Basics for Endocrine System which are useful for the budding clinical pharmacists

1. ENDOCRINE SYSTEM

2. Functions of the Endocrine System
• Controls the processes involved in
movement and physiological equilibrium
• Includes all tissues or glands that secrete
hormones into the blood
• Secretion of most hormones is regulated by a
negative feedback system
• The number of receptors for a specific
hormone can be altered to meet the body’s
demand

3. Endocrine Hormones
• Produced by endocrine (“ductless”) glands
and secreted into the bloodstream.
• Endocrine hormones may affect a wide array
of target cells to produce multiple effects.
• Two types: peptides (small proteins) and
steroids (lipids).

4. Chemical Classification of Hormones
• Steroid Hormones:
– Lipid soluble
– Diffuse through cell membranes
– Endocrine organs
• Adrenal cortex
• Ovaries
• Testes
• placenta

5. Chemical Classification of Hormones
• Nonsteroid Hormones:
– Not lipid soluble
– Received by receptors external to the cell
membrane
– Endocrine organs
• Thyroid gland
• Parathyroid gland
• Adrenal medulla
• Pituitary gland
• pancreas

6. Hormone Actions
• “Lock and Key” approach: describes the
interaction between the hormone and its
specific receptor.
– Receptors for nonsteroid hormones are located on
the cell membrane
– Receptors for steroid hormones are found in the
cell’s cytoplasm or in its nucleus

7. Non steroid/ Peptide Hormones
• Nonsteroid/ Peptide Hormones
– React with specific receptors outside the cell
– This triggers an enzyme reaction with lead to the
formation of a second messenger (c AMP).
– c AMP can produce specific intracellular functions:
• Activates cell enzymes
• Change in membrane permeability
• Promote protein synthesis
• Change in cell metabolism
• Stimulation of cell secretions

8. • Peptide hormones do not enter the cell
directly. These hormones bind to receptor
proteins in the cell membrane.
• When the hormone binds with the receptor
protein, a secondary messenger molecule
initiates the cell response.
• Because peptide hormones are water soluble,
they often produce fast responses.

9. (cytoplasm)
(nucleus)
peptide or amino
acid-derived
hormone
(first messenger)
(extracellular
fluid)
cyclic AMP-
synthesizing
enzyme
cyclic AMP
ATP
inactive
enzyme
(second messenger)
active
enzyme
reactant
product
plasma membrane
nuclear
envelope
receptor
The hormone binds to
a receptor on the plasma
membrane of a target cell
1
The activated enzymes
catalyze specific reactions
4
The second
messenger activates
other enzymes
3
Hormone–receptor binding
activates an enzyme that catalyzes
the synthesis of a second messenger,
such as cyclic AMP
2

10. Steroid Hormones
• Steroid hormones enter through the cell
membrane and bind to receptors inside of the
target cell.
• These hormones may directly stimulate
transcription of genes to make certain
proteins.
• Because steroids work by triggering gene
activity, the response is slower than peptide
hormones.

11. • Steroid Hormones
– Pass through the cell membrane
– Binds to specific receptors
– Then enters the nucleus to bind with the cells
DNA which then activates certain genes
(Direct gene activation).
– mRNA is synthesized in the nucleus and
enters the cytoplasm and promotes protein
synthesis for:
• Enzymes as catalysts
• Tissue growth and repair
• Regulate enzyme function

12. gene
plasma
membrane
ribosome
hormone receptor
steroid hormone
mRNA
(nucleus)
RNA polymerase
DNA
(cytoplasm)
new protein
(extracellular
fluid)
A steroid hormone
diffuses through the
plasma membrane
The hormone binds to a
receptor in the nucleus or to
a receptor in the cytoplasm
that carries it into the nucleus
The hormone–receptor
complex binds to DNA and
causes RNA polymerase to
bind to a nearby promoter
site for a specific gene
RNA polymerase catalyzes
the transcription of DNA into
messenger RNA (mRNA)
The mRNA leaves the
nucleus, then attaches to a
ribosome and directs the
synthesis of a specific protein
product
1
2
3
4
5
nuclear
envelope

13. Overview: The Body’s Long-Distance
Regulators
• Animal hormones are chemical signals that are
secreted into the circulatory system and
communicate regulatory messages within the
body
• Hormones reach all parts of the body, but only
target cells are equipped to respond
• Hormones convey information via the
bloodstream to target cells throughout the body

