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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>
- </blockquote>
- <p> </p>
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