Prostate Cancer & the Androgen Receptor – A Clearer Picture of the Problem

Monday, August 10, 2009
By: Byron J. Richards,
Board Certified Clinical Nutritionist

Prostate cancer is the most widely diagnosed cancer in America.  Men have a 17% risk for getting the problem during their lifetime.  The story of any cancer is essentially survival gone wrong, a problem wherein normal cell function is hijacked and turned to cancer.  How this happens varies considerably for any particular type of cancer, although there are a number of common features.  Any man not wanting prostate cancer in the first place or who is treating this problem should spend some time understanding at least the basics of the androgen receptor.

It is difficult for men to understand that when they go through prostate cancer treatment every effort will be made by physicians to wipe out the function of testosterone in their body.  Testosterone is the primary male androgen.  This treatment has the rather undesirable side effect of making a man somewhat “manless,” so he can live.  New research on the androgen receptor1 explains why a lot of prostate cancer treatment is only temporary in nature – as over time malfunctioning androgen receptors manage to switch from androgen-fueled cancer to driving a process that requires no androgen and spreads aggressively. 

The new study shows that androgen receptors can turn on a totally different set of gene signals to fuel aggressive prostate cancer, requiring no androgen at all to perpetuate the process.  If this problem were easy to understand doctors would have solved it long ago.  So let’s back up and cover some basics and then I will explain what it all means.

Hormones (which are like managers) require receptors to take their instructions and implement them at the cellular level (receptors are like area supervisors).  How receptors behave determines a lot about your health.  Sure, if a man has too much testosterone it could fuel excess androgen receptor function and cause prostate problems.  On the other hand, low testosterone can also fuel excess androgen receptor activity and prostate cancer, as if area supervisors are clamoring for some management direction which is lacking.

Testosterone is made in the testicles, and converted by the enzyme 5-alpha reductase to the more active metabolite 5-alpha dihydrotestosterone (commonly referred to as DHT).  Testosterone and DHT bind to the androgen receptor, and the DNA in your cells then goes to work following the directions given.

The bottom line question for any man is, “How do I keep my area supervisors doing a good job so that they are giving the right directions to my DNA?”  It appears that these area supervisors have a lot of autonomy, don’t always like the directions they are getting from management, and can get rather panicked by problems they think are going on in the workplace. 

In fact, androgen receptors can get conflicting orders from a lot of different areas.  If you would like to review detailed information on how this receptor works click on this link: Review of Androgen Receptor and Prostate Cancer2.

In normal health the secretory prostate cells are killed off at the rate of 1%-2% per day, and replaced with new ones.  This activity is part of normal prostate function and is regulated by the androgen receptor.  When the androgen receptor begins to malfunction, which includes becoming hyper-aroused and stressed out, then far more cells are made than are terminated which leads to the beginning of prostate cancer.

One thing the androgen receptor does is stimulate the production of prostate specific androgen (PSA), thus a rising PSA is reflective of over-active androgen receptors – which may or may not reflect prostate cancer activity, but is representative of risk.

Androgen receptor can be turned up by stress hormones, by inflammatory messages coming from stored fat (IL6), by low adiponectin Protein hormone that modulates metabolism including glucose and fatty acid catabolism. High levels are associated with low body fat. induced by leptin problems and obesity, and by multiple other issues that generally fall under the heading of wear and tear.  Excess IL6 activity3 is key to over-active androgen receptor function.  Underlying IL6 is the core inflammatory gene, NF-kappaB Protein complex that controls DNA transcription and is involved with cellular responses to stress, cytokines, free radicals, UV radiation, oxidized LDL, and infections. 4, which is always over-expressed in advanced prostate cancer. 

Problems with IL6 and NF-kappaB Protein complex that controls DNA transcription and is involved with cellular responses to stress, cytokines, free radicals, UV radiation, oxidized LDL, and infections. fall under the general heading of too much inflammation and are specifically made worse if you are overweight.  Men who are overweight are twice as likely to die from aggressive prostate cancer if they should get prostate cancer.  The handwriting for almost every man is typically on the wall before a prostate cancer diagnosis.  The underlying mechanisms are now clear.  While medical anti-testosterone treatment can buy you time, it is far better not to get the problem in the first place.  It is likely to ruin your sex life.

