Human Physiology, 14th edition (2016)

Endocrine Glands 323

Hormones That Bind to Nuclear

Receptor Proteins

Unlike the water-soluble hormones, the lipophilic steroid and

thyroid hormones do not travel dissolved in the aqueous por-

tion of the plasma; rather, they are transported to their target

cells attached to plasma carrier proteins. These hormones must

then dissociate from their carrier proteins in the blood in order

to pass through the lipid component of the plasma membrane

and enter the target cell, within which their receptor proteins

are located ( fig. 11.4 ).

The receptors for the lipophilic hormones are known as

nuclear hormone receptors because they function within

the cell nucleus to activate genetic transcription (production

of mRNA). The nuclear hormone receptors thus function as

transcription factors that first must be activated by binding

to their hormone ligands. The newly formed mRNA produced

by the activated genes directs the synthesis of specific proteins,

11.2 Mechanisms of Hormone Action

The mechanisms by which hormones act on their target

cells depend on the chemical nature of the hormones.

Nonpolar hormones can easily pass through plasma mem-

branes and so bind to receptor proteins within their target

cells. These are nuclear receptors, which work by regu-

lating gene expression. By contrast, polar hormones do

not enter their target cells but instead bind to receptors on

the plasma membrane. These hormones then exert their

effects through second-messenger systems.

Figure 11.4 The mechanism of steroid hormone

action. (1) Steroid hormones, transported bound to plasma

carrier proteins, dissociate from their plasma carriers and pass

through the plasma membrane of their target cell. (2) The steroid

hormone binds to receptors, which may be in the cytoplasm.

(3) The hormone-bound receptor translocates to the nucleus,

where it binds to DNA. (4) This stimulates genetic transcription,

resulting in new mRNA synthesis. (5) The newly formed mRNA

codes for the production of new proteins, which (6) produce the

hormonal effects in the target cell.

Carrier

protein

Translocation

DNA

mRNA

mRNA

Nucleus

Cytoplasm

Protein

Receptor synthesis

protein

Blood Target cell

Steroid

hormone

response

1

2

3

4

5

6

H

H

H H

H

LEARNING OUTCOMES

After studying this section, you should be able to:

3. Explain the mechanisms of action of steroid and
   thyroid hormones.


4. Describe the mechanisms by which other hormones
   exert their effects on target cells.

Although each hormone exerts its own characteristic effects on
specific target cells, hormones that are in the same chemical
category have similar mechanisms of action. These similarities
involve the location of cellular receptor proteins and the events
that occur in the target cells after the hormone has combined
with its receptor protein.
Hormones are delivered by the blood to every cell in the
body, but only the target cells are able to respond to these
hormones. In order to respond to any given hormone, a target
cell must have specific receptor proteins for that hormone.
Receptor protein–hormone interaction is highly specific.
In addition to this property of specificity, hormones bind to
receptors with a high affinity (high bond strength) and a low
capacity. The latter characteristic refers to the possibility of
saturating receptors with hormone molecules because of the
limited number of receptors per target cell (usually a few
thousand). Notice that the characteristics of specificity and
saturation that apply to receptor proteins are similar to the
characteristics of enzyme and carrier proteins discussed in
chapters 4 and 6.
The location of a hormone’s receptor proteins in its tar-
get cells depends on the chemical nature of the hormone.
Because the lipophilic hormones (steroids and thyroxine)
can pass through the plasma membrane and enter their tar-
get cells, the receptor proteins for lipophilic hormones are
located within the cytoplasm and nucleus. The water-soluble
hormones (catecholamines, polypeptides, and glycoproteins)
cannot pass through the plasma membrane, so their receptors
are located on the outer surface of the membrane. In these
cases, hormone action requires the activation of second mes-
sengers within the cell.