14.6: Growth Hormone and IGF-1
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Source and Control of Secretion
Growth hormone (GH) secretion by the anterior pituitary gland is regulated primarily by hormones from the hypothalamus using negative feedback mechanisms (Figure 14.3). A decline in blood levels of GH results in increased GH secretion, which causes an elevation in GH blood levels. GH secretion is also increased by low blood levels of insulin-like growth factor (IGF-1), also known as somatomedin C, and by exercise. Conversely, elevations in GH result in decreased GH secretion and a decline in GH blood levels. GH secretion is also slowed by high blood levels of IGF-1. Other factors that influence GH secretion include brain neurons and blood levels of glucose, fatty acids, and amino acids.
Growth hormone is secreted in short bursts (i.e., pulses). The accumulation of GH from many large frequent pulses causes blood levels of GH to rise. In young adults, GH secretion and blood levels rise during the night. As secretion diminishes later during the night and GH is removed from the blood, blood levels begin to decline. The blood level of GH reaches a minimum during the following day. Since this cycle is repeated with each succeeding night and day, it is called a circadian rhythm (diurnal rhythm). Though GH blood levels follow a circadian rhythm, IGF-1 levels remain steady.
Effects
The pattern of GH pulses plus the total blood level of GH cause its effects. Growth hormone causes the liver and other target cells to secrete IGF-1. The IGF-1 affects target cells and diffuse to neighboring cells, producing the effects from GH. IGF-¼1 in the blood also promotes the effects from GH. The local effects from IGF-1 may be more important than the effects from IGF-1 in the blood.
The IGF-1 increases passage of amino acids into cells and increases synthesis of proteins from those acids. These chemical changes result in growth, especially of bone and muscle. Growth hormone also causes an increased breakdown of fat to supply energy. The combination of these changes increases the proportion of lean body mass, which consists mainly of the skeletal and muscle systems and the skin, spleen, liver, kidneys and immune cells. Finally, GH increases blood glucose levels and therefore is considered to antagonize insulin.
Age Changes
Age changes in growth hormone have been studied mostly in men. On the average, GH secretion and IGF-1 levels during the day remain unchanged. During the night, there is less rise in GH pulses and blood levels and IGF-1 secretion. The declines in secretions begin for many men at age 30. These age-related decreases have been called somatopause.
When the nighttime rise in GH secretion finally disappears, the circadian rhythm in GH blood levels vanishes and these levels become steady at all times. As a result, both the total amount of GH produced in each 24-hour period and the blood level of IGF-1 decrease. IGF-1 levels in women are also known to decrease with age.
Though many men show the age changes just described, decline in the nighttime surge in GH blood levels shows considerable heterogeneity among individuals. Some elderly men have nighttime surges that are approximately equal to those found in young men. However, virtually no individuals show substantial increases in GH or IGF-1 levels with advancing age.
Decreasing GH and IGF-1 seem to contribute to a gradual decrease in lean body mass. For example, decreased stimulation of bone and muscle may contribute to the age-related decline in the thickness and strength of bone matrix and muscles plus the age-related increase in body fat. The increase in body fat may then reduce GH secretion, and a downward spiral of GH secretion begins as body fat increases. Age changes in the skin and kidneys may also be due in part to decreased GH secretion. The smoothing of the circadian peaks in GH blood levels may contribute to changes in other circadian rhythms, such as sleep patterns. Finally, the effects of lowered GH levels may be amplified because there is an age-related decrease in the responsiveness of cells to IGF-1.
Growth Hormone Supplementation
Though GH production declines, target structures seem to retain their ability to respond to it by producing IGF-1. For example, when older men are injected with GH or artificial substances that stimulate GH secretion, the levels of IGF-1 and lean body mass increase and body fat decreases. Also, loss of matrix from some bones occurs more slowly or is reversed; blood LDLs decline and HDLs increase; skin thickens; immune function and mental functions improve. Recall that an increase in exercise produces almost all these results, perhaps by stimulating GH secretion. However, unlike exercise, injections of GH or GH stimulants cause undesirable increases in blood pressure and blood glucose levels, and they may prevent normal circadian rhythms. Questions remain about the desirability of GH-stimulated enlargement of parts of the body such as the spleen, liver, and kidneys. Other potential problems include heart disease; high blood pressure; arthritis; high blood glucose levels and diabetes mellitus; and faster growth of cancers. The lack of adequate information about the short-term and long-term effects of GH administration argues against the routine use of GH supplementation to stop or reverse GH-related age changes.