ZLY 106

THE ENDOCRINE SYSTEM

Hormones (from the Greek horman, to excite) are chemical signals produced by most plants and
animals. Animal hormones are carried by the circulatory system (usually in the blood) to other
parts of the body, where they may communicate regulatory messages. Hormones are made and
secreted mainly by organs called endocrine glands. Collectively, all the endocrine glands and other
organs with hormone-secreting cells constitute the endocrine system, the body’s main system for
internal chemical regulation, as depicted for a human in Table 1.
Hormonal secretion
The circulatory system carries hormones throughout the body, but a hormone can only bind to a
target cell with receptors for that specific hormone (Fig. 1, bottom-right diagram). Because
hormones reach all parts of the body, the endocrine system is especially important in controlling
whole-body activities. For example, hormones govern our metabolic rate, growth (including
muscle development), maturation, and reproduction. In many cases, a tiny amount of a hormone
influences the activities of an enormous number of target cells in a variety of organs.

Figure 1: Hormone secretion from an endocrine cell. A cell within an endocrine gland (upper-
right diagram) secretes hormone molecules. The hormone is carried via the circulatory system to
all cells of the body, but it only affects target cells that have matching receptors (lower-right
diagram).
Table 1: Major Human Endocrine Glands and Some of Their Hormones
Mechanism of hormonal binding
Hormones trigger changes in target cells in different ways, depending on whether the hormone is
water-soluble or lipid-soluble: Water-soluble hormones trigger responses without entering the
cell, whereas lipid-soluble hormones trigger responses after entering the cell.
Water-soluble hormones
Water-soluble hormones cannot pass through the oily interior of the phospholipid bilayer
of the plasma membrane, but they can bring about cellular changes without entering their target
cells (Figure 2). To start, a water-soluble hormone (1) binds to a specific receptor protein (2) in the
plasma membrane of the target cell. The binding activates the receptor protein, which initiates a
signal transduction pathway: a series of changes to molecules that converts a chemical message
from outside the cell to a specific response inside the cell. The final relay molecule (3) activates a
protein that either carries out a response in the cytoplasm (such as activating an enzyme) or affects
gene regulation in the nucleus (such as turning on or off genes). This is a bit like the game of
“telephone,” with a message passed from one person to the next—but this message is (hopefully)
received exactly as sent!
Figure 2: A hormone that binds to a plasma membrane receptor. Hormones that are water-
soluble cannot cross the phospholipid bilayer but can bind to membrane receptors outside target
cells and activate a signal transduction pathway.
Lipid-soluble hormones
In contrast to water soluble hormone, lipid-soluble hormones pass through the phospholipid bilayer
and trigger responses by binding to including natural ones such as the sex hormones (testosterone,
estrogen, and progesterone) as well as artificial anabolic steroids—work in this manner. As shown
in Figure 3, a lipid-soluble hormone (1) enters a cell by diffusing through the plasma membrane.
If the cell is a target cell, the hormone binds to a receptor protein (2) in the cytoplasm or nucleus.
Rather than triggering a signal transduction pathway, the receptor itself carries the hormone’s
signal (3). The hormone-receptor complex attaches to specific sites on the cell’s DNA in the
nucleus (4). The binding to DNA turns specific genes on or off.

Figure 3: A hormone that binds to an intracellular receptor. Hormones that are lipid-soluble can
cross the phospholipid bilayer and bind to receptors inside target cells. Steroid hormones and
other lipid-soluble hormones affect the cell by turning specific genes on and off.
Control of hormonal secretion
Although hormones carry out vital functions, excessive stimulation of cells by hormones may
produce detrimental effects. For example, hormones that are activated if an animal loses blood
typically help restore blood volume and pressure. This cannot continue indefinitely, however,
because once blood volume and pressure are restored, it would be harmful if they continued to
increase until their levels were above normal. Therefore, once a hormone enters the blood and
performs its functions, it is usually prevented from exerting its effects indefinitely. This is
accomplished in one or more ways:
1. Hormones that bind to plasma membrane receptors may be engulfed by endocytosis into a
cell, where lysosomal enzymes degrade the hormones.
2. Small, water-soluble hormones are excreted in the urine.
3. The liver chemically modifies many hormones to render them inactive and more easily
excretable via the kidneys.
4. Negative feedback processes turn off the signals that were responsible for stimulating the
synthesis and secretion of the hormone.
Generally, these processes ensure that hormone levels in the blood remain within a normal
range under most circumstances, but have the capacity to be increased or decreased beyond that
range if required. One of the ways in which changes in hormone levels are initiated is through
sensory input to an animal’s brain. Thus, the nervous system and endocrine system are functionally
linked in many animals, including all vertebrates.
The Hypothalamus and Pituitary Gland
The hypothalamus is a gland that acts as the main control center of the endocrine system (Figure
4). As part of the brain, the hypothalamus receives information from nerves about the internal
condition of the body and about the external environment. It then responds by sending out
appropriate nervous or endocrine signals. These signals directly control the pituitary gland, a pea-
sized structure that hangs down from the hypothalamus. In response to signals from the
hypothalamus, the pituitary secretes hormones that influence numerous body functions. The
hypothalamus thus exerts master control over the endocrine system by using the pituitary to relay
directives to other glands. As Figure 4 shows, the pituitary gland consists of two distinct parts: a
posterior lobe and an anterior lobe, both tucked in a pocket of skull bone just under the
hypothalamus. The posterior pituitary is actually an extension of the hypothalamus that stores and
secretes hormones made in the hypothalamus. In contrast, the anterior pituitary synthesizes and
secretes its own hormones directly into the blood. The hypothalamus exerts control over the
anterior pituitary by secreting two kinds of hormones into short blood vessels (not illustrated) that
connect the two glands: releasing hormones and inhibiting hormones. Releasing hormones
stimulate the anterior pituitary to secrete specific hormones, whereas inhibiting hormones induce
the anterior pituitary to stop secreting specific hormones.
Figure 4: Location of the hypothalamus and pituitary.

