Hormones and cell signalling

General principles
There are three general classes of hormones: (1) peptide
hormones, e.g. thyroid-stimulating hormone and
adrenocorticotropic hormone; (2) steroid hormones,
e.g. oestrogens, testosterone and cortisol; and (3) derivatives
of the amino acid tyrosine, e.g. thyroxine and
adrenaline (epinephrine). Peptide and amine hormones
are stored in secretory vesicles until needed.
Steroid hormones are not stored: they are synthesized
from intracellular stores of cholesteryl esters after a
stimulus.
Hormone action is initiated by the binding of
hormone to receptors in the cells of target tissues.
Hormonal receptors are large proteins which have
both high affi nity and high specifi city for their hormonal
ligands. Each cell within a target tissue contains
some 2000 to 100 000 receptors. The target tissues for
a particular hormone are those whose cells contain
receptors for that hormone: cells that lack such receptors
do not respond. Thus receptors provide the fi rst
level of specifi city for hormone action. Formation of
the hormone–receptor complex triggers a cascade of
reactions in the target cell, with each stage becoming
more powerfully activated, so that very low concentrations
of circulating hormone can elicit a robust
biological response.
neurilemma
node of
Ranvier
axon bounded
by axolemma
myelin
sheath
nucleus, cytoplasm
Schwann cell
Fig. 3.28 Diagram of a myelinated nerve fi bre. The myelin sheath is an
insulating layer derived from Schwann cell plasma membranes spiralling
concentrically to form a wrapping around the axon. The outer layer of the
myelin, the neurilemma, is a basal lamina beneath which lie the fl attened
nuclei of Schwann cells.
Background physiology and functional anatomy 49
The receptors for peptide hormones and catecholamines
are located in or on the surface of the cell membrane.
These hormones, being hydrophilic, cannot
cross the lipid bilayer of the cell’s plasma membrane
and so many of them recruit a ‘second messenger’ to
mediate their intracellular action. (The hormone is the
‘fi rst messenger’.) The best-known second messenger
is cyclic AMP; others include diacylglycerol and inositol
triphosphate (these are products of membrane
phospholipid breakdown) and calcium ions.
The receptors for the steroid hormones reside within
the cell. The steroid hormones, being hydrophobic, are
able to cross the plasma membrane and bind to their
specifi c receptors. The liganded receptors interact with
specifi c sites on the DNA and directly regulate gene
transcription. The newly formed proteins become the
controllers of new or increased cellular function.
Regulation of hormonal activity
Hormonal activity can be regulated at both the endocrine
gland and the target tissue. Positive or negative
feedback to the endocrine gland may regulate any step
during the synthesis, processing or release of the hormone.
Positive feedback results in additional secretion
of the hormone, while negative feedback has the opposite
effect. Most hormones are controlled through
negative feedback in order to prevent overactivity of
the target tissues and to allow responses to subsequent
signals. The controlled variable is often the degree of
activity of the target tissue. Above a certain level of activity,
feedback signals to the endocrine gland become
powerful enough to shut down hormone production
or prevent secretion.
Formation of the hormone–receptor complex may
cause the number of active receptors to decrease, either
because of inactivation or destruction or because
of decreased production by the cell’s protein-manufacturing
capacity. This down-regulation of receptors
leads to a decreased response of the target tissue to the
hormone. Some hormones can cause up-regulation
of receptors by inducing synthesis of the receptors.
When this occurs, the target tissue becomes progressively
more sensitive to the stimulating effects of the
hormone.