Human Physiology, 14th edition (2016)

Regulation of Metabolism 689

catabolism of fat and the release of fatty acids from adipose tis-

sue during periods of fasting (the post-absorptive state). A rise in

the plasma fatty acid concentration induced by growth hormone

results in decreased rates of glycolysis in many organs. This inhi-

bition 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

“diabetogenic” 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. There is an age-

related decline in growth hormone secretion after the age of

20, accompanied by a decline in IGF-1. This may contribute to

the increased adipose tissue and reduction in muscle mass that

occur during aging.

CLINICAL APPLICATION

Kwashiorkor, or protein malnutrition, is unfortunately com-

mon among starving children in poor countries. Without ade-

quate protein intake, the production of IGF-1 is low despite

elevated growth hormone secretion. This results in low growth

rates, muscle atrophy, and low plasma protein concentration,

among other symptoms. The hypoproteinemia causes a low

plasma colloid osmotic pressure (chapter 14; see fig. 14.9),

which results in edema of the legs and ascites (fluid in the

abdomen), producing a distended belly. Once the children

are provided with sufficient calories and food protein, their

IGF-1 levels rise and health can be restored.

Figure 19.17 A man with acromegaly. This man’s

facial bones have thickened under the influence of excessive

amounts of growth hormone.

Effects of Growth Hormone on Body Growth

The stimulatory effects of growth hormone on skeletal growth

results from stimulation of mitosis in the epiphyseal growth

plates of cartilage in the long bones of children and adolescents.

This action is mediated by the somatomedins, IGF-1 and IGF-2,

which stimulate the chondrocytes to divide and secrete more car-

tilage 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 continued secretion of growth

hormone 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 propor-

tions. 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 hor-

mone 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 ath-

letes who take growth hormone supplements to increase their

muscle mass may also experience body changes that resemble

those of acromegaly.

Dwarfism, defined as an adult height of 4 ft. 10 in. or less

(with an average height of 4 ft.), can be caused by inadequate

secretion of growth hormone during the growing years. Laron

Dwarfism is an interesting variant in which target cells are insensi-

tive to growth hormone because of a mutation in the gene the codes

for the growth hormone receptor. However, most cases of dwarf-

ism are caused by achondroplasia, a condition inherited as an auto-

somal dominant trait that results from a mutated gene coding for

fibroblast growth factor receptor 3 ( FGFR3 ). Defective FDFR3

causes impaired function and cell division of chondrocytes within

the growing portions of bones that grow by endochondral ossifica-

tion (replacement of cartilage with bone).

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