The anterior pituitary secretes growth hormone, also called so-matotropin, in larger amounts than any other of its hormones. As its name implies, growth hormone stimulates growth in children and adolescents. The continued high secretion of growth hormone in adults, particularly under the conditions of fasting and other forms of stress, implies that this hormone can have important metabolic effects even after the growing years have ended.
The secretion of growth hormone is inhibited by somatostatin, which is produced by the hypothalamus and secreted into the hypothalamo-hypophyseal portal system (chapter 11). In addition, there is also a hypothalamic releasing hormone, GHRH, which stimulates growth hormone secretion. Growth hormone thus appears to be unique among the anterior pituitary hormones in that its secretion is controlled by both a releasing and an inhibiting hormone from the hypothalamus. The secretion of growth hormone follows a circadian ("about a day") pattern, increasing during sleep and decreasing during periods of wakefulness.
Growth hormone secretion is stimulated by an increase in the plasma concentration of amino acids and by a decrease in the plasma glucose concentration. These events occur during absorption of a high-protein meal, when amino acids are absorbed. The secretion of growth hormone is also increased during prolonged fasting, when plasma glucose is low and plasma amino acid concentration is raised by the breakdown of muscle protein.
Insulin-like growth factors (IGFs), produced by many tissues, are polypeptides that are similar in structure to proinsulin (chapter 3; see fig. 3.25). They have insulin-like effects and serve as mediators for some of growth hormone's actions. The term somatomedins is often used to refer to two of these factors, designated IGF-1 and IGF-2, because they mediate the actions of somatotropin (growth hormone). The liver produces and secretes IGF-1 in response to growth hormone stimulation, and this secreted IGF-1 then functions as a hormone in its own right, traveling in the blood to the target tissue. A major target is cartilage, where IGF-1 stimulates cell division and growth. IGF-1 also functions as an autocrine regulator (chapter 11), since the chondrocytes (cartilage cells) themselves produce IGF-1 in response to growth hormone stimulation. The growth-promoting actions of IGF-1, acting as both a hormone and an autocrine regulator, thus directly mediate the effects of growth hormone on cartilage. These actions are supported by IGF-2,
■ Figure 19.16 The metabolic effects of growth hormone. The growth-promoting, or anabolic, effects of growth hormone are mediated indirectly via stimulation of insulin-like growth factor 1 (also called somatomedin C) production by the liver.
which has more insulin-like actions. The action of growth hormone in stimulating lipolysis in adipose tissue and in decreasing glucose utilization is apparently not mediated by the somatomedins (fig. 19.16).
The fact that growth hormone secretion is increased during fasting and also during absorption of a protein meal reflects the complex nature of this hormone's action. Growth hormone has both anabolic and catabolic effects; it promotes protein synthesis (anabolism), and in this respect is similar to insulin. It also stimulates the catabolism of fat and the release of fatty acids from adipose tissue during periods of fasting (the postabsorptive state), as growth hormone secretion is increased at night. A rise in the plasma fatty acid concentration induced by growth hormone results in decreased rates of gly-colysis in many organs. This inhibition of glycolysis by fatty acids, perhaps together with a more direct action of growth hormone, results in decreased glucose utilization by the tissues. Growth hormone thus acts to raise the blood glucose concentration, and for that reason is said to have a "diabeto-genic" effect.
Growth hormone stimulates the cellular uptake of amino acids and protein synthesis in many organs of the body. These actions are useful when eating a protein-rich meal; amino acids are removed from the blood and used to form proteins, and the plasma concentration of glucose and fatty acids is increased to provide alternate energy sources (fig. 19.16). The anabolic effect of growth hormone is particularly important during the growing years, when it contributes to increases in bone length and in the mass of many soft tissues.
Before recombinant growth hormone (produced by genetically engineered cells) became available, the supply of growth hormone was very limited because it could only be obtained from the pituitaries of cadavers. Now that recombinant growth hormone is available, children with idiopathic short stature (who do not have pituitary dwarfism) can receive growth hormone injections. In a recent study, such children, injected weekly for 10 years, attained an adult height that was significantly higher than predicted before the treatment. The use of growth hormone treatment for this purpose, however, is medically and ethically very controversial.
The stimulatory effects of growth hormone on skeletal growth results from stimulation of mitosis in the epiphyseal discs of cartilage present in the long bones of growing children and adolescents. This action is mediated by the somatomedins, IGF-1 and IGF-2, which stimulate the chondrocytes to divide and secrete more cartilage matrix. Part of this growing cartilage is converted to bone, enabling the bone to grow in length. This skeletal growth stops when the epiphyseal discs are converted to bone after the growth spurt during puberty, despite the fact that growth hormone secretion continues throughout adulthood.
An excessive secretion of growth hormone in children can produce gigantism. These children may grow up to 8 feet tall, at the same time maintaining normal body proportions. An excessive growth hormone secretion that occurs after the epiphyseal discs have sealed, however, cannot produce increases in height. In adults, the oversecretion of growth hormone results in an elongation of the jaw and deformities in the bones of the face, hands, and feet. This condition, called acromegaly, is accompanied by the growth of soft tissues and coarsening of the skin (fig. 19.17). It is interesting that athletes who take growth hormone supplements to increase their muscle mass may also experience body changes that resemble those of acromegaly.
An inadequate secretion of growth hormone during the growing years results in dwarfism. An interesting variant of this condition is Laron dwarfism, in which there is a genetic insensi-tivity to the effects of growth hormone. This insensitivity is associated with a reduction in the number of growth hormone receptors in the target cells. Genetic engineering has made available recombinant IGF-1, which has recently been approved by the FDA for the medical treatment of Laron dwarfism.
An adequate diet, particularly with respect to proteins, is required for the production of IGF-1. This helps to explain the common observation that many children are significantly taller than their parents, who may not have had an adequate diet in their youth. Children with protein malnutrition (kwashiorkor) have low growth rates and low levels of IGF-1 in the blood, despite the fact that their growth hormone secretion may be abnormally elevated. When these children are provided with an adequate diet, IGF-1 levels and growth rates increase.
■ Figure 19.17 The progression of acromegaly in one individual.
The coarsening of features and disfigurement are evident by age 33 and severe at age 52.
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