Biology 336 - Human Physiology

Lecture 5 – Tuesday, January 28th, 2025

Major classes of endocrine hormones

Reading: Reading: Stanfield, 6th Ed. Chapter 5

Pages 126-134
 Learning objectives
At the end of this lecture, you will be able to:

1. Interpret the results of Arnold Berthold’s 1849 experiment

using roosters, the first formal experiment in endocrinology.

2. Describe the general features of the endocrine system.

3. Identify and describe the major classes of endocrine

hormones, including the amine, peptide, and steroid
hormones.
1. Castration and re-implantation or transplantation of
testes in roosters revealed the existence of a chemical
signaling molecule in the blood.

&

S
2. Which of the following statements about Arnold Berthold’s 1849
experiment on roosters is FALSE?

A. Berthold hypothesized the testes release a chemical signal that

causes male roosters to act aggressively toward one another.
B. Castrated young male roosters were known to be docile and to
not grow large combs and wattles.
O
C. Castrated birds with testes re-implanted into their own
abdominal cavities, as well as control castrated birds, acted
aggressively and grew large wattles and combs.
D. Testes implanted into birds’ abdominal cavities did not form new
neural connections with the body, but they did establish new I
blood vessels.- important to this discovery
. Now neur

very
a
>
pathway ,

E. Berthold had discovered testosterone although the chemical comm

was not isolated and named until years later. through the
blood .

To respond to poll, please go to: www.pollev.com/patrickcafferty

 2. The endocrine system involves hormone
secretion into the interstitial fluid.
• The two major communication
systems of the body are:
1) The nervous system – is
specialized for rapid communication
accomplished through electrical
impulses in neurons.

2) The endocrine system – is

composed of glands and hormone-
secreting cells located in various
organs (such as the heart, kidneys,
liver, and stomach). Signals sent by
the endocrine system have longer
delays but last for greater lengths of
time than nervous signals.

This is not a complete list—see Table 6-1

(pg 157-158) for more detail.
A single endocrine gland may secrete multiple
hormones.

Pancreas
• For example, the pancreas
secretes a number of
hormones, including Insulin
which lowers blood glucose
levels, Glucagon that
increases blood glucose levels,
and Somatostatin that inhibits
secretion of pancreatic
hormones.
A single endocrine gland may secrete multiple
hormones.

Pancreas

• In general, single cell types in

glands secrete only one
hormone, so multiple-hormone
secretion reflects the presence
of different types of endocrine
cells in the same gland.
 Chemical messengers secreted by an endocrine-
gland cell may also be secreted by other cell types.

Ÿ For example, norepinephrine is used as both a

neurotransmitter in the nervous system and is an endocrine
hormone secreted by the adrenal medulla.
 3. Which of the following statements regarding the
endocrine system is true? The endocrine system:

A. releases hormones into the bloodstream for

circulation throughout the body.
B. produces signals that have much longer delays and
last for much greater lengths of time than nervous
system signals.
C. is composed of endocrine glands and hormone-
producing cells located throughout the body.
①
D. all of the above statements regarding the endocrine
system are true.

To respond to poll, please go to: www.pollev.com/patrickcafferty

•Copyright © 2010 Pearson Education, Inc.
 Key points:
• Endocrine hormones are chemical messengers that enter
the blood, that carries them from their site of secretion to the
cells upon which they act.

• Endocrine hormones functionally link various organs

together, for example, the hormone ACTH (adrenocortiotropic
hormone) links the anterior pituitary to the adrenal glands.

• Signals sent by the endocrine system have longer delays

but last for greater lengths of time than nervous system
signals.
 3. Endocrine hormones fall into three major
chemical classes:
A. The amine hormones—derivatives of the amino
acid tyrosine made by the thyroid gland, adrenal
medulla, and hypothalamus.

largest
as

B. Peptide and protein hormones—make up most

hormones and are produced in tissues all over the body.
· derived from cholesterol

C. Steroid hormones—lipids with ring-like structures

primarily produced by the adrenal cortex, the gonads,
and the placenta during pregnancy.
 A. The amine hormones—derivatives of tyrosine.
i. Thyroid hormones—contain iodine and are produced by the
thyroid gland.

