Page 653 - Fundamentals of anatomy physiology

640 Unit 3 Control and Regulation
Thyroid hormones and steroid hormones remain in circu-
lation much longer, because when these hormones enter the
bloodstream, more than 99 percent of them become attached
to special transport proteins. For each hormone an equilib-
rium state exists between its free and bound forms. As the free
hormones are removed and inactivated, bound hormones are
released to replace them. At any given time, the bloodstream
contains a substantial reserve (several weeks’ supply) of bound
hormones.
Mechanisms of Hormone Action
18 Hormones coordinate cell, tissue, and organ activities on a sus-
tained basis. They circulate in the extracellular fluid and bind
to specific receptors on plasma membranes or within target
cells. Binding modifies cellular activities by altering membrane
permeability, activating or inactivating key enzymes, or chang-
ing genetic activity.
To affect a target cell, a hormone must first interact with an process in which the absence of a hormone triggers an increase
appropriate receptor. A hormone receptor, like a neurotrans-
mitter receptor, is a protein molecule to which a particular mol-
ecule binds strongly. Each cell has receptors for several different
hormones, but cells in different tissues have different combina-
tions of receptors. This arrangement is one reason hormones
have different effects on different tissues. For every cell, the
presence or absence of a specific receptor determines the cell’s
hormonal sensitivities. If a cell has a receptor that can bind a
particular hormone, that cell responds to the hormone. If a cell
lacks that receptor, the hormone has no effect on that cell.
Hormone receptors are located either on the plasma mem-
brane or inside the cell. Using a few specific examples, let’s
consider the basic mechanisms involved.
Hormones and Plasma Membrane Receptors
The receptors for catecholamines (E, NE, and dopamine), pep-
tide hormones, and eicosanoids are in the plasma membranes
of their target cells. Catecholamines and peptide hormones
cannot penetrate a plasma membrane because they are not
lipid soluble. Instead, these hormones bind to receptor pro-
teins at the outer surface of the plasma membrane (extracellular
receptors). Eicosanoids are lipid soluble. They diffuse across
the plasma membrane to reach receptor proteins on the inner
surface of the membrane (intracellular receptors).
First and Second Messengers
Communication between the hormone and the cell uses first
and second messengers. A first messenger is a hormone that
binds to a receptor on the plasma membrane surface. A second
messenger is an intermediary molecule that appears due to a
hormone-receptor interaction. Important second messengers
are (1) cyclic AMP (cAMP), a derivative of ATP; (2) cyclic GMP
(cGMP), a derivative of GTP, another high-energy compound;
and (3) calcium ions (Ca2+). Spotlight Figure 18–3 focuses on
cAMP and Ca2+.
When a small number of hormone molecules binds to
membrane receptors, thousands of second messengers may
appear in a cell. This process, called amplification, magnifies the
effect of a hormone on the target cell. Moreover, the arrival of a
single hormone may promote the release of more than one type
of second messenger, or the production of a linked sequence of
enzymatic reactions known as a receptor cascade. Through such
mechanisms, the hormone can alter many aspects of cell func-
tion at the same time.
The presence or absence of a hormone can also affect the
nature and number of hormone receptor proteins in the plasma
membrane. Down-regulation is a process in which the presence
of a hormone triggers a decrease in the number of hormone
receptors. In down-regulation, cells become less sensitive to high
levels of a particular hormone. In contrast, up-regulation is a
in the number of hormone receptors. In up-regulation, cells be-
come more sensitive to low levels of a particular hormone.
The link between the first messenger and the second mes-
senger generally involves a G protein, an enzyme complex
coupled to a membrane receptor. The name G protein refers
to the fact that these proteins bind GTP. p. 446 A G pro-
tein is activated when a hormone binds to its receptor at the
membrane surface. What happens next depends on the nature
of the G protein and its effects on second messengers in the
cytoplasm. Spotlight Figure 18–3 diagrams three major patterns
of response to G protein activation. Roughly 80 percent of pre-
scription drugs target receptors coupled to G proteins.
G Proteins and cAMP. Spotlight Figure 18–3 shows the steps
involved in increasing cAMP levels:
The activated G protein activates the enzyme adenylate
cyclase.
Adenylate cyclase converts ATP to the ring-shaped molecule
cyclic AMP.
Cyclic AMP then functions as a second messenger, typically
by activating a kinase (KI.-na. s). A kinase is an enzyme that
attaches a high-energy phosphate group (˜PO43–) to an-
other molecule in a process called phosphorylation.
Generally, cyclic AMP activates kinases that phosphorylate
proteins. The effect on the target cell depends on the nature
of these proteins. The phosphorylation of plasma mem-
brane proteins, for example, can open ion channels. In the
cytoplasm, many important enzymes can be activated only
by phosphorylation. One important example is the enzyme
that releases glucose from glycogen reserves in skeletal
muscles and the liver.
Many hormones, including calcitonin, parathyroid hor-
mone, ADH, ACTH, epinephrine, FSH, LH, TSH, and glucagon,