Essential Cell Biology 5th edition

566 CHAPTER 16 Cell Signaling
Figure 16–40 Some small, hydrophobic
hormones bind to intracellular receptors
that act as transcription regulators.
Although these signal molecules differ in
their chemical structures and functions, they
all act by binding to intracellular receptor
proteins that act as transcription regulators.
Their receptors are not identical, but they
are evolutionarily related, belonging to the
nuclear receptor superfamily. The sites of
origin and functions of these hormones are
given in Table 16−1 (p. 536).
O
HO
cortisol
CH 2 OH
C O
OH
HO
I
HO
OH
O
estradiol
testosterone
I
H
O CH 2 C COO _
OH
I
+
NH
I
3
thyroxine
of the target cell and bind to receptor proteins located in either the cytosol
or the nucleus. Regardless of their initial location, these intracellular
receptor proteins are referred to as nuclear receptors because, when
activated by hormone binding, they enter the nucleus, where they regulate
the transcription of genes. In unstimulated cells, nuclear receptors
ECB5 e16.09/16.40
are typically present in an inactive form. When a hormone binds, the
receptor undergoes a large conformational change that activates the protein,
allowing it to promote or inhibit the transcription of specific target
genes (Figure 16–41). Each hormone binds to a different nuclear receptor,
and each receptor acts at a different set of regulatory sites in DNA
(discussed in Chapter 8). Moreover, a given hormone usually regulates
different sets of genes in different cell types, thereby evoking different
physiological responses in different target cells.
Nuclear receptors and the hormones that activate them have essential
roles in human physiology (see Table 16−1, p. 536). Loss of these signaling
systems can have dramatic consequences, as illustrated by the effects
of mutations that eliminate the receptor for the male sex hormone testosterone.
Testosterone in humans shapes the formation of the external
genitalia and influences brain development in the fetus; at puberty, the
cortisol
plasma membrane
Figure 16–41 The steroid hormone
cortisol acts by activating a transcription
regulator. Cortisol is one of the hormones
produced by the adrenal glands in response
to stress. It crosses the plasma membrane
of a target cell and binds to its receptor
protein, which is located in the cytosol.
The receptor–hormone complex is then
transported into the nucleus via the
nuclear pores. Cortisol binding activates
the receptor protein, which is then able to
bind to specific regulatory sequences in
DNA and activate (or repress, not shown)
the transcription of specific target genes.
Whereas the receptors for cortisol and some
other steroid hormones are located in the
cytosol, those for other steroid hormones
and for thyroid hormones are already bound
to DNA in the nucleus even in the absence
of hormone.
CYTOSOL
NUCLEUS
nuclear
receptor
protein
ACTIVATED RECEPTOR–CORTISOL
COMPLEX BINDS TO REGULATORY
REGION OF TARGET GENE
AND ACTIVATES TRANSCRIPTION
CONFORMATIONAL
CHANGE ACTIVATES
RECEPTOR PROTEIN
ACTIVATED RECEPTOR–CORTISOL
COMPLEX MOVES INTO NUCLEUS
activated
target gene
TRANSCRIPTION OF
TARGET GENE
DNA