00

Thyroid gland
 A. The amine hormones—derivatives of tyrosine.
i. Thyroid hormones—contain iodine and are produced by the
thyroid gland. thyroid
,
133T4
who I , cannot make
goiter .

enlarged
.
thyroid

Goiter
Goiter: a greatly enlarged thyroid gland that can result from iodine
deficiency. About 50 mg of iodine are required each year for the
formation of adequate quantities of thyroid hormone.
 A. The amine hormones—derivatives of tyrosine.
i. Thyroid hormones—contain iodine and are produced by the
thyroid gland.

E=
Negativa
e

normal Process :
o
3. The anterior hypothalamus a

pituitary ↓ TRreleasingT
secretes large
2. No
⑦
Anterior Pituitary
quantities of
TSH. hormone ↓St a
stimulating
inhibits the hormone)

production of Thyroid
4. TSH TSH. ↓
stimulates the T32T4
thyroid cells to
grow larger and
larger (10-20 X 1. Lack of iodine prevents
normal size). production of both T4 and T3.
 A. The amine hormones—derivatives of tyrosine.
i. Thyroid hormones—contain iodine and are produced by the
thyroid gland.
 4. A simple goiter results from:

A. a lack of Thyroid Stimulating Hormone (TSH).

O
B. a lack of iodine.
C. a lack of iron.
D. overproduction of the hormones thyroxine (T4) and
triiodothyronine (T3).
E. none of the above.

To respond to poll, please go to: www.pollev.com/patrickcafferty

•Copyright © 2010 Pearson Education, Inc.
 5. Is the following statement, True or False?

“Thyroxine and triiodothyronine, the thyroid

hormones, do not have a specific target organ;
instead, they stimulate most of the cells of the body
to metabolize at a faster rate.”

&
A. True B. False

To respond to poll, please go to: www.pollev.com/patrickcafferty

•Copyright © 2010 Pearson Education, Inc.
 A. The amine hormones—derivatives of tyrosine.
i. Thyroid hormones—contain iodine and are produced by the
thyroid gland.

ii. Epinephrine and norepinephrine—are produced

by the adrenal medulla.

iii. Dopamine—is produced by the hypothalamus.

Catecholamines—
have catechol
groups
 B. Peptides and proteins—make up most hormones.

For e.g.—
Insulin and
Glucagon are
peptide
hormones
required for
glucose
homeostasis.
 C. Steroid hormones—lipids with ring-like structures.
All of the steroid hormones are Cortisol (a glucocorticoid) is secreted
derived from Cholesterol. from the adrenal cortex and regulates
metabolism during stress.

Aldosterone (a mineralocorticoid)
stimulates Na+ & H2O reabsorption Testosterone and Estradiol are sex
and K+ & H+ secretion in the kidney. hormones.
 6. Which is the effect of glucagon on blood
glucose level? Glucagon:

A. raises glucose levels

B. has no effect on glucose levels
C. lowers glucose levels
D. slightly lowers glucose levels

To respond to poll, please go to: www.pollev.com/patrickcafferty

 Key points:
• The amine hormones are the iodine-
containing thyroid hormones and the
catecholamines secreted by the adrenal
medulla and the hypothalamus and are
derivatives of the amino acid tyrosine.
• The majority of hormones are
peptides, many of which are
synthesized as larger molecules,
which are then cleaved into
active fragments (for example,
Insulin and Glucagon).

