Principles of Endocrinology -

The Central Endocrine Glands

Chapter 18
 The endocrine system consists of the
ductless glands.
• They are not connected
anatomically. These glands
secrete hormones into the blood. A
hormone travels in the blood,
signaling distant target cells.
• Neurosecretory neurons release
neurohormones. They are also
distributed by the blood to target
cells.
• Target cells are specific for each
hormone or neurohormone. It is
specific, as these cells have
receptors that uniquely bind to a
specific chemical messenger.
The endocrine and nervous systems
are two regulatory systems of the
body.

• The endocrine system mainly controls activities that require

longer duration. This system has several overall functions.
• It regulates organic metabolism and water/electrolyte balance.
It also induces adaptive changes to deal with stress. The
endocrine system promotes smooth, sequential growth and
development.
• Some hormones control reproduction while another one
regulates red blood cell production. Some hormones regulate
circulatory and digestive functions.
• A tropic hormone regulates the secretions of another endocrine
gland. Tropic hormones are secreted by the anterior pituitary
gland.
The endocrine system is a
complex system.
• One endocrine gland can produce multiple hormones. A single
hormone can be produced by more than one endocrine gland.
• A single hormone can have more than one type of target cell
and, therefore, more than one effect. Also, a single target cell
can be influenced by more than one hormone.
• Other factors contribute to the complexity of the system. The
rate of secretion of a hormone can vary over time.
• The same chemical messenger can be a hormone or
neurotransmitter (e.g., norepinephrine).
• Some organs have exclusively endocrine functions. Other
organs (e.g., testis) have endocrine functions and nonendocrine
functions.
Hormones are chemically
classified into three classes.
• Some hormones are proteins or peptides, shorter
protein chains.
• The amines are derived from the amino acid tyrosine.

• They are secreted by the adrenal medulla.

• The proteins/peptides and amines are hydrophilic
(water-soluble) hormones.
• The steroids are secreted by the adrenal cortex and
gonads. These hormones, and the thyroid
hormones, are lipophilic (lipid-soluble).
The mechanisms of hormone
synthesis, storage, and secretion
vary according to the class of
hormone.
• Peptide hormones have precursors called preprohormones.
They are made on ribosomes of the ER. In the Golgi complex
they are converted to prohormones and, finally, active
hormones. The Golgi complex concentrates these hormone into
secretory vesicles.
• These hormones are released from endocrine cells by
exocytosis.
• Cholesterol is the common precursor for all steroid hormones.
A series of enzymatic steps modify this molecule into a different
hormone in a specific endocrine cell. Only the precursor
(cholesterol) is stored. The lipid-soluble hormone is not stored.
• The amine hormones are made from tyrosine. These hormones
are stored until they are secreted.
All hormones are transported in
the blood. However, they are not
transported in the same way.
• Hydrophilic hormones are dissolved in the plasma. Most
lipophilic hormones are bound reversibly to plasma proteins.
These hormones are released by these proteins when they
actively signal target cells.
• Hormones generally produce their effect by altering intracellular
proteins.
• Hydrophilic hormones bind to receptors on the surface of target
cells. Lipophilic hormones pass through target cell membranes
and bind to receptors inside the target cell.
• A few hydrophilic hormones alter the permeability of the target
cell’s membrane.
A hydrophilic hormone usually
activates second-messenger
systems.
– It binds to the target cell surface. This activates an intermediate G
protein. This activates adenyl cyclase which converts intracellular
ATP to cyclic AMP. Cyclic AMP triggers steps that alter the activity of
a protein which is often an enzyme. This produces a physiological
response in the target cell.
• A lipophilic hormone stimulates a gene, promoting protein
synthesis.
– This kind of hormone passes through the target cell membrane. It
binds with a receptor that binds to DNA. This turns on a gene. This
gene makes RNA which makes a specific protein at the ribosome.
This hormone changes the physiological response in the target cell.
– Compared to neural activity, the action of either class of hormone is
usually slow and prolonged. Hormone actions are greatly amplified at
the target cell. Activation of one receptor can activate many proteins.
 Other effects on hormone activity include:
• The concentration of a hormone in the blood is subject to control. It varies
according to homeostatic need.
• The availability of a hormone to its receptor depends on the hormone’s rate of
secretion, its rate of metabolic activation, the extend of its binding to plasma
proteins if it is lipophilic, and its removal from the blood. Removal can be by
metabolic inactivation or urinary excretion.
• Negative feedback maintains the plasma concentration of a hormone at a needed
level. When a hormone’s concentration falls below a certain set point, the gland
increases the secretion of the hormone. When the hormone’s level is above the
set point, the secretion decreases.
• Many endocrine control systems involve neuroendocrine reflexes. Neural input to
a gland regulates the gland’s secretion.
• The secretion rate of many hormones varies by a dirunal or circadian rhythm.
Endocrine disorders result
from the hyposecretion or
hypersecretion of a hormone.
• Factors producing hyposecretion include heredity, dietary
deficiency, immunologic factors, and disease processes.
Hyposecretion can be primary or secondary (due to the
deficiency of the hormone’s tropic hormone).
• Replacement therapy of a hormone can often successfully treat
the conditions from hyposecretion.
• Hypersecretion of a hormone can also be primary or secondary.
Factors producing hypersecretion include tumors on the
endocrine gland and immunologic factors.
• Endocrine dysfunction can also arise from the
unresponsiveness of target cells to a hormone.
The responsiveness of a target cell
can vary by regulating the number of
hormone-specific receptors.

