Human Physiology, 14th edition (2016)

688 Chapter 19

Insulin-like Growth Factors

Insulin-like growth factors (IGFs), produced by many tis-

sues, are polypeptides that are similar in structure to proinsulin

(chapter 3; see fig. 3.23). 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 fac-

tors, 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),

because 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, directly mediate the effects of growth

hormone on cartilage and serve as the major regulator of bone

growth. These actions are supported by IGF-2, which has more

insulin-like actions. The action of growth hormone in stimu-

lating lipolysis in adipose tissue and in decreasing glucose

utilization is apparently not mediated by the somatomedins

( fig. 19.16 ).

Effects of Growth Hormone on Metabolism

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 ana-

bolic and catabolic effects; it promotes protein synthesis (anabo-

lism) and in this respect is similar to insulin. It also stimulates the

hormone in adults, particularly under the conditions of fasting and
other forms of stress, implies that this hormone can have impor-
tant metabolic effects even after the growing years have ended.

Regulation of Growth Hormone Secretion

The secretion of growth hormone is inhibited by somatosta-
tin, which is produced by the hypothalamus and secreted into
the hypothalamo-hypophyseal portal system (chapter 11,
section 11.3). In addition, there is also a growth hormone–
releasing hormone (GHRH), which stimulates growth hor-
mone 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 dur-
ing 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.

Figure 19.15 The metabolic effects of glucocorticoids.
The catabolic actions of glucocorticoids help to raise the blood
concentration of glucose and other energy-carrier molecules.

Glucocorticoids

(e.g., cortisol)

Free

fatty

acids

Adrenal

cortex

Adipose tissue

Triglycerides

Muscles

Protein

Liver

Pyruvic

acid

Amino

acids

Acetyl

CoA

Ketone Glucose

bodies

Blood Free

fatty

acids

Ketone

bodies

Glucose Amino

acids

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.

Insulin-like growth factor 1

Growth hormone

Liver

Cartilage

and bone

Growth

Muscle and

other organs

Protein synthesis

Growth

Adipose tissue

Lipolysis

Release of

fatty acids

Most tissues

Decreased

glucose

utilization