• Steroid hormones are produced

from cholesterol by the adrenal
cortex and the gonads and by the
placenta during pregnancy.
 Warm-up—from last time:
1. Which category of hormones includes
iodine in its molecular structure?
A. steroid
O B. thyroid
C. amine
D. peptide

To respond to poll, please go to: www.pollev.com/patrickcafferty

 Warm-up:

2. A diet that is lacking in

the amino acid
tryptophan could directly
impact the levels of:
O
Pineal gland
A. melatonin
B. dopamine
C. epinephrine
D. testosterone

To respond to poll, please go to: www.pollev.com/patrickcafferty

 Housekeeping:

• Weekly Online Assignment # 2: You can find this

assignment on our Canvas site at on the Topic 3 -
Endocrinology page.

This assignment is due on Friday, January 31st at 12pm

(EDT).
 Housekeeping:
Housekeeping:
Current LA Session Schedule:

Biology 336 LA Session Schedule - Spring 2025

LA Names Day/Times Location
Alex Koeppel/Maeve Shannahan Sun 6-7pm Cox Classroom B
Sophia Kim/Reine Victome Tues 7:30-8:30pm Woodruff Library 314 or Zoom
Kevin Patel/Harry Jing Wed 4-5pm Cox Classroom B
Karthik Valiveti/Maithri Muthukumar Wed 7-8pm Woodruff Library 314
Zoom:
Samir Lohana Fri 1-2pm https://emory.zoom.us/j/3887955227
Beam Yongphiphatwong/Andrew Zoom:
Jung Sat 3-4pm https://emory.zoom.us/j/92071845853

• Once you’ve completed a Problem Set, you can attend a

tutorial session where the LAs will help you complete any
• difficult/challenging questions and answer your questions
Once you’ve completed a Problem Set, you can attend a tutorial session where the LAs will help you complete any difficult/challenging questions and
answer your questions from class.

from class.
 Housekeeping:
Next Alternative Office Hour:

Tomorrow, Friday, January 31stffrom 11:30am-12:30pm-

ish on the 2nd floor lobby of the O. Wayne Rollins Research
Building, 1510 Clifton Rd N.
 Biology 336 - Human Physiology

Lecture 6 – Thursday, January 30th, 2025

Endocrine hormone synthesis, processing, & transport
Reading: Stanfield, 6th ed., pages 13 –16 & 615
 Learning objectives
At the end of this lecture, you will be able to:

1) Compare and contrast the steps involved in (a) peptide and

(b) steroid hormone synthesis, processing, and transport in
the circulation.

2) Distinguish between the hormones produced by the cortex

and medulla of the adrenal gland and explain the
physiological functions these hormones regulate.

3) Define the term “free fraction” and explain the effects of

hormone binding proteins (carriers) on access of steroid
hormones to their sites of action and on steroid hormone half-
life.
 The Three Major Classes of Endocrine
Hormones
A) Amine hormones i) Thyroid hormones (T3 & T4)
ii) Epinephrine & Norepinephrine
iii) Dopamine

B) Peptide and Protein hormones (for example, Insulin and

Glucagon)

C) Steroid hormones (for example, Cortisol, Aldosterone,

Estradiol and Testosterone)
 The Three Major Classes of Endocrine
Hormones
A) Amine hormones i) Thyroid hormones (T3 & T4)
ii) Epinephrine & Norepinephrine
iii) Dopamine

B) Peptide and Protein hormones (for example, Insulin and

Glucagon)
• (a) We will now examine the synthesis, processing,
and transport of peptide and protein hormones.

C) Steroid hormones (for example, Cortisol, Aldosterone,

Estradiol and Testosterone)
 (a) Peptide hormones are made as large,
Tr inactive preprohormones…
…that include a signal sequence, one or more copies of the
hormone, and additional peptide fragments.
endomembrane
All happens in system
② happens before gets
- ⑤happens in secretary resicle.
ough
ER

form that is first

&Phormonestransmitted
:

but not yet

cut atrsstage
,

functional
fully
.

• For example, inactive • The prohormone is next cleaved

Preproinsulin becomes into biologically active Insulin and
-

cleaved (cut) first into C-peptide and both are released

proinsulin. into circulation. activHerteaveol girgetrt circulation
-

• The C-peptide is used as a marker of Insulin secretion.

