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<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: xx-large"
><span style="font-size: large"><blockquote>
<strong>Growth hormone: Hormone of Stress, Aging, & Death?</strong>
</blockquote></span><span style="font-size: medium">
<blockquote>
The name "growth hormone" is misleading; stress produces somatic growth, in a process called
"hormesis." Exercise produces muscle edema, to a degree similar to that produced by GH;
edema stimulates growth, but GH effect isn't limited to bone and muscle.
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: xx-medium"
><span style="font-size: medium"
>Identity of GH: Molecular ambiguity, complex modifications change one substance
into many; its evolution suggests a role in water regulation. Doctrine of a
"specific molecule" and "specific receptor" and specific effects is a
myth.</span></span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: xx-medium"
><span style="font-size: medium"
>The osmoregulatory problem--keeping water under control--is centrally involved
in stress.</span></span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: xx-medium"
><span style="font-size: medium"
>In mammals, the kidneys and bowel are the main regulators of water
balance.</span></span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: xx-medium"
><span style="font-size: medium"
>GH is a stress hormone. Its effects can be produced osmotically, for example
inducing milk production and cartilage growth, by osmotic (dilution)
shock.</span></span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: xx-medium"
><span style="font-size: medium"
>Estrogen produces increased GH, and increases its production in stress.</span
></span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: xx-medium"
><span style="font-size: medium"
>Nitric oxide is a pro-aging free radical induced by estrogen, releasing GH; all
three produce edema.</span></span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: xx-medium"
><span style="font-size: medium"
>Behind edema, hypoxia, hypocarbia; free fatty acids, diabetes, vascular
leakiness, degenerative kidney changes, connective tissue changes,
thickened.basement membrane, retinal degeneration. The same changes occur in
aging: increased permeability; kidney disease, connective tissue
changes.</span></span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: xx-medium"
><span style="font-size: medium"
>The absence of GH protects kidneys against degeneration. Osteoarthritis, a
characteristic aging condition, is caused by estrogen and GH.</span></span
></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: xx-medium"
><span style="font-size: medium"
>Some studies found that heart failure and bone repair aren't improved by GH; GH
is very high during heart failure, in which edema contributes to the
problem; carpal tunnel syndrome, myalgia, tumor growth, gynecomastia, and
many other problems have been produced by GH treatments.</span><span
style="font-family: Lucida Grande"
><span style="font-size: medium"></span></span><span
style="font-size: medium"
><hr /></span><span style="font-family: Lucida Grande"><span
style="font-size: medium"
></span></span><span style="font-size: medium"
>Bovine Growth Hormone is used to make cows give more milk.</span><span
style="font-family: Lucida Grande"
><span style="font-size: medium"></span></span><span style="font-size: medium"
>Human Growth Hormone is supposed to make men lean and muscular, not to increase
their milk production.</span></span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
><hr /><span style="font-family: Lucida Grande"></span>Recently I heard Robert
Sapolsky interviewed, and he was describing the changes that prepare the body
for short-term stress. He said the energy-mobilizing hormones, adrenalin and
cortisol, increase, while the hormones that don't contribute to meeting the
immediate problem, including the sex hormones and growth hormone, are
suppressed, to save energy; growth and reproductive processes can be suspended
for the few minutes of acute stress, to make the body more able to meet its
acute needs. He reiterated: Growth hormone is suppressed by stress.</span></span
></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>Sapolsky has done very interesting work on the suppression of testosterone by
stress, and on the way in which brain cells are killed by prolonged exposure to
glucocorticoids. He showed that if extra glucose is supplied, the brain cells
can survive their exposure to cortisol. In the body, adrenalin and the
glucocorticoids increase the availability of glucose.</span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>In the radio interview, he didn't have time for much detail, but it seemed to me
that he wasn't talking about the same growth hormone that I have been reading
