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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, &amp; 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.&nbsp;<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.&nbsp;<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)."&nbsp;<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.&nbsp;<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."&nbsp;<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."&nbsp;<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.&nbsp;<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."&nbsp;<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>
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