•Copyright © 2010 Pearson Education, Inc.
 Peptide hormone synthesis and processing

1. The preprohormone
contains a signal sequence of
amino acids that directs the
protein into the lumen of the
rough endoplasmic
reticulum.

2. Enzymes
in the ER cut
1. 2. off the signal
sequence
creating an
inactive
prohormone.

•Copyright © 2010 Pearson Education, Inc.

 Peptide hormone synthesis and processing

3. The prohormone passes from

the ER through the Golgi complex.

3.

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 Peptide hormone synthesis and processing
4. Secretory vesicles
4. containing enzymes and
prohormone bud off the
Golgi. The enzymes
chop the prohormone
into one or more active
peptides plus additional
5. peptide fragments.

5. Secretory
vesicles
containing
peptides are
stored in the
cytoplasm
until the cell
receives a
signal for
secretion.
•Copyright © 2010 Pearson Education, Inc.
 Peptide hormone synthesis and processing

6. When a cell receives a

signal, the secretory vesicle
releases its contents by&Ca2+-
dependent exocytosis into
the extracellular space.
6.

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 Peptide hormone synthesis and processing
7. The hormone moves into the circulation for
transport to its target.

Protein hormones, like Insulin, are water

soluble and dissolve easily in the extracellular
fluid for transport throughout the body.
7.

•Copyright © 2010 Pearson Education, Inc.

 Peptide hormone synthesis and processing
8.
8. The hydrophilic hormones are unable to
cross the membranes of target cells, and must
bind to cell surface receptors (for example,
the Insulin receptor tyrosine kinase).

•Copyright © 2010 Pearson Education, Inc.

 Consider the following:
3. The parathyroid hormone (PTH) is an 84 amino acid
protein hormone that helps to maintain calcium levels in
extracellular fluid by mobilizing calcium from bone.

When PTH mRNA is transcribed from the PTH gene and

translated on ribosomes, the ribosomes are found
_________ and the translated PTH polypeptide formed is
_________ the biologically active form of the PTH hormone.

A. in the nucleus; larger than

B. in the cytoplasm; identical in size (84 amino acids) to
O
C. attached to the rough endoplasmic reticulum; larger than
D. attached to the rough endoplasmic reticulum; smaller
than

To respond to poll, please go to: www.pollev.com/patrickcafferty

•Copyright © 2010 Pearson Education, Inc.
 The Three Major Classes of Endocrine
Hormones
A) Amine hormones i) Thyroid hormones (T3 & T4)
ii) Epinephrine & Norepinephrine
iii) Dopamine

B) Peptide and Protein hormones (for example, Insulin and

Glucagon)

C) Steroid hormones (for example, Cortisol, Aldosterone,

Estradiol and Testosterone)
• We will next examine hormones of the adrenal gland
• (b) Details of steroid hormone synthesis,
processing, and transport will follow
 2. The adrenal
glands are
Adrenal glands endocrine glands
located at the top of
each kidney.

outter

Adrenal cortex

middle

Adrenal medulla
 2. Preprohormones are then cleaved to
Key points: prohormones by proteolytic enzymes in
the rough endoplasmic reticulum.

2.
3.
3. The prohormone is
packaged into secretory
1. vesicles by the Golgi
apparatus. In this
1. In many cases, peptide hormones process, the prohormone
are initially synthesized on the is cut to yield the active
ribosomes of endocrine cells as larger hormone and other
molecules known as preprohormones. peptide chains found in
the prohormone.
Key points:

4.