about, and trying to understand, for years. Since people have asked me to write
about the current anti-aging uses of GH, and its use in the dairy industry,
Sapolsky's statements made me decide to think about some of the issues around
the hormone.*</span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>________________________________________________________________________________<span
style="font-family: Lucida Grande"
></span>*If Sapolsky had been talking about just mice and rats, his statement
would have been generally accurate. Adrenaline stimulates rat pituitary cells to
secrete GH, and since both increase the amount of free circulating fatty acids,
it could be that rats' GH is suppressed by a fatty acid excess.</span></span
></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>The "growth hormone" was named long before it was actually found, and the substance
with that name turns out to be involved in many processes other than growth. It
is being given to cows to make them produce more milk, and it is being given to
people with the purpose of making them lean and muscular, and with the hope of
building stronger bones.<span style="font-family: Lucida Grande"></span>It isn't
surprising that the Growth Hormone helps breasts develop and promotes milk
production, since it is very similar to prolactin. GH and prolactin are members
of a family of proteins that have diverged from each other in evolution, but
they still have many overlapping effects.</span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>When GH is treated as a drug, it is supposed to have a discrete identity, based on
the sequence of its amino acids. But the natural hormone (disregarding the
existence of a variety of closely related peptides with slightly different amino
acid composition) varies with time, being chemically modified even before it is
secreted. For example, its acidic amino acids may be methylated, and its lysine
groups may combine with sugars or carbon dioxide. The history of the protein in
the body determines its exact structure, and therefore its biological
effects.</span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>Male animals secrete GH in pulses, but females secrete it more steadily. This
pattern of secretion "masculinizes" or "feminizes" the liver (and other organs),
determining the pattern of enzyme activity. It would be possible (though very
difficult) to arrange a system for delivering doses in a pulsed, intermittent
manner. In cows, this apparently isn't necessary, since the purpose of the
growth hormone is presumably to "feminize" the milk-producing system. But the
normal pattern of secretion is much more complex than simply being "pulsed" or
"continuous," since it, like prolactin secretion, is responsive to changes in
thyroid, estrogen, diet, stress, and many other factors.<span
style="font-family: Lucida Grande"
></span>For example, hormones in this family are, as far back in evolution as
they have been studied, involved in the regulation of water and minerals. It is
well established that increased water (hypotonicity) stimulates prolactin, and
increased sodium inhibits its secretion. Growth hormone is also closely involved
with the regulation of water and salts.</span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>One of the best known metabolic effects of GH is that, like adrenalin, it mobilizes
fatty acids from storage. GH is known to antagonize insulin, and one of the ways
it does this is simply by the ability of increased free fatty acids to block the
oxidation of glucose. At puberty, the increased GH creates a mild degree of
diabetes-like insulin resistance, which tends to increase progressively with
age.<span style="font-family: Lucida Grande"></span></span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>In his book, Why Zebras Don't Get Ulcers, Sapolsky acknowledges some situations in
which GH is increased by stress in humans, but I think he misses the real ways
in which it operates in stress. One of the interesting features of cortisol,
which Sapolsky showed killed brain cells by making them unable to use glucose
efficiently, is that it makes cells take up unsaturated fatty acids more easily,
interfering with their energy production. Since growth hormone also has this
kind of "diatebetogenic" action, it might be desirable to suppress its secretion
during stress, but in fact, there are several kinds of stress that clearly
increase its secretion, and in animals as different as fish, frogs, cows, and
people it can be seen to play roles in water and salt regulation, growth and
development, stress, and starvation.<span
style="font-family: Lucida Grande"
></span></span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>Heat, hypoglycemia, running, and some types of shock are known to stimulate growth
hormone secretion, sometimes to levels ten or twenty times higher than normal.
