1. Chapter 18
The Endocrine System

2. Introduction
The nervous and endocrine systems coordinate all of the body systems
The nervous system does so through the action of neurons, and the neurotransmitters they secrete
The endocrine
system uses
hormones produced
by endocrine structures
to produce their
effects

3. Types of Hormones
Hormones are simply mediator molecules that have effects on cells in the local environment, or in a distant part of the body
Some hormones, called autocrine hormones are local hormones that are secreted, and bind to the same cell. We will see examples of
autocrine stimulation
when we study the
immune system in
chapter 22

4. Types of Hormones Hormones as mediator molecules …
Paracrine hormones are local hormones that are secreted into interstitial fluid and act on nearby cells

5. Types of Hormones Hormones as mediator molecules …
Endocrine hormones are secreted into interstitial fluid and then absorbed into the bloodstream to be carried systemically
to any cell that
displays the
appropriate type
of receptor

6. Solubility of Hormones
Hormones can be divided into two broad chemical classes. This chemical classification is useful because the two classes exert their effects differently
Lipid soluble hormones bind to receptors in the cytoplasm or nucleus of the cell
Water soluble hormones bind to receptors on the surface of the cell

7. Solubility of Hormones
Lipid soluble hormones consist of steroid hormones, thyroid hormones, and the gas nitric oxide
Steroid hormones are derived from cholesterol
Thyroid hormones (T3 and T4) are synthesized by attaching iodine to the amino acid tyrosine
The gas nitric oxide (NO) is both a hormone and a neurotransmitter. Its synthesis is catalyzed by the enzyme nitric oxide synthase

8. Solubility of Hormones
Lipid soluble hormones require a carrier protein for transport in the watery environment of the blood
Once they arrive at their
destination, however, they
are able to freely pass
through the plasma
membrane to bind to
receptors located in the cytoplasm
or the nucleus of the target cell
When a lipid soluble hormone enters a cell and binds with intracellular receptors (in the cytoplasm or the nucleus), the activated receptor–hormone complex alters gene expression: It turns specific genes of the nuclear DNA on or off.

9. Lipid-Soluble Hormone Action Lipid-soluble hormone diffuses into cell1
Lipid-soluble
hormone
diffuses into cell
Blood capillary
Activated
receptor-hormone
complex alters
gene expression
Nucleus
Receptor
mRNA
Newly formed
mRNA directs
synthesis of
specific proteins
on ribosomes
DNA
Cytosol
Target cell
New proteins alter
cell's activity
Transport
protein
Free hormone
Ribosome
New 2 3 4 1
Lipid-soluble
hormone
diffuses into cell
Blood capillary
Activated
receptor-hormone
complex alters
gene expression
Nucleus
Receptor
mRNA
Newly formed
mRNA directs
synthesis of
specific proteins
on ribosomes
DNA
Cytosol
Target cell
Transport
protein
Free hormone
Ribosome 2 3 1
Lipid-soluble
hormone
diffuses into cell
Blood capillary
Activated
receptor-hormone
complex alters
gene expression
Nucleus
Receptor
mRNA
DNA
Cytosol
Target cell
Transport
protein
Free hormone 2 1
Lipid-soluble
hormone
diffuses into cell
Blood capillary
Target cell
Transport
protein
Free hormone
Lipid-Soluble
Hormone
Action

10. Solubility of Hormones
Water soluble hormones include peptide and protein hormones (and others with an amine group), and a group of local hormones derived from the arachidonic acid on our cell membranes called eicosanoids
Peptide hormones and protein hormones are amino acid polymers
The two major types of eicosanoids are prostaglandins and leukotrienes – both play a role in mediating the inflammatory response

11. Solubility of Hormones
Water soluble hormones are easy to transport in the watery blood. The plasma membrane of target cells, however, is impermeable to them
Water soluble hormones exert their effects by binding to receptors exposed to the interstitial fluid on the surface of target cells
the hormone binding to its receptor acts as the first messenger in a cascade of signal transduction

12. Solubility of Hormones
The first messenger (the hormone) then causes production of a second messenger inside the cell, where specific hormone-stimulated responses take place
One common second messenger is
cyclic AMP (cAMP). Neuro-
transmitters, neuropeptides, and
several sensory transduction
mechanisms (vision) also act via
second-messenger systems
Many hormones exert at least some of their physiological effects through the increased synthesis of cAMP. Examples include antidiuretic hormone (ADH), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), glucagon, epinephrine, and hypothalamic releasing hormones.

