Quote: (07-08-2016 08:47 AM)PhDre Wrote:
Thomas, thank you for the great post.
I have a few questions.
Quote: (07-06-2016 01:19 PM)Thomas the Rhymer Wrote:
It should also be noted that prostate cancer is thought to be especially stimulated by Testosterone and that having this cancer is a contra-indication to getting Testosterone treatment.
Although this is still the point of view thought in medical school, more recent work seems to reject this notion.
http://www.lifeextension.com/Magazine/20...er/Page-01
Saturation explains the paradox in this way. At very low levels of T, near the castrate range, prostate growth is very sensitive to changes in T concentration. Thus, severely lowering testosterone will definitely cause prostate cancer to shrink; adding testosterone back will cause the cancer to regrow. However, once we get above the point where the prostate is saturated with testosterone, adding more testosterone will have little, if any, further impact on prostate cancer growth. Experimental studies suggest the concentration at which this saturation occurs is quite low.
In other words, the old analogy I learned in training was false. Testosterone is not like food for a hungry tumor. Instead, a much better analogy is, “Testosterone is like water for a thirsty tumor.” Once the thirst has been satisfied, prostate tumors have no use for additional testosterone. And the vast majority of men with low testosterone appear to have prostates that are not particularly thirsty.
A rat study I’ve seen suggested that prostate cancer was stimulated by estradiol, but not by testosterone.
What is your take on this?
Testosterone clearly drives prostate cancer, given that anti-testosterone treatments usually causes dramatic reductions in prostate cancer growth. However, the 'rate-limiting factor' is not testosterone, but testosterone receptors. In other words, it's the interaction between testosterone and testosterone receptors that determines growth of prostate cancer, not simply the level of testosterone.
This is the 'saturation' model of prostate cancer and it evolved to explain why massively high doses of testosterone do not seem to increase the risk of prostate cancer.
This model is still theoretical and it is unclear what the clinical significance of it is. In other words: If I give a patient testosterone, to what extent a am I slaking the tumour's thirst? As a generalist doctor, I don't know. Hence, for now, I would still not give testosterone to a known prostate cancer patient unless it was under a specialist urologist's recommendation.
Oestrogen could very well play a role in prostate cancer (the actual chemical reactions that trigger it are still unknown, after all) but given that anti-testosterone drugs work so well in prostate cancer, it's generally accepted that testosterone is the main culprit. Obviously, medical knowledge is continuously changing and new data may change our understanding over time.
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Quote: (07-06-2016 01:19 PM)Thomas the Rhymer Wrote:
Of note is that semen is rich in Zinc. It is unknown what zinc does in semen, or even how zinc even gets into semen. What is clear is that zinc deficiency causes infertility, so zinc must have a critical role to play in sperm and semen, but the exact nature of this role is still a mystery.
I thought that zinc was important for the proteins that influence the transport of cholesterol to the mitochondria (like StAR), where the cholesterol is converted to pregnenolone, but I might be wrong.
This is plausible but as far as I know there is no proof of this. There are multiple theories of zinc's role in sperm and none of them are properly proven.
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Quote: (07-06-2016 01:19 PM)Thomas the Rhymer Wrote:
The most common cause of this condition is liver disease, but in any case these patients require further investigations to find out what exactly is the source of the excess sex hormone binding globulin, and that diseased source must be managed
Can you explain the hepatic metabolism of SHBG or is this process still unknown?
I am in this case and alternative therapies serve me well, but I would like to have a deeper understanding. Unfortunately I cannot find any text/papers that discusses SHBG metabolism; they all seem to focus on the correlation between SHBG/insulin/diabetes.
Thanks again for the very informative post!
Liver disease is the common example simply because the liver makes so much of SHBG. Other tissues can also make SHBG too.
Liver diseases have odd effects at times - other organs tend to shut down when sick, whereas the liver at times overcompensates when sick. So it starts manufacturing too much SHBG in the presence of liver disease. Other glonulins are also released too much, so it's not only SHBG. The exact mechanisms why the liver does this are still not entirely understood.
Another mechanism that enhances the effect of SHBG is the fact that the liver production of albumin drops when the liver is diseased. Albumin binds harmlessly to testosterone and helps transport it from place to place. Unlike SHBG, it does not inactivate testosterone. So when albumin level drop, there is less competition for SHBG and it is allowed to inactive more testosterone. This is referred to as an altered albumin-globulin ratio.
Once made by the liver, SHBG goes into the blood stream and then rapidly goes into tissues all over the body. Once there, it probably slowly degrades with time by spontaneous chemical breakdown.