(Two kinds of stress that usually don't increase GH are cold and
stimulus-deprivation.) I consider the growth hormone to be, almost as much as
prolactin, a stress-inducible hormone. That's why I reasoned that, if an
endocrinologist as good as Sapolsky can misunderstand GH to that degree, the
public is even more likely to misunderstand the nature of the material, and to
believe that it somehow acts just on muscle, fat, and bones.<span
style="font-family: Lucida Grande"
></span></span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>And the normally functioning pituitary appears to be unnecessary to grow to normal
height. (Kageyama, et al., 1998.)<span style="font-family: Lucida Grande"></span
></span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>W. D. Denckla discovered that the pituitary hormones are in some way able to
accelerate the process of aging. They block the actions of thyroid hormone,
decreasing the ability to consume oxygen and produce energy. The diabetes-like
state that sets in at puberty involves the relative inability to metabolize
glucose, which is an oxygen-efficient energy source, and a shift to fat
oxidation, in which more free radicals are produced, and in which mitochondrial
function is depressed. Diabetics, even though it is supposedly an inability of
their cells to absorb glucose that defines their disease, habitually waste
glucose, producing lactic acid even when they aren't "stressed" or exerting
themselves enough to account for this seemingly anaerobic metabolism. It was
noticing phenomena of this sort, occurring in a great variety of animal species,
in different phyla, that led Denckla to search for what he called DECO
(decreasing consumption of oxygen) or "the death hormone." (Vladimir Dilman
noticed a similar cluster of events, but he consistently interpreted everything
in terms of a great genetic program, and he offered no solution beyond a
mechanistic treatment of the symptoms.)<span
style="font-family: Lucida Grande"
></span></span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>Simply increasing the amount of free fatty acids in the blood will act like DECO or
"the death hormone," but growth hormone has more specific metabolic effects than
simply increasing our cells' exposure to fatty acids. The hormone creates a bias
toward oxidizing of the most unsaturated fatty acids (Clejan and Schulz), in a
process that appears to specifically waste energy.<span
style="font-family: Lucida Grande"
></span>Growth hormone plays an important role in puberty, influencing ovarian
function, for example. <span style="font-family: Lucida Grande"></span
></span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>Removing animals' pituitaries, Denckla found that their aging was drastically
slowed. He tried to isolate the death hormone from pituitary extracts. He
concluded that it wasn't prolactin, although prolactin had some of its
properties. In the last publication of his that I know of on that subject, he
reported that he was unable to isolate the death hormone, but that it was "in
the prolactin fraction." Since rats have at least 14 different peptides in their
prolactin family, not counting the multitude of modifications that can occur
depending on the exact conditions of secretion, it isn't surprising that
isolating a single factor with exactly the properties of the chronically
functioning aging pituitary hasn't been successful.<span
style="font-family: Lucida Grande"
></span></span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>Denckla's experiments are reminiscent of many others that have identified changes
in pituitary function as driving forces in aging and degenerative diseases.<span
style="font-family: Lucida Grande"
></span></span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>Menopause, for example, is the result of overactivity of the pituitary gonatropins,
resulting from the cumulatively toxic effects of estrogen in the
hypothalamus.<span style="font-family: Lucida Grande"></span></span></span
></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>A. V. Everitt, in his book on the hypothalamus and pituitary in aging, reported on
studies in which estrogen caused connective tissues to lose their elasticity,
and in which progesterone seemed to be an antiestrogenic longevity factor.
Later, he did a series of experiments that were very similar to Denckla's, in
which removal of the pituitary slowed the aging process. Several of his
experiments strongly pointed to the prolactin-growth hormone family as the aging
factors. Removal of the pituitary caused retardation of aging similar to food
restriction. These pituitary hormones, especially prolactin, are very responsive
to food intake, and the growth hormone is involved in the connective tissue and
kidney changes that occur in diabetes and aging. <span
style="font-family: Lucida Grande"
></span></span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>A mutant dwarf mouse, called "little," has only 5% to 10% as much growth hormone as
normal mice, and it has an abnormally long lifespan.<span
style="font-family: Lucida Grande"
></span></span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>Many experiments show that prolactin and estrogen have synergistic effects in
causing tissue degeneration, including cancerization, and that their effects
tend to operate with fewer protective restraining influences in old age.
Estrogen stimulates both prolactin and growth hormone secretion. Thirty years
ago, people were warning that estrogen contraceptives might produce diabetes,
because they caused chronic elevation of growth hormone and free fatty
acids.<span style="font-family: Lucida Grande"></span>Since estrogen causes a
slight tendency to retain water while losing sodium, producing hypotonic body
fluids, and since hypotonicity is a sufficient stimulus to cause prolactin
secretion, I have proposed that it is estrogen's effect on the body fluids which
causes it to stimulate prolactin. In pregnancy, the fetus is exposed to fluids
more hypotonic than can be accounted for by estrogen and prolactin alone; since
GH lowers the salt concentration of fish when they enter the ocean from
freshwater, it seems to be a candidate for this effect in pregnancy.<span
style="font-family: Lucida Grande"
></span></span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>Growth itself is an intrinsic property of all cells, but the growth hormone does
have its greatest influence on certain tissues, especially cartilage. Gigantism
and acromegaly were what originally made people interested in looking for a
growth hormone, and these are characterized by continued, exaggerated
enlargement of bones and cartilage. In old age, cartilaginous structures such as
the bones and ears keep enlarging. The fact that simply diluting the culture
medium is sufficient to stimulate the growth of cartilage suggests that the
growth hormone might be acting by its effects on water metabolism. In fish which
enter fresh water from the ocean, pituitary hormones of this family help them to
balance salts in this new environment, but in the process, they develop
osteoporosis and skeletal deformity, of the sort that occur more gradually in
other animals with aging.<span style="font-family: Lucida Grande"></span></span
></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>Growth hormone clearly causes edema, and this is probably involved in the
pathological processes that it can produce. The expansion of extracellular water
has been reported, but others have concluded that the increased weight of
muscles following GH treatment must be the result of "growth," "because
microscopic examination didn't show edema." Statements of that sort give
incompetence a bad name, because any student of biology or biochemistry has to
know, before he does almost any experiment, that the way to determine the water
content of a tissue is to compare the wet weight to the weight after thorough
drying. Looking for water under a microscope is the sort of thing they do at
drug companies to pretend that they have done something.<span
style="font-family: Lucida Grande"
></span></span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>Estrogen, growth hormone, and nitric oxide, which tend to work as a system, along
with free fatty acids, all increase the permeability of blood vessels. The
leaking of albumin into the urine, which is characteristic of diabetes, is
promoted by GH. In diabetes and GH treatment, the basement membrane, the
jelly-like material that forms a foundation for capillary cells, is thickened.
