Endocrine Glands and Their Major Hormones

Endocrine Chemical
gland Associated hormones class Effect

Pituitary
Growth hormone (GH) Protein Promotes growth of body tissues
(anterior)

Pituitary
Prolactin (PRL) Peptide Promotes milk production
(anterior)

Pituitary Thyroid-stimulating
Glycoprotein Stimulates thyroid hormone release
(anterior) hormone (TSH)

Pituitary Adrenocorticotropic
Peptide Stimulates hormone release by adrena
(anterior) hormone (ACTH)

Pituitary Follicle-stimulating
Glycoprotein Stimulates gamete production
(anterior) hormone (FSH)

Pituitary
Luteinizing hormone (LH) Glycoprotein Stimulates androgen production by go
(anterior)

Pituitary Antidiuretic hormone

Peptide Stimulates water reabsorption by kidn
(posterior) (ADH)

Pituitary
Oxytocin Peptide Stimulates uterine contractions during
(posterior)

Thyroxine (T ),
Thyroid Amine Stimulate basal metabolic rate
4

triiodothyronine (T )
3

Thyroid Calcitonin Peptide Reduces blood Ca  levels

2+

Parathyroid Parathyroid hormone (PTH) Peptide Increases blood Ca levels

2+ 

Adrenal
Aldosterone Steroid Increases blood Na  levels
+

(cortex)

Adrenal Cortisol, corticosterone,

Steroid Increase blood glucose levels
(cortex) cortisone

Adrenal Epinephrine,
Amine Stimulate fight-or-flight response
(medulla) norepinephrine

Pineal Melatonin Amine Regulates sleep cycles

Pancreas Insulin Protein Reduces blood glucose levels

 Endocrine Chemical
gland Associated hormones class Effect

Pancreas Glucagon Protein Increases blood glucose levels

Stimulates development of male seco

Testes Testosterone Steroid
characteristics and sperm production

Stimulate development of female seco

Ovaries Estrogens and progesterone Steroid
characteristics and prepare the body f
Table17.2

Types of Hormones

The hormones of the human body can be divided into two major groups on the basis of their
chemical structure. Hormones derived from amino acids include amines, peptides, and proteins.
Those derived from lipids include steroids (Figure 17.3). These chemical groups affect a
hormone’s distribution, the type of receptors it binds to, and other aspects of its function.
Figure 17.3 Amine, Peptide, Protein, and Steroid Hormone Structure

Amine Hormones

Hormones derived from the modification of amino acids are referred to as amine hormones.
Typically, the original structure of the amino acid is modified such that a –COOH, or carboxyl,
group is removed, whereas the −NH+3−NH3+, or amine, group remains.
Amine hormones are synthesized from the amino acids tryptophan or tyrosine. An example of a
hormone derived from tryptophan is melatonin, which is secreted by the pineal gland and helps
regulate circadian rhythm. Tyrosine derivatives include the metabolism-regulating thyroid
hormones, as well as the catecholamines, such as epinephrine, norepinephrine, and dopamine.
Epinephrine and norepinephrine are secreted by the adrenal medulla and play a role in the fight-
or-flight response, whereas dopamine is secreted by the hypothalamus and inhibits the release of
certain anterior pituitary hormones.

Peptide and Protein Hormones

Whereas the amine hormones are derived from a single amino acid, peptide and protein
hormones consist of multiple amino acids that link to form an amino acid chain. Peptide
hormones consist of short chains of amino acids, whereas protein hormones are longer
polypeptides. Both types are synthesized like other body proteins: DNA is transcribed into
mRNA, which is translated into an amino acid chain.

Examples of peptide hormones include antidiuretic hormone (ADH), a pituitary hormone

important in fluid balance, and atrial-natriuretic peptide, which is produced by the heart and
helps to decrease blood pressure. Some examples of protein hormones include growth hormone,
which is produced by the pituitary gland, and follicle-stimulating hormone (FSH), which has an
attached carbohydrate group and is thus classified as a glycoprotein. FSH helps stimulate the
maturation of eggs in the ovaries and sperm in the testes.

Steroid Hormones

The primary hormones derived from lipids are steroids. Steroid hormones are derived from the
lipid cholesterol. For example, the reproductive hormones testosterone and the estrogens—which
are produced by the gonads (testes and ovaries)—are steroid hormones. The adrenal glands
produce the steroid hormone aldosterone, which is involved in osmoregulation, and cortisol,
which plays a role in metabolism.

Like cholesterol, steroid hormones are not soluble in water (they are hydrophobic). Because
blood is water-based, lipid-derived hormones must travel to their target cell bound to a transport
protein. This more complex structure extends the half-life of steroid hormones much longer than
that of hormones derived from amino acids. A hormone’s half-life is the time required for half
the concentration of the hormone to be degraded. For example, the lipid-derived hormone
cortisol has a half-life of approximately 60 to 90 minutes. In contrast, the amino acid–derived
hormone epinephrine has a half-life of approximately one minute.