14. Control Pathways and Feedback Loops
• The endocrine system secretes hormones that
coordinate slower but longer-acting responses
including reproduction, development, energy
metabolism, growth, and behavior
• A common feature is a feedback loop
connecting the response to the initial stimulus
• Negative feedback regulates many hormonal
pathways involved in homeostasis

15. • Signaling by any of these hormones involves
three key events:
– Reception
– Signal transduction
– Response

16. Negative Feedback
• Negative feedback is the primary mechanism
through which your endocrine system
maintains homeostasis
• Secretion of a specific hormone s turned on
or off by specific physiological changes
(similar to a thermostat)
• EXAMPLE: plasma glucose levels and insulin
response

18. Number of Receptors
• Down-regulation: is the decrease of
hormone receptors which decreases the
sensitivity to that hormone
• Up-regulation: is the increase in the number
of receptors which causes the cell to be more
sensitive to a particular hormone

19. Four methods of cell-to-cell communication are found in the human body, ranging
from direct to remote communication.

20. • Binding of a hormone to its receptor initiates a
signal transduction pathway leading to
responses in the cytoplasm or a change in gene
expression
• The same hormone may have different effects
on target cells that have
– Different receptors for the hormone
– Different signal transduction pathways
– Different proteins for carrying out the response

21. Paracrine Signaling by Local
Regulators
• In paracrine signaling, non hormonal chemical
signals called local regulators elicit responses in
nearby target cells
• Types of local regulators:
– Neurotransmitters
– Cytokines and growth factors
– Prostaglandins help regulate aggregation of
platelets, an early step in formation of blood clots

22. Parts of the Endocrine System
• Hypothalamus
• Pituitary
• Pineal
• Thyroid
• Parathyroid
• Thymus
• Adrenal Glands
• Pancreas
• Testes
• Ovaries

23. Hypothalamus
• The hypothalamus is a region in the brain which controls an
immense amount of our bodily functions.
• It is located in the middle of the base of the brain and
encapsulates the ventricle portion of the third ventricle.
• The thalamus receives sensory information, relays some to the
hypothalamus.
• Hypothalamus monitors the body for temperature, pH, other
conditions.
• Hypothalamus signals pituitary gland if conditions need to be
corrected.

24. Pituitary Gland
The pituitary gland, which is located in the center of the skull, just behind the bridge of the nose, is
about the size of a pea.
It is an important link between the nervous system and the endocrine system and releases many
hormones which affect growth, sexual development, metabolism and the system of reproduction.
The "hypothalamus" is a tiny cluster of brain cells just above the pituitary gland, which transmits
messages from the body to the brain.
The pituitary gland has two distinct parts, the anterior and the posterior lobes, each of which releases
different hormones which affect bone growth and regulate activity in other glands. This gland was once
believed to be the main controlling gland of the body, but we now know that, important as it is, it is
subservient to a master gland called the hypothalamus, which is the needed link between the pituitary
gland and the brain.
This "master gland" is really a way station between the body and the brain and sorts out messages going
to and from the brain. It responds to the body through the pituitary gland, which is suspended just
below it. It sometimes replies by nerve impulses and sometimes with needed hormones. The pituitary
gland then makes hormones of its own in answer to the body's needs.

25. Pineal Gland
The pineal gland was called the "third eye" by ancient people. It was thought to have mystical
powers. The pineal does contain a complete map of the visual field of the eyes, and it plays several
significant roles in human functioning.
It is the center for the production of the hormone melatonin. It regulates daily body rhythms, most
notably the day/night cycle, prevents jet lag, is implicated in seasonal affective disorder, coordinates
fertility, and allows for deep restful sleep patterns.
The pineal gland or in its Latin and anatomical name "epiphysis cerebri", is a tiny bean-size brain
organ or "gland" which is connected to the brain and nervous systems through a complex network
of bidirectional links. the "pineal master gland" acts as a true "director of the hormonal orchestra"
in the course of growth, puberty, fertility and aging.

