From: Robert Coyote (coyyote@hotmail.com)
Date: Thu Feb 07 2002 - 17:03:24 MST
Here is the complete article I snipped the early information from, pardon
for not including it all for proper context, my bad.
INSULIN-LIKE GROWTH FACTOR 1: PLEIOTROPIC EFFECTS
The expression of some genes is more favorable when it takes place in young
animals than when it takes place after animals are older. The existence of
differences in the effect of a gene's expression depending upon where it
acts or the time of its expression are called pleiotropic effects.
The effect of insulin-like growth factor-1 (IGF-1) looks more and more like
a pleiotropic effect. In mammals, IGF-1, released in response to growth
hormone, stimulates growth and wound healing. As mammals age, however, it
appears that IGF-1 may increase the likelihood of developing cancer, because
it increases cellular division. It is well known that mitogens, substances
that increase cell division, can increase the risk of cancer simply because
the more times a cell divides, the more chances there are for a mistake to
take place that will result in loss of proliferative control. In older
humans, elevated levels of IGF-1 have been reported to be associated with
increased risks of prostate and breast cancer.
Thus, we find that IGF-1 is associated with retinopathy because it
stimulates the neovascularization (excess formation of blood vessels in the
retina) that underlies retinopathy. While it is obviously important to be
able to grow new blood vessels in case of injury, in response to exercise,
and during preadult growth and development, in the long run there may be a
pathological downside of excessive growth of blood vessels in some places,
such as the retina (retinopathy) or in tumors (angiogenesis).
With regard to calorically restricted mice, there has been a report1 that
the IGF-1 receptor density increases with age (as compared to no consistent
changes in ad lib-fed animals with age), accompanied by a decrease in IGF-1
levels and an increase in growth-hormone release. IGF-1 levels increase in
ad lib-fed aging mice and in aging humans, while growth-hormone release
decreases with age.
The amplitude of growth-hormone secretory pulses decreases with age in ad
lib-fed animals, and short-term caloric restriction in young animals also
results in a decline in the amplitude of growth hormone. However, in older
caloric-restricted animals, growth-hormone pulses were similar to those in
young ad lib-fed mice, with both the number of pulses of growth hormone and
mean growth hormone concentrations increased substantially compared to older
ad lib-fed mice. Apparently, there is a long-term adjustment that takes
place in the growth hormone and IGF-1 axis in chronically calorically
restricted mice so that, even with 40% less food (called "moderate caloric
restriction" to distinguish it from outright starvation), the animals have
greater protein synthesis, along with greater growth-hormone and lower IGF-1
levels.
Another study2 reports that in 24 postmenopausal women aged 57 and older who
had taken long-term estrogen replacement treatment (83% for ten years or
more), there were higher growth-hormone levels and lower IGF-1 levels than
in estrogen nonusers. The long-term estrogen users had higher mean
circulating GH levels and more frequent GH secretory bursts (though the
amplitude of the GH bursts was no greater than in the nonusers), along with
lower IGF-1 levels. All hormone users were taking 0.625 mg a day of Premarin
for at least three years prior to the study. Whether the higher GH/lower
IGF-1 has similar youth-promoting implications to the higher GH/lower IGF-1
of caloric restriction is something we don't know. It should be noted that
the decrease in IGF-1 levels was specific to oral estrogen replacement
therapy (ERT) and did not apply to transdermal ERT. The authors state that
oral but not transdermal ERT results in high liver-portal estrogen
concentrations, and estrogen inhibits liver IGF-1 synthesis. Hence, the
lower IGF-1 levels may be a direct effect on the liver.
References
Sonntag et al, "Pleiotropic Effects of Growth Hormone and Insulin-like
Growth Factor (IGF-1) on Biological Aging: Inferences from Moderate
Caloric-Restricted Animals," J. Gerontol.: Biological Sciences
54A(12):B521-B538 (1999).
Moe et al, "Growth Hormone in Postmenopausal Women After Long-Term Oral
Estrogen Replacement Therapy," J. Gerontol.: Biological Sciences
53A(2):B117-B124 (1998).
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