Pathways of Hormone Action

The message a hormone sends is received by a hormone receptor, a protein located either inside
the cell or within the cell membrane. The receptor will process the message by initiating other
signaling events or cellular mechanisms that result in the target cell’s response. Hormone
receptors recognize molecules with specific shapes and side groups, and respond only to those
hormones that are recognized. The same type of receptor may be located on cells in different
body tissues, and trigger somewhat different responses. Thus, the response triggered by a
hormone depends not only on the hormone, but also on the target cell.

Once the target cell receives the hormone signal, it can respond in a variety of ways. The
response may include the stimulation of protein synthesis, activation or deactivation of enzymes,
alteration in the permeability of the cell membrane, altered rates of mitosis and cell growth, and
stimulation of the secretion of products. Moreover, a single hormone may be capable of inducing
different responses in a given cell.

Pathways Involving Intracellular Hormone Receptors

Intracellular hormone receptors are located inside the cell. Hormones that bind to this type of
receptor must be able to cross the cell membrane. Steroid hormones are derived from cholesterol
and therefore can readily diffuse through the lipid bilayer of the cell membrane to reach the
intracellular receptor (Figure 17.4). Thyroid hormones, which contain benzene rings studded
with iodine, are also lipid-soluble and can enter the cell.

The location of steroid and thyroid hormone binding differs slightly: a steroid hormone may bind
to its receptor within the cytosol or within the nucleus. In either case, this binding generates a
hormone-receptor complex that moves toward the chromatin in the cell nucleus and binds to a
particular segment of the cell’s DNA. In contrast, thyroid hormones bind to receptors already
bound to DNA. For both steroid and thyroid hormones, binding of the hormone-receptor
complex with DNA triggers transcription of a target gene to mRNA, which moves to the cytosol
and directs protein synthesis by ribosomes.

Figure 17.4 Binding of Lipid-Soluble Hormones A steroid hormone directly initiates the

production of proteins within a target cell. Steroid hormones easily diffuse through the cell
membrane. The hormone binds to its receptor in the cytosol, forming a receptor–hormone
complex. The receptor–hormone complex then enters the nucleus and binds to the target gene on
the DNA. Transcription of the gene creates a messenger RNA that is translated into the desired
protein within the cytoplasm.

Pathways Involving Cell Membrane Hormone Receptors

Hydrophilic, or water-soluble, hormones are unable to diffuse through the lipid bilayer of the cell
membrane and must therefore pass on their message to a receptor located at the surface of the
cell. Except for thyroid hormones, which are lipid-soluble, all amino acid–derived hormones
bind to cell membrane receptors that are located, at least in part, on the extracellular surface of
the cell membrane. Therefore, they do not directly affect the transcription of target genes, but
instead initiate a signaling cascade that is carried out by a molecule called a second messenger.
In this case, the hormone is called a first messenger.

The second messenger used by most hormones is cyclic adenosine monophosphate (cAMP). In
the cAMP second messenger system, a water-soluble hormone binds to its receptor in the cell
membrane (Step 1 in Figure 17.5). This receptor is associated with an intracellular component
called a G protein, and binding of the hormone activates the G-protein component (Step 2). The
activated G protein in turn activates an enzyme called adenylyl cyclase, also known as adenylate
cyclase (Step 3), which converts adenosine triphosphate (ATP) to cAMP (Step 4). As the second
messenger, cAMP activates a type of enzyme called a protein kinase that is present in the
cytosol (Step 5). Activated protein kinases initiate a phosphorylation cascade, in which
multiple protein kinases phosphorylate (add a phosphate group to) numerous and various cellular
proteins, including other enzymes (Step 6).

Figure 17.5 Binding of Water-Soluble Hormones Water-soluble hormones cannot diffuse

through the cell membrane. These hormones must bind to a surface cell-membrane receptor. The
receptor then initiates a cell-signaling pathway within the cell involving G proteins, adenylyl
cyclase, the secondary messenger cyclic AMP (cAMP), and protein kinases. In the final step,
these protein kinases phosphorylate proteins in the cytoplasm. This activates proteins in the cell
that carry out the changes specified by the hormone.

The phosphorylation of cellular proteins can trigger a wide variety of effects, from nutrient
metabolism to the synthesis of different hormones and other products. The effects vary according
to the type of target cell, the G proteins and kinases involved, and the phosphorylation of
proteins. Examples of hormones that use cAMP as a second messenger include calcitonin, which
is important for bone construction and regulating blood calcium levels; glucagon, which plays a
role in blood glucose levels; and thyroid-stimulating hormone, which causes the release of T  and
3

T  from the thyroid gland.