• By permissiveness one hormone must be present in

sufficient amounts for the full effect of another
hormone to occur.
• By synergism several hormones complement each
other and combine effects.
• By antagonism causes the decrease in another
hormone’s receptors and therefore diminishes the
effectiveness of the other hormone.
The pineal gland is a small
structure in the brain.
• It secretes the hormone melatonin. It helps keep the body’s inherent circadian
rhythms in synchrony with the light-dark cycle.
• The suprachiasmatic nucleus (SCN) has a major role in establishing many of the
body’s inherent daily rhythms.
• It secretes clock proteins. Cyclic changes in their concentration changes the
neural output from the SCN. This can produce cyclic changes in effector organs
through the day.
• The SCN works in conjunction with the pineal gland and pineal gland to regulate
circadian rhythms.
• Daily changes in light intensity is the major environmental cue used to adjust the
SCN master clock.
• Other neural and blood-borne signals may be involved in the timekeeping in the
body.
• Melatonin has other functions not related to circadian timekeeping. It
accomplishes natural sleep without hypnosis. It inhibits hormones that stimulate
reproductive activity. It is also an effective antioxidant.
 The pituitary gland is a
small structure at the
base of the brain.
• The posterior lobe is the neurohypophysis. It is
composed of nervous tissue. The anterior lobe is
the adenohypophysis. It is glandular tissue.
• The posterior lobe and the hypothalamus act as a
unit to secrete vasopressin and oxytocin. The
axons of the hypothalamus pass from the brain
into capillaries in the posterior lobe.
• The posterior lobe does not produce vasopressin
and oxytocin. They are produced by hypothalmic
neurons. They are stored in neuron terminals in
the posterior lobe.
• Vasopressin (ADH) signals the kidneys to retain
water. It also signals the smooth muscle in the
walls of arterioles. Its main role is regulating water
balance.
The anterior pituitary secretes six
hormones. Many are tropic.
• By a vascular network with the hypothalamus, each anterior pituitary
hormone is secreted through signaling by a releasing hormone from
this region of the brain.
• The thyroid-stimulating hormone (TSH) stimulates the secretion and
growth of the thyroid gland.
• The adrenocorticotropic hormone (ACTH) stimulates the growth and
secretion of hormones from the adrenal cortex.
• The follicle-stimulating hormone (FSH) stimulates growth and
development of the ovarian follicles in females and sperm
production in males.
• The luteinizing hormone (LH) stimulates ovulation and luteinization
(female) and stimulates testosterone secretion in the male.
• Prolactin enhances breast development in females.
Hypothalmic releasing and inhibiting
hormones regulate anterior pituitary
hormone secretion.
• TRH stimulates the release of TSH.
• CRH stimulates the release of ACTH.
• GnRH stimulates the release of FSH and LH.
• GHRH stimulates the release of the growth hormone.
• GHIH inhibits the release of the growth hormone and
TSH.
• PRH stimulates the release of prolactin.
• PIH inhibits the release of prolactin.
• A hypothalmic hormone controls the output of an
anterior pituitary hormone. The tropic hormone
regulates the secretion of the target endocrine
gland’s hormone.
The hypothalmic regulatory