4. Peptide and protein hormones are made in advance

and are stored until needed in secretory vesicles.
 2. Cells of each layer of the adrenal gland express
distinct enzymes to synthesize specific hormones.
Ÿ Each adrenal gland is two embryologically distinct tissues that merged during
development. The adrenal gland secretes multiple hormones.
• The adrenal medulla occupies a ¼ of the mass and secretes
catecholamines (4 times more Epinephrine than Norephinephrine) involved in
rapid fight-or-flight response.
Epinephrine &
Norepinephrine

Androgens &
small amount
of Cortisol
Cortisol &
small amount
The paired of androgens
adrenal
glands sit on
top of the
kidneys like
little caps.
• The adrenal cortex occupies the outer ¾ of the gland and is composed of 3
distinct layers. In certain diseases, the adrenal cortex may secrete decreased
• or increased amounts of various steroids.
Copyright © 2010 Pearson Education, Inc.
 Sex differences in sport
performance
“Not only are boys generally superior at throwing, but
they also tend to be much more skilled at visually
tracking and intercepting flying objects; 87 percent of
boys outperform the average girl in tests of targeting
skills. And the difference appears to be at least partly a
result of exposure to testosterone in the womb. Girls who
are exposed to high levels of testosterone in the womb
because of a genetic condition called congenital
adrenal hyperplasia, in which the fetal adrenal glands
overproduce male hormones, perform like boys, not girls,
on these tasks.”

David Epstein (2013) “The Sports Gene” pg 62

•Copyright © 2010 Pearson Education, Inc.
 Consider the following:

4. The adrenal cortex produces only:

O
A. steroid hormones
B. amine hormones
C. catecholamine hormones 3 medulla
D. peptide hormones
E. glycoprotein hormones

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b. Overview of steps involved in steroid hormone
synthesis
1. Cells in both the
gonads and the adrenal
cortex are stimulated to
synthesize steroid
hormones by the
binding of an anterior
pituitary gland
hormone ( ) to its
cell surface receptor
( ).

Gonad or
adrenal cortical
endocrine cell
b. Overview of steps involved in steroid hormone
synthesis
1. Cells in both the 5. a) Take ~1 minute to think
gonads and the adrenal about the signal transduction
cortex are stimulated to
synthesize steroid steps that follow receptor
hormones by the activation to activation of
binding of an anterior Protein Kinase A.
pituitary gland
hormone ( ) to its
cell surface receptor 5. b) Briefly discuss the
( ). signal transduction steps
leading to Protein Kinase A
with your neighbor.

5. c) Type the signal transduction steps leading to

Protein Kinase A in Poll Everywhere.

To respond to poll, please go to: www.pollev.com/patrickcafferty

 Overview of steps involved in steroid hormone
synthesis

2. Activation of these G
protein linked receptors
leads to adenylyl
cyclase activation,
cAMP production, and
PKA activation.

Gonad or
adrenal cortical
endocrine cell
 Overview of steps involved in steroid hormone
synthesis

3. PKA phosphorylates
numerous target proteins,
including the enzyme
cholesterol esterase.

Gonad or
adrenal cortical
endocrine cell
 Overview of steps involved in steroid hormone
synthesis
• See the animation of the receptor
mediated endocytosis of LDL posted
on Canvas.

- This illustrates how

cholesterol/LDL complexes
enter gonad or adrenal cortical
cells.
4. Inside the cell, cholesterol is stored in a
large, non-membrane bound form. PKA
activates cholesterol esterase, an enzyme
that releases free cholesterol that is
transported to the mitochondrion.

Ultrastructure of a
steroidogenic cell:

• Note the abundance

of lipid droplets,
smooth
endoplasmic
reticulum, and
mitochondria.
 Overview of steps involved in steroid hormone
synthesis
5. Cholesterol is modified in a
step-wise manner by a series of
enzymes located in the
mitochondria and smooth
endoplasmic reticulum (SER) in
order to produce specific steroid
hormones.

Gonad or
The intermediate products of
steroid biosynthesis must be adrenal cortical
shuttled between the mitochondria endocrine cell
and SER.
 Overview of steps involved in steroid hormone
[H] [CO] Num synthesis
TH-CD Z chemn
+ =
↓ ↓
hormone carrier protein
(free fraction)

6. Steroid hormones are

hydrophobic and diffuse
easily across membranes,
both out of their parent cell
and into their target cell.
*
This property also means
that steroid-secreting cells
cannot store hormones in
secretory vesicles.

