary by Dr. John Crisler on November 28, 2017
No, because DHT inhibits aromatase. But once T is bound to SHBG, it cannot be converted to E.
Check out the accompanying picture. Higher SHBG leads to more Free SHBG floating around, which can then bind to its own receptor on the cell membrane surface. Then either a Free T or Free E molecule can bind to it, and induce a reaction cascade inside the cell. This is how sex hormones can have actions without actually entering the nucleus inside the cell. This is new information for many, and explains some of the more difficult cases in TRT medicine.
It's also why high(er) SHBG is better than low(er) SHBG.....once the guy is on TRT. But not before—when it makes it harder for the body to make enough T to get enough FT left over.
The situation we are used to seeing is where a T or E molecule is powerfully bound to SHBG. Some think two sex hormone molecules--perhaps even a T and an E molecule--may even bind on the SHBG molecule.
This is why SHBG is the centerpiece of every proper sex hormone evaluation. It's level dramatically affects not only the patient's response, but what TRT regimen is likely to work the best.
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