26. Thymus
The thymus is a gland that forms part of the immune system. It is situated in the upper part of the
chest, behind the breastbone, and is made up of two lobes that join in front of the trachea. Each
lobe is made of lymphoid tissue, consisting of tightly packed white blood cells and fat.
The thymus enlarges from about the 12th week of gestation until puberty, when it begins to shrink.
Its function is to transform lymphocytes (white blood cells developed in the bone marrow) into T-
cells (cells developed in the thymus). These cells are then transported to various lymph glands,
where they play an important part in fighting infections and disease. Swelling of lymph glands and
fever are a signal that immune cells are multiplying to fight off invaders of the body: bacteria, fungi,
viruses or parasites.

27. Thyroid Gland
The thyroid gland is shaped like a butterfly and usually weighs less than one
ounce. The thyroid cartilage covers the larynx and produces the prominence on the neck
known as the "Adam's Apple". The thyroid gland controls the rate at which the body
produces energy from nutrients. If the body does not get enough iodine, the thyroid gland
cannot produce a proper amount of hormones for this conversion process. The result can
be a goiter, an enlargement of the thyroid gland. In some parts of the world, iodine is so
scarce that most of the population have goiters.

28. Parathyroid
Glands
There are four parathyroid glands, which are located
behind the thyroid. The sole purpose of the gland is to
regulate the calcium level in our bodies within a very
narrow range in which our muscular and nervous
systems can function properly.

29. Pancreas
The Pancreas has two main functions: to produce
pancreatic endocrine hormones, which help regulate
many aspects of our metabolism, and to produce
pancreatic digestive enzymes.

30. Adrenal Gland
The adrenal glands are found on top of both of
the kidneys. The center of the adrenal
consists of the medulla which produces
epinephrine and nor epinephrine.

31. Testes
The scrotum is a sac that hangs under the penis and holds the testes. It is
divided internally into two halves by a membrane; each half containing a testis. It
has an outer layer of thin, wrinkled skin over a layer of tissue which contains
muscle. The testicle lies inside the scrotum and produces as many as 12 trillion
sperm in a male's lifetime, about 400 million of which are ejaculated in one average
intercourse. Each sperm takes about seventy-two days to mature and its maturity is
overseen by a complex interaction of hormones. The scrotum has a built-in
thermostat, which keeps the sperm at the correct temperature. It may be surprising
that the testicles should lie in such a vulnerable place, outside the body, but it is too
hot inside. The sperm production needs a temperature which is three to five
degrees below body temperature. If it becomes too cool on the outside, the scrotum
will contract to bring the testes closer the body for warmth.

32. Ovaries
The ovaries produce a female hormone,
called estrogen, and store female sex
cells, or “ova.”

33. Endocrine Hormones
Gland Hormones Functions
Thyroid Thyroxine Regulates metabolism
Calcitonin Inhibits release of calcium from the bones
Parathyroid's Parathyroid hormone Stimulates the release of calcium from the bones.
Islet cells (in the
pancreas)
Insulin Decreases blood sugar by promoting uptake of glucose by cells.
Glucagon Increases blood sugar by stimulating breakdown of glycogen in the liver.
Testes Testosterone Regulates sperm cell production and secondary sex characteristics.
Ovaries Estrogen Stimulates egg maturation, controls secondary sex characteristics.
Progesterone Prepares the uterus to receive a fertilized egg.
Adrenal cortex Epinephrine Stimulates “fight or flight” response.
Adrenal
medulla
Glucocorticoids Part of stress response, increase blood glucose levels and decrease immune
response.
Aldosterone Regulates sodium content in the blood.
Testosterone (in both
sexes)
Adult body form (greater muscle mass), libido.
Pineal gland Melatonin Sleep cycles, reproductive cycles in many mammals.

34. • The hypothalamus and
pituitary integrate many
functions of the vertebrate
endocrine system
• The hypothalamus and the
pituitary gland control
much of the endocrine
system
• Tropic hormones, hormones
that regulate endocrine
organs
• Tropic hormones are
secreted into the blood and
transported to the anterior
pituitary
Hypothalamus & Pituitary