hormones reach the anterior
pituitary by a vascular link.
• This is a capillary to capillary connection, the hypothalmic-
hypophyseal portal system. Blood is this system carries
hypothalmic signals to the anterior pituitary.
• Regulation of the secretion of the hypothalmic hormones depends
on numerous inputs. Their complete regulation is not well
understood.
• Target gland hormones inhibit hypothalmic and anterior pituitary
hormone secretion via negative feedback.
• For example, a rise in cortisol from the adrenal cortex can feed
back and reduce CRH secretion (hypothalamus) and the sensitivity
of the ACTH secreting cells (anterior pituitary) to CRH.
• If cortisol falls in the blood, the direction of the other responses is
reversed.
The endocrine system controls
growth.
• Growth is signaled by the growth hormone. There are other factors that
influence growth.
• Growth capacity is genetically determined. Adequate diet, freedom
from chronic disease and stress, and normal levels of other growth-
influencing hormones are other factors.
• The growth hormone does not play a role in fetal development. In
children there is a postnatal growth spurt. The growth hormone may
play a role in the later-occurring pubertal growth spurt. Androgens also
contribute at this time.
 The growth hormone has
metabolic effects.
• It mobilizes fat stores as a major energy source
while conserving glucose for glucose-dependent
tissues. This metabolic action is unrelated to
growth.
• The growth hormone promotes growth by
signaling an increase in the number of cells and
size of cells in target organs. It stimulates the
uptake of amino acids and protein synthesis in
target cells.
• The growth hormone stimulates growth in the
length and thickness of long bones.
• It stimulates the lengthening of bones at the
epiphyseal plate. It stimulates osteoblast activity
and the proliferation of epiphyseal cartilage. New
bone tissue replaces cartilage in this region.
• It stimulates bone thickness by activating
osteoblasts under the periosteum.
The growth hormone exerts its effects indirectly
by stimulating somatomedins.
• These substances are also called insulin-like
growth factors. They are stimulated by the growth
hormone and mediate most of the growth-
promoting effects of the hormone.
• The main source of these factors is the liver.
Their production depends on adequate nutrition.
Their production is also related to age.
• The secretion of the growth hormone is regulated
by GHRH and GHIH.
• Many factors influence the secretion of the growth
hormone. It increases one hour after a deep
sleep. Exercise can increase the secretion of the
growth hormone. An abundance of amino acids
increases its release.
A deficiency or excess of the growth
hormone changes growth patterns.
• A hyposecretion produces dwarfism in a child. In Laron dwarfism,
tissues fail to repond to the growth hormone.
• In adults a growth hormone deficiency reduces muscle mass and
strength.
• A hypersecretion of the growth hormone produces gigantism in the
child.
• If hypersecretion occurs after the epiphyseal plates have closed,
acromegaly develops. Only certain bones are affected.
• Other hormones in addition to the growth hormone are essential for
normal growth. The thyroid hormone is essential for growth. Insulin is
a growth promoter. Androgens play a role in a pubertal growth spurt.