Growth Hormones
Growth Hormones
Aging and growth hormone therapy in adults
Several polypeptide hormones play important roles in growth and cell reproduction in humans and other vertebrates. The major human growth hormone (hGH), sometimes also called somatotropin or somatropin, is a protein made up of 191 amino acids secreted by the anterior pituitary and coordinates normal growth and development. Human growth is characterized by two spurts, one at birth and the other at puberty. hGH plays an important role at both of these times.
Normal individuals have measurable levels of hGH throughout life. Yet, levels of hGH fluctuate during the day and are affected by eating and exercise. Receptors that respond to hGH exist on cells and tissues throughout the body. The most obvious effect of hGH is on linear skeletal development. However, the metabolic effects of hGH on muscle, liver, and fat cells are critical to its function. Humans have two forms of hGH, and the functional difference between the two is unclear. They are both formed from the same gene, but one lacks the amino acids in positions 32 through 46.
Additional hormones that affect growth are the somatomedins, thyroid hormones, androgens, estrogens, glucocorticoids, and insulin. Somatomedins are small proteins produced in the liver in response to stimulation by hGH. The two major somatomedins are insulin-like growth factor I and II (IGF-I and IGF-II). IGF-I causes increased cartilage growth and collagen formation, and its plasma levels peak between the ages of 13 and 17 years. IGF-II is important during fetal development and is present at constant levels in adult brains; however, its neuronal role is unclear. IGH-II increases protein synthesis as well as RNA (ribonucleic acid) and DNA synthesis. Levels of all these hormones are measured in the plasma, which is the liquid, cell-free, portion of blood.
Normal growth
Normal growth is regulated by hormones, but is also greatly influenced by genetic makeup and nutrition. Parental stature and growth patterns are usually indicative of the same in their offspring. Poor nutrition will negatively affect the growth process. This nutritional boost to growth occurs at conception, and must continue through embryonic and fetal development.
Newborn babies have high hGH levels, which continue through early infancy. Baseline plasma levels of hGH are normal, however, through childhood until puberty, when the resting plasma hGH level increases. Metabolically, hGH functions to increase the rate of protein synthesis in muscle, increase the rate of fat breakdown in fatty tissue, and decrease the rate of glucose use by tissues, resulting in an increase in glucose output by the liver. In the gastrointestinal tract, (GI) growth hormone increases absorption of calcium, an increase in metabolic rate, and a decrease in sodium and potassium excretion. The sodium and potassium are thought to be diverted to growing tissues. In essence, hGH frees up energy to build up tissues. hGH creates an increase in both cell sizes and numbers.
hGH is produced in the anterior portion of the pituitary gland under the control of hormonal signals in the hypothalamus. Two hypothalamic hormones regulate hGH; they are growth hormone-releasing hormone (GHRH) and growth hormone-inhibiting hormone (GHIH). When blood glucose levels fall, GHRH triggers the secretion of stored hGH. As blood glucose levels rise, GHRH release is turned off. Increases in blood protein levels trigger a similar response. As a result of this hypothalamic feedback loop, hGH levels fluctuate throughout the day. Normal plasma hGH levels are 1 to 3 ng/ml with peaks as high as 60 ng/ml. In addition, plasma glucose and amino acid availability for growth is also regulated by the hormones: adrenaline, glucagon, and insulin.
Most hGH is released at night. Peak spikes of hGH release occur around ten in the evening, midnight, and two in the morning. The logic behind this night-time release is that most of hGH’s effects are mediated by other hormones, including the somato-medins, IGH-I and IGH-II. As a result, the effects of hGH are spread out more evenly during the day. There is also evidence that GH secretion in humans follows a sexually dimorphic pattern, meaning that secretion patterns and levels of hormone are different in males and females.
Other fluctuations in growth occur naturally or because of illness. Growth slows in sick children, so that resources are channeled to heal. However, most children experience a catch-up acceleration of growth after a sick period. This growth can be as much as 400 above normal, but resumes normal levels once the child has caught up. Children given long treatments with steroids may experience hindered growth, as steroids stop growth.
Factors influencing hGH secretion include diet (nutrition) and stressors. Inhibition of hGH secretion occurs with high blood glucose levels, steroid use, and during REM sleep. Human growth hormone secretion increases with ingestion of a protein meal, deep sleep, low blood glucose levels, fasting, exercise, physical stress (such as infection or trauma), and psychological stress.
A second major growth spurt occurs at puberty with the coupled effect of sex hormones on growth. Puberty usually occurs earlier in girls (around the ages of age 10 to 12 years) than in boys (a few months later). During puberty, the epiphyseal ends of long bones begin to close, signaling the end of length growth. This closure is usually completed by the age of 20 years.