35. HYPOTHALAMUS
Secreted hormone Abbreviation Produced by
Thyrotropin - releasing hormone TRH Parvocellular neurosecretory neurons
Dopamine
(Prolactin - inhibiting hormone)
DA or PIH Dopamine neurons of the arcuate nucleus
Growth hormone-releasing hormone GHRH Neuroendocrine neurons of the Arcuate nucleus
Somatostatin
(growth hormone-inhibiting hormone)
SS, GHIH, or SRIF Neuroendocrine cells of the Periventricular nucleus
Gonadotropin - releasing hormone GnRH or LHRH Neuroendocrine cells of the Preoptic area
Corticotropin - releasing hormone CRH or CRF
Parvocellular neurosecretory neurons of
the Periventricular Nucleus
Oxytocin OT or OXT
Magnocellular neurosecretory neurons of
the Supraoptic nucleus and Para ventricular nucleus
Vasopressin
(anti diuretic hormone)
ADH or AVP or VP
Parvocellular neurosecretory neurons, Magnocellular
neurosecretory neurons of the Paraventricular nucleus
and Supraoptic nucleus

37. Pituitary

38. The Structure and Function of the
Pituitary Gland
Hypophysis: has two parts
Anterior = adenohypophysis
– Activity directed by the hypothalamus
– Secretes six tropic hormones
– Regulates the adrenal gland
Posterior = neurohypophysis
– Receives hormones secreted by the hypothalamus and
then stores them for subsequent release

40. • The pituitary is the “master gland” that signals other glands
to produce their hormones when needed.
• The anterior lobe of the pituitary receives signals from the
hypothalamus, and responds by sending out the
appropriate hormone to other endocrine glands.
• The posterior pituitary receives oxytocin or antidiuretic
hormone (ADH) from the hypothalamus, relays them to the
body as necessary.
• Located on the underneath side of the brain.
• Small pea-sized gland is divided into an anterior lobe and a
posterior lobe.
• Both lobes are controlled by the hypothalamus in the brain

41. The Anterior Pituitary
Secretes seven hormones
 Growth hormone (GH), also
called somatotropin, promotes
growth of the body by
stimulating cells to rapidly
increase in size and divide.
 Thyroid-stimulating hormone
(TSH) regulates the function of
the thyroid gland.
 Adrenocorticotropin hormone
(ACTH) regulates the function of
the adrenal cortex.
 Prolactin (PRL) stimulates milk
production in the breast
following pregnancy and birth.
 Follicle-stimulating hormone
(FSH) responsible for the
development of ova in ovaries
and sperm in testes; also
stimulates the ovary to secrete
estrogen.
 Luteinizing hormone (LH)
stimulates secretion of sex
hormones in both males and
females and plays a role in
releasing ova in females.
 Melanocyte-stimulating hormone
(MSH) stimulates melanocytes to
produce more melanin, darkening
the skin.

42. The Posterior Pituitary
Secretes two hormones
Antidiuretic hormone (ADH), also called
vasopressin, promotes water reabsorption by
the kidney tubules.
Oxytocin stimulates uterine contractions
during labor and delivery, and after birth the
release of milk from the mammary glands.

43. Neurosecretory cells
of the hypothalamus
Endocrine cells of the
anterior pituitary
Portal vessels
Pituitary hormones
(blue dots)
Pain receptors
in the brain
Endorphin Growth hormone
BonesLiver
MSH
Melanocytes
Prolactin
Mammary
glands
ACTH
Adrenal
cortex
TSH
ThyroidTestes or
ovaries
FSH and LH
TARGET
HORMONE
Hypothalamic
releasing
hormones
(red dots)
Tropic Effects Only
FSH, follicle-stimulating hormone
LH, luteinizing hormone
TSH, thyroid-stimulating hormone
ACTH, adrenocorticotropic hormone
Nontropic Effects Only
Prolactin
MSH, melanocyte-stimulating hormone
Endorphin
Nontropic and Tropic Effects
Growth hormone

44. Pituitary Hormones
Pituitary Hormone Functions
Follicle-stimulating
hormone
Stimulates egg maturation in the ovary and release of sex hormones.
Luteinizing hormone Stimulates maturation of egg and of the corpus luteum surrounding the
egg, which affects female sex hormones and the menstrual cycle.
Thyroid-stimulating
hormone
Stimulates the thyroid to release thyroxin.
Adreno corticotropic
hormone
Causes the adrenal gland to release cortisol.
Melanocyte-stimulating
hormone
Stimulates synthesis of skin pigments.
Growth hormone Stimulates growth during infancy and puberty.
Antidiuretic hormone Signals the kidney to conserve more water.
Oxytocin Affects childbirth, lactation, and some behaviors.

