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Prostate disease and the pharmaceutical industry
Prostate Cancer
How hormone medicines work in prostate cancer
In the 1940s the removal of the testicles from a dog with
prostate cancer was shown to cause the tumour to get smaller
(regression). A similar operation in humans, or treating men
with female hormones also leads to regression, reduces PSA
levels and decreases prostate size. Further, men castrated
before puberty never get prostate cancer. All these observations
suggest strongly that male sex hormones are in some way linked
to the development of prostate cancer.
The regulation of male sexuality is under the control of
several organs and involves several hormones. Some of these
have provided targets for medicines development.
Two small organs in the brain, the hypothalamus and the pituitary
gland, are important here. The hypothalamus produces luteinising
hormone releasing hormone (LHRH, which stimulates the nearby
pituitary gland. In response, the pituitary releases two further
hormones into the blood stream called luteinising hormone
(LH) and adrenocorticotropic hormone (ACTH). LH acts on the
testes and the ACTH on the adrenal gland situated above the
kidney. Both of these glands release testosterone in response.
Testosterone helps maintain male physical characteristics
and contributes to sex drive and activity. Testosterone also
stimulates sperm formation and acts on the prostate to produce
secretions that form part of semen.
However, high testosterone levels also act on the brain to
stop the secretion of LHRH, which in turn closes down the
production of LH by the pituitary. As the amount of testosterone
in the blood falls, the pituitary reactivates and more LH
is made. Hence, LH and testosterone levels rise and fall in
response to each other, a process called negative feedback
control, and this regulates the activity of the pituitary
gland and the testes.
Scientists have exploited these mechanisms to develop two
types of medicine – LHRH agonists which mimic the action of
natural LHRH, and antiandrogens that block the binding of
testosterone in the prostate gland. Both are used to treat
prostate cancer, either alone or in combination.
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