4

Overall, the phosphorylation cascade significantly increases the efficiency, speed, and specificity
of the hormonal response, as thousands of signaling events can be initiated simultaneously in
response to a very low concentration of hormone in the bloodstream. However, the duration of
the hormone signal is short, as cAMP is quickly deactivated by the enzyme phosphodiesterase
(PDE), which is located in the cytosol. The action of PDE helps to ensure that a target cell’s
response ceases quickly unless new hormones arrive at the cell membrane.

Importantly, there are also G proteins that decrease the levels of cAMP in the cell in response to
hormone binding. For example, when growth hormone–inhibiting hormone (GHIH), also known
as somatostatin, binds to its receptors in the pituitary gland, the level of cAMP decreases, thereby
inhibiting the secretion of human growth hormone.

Not all water-soluble hormones initiate the cAMP second messenger system. One common
alternative system uses calcium ions as a second messenger. In this system, G proteins activate
the enzyme phospholipase C (PLC), which functions similarly to adenylyl cyclase. Once
activated, PLC cleaves a membrane-bound phospholipid into two molecules: diacylglycerol
(DAG) and inositol triphosphate (IP ). Like cAMP, DAG activates protein kinases that initiate
3

a phosphorylation cascade. At the same time, IP  causes calcium ions to be released from storage
3

sites within the cytosol, such as from within the smooth endoplasmic reticulum. The calcium
ions then act as second messengers in two ways: they can influence enzymatic and other cellular
activities directly, or they can bind to calcium-binding proteins, the most common of which is
calmodulin. Upon binding calcium, calmodulin is able to modulate protein kinase within the cell.
Examples of hormones that use calcium ions as a second messenger system include angiotensin
II, which helps regulate blood pressure through vasoconstriction, and growth hormone–releasing
hormone (GHRH), which causes the pituitary gland to release growth hormones.

Factors Affecting Target Cell Response

You will recall that target cells must have receptors specific to a given hormone if that hormone
is to trigger a response. But several other factors influence the target cell response. For example,
the presence of a significant level of a hormone circulating in the bloodstream can cause its
target cells to decrease their number of receptors for that hormone. This process is
called downregulation, and it allows cells to become less reactive to the excessive hormone
levels. When the level of a hormone is chronically reduced, target cells engage
in upregulation to increase their number of receptors. This process allows cells to be more
sensitive to the hormone that is present. Cells can also alter the sensitivity of the receptors
themselves to various hormones.

Two or more hormones can interact to affect the response of cells in a variety of ways. The three
most common types of interaction are as follows:

 The permissive effect, in which the presence of one hormone enables another hormone to
act. For example, thyroid hormones have complex permissive relationships with certain
reproductive hormones. A dietary deficiency of iodine, a component of thyroid
hormones, can therefore affect reproductive system development and functioning.
 The synergistic effect, in which two hormones with similar effects produce an amplified
response. In some cases, two hormones are required for an adequate response. For
example, two different reproductive hormones—FSH from the pituitary gland and
estrogens from the ovaries—are required for the maturation of female ova (egg cells).
 The antagonistic effect, in which two hormones have opposing effects. A familiar
example is the effect of two pancreatic hormones, insulin and glucagon. Insulin increases
the liver’s storage of glucose as glycogen, decreasing blood glucose, whereas glucagon
stimulates the breakdown of glycogen stores, increasing blood glucose.

Regulation of Hormone Secretion

To prevent abnormal hormone levels and a potential disease state, hormone levels must be
tightly controlled. The body maintains this control by balancing hormone production and
degradation. Feedback loops govern the initiation and maintenance of most hormone secretion in
response to various stimuli.

Role of Feedback Loops

The contribution of feedback loops to homeostasis will only be briefly reviewed here. Positive
feedback loops are characterized by the release of additional hormone in response to an original
hormone release. The release of oxytocin during childbirth is a positive feedback loop. The
initial release of oxytocin begins to signal the uterine muscles to contract, which pushes the fetus
toward the cervix, causing it to stretch. This, in turn, signals the pituitary gland to release more
oxytocin, causing labor contractions to intensify. The release of oxytocin decreases after the birth
of the child.