Abnormal growth
A number of hormonal conditions can lead to excessive or diminished growth. Because of its critical role in producing hGH and other hormones, an aberrant pituitary will often yield altered growth. Dwarfism (very small stature) can be due to lack or under-production of hGH, lack of IGH-I, abnormalities in GH receptor or other changes leading to irresponsiveness of the target tissues to GH. Overproduction of hGH or IGH-I or an exaggerated response to these hormones can lead to gigantism or acromegaly both characterized by a very large stature.
Short stature can result not only from total absence of hGH, but also from GH deficiency. Children deficient in hGH have normal size at birth, but their postnatal growth is decreased leading to short stature, delayed bone maturation and delayed puberty. In contrast, absence of hGH can cause smaller birth lengths.
Gigantism is the result of hGH overproduction in early childhood leading to a skeletal height up to 8 ft (2.5 m) or more. Another condition, called acromegaly results from overproduction of hGH in adulthood. In this condition, the epiphyseal plates of the long bones of the body do not close, and they remain responsive to additional stimulated growth by hGH leading to increased bone thickness and length. People diagnosed with acromegaly develop increasingly enlarged and exaggerated facial bones. Also, acromegalic patients have pronounced, enlarged joints such as in the hands, feet, and spine.
Simple variation in height are due, in part, to a range of hGH levels due to factors already mentioned. However, parents concerned about their child’s growth should discuss this with a pediatrician. hGH levels can be evaluated, and hormone therapy using synthetic hGH is a possibility. The hGH that is ther-apeutically used is now produced using genetic engineering. Recombinant human growth hormone (rhGH) is a protein produced from genetically altered cells. General growth patterns vary normally, however, and bone age is actually a more accurate reflection of regular development than age itself. Some children can be as much as a year off of average development. These children’s growth rates may catch up or slow down compared to their peers. Growth patterns often follow family trends, such that if a boy’s father was relatively small until puberty, during which time he outgrew his peers, and then the boy may repeat this path. Some debate exists over the use of genetically engineered hGH to treat small stature. Some have debated that using hGH simply to make people taller is unethical and an example of science tampering with processes best left untouched.
Aging and growth hormone therapy in adults
Studies on mouse models aberrant in GH signaling indicate that dwarf mice live longer than normal or oversized ones. It appears that the impairment of GH
KEY TERMS
Amino acid— An organic compound whose molecules contain both an amino group (-NH2) and a carboxyl group (-COOH). One of the building blocks of a protein.
Epiphyseal closure— Closure of the epiphyses, the cartilaginous stretch next to a bone’s end, which signifies the end of linear growth.
Hypothalamus— A region of the brain comprised of several neuronal centers, one of which regulates human growth hormone production in the pituitary.
Plasma— The non-cellular, liquid portion of blood.
Somatotrophs— Cells in the anterior pituitary which produce somatotropin, human growth hormone (hGH).
signaling reduces IGF-1 levels dramatically, and implicates IGF-1 as regulator of aging. However, in presence of some other hormonal abnormalities in some of the mouse models it is impossible to dissect out the effects of GH and IGF-1 alone.
Independent of the animal studies, the use of GH for fighting off obesity, increasing energy, and as an anti-aging hormone increases. As people age GH levels GH decrease. Some people want to prolong youth, so a market for drugs to prolong youth has been created, and it steadily increases as more people strive to stay young and active. Some people have a medical condition known as growth hormone deficiency. Defining it is problematic as there is not one universal definition. Growth hormone deficiency occurring in adults is associated with increased abdominal fatness, reduced muscle mass and strength, increased risk for cardiovascular disease, memory difficulties, and psychological problems. Treatment of adults with GH deficiency by hormone replacement is not universally accepted and is still being tested for efficacy and long-term side effects. The trials up to date indicate that patients treated with GH had reduced fat-mass and some improvements in quality of life.
Recent advances
Growth hormones that were made synthetically became available for the first time in the United States in 2005. The companies that offer such products claim that their synthetic counterparts to natural growth hormones are identical in characteristics.
See also Physiology.
Resources
BOOKS
Anatomy & Physiology Made Incredibly Easy. Philadelphia, PA: Lippincott Williams & Wilkins, 2005.
Campbell, Neil A. Essential Biology with Physiology. San Francisco, CA: Pearson/Benjamin CUmmings, 2004.
Germann, William J. Principles of Human Physiology. San Francisco, CA: Pearson Benjamin Cummings, 2005.
Van De Graaff, Kent M., and R. Ward Rhees, eds. Human Anatomy and Physiology: Based on Schaum’s Outline of Theory and Problems of Human Anatomy and Physiology. New York: McGraw-Hill, 2001.
PERIODICALS
Partridge, Linda, and David Gems, “Mechanisms of Aging: Public Or Private?” Nature Reviews: Genetics (March 2002):165–175.
Carter, Christy S., Ramsey, Melinda M., and William E. Sonntag, “A Critical Analysis of the Role of Growth Hormone and IGF-1 in Aging and in Lifespan.” Trends in Genetics (June 2002):295–301
Louise Dickerson