When a stimulus activates

the endocrine cell,
precursors in the cytoplasm
are rapidly converted to
active hormone. The
hormone concentration in the Gonad or
cytoplasm rises, and the adrenal cortical
hormones move out of the endocrine cell
cell by simple diffusion.
6. Which of the following approaches should be taken
to stimulate steroid hormone synthesis and secretion in
adrenal cortical cells lacking Protein Kinase A (PKA)
expression?

A. Increasing the activity of Cholesterol esterase in the

adrenal cortical cells.
B. Increasing the activity of Adenylyl cyclase in the
adrenal cortical cells.
C. Increasing the secretion of Adrenocorticotropic
hormone (ACTH) from the anterior pituitary gland.
D. Increasing the expression of Low-Density Lipoprotein
(LDL) Receptors by the adrenal cortical cells.
E. Inhibiting the activity of Adenylyl cyclase in the
adrenal cortical cells.

To respond to poll, please go to: www.pollev.com/patrickcafferty

 Key points:

• Most steroid
hormones are made
in the adrenal
cortex or gonads
(ovaries and testes).

• Steroid hormones are not stored in the endocrine cell

because of their hydrophobic nature. Instead, steroid
hormones are made on demand and readily diffuse out of the
endocrine cell.

• The final hormone produced by a cell depends on the types

and amounts of enzymes expressed by that cell.
 3. Most of the steroid hormone molecules found in the
blood are bound to protein carrier molecules.
• Steroid and thyroid hormones are not very soluble in plasma or other bodily
fluids—they are largely transported bound to protein carrier molecules.

• Some hormones have

specific carriers, such as
Corticosteroid-Binding
Globulin. Others simply
bind to general plasma
proteins, such as Albumin.

• Even though the steroid

hormones exist in plasma
mainly bound to large
proteins, small
concentrations do exist
dissolved in plasma.
Only the free hormone can
diffuse out of capillaries
and encounter target cells.
•Copyright © 2010 Pearson Education, Inc.
 Consider the following:

7. Is the following statement True or False?

“Hormone that is bound up by transporter proteins in the

blood is not part of the free fraction and is unavailable for
cell signaling.”

O
A) True
B) False

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•Copyright © 2010 Pearson Education, Inc.
 Consider the following:3354 +

normous
drophobic : striodsd
hormones
my
Thy

8. Which hormone would exist with a free fraction in

the blood?
signalling
A) serotonin Protein are

moleculadophi
e lia
.

B) insulin
C) dopamine
⑧
D) thyroid hormone (T3374)
E) epinephrine

To respond to poll, please go to: www.pollev.com/patrickcafferty

•Copyright © 2010 Pearson Education, Inc.
 Consider the following:

9. The half-life of a lipid-soluble hormone in blood is:

A) directly proportional to its rate of secretion.

① B) directly proportional to the affinity of the hormone
for its plasma protein carrier.
C) directly proportional to the number of hormone
receptors present in target tissue.
D) inversely proportional to the concentration of the
hormone’s plasma protein carrier.
E) inversely proportional to the molecular weight of the
hormone.

To respond to poll, please go to: www.pollev.com/patrickcafferty

•Copyright © 2010 Pearson Education, Inc.
 Key points:

• Like the parent molecule, cholesterol, steroid hormones are

not very soluble in plasma and other body fluids. For this
reason, most of the steroid hormone molecules found in the
blood are bound to protein carrier molecules.
Biology 336 - Human Physiology

Lecture 7 – Tuesday, February 4th, 2025

Blood Glucose Metabolism
Reading: Stanfield, 6th ed., pages 13 –16 & 615
 Learning objectives
At the end of this lecture, you will be able to:

1. Identify both normal and abnormal results for the Oral

Glucose Tolerance Test.