45. Diseases of the Anterior Pituitary
Hyperpituitarism
– Giantism
– Acromegaly
Hypopituitarism
– Absence of tropic hormones
– Pituitary dwarf

46. Hyperpituitarism – Anterior Pituitary
Giantism: hypersecretion of growth hormone
prior to puberty
– Retards normal closure of bone seal
– Decreased sexual development
– Mental development normal or retarded
Etiology: adenoma
Treatment: removal of adenoma or radiation
to reduce the size of the tumor

47. Hyperpituitarism – Anterior Pituitary
Acromegaly
– Hypersecretion of growth hormone after puberty
– Long bones no longer grow
– Excessive growth of soft tissue
– Enlargement of the face with coarse facial features
– Protrusion of the tongue
– Curvature of the spine
Etiology: adenoma
Treatment: surgical removal, radiation, supportive
treatments

48. Hypopituitarism – Pituitary
Etiology
– Damage to the anterior lobe of the pituitary gland
– Fracture at the base of the skull, tumor, ischemia
– Inadequate secretion of hormones
Mild or severe
Panhypopituitarism: entire anterior lobe is destroyed
– No pituitary hormones are secreted
Pituitary dwarf

49. Abnormalities – Absence of Tropic
Hormones
Lack of thyroid hormone: lethargy
Lack of ACTH: salt imbalance, improper metabolism
of nutrients
– ACTH essential for life
Absence of gonadotropic hormones
– Depresses sexual function
– Before puberty – impaired sexual development
– After puberty
– Cessation of menstruation
– Aspermia in males

50. Pituitary Dwarf
May occur in children
– Inadequate growth hormone
– Mentally bright but small and underdeveloped
sexually
– All growth processes are retarded; teeth are late
in erupting.
– Replacement therapy with injections of growth
hormone is currently used to treat children with
pituitary dwarfism.

51. Hypopituitarism – Treatment
Hormonal supplements
– Thyroxine, cortisone, growth hormone, and sex
hormones can compensate for the dysfunctional
glands.

52. Function of the Posterior
Pituitary Gland
Posterior pituitary, or neurohypophysis
– Secretes oxytocin, and vasopressin (ADH)
Oxytocin: causes smooth muscle contraction
of the uterine muscles
ADH: prevents excessive water loss through
the kidneys

53. Hyposecretion of the
Posterior Pituitary Gland
Diabetes insipidus
– Deficiency of ADH
– In the absence of ADH, water is not reabsorbed by the
kidney and is lost in the urine. Extreme thirst or polydipsia
and excessive production of diluted urine or polyuria
results.
A central diabetes insipidus can result from
inadequate production of ADH by the hypothalamus
or failure of the pituitary gland to release ADH into
the bloodstream.

54. Hyposecretion of the
Posterior Pituitary Gland (continued)
Nephrogenic diabetes insipidus: ADH levels are
normal
– Involves a defect in the kidney; the kidney fails to
concentrate urine in response to the instructions of ADH.
Excessive water loss can quickly lead to dehydration.
Treatment: the underlying cause of diabetes
insipidus must be corrected. Modified forms of ADH
may be taken orally, by injection, or by nasal spray to
maintain normal urine output.

55. The Thyroid Gland
Resembles a butterfly in
shape; has right and left
lobes
Located on either side of
the trachea and larynx
Thyroid cartilage, or
Adam’s apple, is located
just below the thyroid
gland
Produces the
hormones thyroxine,
also known as T4, and
triiodothyronine, which
is called T3
These are produced in
the thyroid gland from
the mineral iodine.

56. Structure and Function of the
Thyroid Gland
Regulates metabolic rate
Secretes thyroxine, governs cellular oxygen
consumption, and thus, energy and heat production;
the more oxygen that is used, the more calories are
metabolized (“burned up”). Thyroxine assures that
enough body heat is produced to maintain normal
temperature even in a cold environment.

57. Structure and Function of the
Thyroid Gland (continued)
Structure of the thyroid gland
– Located in the neck region, one lobe on either side of the
trachea; a connecting strip, or isthmus, anterior to the
trachea, connects the two lobes
– Just below the Adam’s apple, the protrusion formed by
part of the larynx
– The thyroid gland consists of follicles, microscopic sacs.
Within these protein-containing follicles, the thyroid
hormones, thyroxine and triiodothyronine, are made. Thin-
walled capillaries run between the follicles in a position
ideal to receive the thyroid hormones.