Hypothalamus control of ADH and other hormones

Figure 5 shows how the hypothalamus operates through the posterior pituitary to direct the activity
of the kidneys. The hypothalamus makes antidiuretic hormone (ADH), which is stored and
released by the posterior pituitary. ADH helps kidney cells reabsorb water, preventing dehydration
by decreasing urine volume when the body needs to retain water. When the body has too much
water, the hypothalamus slows the release of ADH from the pituitary. Some drugs, such as caffeine
and alcohol, act as a diuretic by inhibiting the release of ADH, which in turn increases the output
of urine. This can lead to dehydration. In response to releasing hormones secreted by the
hypothalamus, the anterior pituitary synthesizes and releases many different hormones that
influence a broad range of body activities. For example, it releases follicle-stimulating hormone
(FSH) and luteinizing hormone (LH), which help regulate the menstrual cycle.
Figure 5: ADH and osmoregulation. The hypothalamus regulates water homeostasis by
synthesizing ADH. Molecules of this hormone travel via long cellular extensions (gray) to the
posterior pituitary, where they are released into the blood. Eventually, the ADH reaches target
cells in the kidneys.
Hormonal Control of Metabolism and Energy Balance
An important function of the endocrine system is to control metabolic rate and energy balance.
Hormones are partly responsible for regulating energy use by modulating appetite, digestion,
absorption of nutrients, and the levels of energy sources like glucose in the blood and its transport
into cells. Although many hormones are involved in these processes, those from the thyroid gland,
pancreas, adipose tissue, and the adrenal glands play particularly important roles.
Thyroid Hormones
Thyroid Hormones contain Iodine and Regulate Metabolic Rate The thyroid gland lies within the
neck of vertebrates. In mammals, it straddles the trachea just below the larynx (Figure 6). It
consists of many small, spherical structures called follicles that consist of a shell of epithelial cells
called follicular cells and a core of a gel-like substance called the colloid. The colloid consists
primarily of large amounts of the protein thyroglobulin (TG), which plays a major role in the
synthesis of thyroid hormones.
 Figure 6: Location and structure of the thyroid gland

Hormones of the Pancreas and Adrenal Glands

Regulation of energy availability to cells is in large part the job of the hormones of the pancreas
and the adrenal glands. The pancreas is a complex organ consisting of two parts, exocrine and
endocrine cells (Figure 7). Most of the mass of the pancreas comprises exocrine glands. An
exocrine gland is one in which epithelial cells secrete chemicals into a duct, which carries those
molecules directly to another structure or to the outside surface of the body. Examples of exocrine
glands include the sweat glands, salivary glands, liver, and pancreas. The secretions of the exocrine
pancreas empty into the small intestine, where they aid digestion. The non-exocrine portion of the
pancreas consists of endocrine cells that produce peptide hormones, notably insulin and glucagon.
Spherical clusters of endocrine cells called islets of Langerhans are scattered in great
numbers throughout the pancreas. Within the islets are alpha cells, which make glucagon, and beta
cells, which make insulin. The actions of these two hormones are antagonistic with respect to each
other—insulin lowers and glucagon raises blood glucose concentrations.
Figure 7: Location, appearance, and internal structure of the mammalian pancreas. Amidst the
exocrine pancreas are scattered islets of Langerhans, which are endocrine tissue. Only the exocrine
products are secreted into the intestine; the hormones from the islets of Langerhans are secreted
into the blood (not shown).

Maintaining normal glucose and other nutrient levels in the blood is a vital process that
keeps cells functioning optimally. When an animal has not fed for some time, its energy stores
become depleted, and the blood glucose level falls. Under these conditions, glucagon is secreted
into the blood, where it acts on the liver (Figure 8, right side). The liver contains a limited supply
of glucose in the form of stored glycogen. Glucagon stimulates the breakdown of glycogen into
many molecules of glucose, which are then secreted into the blood. This process, known as
glycogenolysis, is stimulated within seconds by glucagon. A second action of glucagon on the liver
is important for responses to prolonged fasting. In that case, glucagon stimulates the process of
gluconeogenesis, by which noncarbohydrates are converted into glucose, which is then released
into the blood.
Figure 8: Mechanisms that help maintain glucose homeostasis in the blood. Glucagon and insulin
respond in opposite ways to changes in plasma glucose concentrations. When the plasma glucose
concentration decreases below normal (right), the insulin level decreases, and glucagon increases.
When the plasma glucose concentration increases above normal (left), the insulin level increases,
and glucagon decreases. Both of these mechanisms return the plasma glucose concentration to
normal. In addition, through their action on the liver, hormones from the adrenal medulla and
adrenal cortex play significant roles in elevating glucose levels (not shown).