hypophysiotropic hormones secreted by the hypothalamus.
Growth hormone secretion is stimulated by growth hormone-
releasing hormone (GHRH) and inhibited by somatostatin.
As a result of changes in these two signals, which are usually
180 degrees out of phase with each other (i.e., one is high
when the other is low), growth hormone secretion occurs in
episodic bursts and manifests a striking daily rhythm. During
most of the day, little or no growth hormone is secreted,
although bursts may be elicited by certain stimuli, including
stress, hypoglycemia, and exercise. In contrast, 1 to 2 hours
after a person falls asleep, one or more larger, prolonged bursts
of secretion may occur. The negative feedback controls that
growth hormone and IGF-1 exert on the hypothalamus and
anterior pituitary are summarized in Figure 11–28.
In addition to the hypothalamic controls, a variety of hor-
mones—notably the sex hormones, insulin, and the thyroid hor-
mones, as described in the paragraphs that follow—inﬂ uence the
secretion of growth hormone. The net result of all these inputs
is that the secretion rate of growth hormone is highest during
adolescence (the period of most rapid growth), next highest in
children, and lowest in adults. The decreased growth hormone
secretion associated with aging is responsible, in part, for the
decrease in lean-body and bone mass, the expansion of adipose
tissue, and the thinning of the skin that occur as people age.
The ready availability of human growth hormone pro-
duced by recombinant-DNA technology has greatly facilitated
the treatment of children with short stature due to growth hor-
mone deﬁ ciency. Controversial at present is the administration
of growth hormone to short children who do not have growth
hormone deﬁ ciency, to athletes in an attempt to increase muscle
mass, and to normal elderly persons to reverse growth hormone–
related aging changes. It should be clear from Table 11–5 that
, growth hormone exerts most of its cell
division-stimulating (mitogenic) effect not
on cells but
through the mediation of a mitogen whose synthe-
sis and release are induced by growth hormone. This mitogen
insulin-like growth factor 1 (IGF-1)
known as somatomedin C). Despite its similarity to insulin,
this messenger has its own unique effects distinct from those
of insulin. Under the inﬂ uence of growth hormone, IGF-1 is
secreted by the liver, enters the blood, and functions as a hor-
mone. In addition, growth hormone stimulates many other
types of cells, including bone, to secrete IGF-1, and at these sites
IGF-1 functions as an autocrine or paracrine agent. The relative
importance of IGF-1 as a hormone versus autocrine/paracrine
agent in any given organ or tissue remains controversial.
Current concepts of how growth hormone and IGF-1
interact on the epiphyseal plates of bone are as follows: (1)
growth hormone stimulates the chondrocyte precursor cells
(prechondrocytes) and/or young differentiating chondrocytes
in the epiphyseal plates to differentiate into chondrocytes;
(2) during this differentiation, the cells begin both to secrete
IGF-1 and to become responsive to IGF-1; (3) the IGF-1 then
acts as an autocrine or paracrine agent (probably along with
blood-borne IGF-1) to stimulate the differentiating chondro-
cytes to undergo cell division.
The importance of IGF-1 in mediating the major
by the fact that
(abnormally short stature) can be
caused not only by decreased growth hormone secretion, but
also by decreased production of IGF-1 or failure of the tissues
to respond to IGF-1. For example, one uncommon form of
short stature (called
growth hormone insensitivity syndrome,
), is due to a genetic mutation that causes
the growth hormone receptor to fail to respond to growth hor-
mone. The result is failure to produce IGF-1 in response to
The secretion and activity of IGF-1 can be inﬂ uenced by
the nutritional status of the individual and by many hormones
other than growth hormone. For example, malnutrition dur-
ing childhood inhibits the production of IGF-1 even though
plasma growth hormone concentration is elevated and should
be stimulating IGF-1 secretion.
In addition to its speciﬁ c growth-promoting effect
on cell division via IGF-1, growth hormone directly stimu-
lates protein synthesis in various tissues and organs, par-
ticularly muscle. It does this by increasing cells’ amino acid
uptake and both the synthesis and activity of ribosomes. All of
these events are essential for protein synthesis. This anabolic
effect on protein metabolism facilitates the ability of tissues
and organs to enlarge.
summarizes the multiple
effects of growth hormone.
shows the control of growth hormone
secretion. Brieﬂ y, the control system begins with two of the
Major Effects of Growth Hormone
1. Promotes growth: Induces precursor cells in bone and other
tissues to differentiate and secrete insulin-like growth factor 1
(IGF-1), which stimulates cell division. Also stimulates liver
to secrete IGF-1.
2. Stimulates protein synthesis, predominantly in muscle.
3. Anti-insulin effects (particularly at high concentrations):
a. Renders adipocytes more responsive to stimuli that
induce breakdown of triglycerides, releasing fatty acids
into the blood.
b. Stimulates gluconeogenesis.
c. Reduces the ability of insulin to stimulate glucose uptake
by adipose and muscle cells, resulting in higher blood