58. The Thyroid Gland
Also secretes calcitonin in response to
hypercalcemia (too high blood calcium level).
Its action is the opposite of parathyroid
hormone and stimulates the increased
deposition of calcium into bone, thereby
lowering blood levels of calcium.

59. The thyroid gland.

60. Function of the Thyroid Gland
The thyroid gland synthesizes, stores, and releases
thyroid hormones, which contain iodine.
– Most of the iodide ions of the body are taken into the
thyroid gland by a mechanism called the iodide trap.
– Iodine combines with an amino acid; two of these groups
join, and the thyroid hormones are formed.
The hormones are stored until needed and then
released into the blood capillaries. In the blood, the
thyroid hormones combine with plasma proteins.

61. Effects of Thyroid Hormones
Thyroxine: secreted in the largest quantity.
– Thyroxine stimulates cellular metabolism by increasing the
rate of oxygen use with subsequent energy and heat
production.
– Nutrients are converted to energy in the presence of
oxygen and the waste products of metabolism, including
carbon dioxide, are formed.
– As cellular metabolism increases, respiration and cardiac
output increases.
– Heat is produced through cellular metabolism
– Increases secretion of digestive enzymes and movement
through the digestive system.

62. Figure 13-9: Effects of thyroxine.

63. Control of Circulating
Thyroxine Level
Anterior pituitary gland stimulates the thyroid by
releasing thyroid-stimulating hormone, TSH.
The thyroid, in turn, releases thyroxine, which
circulates in the blood to all cells and tissues. When
the level of circulating thyroxine is high, the anterior
pituitary is inhibited and stops releasing TSH
(negative feedback mechanism).
– An adequate level of thyroxine prevents further synthesis
of the hormone. When the level of thyroxine falls, the
anterior pituitary is released from the inhibition, and once
again sends out TSH. This feedback mechanism is shown in
Figure 13.10.

64. Figure 13-10: Control of thyroxine secretion through negative
feedback.

65. Negative Feedback Failure
Constitutes one basis for a thyroid disease
The thyroid gland may be perfectly healthy, but if the
body’s iodine supply is inadequate, the gland cannot
produce thyroxine.
It is possible for the thyroid gland to be over-
stimulated or understimulated by the anterior
pituitary.
The thyroid gland itself may be diseased, with a
resultant hyperactivity or hypoactivity. These are
some of the conditions that will be discussed.

66. Goiter
An enlargement of the thyroid gland.
May be caused by hypoactivity or hyperactivity of the
thyroid or a deficiency in iodine needed to synthesize
thyroid hormones
Types: diffuse colloidal goiter or nontoxic goiter
Endemic goiter because it is common in a particular
geographic region
– The usual cause of an endemic goiter is insufficient iodine
in the diet.

67. Goiter (continued)
 Etiology of goiter
– Continuous secretion of thyroid-stimulating hormone causes the
thyroid gland to enlarge as a compensatory mechanism.
– An enlargement of the neck is generally the only symptom. Usually
enough thyroxine is produced to prevent the symptoms of
hypothyroidism.
 Treatment: iodides: the use of iodized salt prevents endemic goiter
formation. If the goiter is very advanced, surgery may be necessary. A very
large goiter puts pressure on the esophagus, causing difficulty in
swallowing, or presses on the trachea, causing a cough or choking
sensation.
 Other factors can cause a simple diffuse colloidal goiter; for example, a
defect in the thyroxine-synthesizing mechanism. A young girl entering
adolescence may develop this type of goiter because of an increased need
for thyroxine at this time.

68. Graves’ Disease
 Goiter develops; the entire gland hypertrophies, and there are
no nodules
 Severe hyperthyroidism
 More common in women than in men and usually affects
young women
 Characteristic facial expression is strained and tense, and
there is a stare in the eyes. The eyeballs protrude outward, a
condition called exophthalmos. This is caused by edema in the
tissue behind the eyes. The bulging of the eyes can be so
severe that the eyelids do not close, and the swelling
sometimes damages the optic nerve. This symptom generally
persists even when the hyperthyroidism is corrected.