The reason for this isn't known, but it could be a compensatory"anti-leak"
response tending to reduce the leakage of proteins and fats.<span
style="font-family: Lucida Grande"
></span></span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>Besides being involved in kidney degeneration, vascular leakiness contributes to
brain edema, and probably contributes to the "autoimmune" diseases.<span
style="font-family: Lucida Grande"
></span></span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>Whatever the exact mechanism may be, it is clearly established that GH contributes
to kidney degereration, and the lack of GH, even the removal of the pituitary,
is protective against kidney degeneration.<span
style="font-family: Lucida Grande"
></span></span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>Denckla's and Everitt's experiments can be interpreted much more clearly now that
GH's essential contribution to kidney degeneration is known. Growth Hormone may
not be precisely the Death Hormone that Denckla was looking for, but it is very
close to it. Anti-thyroid effects have been seen, and possibly even anti-growth
effects during gestation, and in kidney disease. In newborns, high GH is
associated with smaller size and slower growth; in one study, this was
associated wtith rapid breathing, presumably hyperventilation which is
associated with stress. The shift to the diabetes-like fatty acid oxidation
would be expected to inhibit respiration, and the chronic elevation of serum
free fatty acids will have a generalized antithyroid effect. Under the influence
of GH, the proportion of unsaturated fatty acids is increased, as occurs under
the influence of estrogen.<span style="font-family: Lucida Grande"></span></span
></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>Growth hormone blocks gonadotropin-stimulated progesterone production, and this
could also affect thyroid and respiratory metabolism.<span
style="font-family: Lucida Grande"
></span></span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>The increase of GH during sleep might seem to be utterly incompatible with the idea
that it is a stress hormone, but in fact the other stress hormones, adrenalin,
cortisol, and prolactin also tend to increase during night-time sleep. Thyroid
function and progesterone function decrease at night. As I have argued
previously darkness is one of our major stressors. Considering GH's tendency to
cause edema, tissue swelling, it could play a role in the nocturnal increase of
the viscosity of blood, as the volume of blood is decreased by the leakage of
fluid into the tissues. Another process with potentially deadly results that
increase withaging and stress, is the passage of bacteria from the intestine
into the blood stream; this process is increased under the influence of GH.<span
style="font-family: Lucida Grande"
></span></span></span></span>
</blockquote>
<blockquote>
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
style="font-size: medium"
>Acute, short term studies definitely show growth hormone to be a stress hormone
with some destabilizing effects. Over a lifetime, it is possible that such
things as chronically increased levels of unsaturated fatty acids in the blood,
and increased leakiness of the blood vessels, could cumulatively produce the
effects that Denckla ascribed to the Death Hormone.<span
style="font-family: Lucida Grande"
></span><h3>REFERENCES</h3><span style="font-family: Lucida Grande"></span
>Intern Med 1998 May;37(5):472-5. A hypopituitary patient who attained tall
stature without growth hormone. Kageyama K, Watanobe H, Nasushita R, Nishie M,
Horiba N, Suda T. "We describe an unusual patient with hypopituitarism who
attained tall stature even without growth hormone (GH)." <span
style="font-family: Lucida Grande"
></span>Pediatr. Pulmonol. 1998 26(4):241-9. Sleep, respiratory rate, and growth
hormone in chronic neonatal lung disease, D. Fitzgerald, et al.<span
style="font-family: Lucida Grande"
></span>"Insulin resistance in puberty [editorial]," Anonymousm Lancet, 1991 May
25, 337:8752, 1259-60. <span style="font-family: Lucida Grande"></span>"The
gonadotropic function of insulin," Poretsky L; Kalin MF, Endocr Rev, 1987 May,
8:2, 132-4.1.<span style="font-family: Lucida Grande"></span><hr /><span
style="font-family: Lucida Grande"
