Human Physiology, 14th edition (2016)

326 Chapter 11

extracellular signals (hormones) are transduced into intracel-

lular signals (second messengers).

When these hormones bind to membrane receptor proteins,

they must activate specific proteins in the plasma membrane

in order to produce the second messengers required to exert

their effects. On the basis of the membrane enzyme activated,

we can distinguish second-messenger systems that involve the

activation of (1) adenylate cyclase, (2) phospholipase C, and

(3) tyrosine kinase.

Adenylate Cyclase–Cyclic AMP

Second-Messenger System

Cyclic adenosine monophosphate (abbreviated cAMP ) was

the first “second messenger” to be discovered and is the best

understood. When epinephrine and norepinephrine bind to their

b -adrenergic receptors (chapter 9), the effects of these hor-

mones are due to cAMP production within the target cells. It

was later discovered that the effects of many (but not all) poly-

peptide and glycoprotein hormones are also mediated by cAMP.

When one of these hormones binds to its receptor pro-

tein, it causes the dissociation of a subunit from the com-

plex of G-proteins (discussed in chapter 7; see table 7.6).

This G-protein subunit moves through the membrane

until it reaches the enzyme adenylate (or adenyl ) cyclase

( fig. 11.8 ). The G-protein subunit then binds to and activates

Hormones That Use Second Messengers

Hormones that are catecholamines (epinephrine and nor-
epinephrine), polypeptides, and glycoproteins cannot pass
through the lipid barrier of the target cell’s plasma membrane.
Although some of these hormones may enter the cell by pino-
cytosis, most of their effects result from their binding to recep-
tor proteins on the outer surface of the target cell membrane.
Because they exert their effects without entering the target
cells, the actions of these hormones must be mediated by other
molecules within the target cells. If you think of hormones
as “messengers” from the endocrine glands, the intracellu-
lar mediators of the hormone’s action can be called second
messengers. (The concept of second messengers was intro-
duced in chapter 6, section 6.5.) Second messengers are thus
a component of signal-transduction mechanisms, because

Figure 11.6 The mechanism of thyroid hormone
action. (1) Thyroxine (T 4 ), carried to the target cell bound
to its plasma carrier protein, dissociates from its carrier and
passes through the plasma membrane of its target cell. (2) In
the cytoplasm, T 4 is converted into T 3 (triiodothyronine), which
(3) uses binding proteins to enter the nucleus. (4) The hormone-
receptor complex binds to DNA, (5) stimulating the synthesis of
new mRNA. (6) The newly formed mRNA codes for the synthesis
of new proteins, which (7) produce the hormonal effects in the
target cell.

Nucleus

Cytoplasm

1

2

3

4

5

6

7

Receptor

protein

Carrier

protein

(TBG)

mRNA

Protein

synthesis

Thyroid

hormone

response

Binding

protein

Blood Target cell

DNA

mRNA

T 4

T 4 T 4

T 3

T 3

T 3

T 3

Figure 11.7 The receptor for triiodothyronine

(T 3 ). The nuclear receptor protein for T 3 forms a dimer with the

receptor protein for 9- cis -retinoic acid, a derivative of vitamin A.

This occurs when each binds to its ligand and to the hormone-

response element of DNA. Thus, 9- cis -retinoic acid is required for

the action of T 3. The heterodimer formed on the DNA stimulates

genetic transcription.

DNA

TR receptor

(for

triiodothyronine)

Dimerization

RXR receptor

(for 9-cis-

retinoic acid)

mRNA

9-cis-retinoic T 3 Triiodothyronine

acid

Hormone-

response

element

Genetic

transcription