69. Graves’ Disease (continued)
 The person has a tremendous appetite but loses weight to the
point of appearing emaciated, as calories are burned up at a
rapid rate. Thyroxine speeds the passage of food through the
digestive tract. There is no time for the normal reabsorption
of water from the large intestine, so diarrhea frequently
accompanies the disease.
 Tachycardia, rapid pulse rate, and palpitation are also among
the symptoms. The person is extremely nervous, excitable,
and is always tired but has difficulty sleeping because of the
hyperactivity of the body. The high metabolic rate causes
excessive heat production, which results in profuse
perspiration. The skin is always moist, and an insatiable thirst
follows the loss of water.

70. Signs and Symptoms of
Graves’ Disease
 Exophthalmos
 Profuse perspiration
 Hand tremors
 Goiter
 Weight loss
 Nervousness/excitability
 Rapid pulse
 Polydipsia
 Diarrhea
 Tachypnea
 Insomnia
 Graves’ disease is an autoimmune condition in which antibodies to a thyroid antigen
stimulate hyperactivity of the thyroid gland. This causes the thyroid to produce too much
thyroxine.
 Graves’ disease can sometimes be treated with medication that inhibits the synthesis of
thyroxine, or by administration of radioactive iodine, which destroys the thyroid gland.
Removal of the thyroid gland, however, may be necessary. If the gland is removed, hormonal
supplements must be given. Partial removal of the thyroid gland allows the remaining portion
to secrete hormones.

71. Cretinism
 Congenital thyroid deficiency in which thyroxine is not synthesized;
thyroxine is essential to both physical and mental development.
 Mental retardation and an abnormal, dwarfed stature
 Etiology: error in fetal development if the thyroid gland fails to form or is
nonfunctional, or may be endemic where the mother suffers from an
inadequate iodine supply
 The cretin is a dwarf with a stocky stature and a characteristically
protruding abdomen. The sexual organs do not develop, and the face of
the cretin is typically misshapen: a broad, sunken nose, small eyes set far
apart, puffy eyelids, and a short forehead. A thick tongue protrudes from a
wide-open mouth, and the face is expressionless.
 The earlier this condition is diagnosed and treated with thyroxine, the
more optimistic is the prognosis. Lifelong hormonal therapy will be
required.

72. 72
The Parathyroid Glands
• Most people have four
• On posterior surface of
thyroid gland
(sometimes embedded)

73. 73
Parathyroids
(two types of cells)
• Rare chief cells
• Abundant oxyphil cells
(unknown function)
• Chief cells produce PTH
– Parathyroid hormone, or
parathormone
– A small protein hormone

74. 74
Function of PTH
(parathyroid hormone or “parathormone”)
• Increases blood Ca++ (calcium) concentration
when it gets too low
• Mechanism of raising blood calcium
1. Stimulates osteoclasts to release more Ca++ from bone
2. Decreases secretion of Ca++ by kidney
3. Activates Vitamin D, which stimulates the uptake of Ca++
from the intestine
• Unwitting removal during thyroidectomy was lethal
• Has opposite effect on calcium as calcitonin
(which lowers Ca++ levels)

75. 75
Adrenal (suprarenal) glands
(“suprarenal” means on top of the kidney)
• Each is really two endocrine glands
– Adrenal cortex (outer)
– Adrenal medulla (inner)
• Unrelated chemicals but all help with extreme situations

76. 76
Adrenal Gland
• Adrenal cortex
– Secretes lipid-based steroid hormones, called
“corticosteroids” – “cortico” as in “cortex”
• MINERALOCORTICOIDS
– Aldosterone is the main one
• GLUCOCORTICOIDS
– Cortisol (hydrocortisone) is the main one
• Adrenal medulla
– Secretes epinephrine and norepinephrine

77. 77
Aldosterone, the main mineralocorticoid
• Secreted by adrenal cortex in response to a
decline in either blood volume or blood
pressure (e.g. severe hemorrhage)
– Is terminal hormone in renin-angiotensin
mechanism
• Prompts distal and collecting tubules in kidney
to reabsorb more sodium
– Water passively follows
– Blood volume thus increases

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Cortisol, the most important glucocorticoid
(Glucocorticoid receptors are found in the cells of most vertebrate tissues)
• It is essential for life
• Helps the body deal with stressful situations within
minutes
– Physical: trauma, surgery, exercise
– Psychological: anxiety, depression, crowding
– Physiological: fasting, hypoglycemia, fever, infection
• Regulates or supports a variety of important
cardiovascular, metabolic, immunologic, and
homeostatic functions including water balance
People with adrenal insufficiency: these stresses can cause hypotension, shock and death:
must give glucocorticoids, eg for surgery or if have infection, etc.