></span>Circulation 1991 Jun;83(6):1880-7. Pathogenesis of edema in constrictive
pericarditis. Studies of body water and sodium, renal function, hemodynamics,
and plasma hormones before and after pericardiectomy. Anand IS, Ferrari R, Kalra
GS, Wahi PL, Poole-Wilson PA, Harris PC. "BACKGROUND. The pathogenesis of sodium
and water accumulation in chronic constrictive pericarditis is not well
understood and may differ from that in patients with chronic congestive heart
failure due to myocardial disease. This study was undertaken to investigate some
of the mechanisms. METHODS AND RESULTS. Using standard techniques, the
hemodynamics, water and electrolyte spaces, renal function, and plasma
concentrations of hormones were measured in 16 patients with untreated
constrictive pericarditis and were measured again in eight patients after
pericardiectomy. The average hemodynamic measurements were as follows: cardiac
output, 1.98 l/min/m2; right atrial pressure, 22.9 mm Hg; pulmonary wedge
pressure, 24.2 mm Hg; and mean pulmonary artery pressure 30.2 mm Hg. The
systemic and pulmonary vascular resistances (36.3 +/- 2.5 and 3.2 +/- 0.3 mm
Hg.min.m2/l, respectively) were increased. Significant increases occurred in
total body water (36%), extracellular volume (81%), plasma volume (53%), and
exchangeable sodium (63%). The renal plasma flow was only moderately decreased
(49%), and the glomerular filtration rate was normal. Significant increases also
occurred in plasma concentrations of norepinephrine (3.6 times normal), renin
activity (7.2 time normal), aldosterone (3.4 times normal), cortisol (1.4 times
normal), growth hormone (21.8 times normal), and atrial natriuretic peptide (5
times normal)." "The arterial pressure is maintained more by the expansion of
the blood volume than by an increase in the peripheral vascular
resistance." <span style="font-family: Lucida Grande"></span>J Clin
Endocrinol Metab 1991 Apr;72(4):768-72 Expansion of extracellular volume and
suppression of atrial natriuretic peptide after growth hormone administration in
normal man. Moller J, Jorgensen JO, Moller N, Hansen KW, Pedersen EB,
Christiansen JS. University Department of Endocrinology and Internal Medicine,
Aarhus Kommunehospital, Denmark. "Sodium retention and symptoms and signs of
fluid retention are commonly recorded during GH administration in both
GH-deficient patients and normal subjects." "GH caused a significant increase in
ECV (L): 20.45 +/- 0.45 (GH), 19.53 +/- 0.48 (placebo) (P less than 0.01),
whereas plasma volume (L) remained unchanged 3.92 +/- 0.16 (GH), 4.02 +/- 0.13
(placebo)."<span style="font-family: Lucida Grande"></span>Edema of cardiac
origin. Studies of body water and sodium, renal function, hemodynamic indexes,
and plasma hormones in untreated congestive cardiac failure. Anand IS, Ferrari
R, Kalra GS, Wahi PL, Poole-Wilson PA, Harris PC. "This study provides data on
plasma hormone levels in patients with severe clinical congestive cardiac
failure who had never received therapy and in whom the presence of an
accumulation of excess water and sodium had been established." "Total body water
content was 16% above control, extracellular liquid was 33% above control,
plasma volume was 34% above control, total exchangeable sodium was 37% above
control, renal plasma flow was 29% of control, and glomerular filtration rate
was 65% of control. Plasma norepinephrine was consistently increased (on average
6.3 times control), whereas adrenaline was unaffected. Although plasma renin
activity and aldosterone varied widely, they were on average above normal (renin
9.5 times control, aldosterone 6.4 times control). Plasma atrial natriuretic
peptide (14.3 times control) and growth hormone (11.5 times control) were
consistently increased. Cortisol was also increased on average (1.7 times
control). Vasopressin was increased only in one patient." <span
style="font-family: Lucida Grande"
></span>J Pediatr Endocrinol 1994 Apr-Jun;7(2):93-105. Studies on the renal
kinetics of growth hormone (GH) and on the GH receptor and related effects in
animals. Krogsgaard Thomsen M, Friis C, Sehested Hansen B, Johansen P, Eschen C,
Nowak J, Poulsen K. "Growth hormone (GH) is filtered through the kidney, and may
exert effects on renal function when presented via the circulation.