Your prostate gland has the poorest circulation to it of any gland or area in your body.  Common sense will tell you that exercise that helps circulation will bring needed oxygen and nutrients to your prostate that help it function normally, whereas a lack of exercise and progressive weight gain are blatant enemies.

Your prostate needs many nutrients for normal function, including zinc, tocotrienol Specialized form of vitamin E. Powerful antioxidant showing positive benefits for cholesterol, cardiovascular, neurological health and cancer risk reduction. E5, fish oil, selenium, lycopene It is a bright red carotene and carotenoid pigment and phytochemical found in red colored fruits and vegetables such as tomatoes, carrots, watermelon, and papayas. Research suggests amelioration of cardiovascular disease, cancer, diabetes, osteoporosis, and infertility. , and cruciferous vegetables.  Nutrients like saw palmetto and quercetin help modulate the function of 5-alpha reductase, which may help dampen androgen receptor activity and reduce prostate swelling6 and prostate cancer7 activity.  Both saw palmetto8 and quercetin9 have demonstrated anti-prostate cancer activity in cell studies.

In fact, a number of nutrients have been shown to help modulate the activity of the androgen receptor.  For example, the above review study on the androgen receptor states “A number of naturally occurring compounds or their derivatives have been found to regulate androgen receptor bioavailability in prostate cancer cell lines. These compounds include silymarin, vitamin D310, vitamin E derivatives, and polyphenols antioxidant shown to affect cell-to-cell signaling, receptor sensitivity, inflammatory enzyme activity or gene regulation. Found in many different fruits, vegetables, red wine, grains, honey, and legumes. such as resveratrol Natural phenol or type of antioxidant found in red grapes, red wine. Research has shown beneficial effects as anti-cancer and anti-inflammatory agents along with supporting healthy blood sugar and cardiovasculature function. and epigallocatechin gallate.”

The bottom line is that you have to keep your androgen receptors happy.  That means keeping them cooled off and not letting them get stressed out.  That means taking care of yourself.  Regular exercise, enough sleep, stress managed well, lots of fresh fruits and vegetables, losing weight if overweight, and multiple nutrients, as desired.  If you have symptoms of a swollen prostate make it a priority to reduce them.

You really don’t want to wake up one day to androgen receptors that are all bent out of shape.


Referenced Studies:
  1. ^ How the Androgen Receptor Fuels Prostate Cancer Progression    Myles Brown, et al.
  2. ^ Review of Androgen Receptor and Prostate Cancer  Endocr Rev.  Heinlein CA, Chang C.
  3. ^ IL6 and Prostate Cancer  Clin Cancer Res.  Chun JY, Nadiminty N, Dutt S, Lou W, Yang JC, Kung HJ, Evans CP, Gao AC.
  4. ^ NF-kappaB and Prostate Cancer  Am J Pathol.  Zhang L, Altuwaijri S, Deng F, Chen L, Lal P, Bhanot UK, Korets R, Wenske S, Lilja HG, Chang C, Scher HI, Gerald WL.
  5. ^ Gamma Tocotrienol and Prostate Cancer  Br J Cancer.   Yap WN, Chang PN, Han HY, Lee DT, Ling MT, Wong YC, Yap YL.
  6. ^ Reducing Prostatitis  Drugs.   Murphy AB, Macejko A, Taylor A, Nadler RB.
  7. ^ 5-alpha Reductase and Prostate Cancer  BJU Int.  Vis AN, Schröder FH.
  8. ^ Saw Palmetto and Prostate Cancer  Biochem Biophys Res Commun.  Scholtysek C, Krukiewicz AA, Alonso JL, Sharma KP, Sharma PC, Goldmann WH.
  9. ^ Quercetin and Prostate Cancer   Prostate.   Aalinkeel R, Bindukumar B, Reynolds JL, Sykes DE, Mahajan SD, Chadha KC, Schwartz SA.
  10. ^ Vitamin D and Prostate Cancer  International Journal of Cancer  Yi-Fen Lee, et al.

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