13. Water-Soluble Hormone Action 1 2 4 3 5 1 2 6 4 3 5 1 1 2 4 3 1 2 3 1 2
Receptor
cAMP serves as a
second messenger
to activate protein
kinases
G protein
Protein kinases
cAMP
Activated
protein
Protein—
Second messenger
Activated adenylate
cyclase converts
ATP to cAMP
Activated protein
phosphorylate
cellular proteins
Millions of phosphorylated
proteins cause reactions that
produce physiological responses
Blood capillary
Binding of hormone (first messenger)
to its receptor activates G protein,
which activates adenylate cyclase
Adenylate cyclase
Target cell P
ADP
Protein
ATP 1 2 4 3 5
Water-soluble
hormone
Receptor
cAMP serves as a
second messenger
to activate protein
kinases
G protein
Protein kinases
cAMP
Activated
protein
Protein—
Second messenger
Phosphodiesterase
inactivates cAMP
Activated adenylate
cyclase converts
ATP to cAMP
Activated protein
phosphorylate
cellular proteins
Millions of phosphorylated
proteins cause reactions that
produce physiological responses
Blood capillary
Binding of hormone (first messenger)
to its receptor activates G protein,
which activates adenylate cyclase
Adenylate cyclase
Target cell P
ADP
Protein
ATP 1 2 6 4 3 5
Water-soluble
hormone
Receptor
G protein
Blood capillary
Binding of hormone (first messenger)
to its receptor activates G protein,
which activates adenylate cyclase
Adenylate cyclase
Target cell 1
Water-soluble
hormone
Receptor
cAMP serves as a
second messenger
to activate protein
kinases
G protein
Protein kinases
cAMP
Activated
protein
Second messenger
Activated adenylate
cyclase converts
ATP to cAMP
Activated protein
phosphorylate
cellular proteins
Blood capillary
Binding of hormone (first messenger)
to its receptor activates G protein,
which activates adenylate cyclase
Adenylate cyclase
Target cell
ATP 1 2 4 3
Protein— P
ADP
Protein
Water-soluble
hormone
Receptor
cAMP serves as a
second messenger
to activate protein
kinases
G protein
Protein kinases
cAMP
Second messenger
Activated adenylate
cyclase converts
ATP to cAMP
Blood capillary
Binding of hormone (first messenger)
to its receptor activates G protein,
which activates adenylate cyclase
Adenylate cyclase
Target cell
ATP 1 2 3
Activated
protein
Water-soluble
hormone
Receptor
G protein
cAMP
Second messenger
Activated adenylate
cyclase converts
ATP to cAMP
Blood capillary
Binding of hormone (first messenger)
to its receptor activates G protein,
which activates adenylate cyclase
Adenylate cyclase
Target cell
ATP 1 2
Water-Soluble
Hormone
Action

14. Effects of Hormones
Prostaglandins (PGs) and leukotrienes are eicosanoid hormones with local control. They are synthesized from membrane lipids and have widespread effects
PG’s mediate pain, platelet aggregation, fever, and inflammation. They regulate smooth muscle contraction, gastric acid secretion, and airway size
aspirin is a drug that works by inhibiting an enzyme necessary for synthesis of certain PGs: the ones that facilitate pain and the inflammatory response

15. Effects of Hormones
Endocrine hormones control a variety of physiological processes. Among other things, they:
Balance the composition and volume of body fluids
Regulate metabolism and energy production
Direct the rate and timing of growth and development
Exert emergency control during physical and mental stress (trauma, starvation, hemorrhage)
Oversee reproductive mechanisms

16. EFFECTS OF HORMONES (Interactions Animation)
Introduction to endocrine hormones: Regulation, secretion and concentration
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17. Endocrine System Glands
Glands that secrete endocrine hormones into the bloodstream are called endocrine glands
They are one of two major types of glands in the body, the other being exocrine glands (which
secrete their products into ducts )
In this chapter we will focus our
study on the endocrine glands
and the widespread effects of
endocrine hormones