Investigations on kidney-related aspects of GH are increasing in number." "Short
term administration of GH to rats and humans elicited electrolyte and water
retention that may cause edema in adults."<span
style="font-family: Lucida Grande"
></span>Mech Ageing Dev 1983 Jul-Aug;22(3-4):233-51 The anti-aging action of
hypophysectomy in hypothalamic obese rats: effects on collagen aging,
age-associated proteinuria development and renal histopathology. Everitt AV,
Wyndham JR, Barnard DL Hypophysectomy in young male Wistar rats aged 70 days,
like food restriction begun at the same age, retarded the life-long rate of
collagen aging in tail tendon fibres and inhibited the development of
age-associated proteinuria and renal histopathology. Hypothalamic lesions which
increased the food intake of hypophysectomized rats from 7 g to 15 g/day and
produced obesity did not alter the rate of either collagen aging or proteinuria
development, nor reduce life expectancy, but increased the incidence of abnormal
glomeruli. In the intact rats elevation of food intake from 7 g to 15 g/day
increased the rate of proteinuria development, but did not affect the rate of
collagen aging. Hypophysectomy was found to have a greater anti-collagen aging
effect than food restriction, when food intakes were the same in both groups.
These studies suggest a pituitary-hormonal effect on collagen aging and a
food-pituitary-hormone-mediated effect on the development of age-associated
proteinuria. <span style="font-family: Lucida Grande"></span>Growth Dev
Aging 1992 Summer;56(2):85-93. Morphometrical analysis of the short-term effects
of hypophysectomy and food restriction on skeletal muscle fibers in relation to
growth and aging changes in the rat. Shorey CD, Manning LA, Grant AL, Everitt
AV.<span style="font-family: Lucida Grande"></span>Metabolism of glomerular
basement membrane in normal, hypophysectomized, and growth-hormone-treated
diabetic rats," Reddi AS, Exp Mol Pathol, 1985 Oct, 43:2, 196-208. "The in vivo
synthesis of the renal glomerular basement membrane (GBM) collagen was studied
in normal, hypophysectomized (hypox), diabetic, and growth-hormone (GH)-treated
diabetic rats...." "A significant decrease in both proline and hydroxyproline
specific activities were observed in GBM of hypox rats at all periods of study.
Administration of GH to hypox rats returned the GBM collagen synthesis to
normal. Diabetic GBM had higher proline and hydroxyproline specific activities
when compared to normal rats. Treatment of diabetic rats with GH for 10 days
further increased both proline and hydroxyproline specific activities when
compared either to diabetic or normal rats treated with GH. The activity of
glucosyltransferase, an enzyme involved in the biosynthesis of the disaccharide
unit of GBM collagen was found to be decreased in glomeruli of hypox rats. In
contrast, the activity of N-acetyl-beta-glucosaminidase, a
glycoprotein-degrading enzyme, was found to be significantly increased in hypox
rats. GH treatment restored both enzyme activities to normal. The results of the
present study show that GBM collagen synthesis is decreased in hypox rats and
increased in diabetic rats. ....not only normalized GBM collagen synthesis in
hypox rats but also caused significant increase in diabetic rats. This suggests
that the renal GBM metabolism is influenced by GH, and this may be of particular
significance in view of GH involvement in diabetic microvascular
complications."<span style="font-family: Lucida Grande"></span>Ciba Found Symp
1982;(90):263-78 Prolactin and growth hormone receptors. Friesen HG, Shiu RP,
Elsholtz H, Simpson S, Hughes J The two hormones prolactin and growth hormone
exhibit considerable structural homology as well as exerting similar biological
effects, especially the primate hormones. One effect of prolactin that deserves
greater attention is its action on the immune system including the stimulation
of growth of experimental lymphomas, both in vivo and in vitro." <span
style="font-family: Lucida Grande"
></span>N Engl J Med 1999 Sep 9;341(11):785-92. Increased mortality associated
with growth hormone treatment in critically ill adults.</span></span></span>
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