The more common method of hormone regulation is the negative feedback loop. Negative
feedback is characterized by the inhibition of further secretion of a hormone in response to
adequate levels of that hormone. This allows blood levels of the hormone to be regulated within
a narrow range. An example of a negative feedback loop is the release of glucocorticoid
hormones from the adrenal glands, as directed by the hypothalamus and pituitary gland. As
glucocorticoid concentrations in the blood rise, the hypothalamus and pituitary gland reduce their
signaling to the adrenal glands to prevent additional glucocorticoid secretion (Figure 17.6).
Figure 17.6 Negative Feedback Loop The release of adrenal glucocorticoids is stimulated by
the release of hormones from the hypothalamus and pituitary gland. This signaling is inhibited
when glucocorticoid levels become elevated by causing negative signals to the pituitary gland
and hypothalamus.

Role of Endocrine Gland Stimuli

Reflexes triggered by both chemical and neural stimuli control endocrine activity. These reflexes
may be simple, involving only one hormone response, or they may be more complex and involve
many hormones, as is the case with the hypothalamic control of various anterior pituitary–
controlled hormones.

Humoral stimuli are changes in blood levels of non-hormone chemicals, such as nutrients or
ions, which cause the release or inhibition of a hormone to, in turn, maintain homeostasis. For
example, osmoreceptors in the hypothalamus detect changes in blood osmolarity (the
concentration of solutes in the blood plasma). If blood osmolarity is too high, meaning that the
blood is not dilute enough, osmoreceptors signal the hypothalamus to release ADH. The
hormone causes the kidneys to reabsorb more water and reduce the volume of urine produced.
This reabsorption causes a reduction of the osmolarity of the blood, diluting the blood to the
appropriate level. The regulation of blood glucose is another example. High blood glucose levels
cause the release of insulin from the pancreas, which increases glucose uptake by cells and liver
storage of glucose as glycogen.

An endocrine gland may also secrete a hormone in response to the presence of another hormone
produced by a different endocrine gland. Such hormonal stimuli often involve the hypothalamus,
which produces releasing and inhibiting hormones that control the secretion of a variety of
pituitary hormones.

In addition to these chemical signals, hormones can also be released in response to neural
stimuli. A common example of neural stimuli is the activation of the fight-or-flight response by
the sympathetic nervous system. When an individual perceives danger, sympathetic neurons
signal the adrenal glands to secrete norepinephrine and epinephrine. The two hormones dilate
blood vessels, increase the heart and respiratory rate, and suppress the digestive and immune
systems. These responses boost the body’s transport of oxygen to the brain and muscles, thereby
improving the body’s ability to fight or flee.

EVERYDAY CONNECTION

Bisphenol A and Endocrine Disruption

You may have heard news reports about the effects of a chemical called bisphenol A (BPA) in
various types of food packaging. BPA is used in the manufacturing of hard plastics and epoxy
resins. Common food-related items that may contain BPA include the lining of aluminum cans,
plastic food-storage containers, drinking cups, as well as baby bottles and “sippy” cups. Other
uses of BPA include medical equipment, dental fillings, and the lining of water pipes.

Research suggests that BPA is an endocrine disruptor, meaning that it negatively interferes with
the endocrine system, particularly during the prenatal and postnatal development period. In
particular, BPA mimics the hormonal effects of estrogens and has the opposite effect—that of
androgens. The U.S. Food and Drug Administration (FDA) notes in their statement about BPA
safety that although traditional toxicology studies have supported the safety of low levels of
exposure to BPA, recent studies using novel approaches to test for subtle effects have led to
some concern about the potential effects of BPA on the brain, behavior, and prostate gland in
fetuses, infants, and young children. The FDA is currently facilitating decreased use of BPA in
food-related materials. Many US companies have voluntarily removed BPA from baby bottles,
“sippy” cups, and the linings of infant formula cans, and most plastic reusable water bottles sold
today boast that they are “BPA free.” In contrast, both Canada and the European Union have
completely banned the use of BPA in baby products.

The potential harmful effects of BPA have been studied in both animal models and humans and
include a large variety of health effects, such as developmental delay and disease. For example,
prenatal exposure to BPA during the first trimester of human pregnancy may be associated with
wheezing and aggressive behavior during childhood. Adults exposed to high levels of BPA may
experience altered thyroid signaling and male sexual dysfunction. BPA exposure during the
prenatal or postnatal period of development in animal models has been observed to cause
neurological delays, changes in brain structure and function, sexual dysfunction, asthma, and
increased risk for multiple cancers. In vitro studies have also shown that BPA exposure causes
molecular changes that initiate the development of cancers of the breast, prostate, and brain.
Although these studies have implicated BPA in numerous ill health effects, some experts caution
that some of these studies may be flawed and that more research needs to be done. In the
meantime, the FDA recommends that consumers take precautions to limit their exposure to BPA.
In addition to purchasing foods in packaging free of BPA, consumers should avoid carrying or
storing foods or liquids in bottles with the recycling code 3 or 7. Foods and liquids should not be
microwave-heated in any form of plastic: use paper, glass, or ceramics instead.