18. Control of Hormones
When stimulated, an endocrine gland will release its hormone in frequent bursts, increasing the concentration of the hormone in the blood
Hormone secretion is regulated by signals from the nervous system, chemical changes in the blood, and other hormones
Most hormonal regulatory systems work via negative feedback, but a few operate via positive feedback

19. Control of Hormones
In a negative feedback system the hormone output reverses a particular stimulus. For example:
Blood Ca2+ level is controlled by the parathyroid hormone (PTH). If blood Ca2+ is low, there is a stimulus for the parathyroid glands to release more PTH. PTH then exerts its effects in the body until the Ca2+ level returns to normal. If the level gets too high the body will cease PTH production and secrete calcitonin lower the Ca2+ levels.

20. Control of Hormones
This example shows how PTH and calcitonin have negative feedback influence on one another

21. Control of Hormones
In a positive feedback system the hormone output reinforces and encourages the stimulus. For example, during childbirth, the hormone oxytocin stimulates contractions of the uterus, and uterine contractions in turn stimulate more oxytocin release, a positive feedback effect

22. CONTROL OF HORMONES (Interactions Animation)
Hormones Summary
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23. The Endocrine System
The endocrine system consists of the pituitary, thyroid, parathyroid, adrenal and pineal glands
Some of the most important glands of the endocrine system are not exclusively endocrine glands: The hypothalamus, thymus, pancreas, ovaries, and testes are paramount;
the kidneys, stomach, liver,
small intestine, skin, heart,
and placenta also contribute

24. The Endocrine System

25. The Hypothalamus
The hypothalamus is the major link between the nervous and endocrine systems
It receives input from several regions in the brain including the
thalamus, the
RAS, and
the limbic
system

26. The Pituitary Gland
The hypothalamus mainly controls the pituitary gland, which is also called the hypophysis
The pituitary hangs down from the hypothalamus
on a stalk called the infundibulum
The gland is divided into an anterior adenohypophysis and a posterior neurohypophysis - the anterior pituitary accounts
for about 75% of the total
weight of the gland

27. The Adenohypophysis
The anterior pituitary (adenohypophysis) is anatomically and functionally connected to the hypothalamus by blood vessels that form a portal system called the hypophyseal portal system
In a portal system, blood flows from one capillary network into a portal vein, and then into a second capillary network before returning to the heart
The name of the portal system indicates the location of the second capillary network

28. The Adenohypophysis Specialized neurosecretory cells in the
hypothalamus secrete releasing hormones
into the hypophyseal portal system
that supplies blood to the
anterior pituitary
gland

29. The Adenohypophysis
The second capillary system of the hypophyseal portal system delivers the hypothalamic releasing hormones to the anterior pituitary
5 types of anterior pituitary cells secrete seven hormones

30. Anterior Pituitary Hormones
Hypothalamus Hormone
Hormone released from Adenohypophysis
Major Function/ Target
Growth hormone releasing hormone (GHRH)
Human Growth Hormone (hGH)
Also called somatostatin, stimulates secretion of insulin-like growth factors (IGFs) that promote growth
Thyrotropin releasing hormone (TRH)
Thyroid Stimulating Hormone (TSH)
Stimulates synthesis and secretion of thyroid hormones by the thyroid gland
Prolactin releasing hormone
(PRH)
Prolactin (PRL)
Stimulates breast growth, and development of the mammary glands

31. Anterior Pituitary Hormones
Hypothalamus Hormone
Hormone released from Adenohypophysis
Major Function/ Target
Gonadotropic releasing hormone (GnRH)
Follicle Stimulating hormone (FSH)
Ovaries initiate development of oocytes; testes initiate development of spermatozoa
Luteinizing hormone (LH)
Ovaries stimulate ovulation; testes stimulate testosterone production

32. Anterior Pituitary Hormones
Hypothalamus Hormone
Hormone released from Adenohypophysis
Major Function/ Target
Corticotropin releasing hormone (CRH)
Adrenocorticotropic Hormone (ACTH)
Stimulates release of mineralocorticoid, glucocorticoid, and androgen hormones from the adrenal cortex
Melanocyte Stimulating hormone (MSH)
Stimulate the production and release of melanin by melanocytes in skin and hair. MSH signals to the brain have effects on appetite and sexual arousal