79. 79
Cortisol, continued
• Keeps blood glucose levels high enough to support
brain’s activity
– Forces other body cells to switch to fats and amino acids as
energy sources
• Catabolic: break down protein
• Redirects circulating lymphocytes to lymphoid and
peripheral tissues where pathogens usually are
• In large quantities, depresses immune and inflammatory
response
– Used therapeutically
– Responsible for some of its side effects

80. 80
Hormonal stimulation of glucocorticoids
HPA axis (hypothalamic/pituitary/adrenal axis)
• With stress, hypothalamus sends CRH to anterior
pituitary (adenohypophysis)
• Pituitary secretes ACTH
• ACTH goes to adrenal cortex where stimulates
glucocorticoid secretion
– Sympathetic nervous system can also stimulate it
• Adrenal cortex also secretes DHEA
(dehydroepiandrosterone)
– Converted in peripheral tissues to testosterone and
estrogen (also steroid hormones)
– Unclear function in relation to stress

81. 81
• Steroid-secreting cells
have abundant smooth
ER
– As opposed to rough ER in
protein-secreting cells
• Steroids directly diffuse
across plasma membrane
– Not exocytosis
• Abundant lipid droplets
– Raw material from which
steroids made
In general:

82. 82
Adrenal medulla
• Part of autonomic
nervous system
• Spherical chromaffin
cells are modified
postganglionic
sympathetic neurons
– Secrete epinephrine and
norepinephrine
– Amine hormones
– Fight, flight, fright
• Vesicles store the
hormones

83. 83
The Pineal Gland
• At the end of a short stalk on the roof of the
diencephalon
• Pinealocytes with dense calcium particles
• Can be seen on x-ray (because of Ca++)
• Melatonin helps regulate the circadium
rhythm
– The biological clock of the diurnal (night/day)
rhythm
– Complicated feedback via retina’s visual input

84. 84
The Pancreas
Exocrine and endocrine cells
• Acinar cells (forming most of the pancreas)
– Exocrine function
– Secrete digestive enzymes
• Islet cells (of Langerhans)
– Endocrine function

85. 85
Pancreatic islet
endocrine cells
Alpha cells: secrete glucagon
raises blood sugar
mostly in periphery
Beta cells: secrete insulin
lowers blood sugar
central part (are more abundant)
Also rare Delta cells:secrete somatostatin
inhibits glucagon

86. 86
The Gonads (testes and ovaries)
main source of the steroid sex hormones
• Testes
– Interstitial cells secrete androgens
– Primary androgen is testosterone
• Maintains secondary sex characteristics
• Helps promote sperm formation
• Ovaries
– Androgens secreted by thecal folliculi
• Directly converted to estrogens by follicular granulosa cells
– Granulosa cells also produce progesterone
– Corpus luteum also secretes estrogen and progesterone

87. 87
Endocrine cells in various organs
• The heart: atrial natriuretic peptide (ANP)
– Stimulates kidney to secrete more salt
– Thereby decreases excess blood volume, high BP and
high blood sodium concentration
• GI tract & derivatives: Diffuse neuroendocrine
system (DNES)

88. 88
Endocrine cells in various organs continued
• The heart: atrial natriuretic peptide (ANP)
– Stimulates kidney to secrete more salt
– Thereby decreases excess blood volume, high BP and high blood sodium
concentration
• GI tract & derivatives: Diffuse neuroendocrine system (DNES)
• The placenta secretes steroid and protein hormones
– Estrogens, progesterone
– CRH
– HCG
• The kidneys
– Juxtaglomerular cells secrete renin
• Renin indirectly signals adrenal cortex to secrete aldosterone
– Erythropoietin: signals bone marrow to increase RBC production
• The skin
– Modified cholesterol with uv exposure becomes Vitamin D precursor
– Vitamin D necessary for calcium metabolism: signals intestine to absorb CA++