Human Physiology, 14th edition (2016)

(Tina Sui) #1

322 Chapter 11


Priming Effects
Variations in hormone concentration within the normal, physi-
ological range can affect the responsiveness of target cells. This
is due in part to the effects of polypeptide and glycoprotein hor-
mones on the number of their receptor proteins in target cells.
More receptors may be formed in the target cells in response to
particular hormones. Small amounts of gonadotropin-releasing
hormone (GnRH) secreted by the hypothalamus, for example,
increase the sensitivity of anterior pituitary cells to further
GnRH stimulation. This is a priming effect, caused in large part
by the upregulation of receptors. In this process, increased
numbers of receptor proteins for the hormone being primed (in
this case, GnRH) are inserted into the plasma membrane. Sub-
sequent stimulation by GnRH thus causes a greater response
from the anterior pituitary.

Desensitization and Downregulation
Prolonged exposure to high concentrations of polypeptide hor-
mones has been found to desensitize the target cells. Subse-
quent exposure to the same concentration of the same hormone
thus produces less of a target tissue response. This desensitiza-
tion is partly due to downregulation of receptors—a decrease
in the number of receptor proteins for a polypeptide hormone
caused by continuous exposure of the target cells to high con-
centrations of the hormone. Such desensitization and down-
regulation of receptors has been shown to occur, for example,
in adipose cells exposed to high concentrations of insulin and
in testicular cells exposed to high concentrations of luteinizing
hormone (LH).
In order to prevent desensitization from occurring under nor-
mal conditions, many polypeptide and glycoprotein hormones
are secreted in spurts rather than continuously. This pulsatile
secretion is an important aspect, for example, in the hormonal
control of the reproductive system. The pulsatile secretion of
GnRH and LH is needed to prevent desensitization; when these
hormones are artificially presented in a continuous fashion, they
produce a decrease (rather than the normal increase) in gonadal
function. This effect has important clinical implications, as will
be described in chapter 20, section 20.2.

The effects of hormones are very dependent on concen-
tration. Normal tissue responses are produced only when the
hormones are present within their normal, or physiological,
range of concentrations. When some hormones are taken in
abnormally high, or pharmacological, concentrations (as
when they are taken as drugs), their effects may be differ-
ent from those produced by lower, more physiological, con-
centrations. In part, this can be caused by the binding of the
hormone at pharmacological concentrations to the receptors
of different (but closely related) hormones, so that abnormal
effects are produced. In the case of steroid hormones, phar-
macological concentrations may cause the abnormal pro-
duction of derivatives with different biological effects. For
example, pharmacological amounts of androgens result in
the production of abnormal amounts of estrogens, which are
derived from androgens (see fig. 11.2 ).
Pharmacological doses of hormones, particularly of ste-
roids, can thus have widespread and often damaging side
effects. People with inflammatory diseases who are treated with
high doses of cortisone over long periods of time, for example,
may develop osteoporosis and characteristic changes in soft tis-
sue structure. Contraceptive pills, which contain sex steroids,
have a number of potential side effects that could not have been
predicted in 1960, when “the pill” was first introduced. At that
time, the concentrations of sex steroids were much higher than
they are in the pills presently being marketed.


FITNESS APPLICATION
Anabolic steroids are androgens (male hormones), which
promote protein synthesis in muscles as well as many other
effects. Use for bodybuilding, weightlifting, and other non-
medical reasons is illegal and prohibited by athletic organi-
zations. Testosterone (the androgen secreted by the testes)
is converted in adipose tissue and the liver into estrogens
(female hormones), which can thereby be present in abnor-
mally high amounts in a male taking anabolic steroids. This
can cause the appearance of breasts in men—a condi-
tion called gynecomastia. Other effects include premature
male-pattern baldness and an enlarged prostate. Because
high levels of androgens inhibit the pituitary gonadotropic
hormones (FSH and LH, discussed later), the testes atro-
phy (shrink) and sperm count is reduced. Women taking
anabolic steroids become masculinized, with reduced fat,
coarsening of the skin, increased growth of body hair and
growth of the clitoris, and deepening of the voice. Adoles-
cents taking anabolic steroids experience premature clos-
ing of the bone growth plates (epiphyseal discs; chapter 19,
section 19.6) and a cessation of growth. Other effects on
males and females include acne, increased aggressive-
ness, increased risk of cardiovascular diseases because of
a rise in LDL and a fall in HDL cholesterol (the “bad” and
“good” cholesterol, respectively), and increased risk of liver
diseases and liver cancer.

| CHECKPOINT

1a. Compare the four chemical classes of hormones with
reference to hormones within each class.
1b. Define prohormone and prehormone, and give
examples of each of these molecules.
1c. Describe the common characteristics of hormones
and neurotransmitters.
2a. List the terms used to describe hormone interactions
and give examples of these effects.
2b. Explain how the response of the body to a given
hormone can be affected by the concentration of that
hormone in the blood.
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