33. ANTERIOR PITUITARY HORMONES (Interactions Animation)
hGH Growth and Development
hGH Stimulating Glycogenolysis
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34. ANTERIOR PITUITARY HORMONES (Interactions Animation)
ACTH and Cortisol
Cortisol
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35. ANTERIOR PITUITARY HORMONES (Interactions Animation)
TRH and TSH
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36. Anterior Pituitary Hormones
Tropic hormones are hormones produced and secreted by the anterior pituitary that target other endocrine glands
All hormones in the previous lists target other endocrine glands (are trophic hormones) except hGH, Prolactin, and MSH, which directly target the end organs

37. The neurohypophysis
The posterior pituitary (neurohypophysis) is embryologically derived from and anatomically connected to the hypothalamus – it releases, but does not synthesize any hormones
When stimulated, neurosecretory
cells in the hypothalamus
release oxytocin and
ADH from their axon
terminals located in
the posterior pituitary

38. The neurohypophysis
Oxytocin targets smooth muscle in the uterus and breasts. In the uterus, oxytocin stimulates uterine contractions, and in response to the sucking from an infant, oxytocin stimulates “milk letdown” in the breasts
ADH targets the collecting ducts in the kidney and sweat glands in the skin to minimize water loss. It also directly causes arterioles to constrict thereby increasing blood pressure

39. The neurohypophysis
This graphic demonstrates the regulation of ADH secretion

40. POSTERIOR PITUITARY HORMONES
Antidiuretic Hormone Animation
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41. Pituitary Gland Disorders
Acromegaly occurs as a result of excess HGH during adulthood. This disease is marked by enlargement and elongation of the bones of the face, jaw, cheeks, and hands (the long bones of
the extremities are
unaffected because the
growth plates have
already closed)

42. Pituitary Gland Disorders
Diabetes Insipidus (DI) is very different from the disease called sugar diabetes (diabetes mellitus)
DI is caused by the insufficient release of ADH from the neurohypophysis. Without ADH acting on the collecting ducts in the kidneys, the normal urine output of 1–1.5 liters per day increases to over 2.5 liters per day and dehydration and hypernatremia results

43. The Thyroid Gland
The butterfly-shaped thyroid gland is located inferior to the larynx and anterior to the trachea. It has two laterally placed lobes separated by a bridge-like isthmus

44. The Thyroid Gland
Most of the thyroid gland is composed of spherical groups of follicular cells called thyroid follicles
The follicles store
a 100-day supply
of its two hormones
in an inactive
gel-like substance
called TGB (for
thyroglobulin)

45. Thyroid Hormones
TGB is a large glycoprotein made from the oxidation and iodination of molecules of the amino acid. tyrosine
The two hormones released
from TGB are:
thyroxine or T4
(tetraiodothyronine)
and T3
(triiodothyronine)

46. Thyroid Hormones
In the blood, T3 and T4 are bound to pre-albumins, albumin, and a specific carrier protein called thyroid-binding globulin (TBG)
Most T4 released from the thyroid is converted “peripherally” (by enzymes in the blood) into T3 , which is a more active hormone
Together with hGH and insulin, thyroid hormones accelerate body growth, particularly the growth of the nervous and skeletal systems

47. Thyroid Hormones
Thyroid-stimulating hormone (TSH) is released by the anterior pituitary gland in response to TRH secreted into the portal system
The hypothalamus
responds to higher
circulating levels of
T3 and T4 via negative
feedback to inhibit
TRH secretion

48. Thyroid Hormone Regulation 1 2 3 5 4 1 2 3 4 1 2 3 1 2 1 T3 and T4
released into
blood by
follicular cells
Elevated
T3inhibits
release of
TRH and
TSH
(negative
feedback)
TRH, carried
by hypophyseal
portal veins to
anterior pituitary,
stimulates
release of TSH
by thyrotrophs
TSH released into
blood stimulates
thyroid follicular cells
Thyroid
follicle
Low blood levels of T3
and T3 or low metabolic
rate stimulate release of
Hypothalamus
Anterior
pituitary
TRH
Actions of Thyroid Hormones:
Increase basal metabolic rate
Stimulate synthesis of Na+/K+ ATPase
Increase body temperature (calorigenic effect)
Stimulate protein synthesis
Increase the use of glucose and fatty acids for ATP production
Stimulate lipolysis
Enhance some actions of catecholamines
Regulate development and growth of nervous tissue and bones 1 2 3 5 4
T3 and T4
released into
blood by
follicular cells
TRH, carried
by hypophyseal
portal veins to
anterior pituitary,
stimulates
release of TSH
by thyrotrophs
TSH released into
blood stimulates
thyroid follicular cells
Thyroid
follicle
Low blood levels of T3
and T3 or low metabolic
rate stimulate release of
Hypothalamus
Anterior
pituitary
TSH
TRH
Actions of Thyroid Hormones:
Increase basal metabolic rate
Stimulate synthesis of Na+/K+ ATPase
Increase body temperature (calorigenic effect)
Stimulate protein synthesis
Increase the use of glucose and fatty acids for ATP production
Stimulate lipolysis
Enhance some actions of catecholamines
Regulate development and growth of nervous tissue and bones 1 2 3 4
TRH, carried
by hypophyseal
portal veins to
anterior pituitary,
stimulates
release of TSH
by thyrotrophs
TSH released into
blood stimulates
thyroid follicular cells
Thyroid
follicle
Low blood levels of T3
and T3 or low metabolic
rate stimulate release of
Hypothalamus
Anterior
pituitary
TSH
TRH
Actions of Thyroid Hormones:
Increase basal metabolic rate
Stimulate synthesis of Na+/K+ ATPase
Increase body temperature (calorigenic effect)
Stimulate protein synthesis
Increase the use of glucose and fatty acids for ATP production
Stimulate lipolysis
Enhance some actions of catecholamines
Regulate development and growth of nervous tissue and bones 1 2 3
TRH, carried
by hypophyseal
portal veins to
anterior pituitary,
stimulates
release of TSH
by thyrotrophs
Low blood levels of T3
and T3 or low metabolic
rate stimulate release of
Hypothalamus
TSH
TRH
Actions of Thyroid Hormones:
Increase basal metabolic rate
Stimulate synthesis of Na+/K+ ATPase
Increase body temperature (calorigenic effect)
Stimulate protein synthesis
Increase the use of glucose and fatty acids for ATP production
Stimulate lipolysis
Enhance some actions of catecholamines
Regulate development and growth of nervous tissue and bones 1 2
Anterior
pituitary
Low blood levels of T3
and T3 or low metabolic
rate stimulate release of
Hypothalamus
TRH
Actions of Thyroid Hormones:
Increase basal metabolic rate
Stimulate synthesis of Na+/K+ ATPase
Increase body temperature (calorigenic effect)
Stimulate protein synthesis
Increase the use of glucose and fatty acids for ATP production
Stimulate lipolysis
Enhance some actions of catecholamines
Regulate development and growth of nervous tissue and bones 1
Anterior
pituitary
Thyroid Hormone
Regulation

49. Thyroid Hormones
A goiter is an enlargement of the thyroid gland and may be associated with hyperthyroidism, hypothyroidism, or euthyroidism
In many third-word countries
dietary iodine intake is inadequate;
the resultant low level of thyroid
hormone in the blood stimulates
secretion of TSH, which causes
thyroid gland enlargement

50. The Parathyroid Glands
The parathyroid glands are small, round masses of tissue attached to the posterior surface of the lateral lobes of the thyroid gland
There are usually two
parathyroid glands
attached to each
lobe of the thyroid,
one superior and one inferior

51. Parathyroid Hormones
Calcitonin (Thyrocalcitonin) is made by the parafollicular (C-cells) of the thyroid gland and
when secreted lowers the blood calcium level
An increase in blood calcium will stimulate the C-cells of the thyroid to secrete calcitonin
Increased calcitonin will cause a negative feedback inhibition of parathyroid hormone (PTH) which
causes a decrease in blood calcium and an increase in blood phosphate levels