2. Explain the relationship between insulin and glucose levels

in the blood.

3. Predict the potential signal transduction pathways activated

by hydrophilic and hydrophobic signaling molecules.

4. Draw reflex arcs to illustrate and compare normal

physiological and pathophysiological states.
15. Based on your answer to the preceding question,
what kind of receptor(s) might be activated by the insulin
hormone? Select all that apply.

A) Intracellular receptor
B) G-protein linked receptor
C) Ion channel linked receptor
②
D) Enzyme-linked receptor

The reporter will enter your team's response into Poll

Everywhere at: www.pollev.com/patrickcafferty

You can use a phone, tablet, or computer to respond to Poll

Everywhere questions.
 Insulin receptor mechanism of action
• Take one minute in
your group to discuss
and list advantages/
disadvantages of this
system of post-
translational control
over transcribing and
translating new GLUT-4
receptors
(transcriptional/
translational control).
pro fast
:
response
the
con : waste
making
energy protein .
• Then, have your group reporter type your group
consensus answer into Poll Everywhere at:
www.pollev.com/patrickcafferty
 Donald Ritchie
developed a rare case
of adult-onset type 1
diabetes at age 51
 The actions of glucagon are considered to be
antagonistic to the actions of insulin. Since some
types of diabetes are caused by a lack of insulin,
might correcting for this by lowering the levels of
glucagon work to counteract the effects of diabetes?

A. No.
B. Yes.
C. There is not enough information to answer this
question.

• Your group reporter will report your group consensus answer

using Poll Everywhere at: www.pollev.com/patrickcafferty
The actions of glucagon are considered to be
antagonistic to the actions of insulin. Since some types
of diabetes are caused by a lack of insulin, might
correcting for this by lowering the levels of glucagon
work to counteract the effects of diabetes?

Explain your answer to the question above.

Why did you chose (A) No, (B) Yes, or (C) There is not
enough information to answer this question?

• Your group reporter will report your group consensus answer

using Poll Everywhere at: www.pollev.com/patrickcafferty
Biology 336 - Human Physiology

Lecture 8 – Thursday, February 6th, 2025

Hypothalamus and the Pituitary
Reading: Stanfield, 6th Ed. Chapter 6 pages 148-155
 Learning objectives
At the end of this lecture, you will be able to:

1) Describe the structure and function of the hypothalamus and

pituitary.

2) Describe the organization of and the hormones associated

with the posterior pituitary.

3) Describe the organization of and hormones produced by the

anterior pituitary gland.

4) Explain the action of hypophysiotropic hormones upon the

release of anterior pituitary gland hormones.
 Learning objectives
At the end of this lecture, you will be able to:

5) Draw a diagram to illustrate the difference between long-loop

and short-loop feedback regulation.

6) Describe the relationship of stress and the hypothalamic-

pituitary-adrenal (HPA) pathway.

7) Explain the physiological actions of Cortisol.

1. The hypothalamus is the most important control area
for homeostatic regulation of the internal environment.
• Together the hypothalamus and pituitary function to
regulate virtually every body system.
The hypothalamus lies
under the thalamus on
the underside of the
brain.

thalamus

hypothalamus

• Behaviors having to do with

preservation of the individual
(for example eating and
drinking) and preservation of
Coronal plane the species (reproduction).
 The pituitary is actually two glands with different
embryological origins that fused during development.
The pituitary gland sits in a The pituitary gland is connected to the
protected pocket of bone hypothalamus by the infundibulum
and is connected to the base (Latin for “funnel”) or pituitary stalk,
of the brain just under the containing axons from neurons in the
hypothalamus by a thin hypothalamus and small blood
stalk. vessels.

Sphenoid bone

The posterior pituitary gland is not

The anterior pituitary a gland but rather an extension of
gland is a true endocrine the neural components of the
gland of epithelial origin. hypothalamus.
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 hypothalamus

Lateral
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 infundibulum

Lateral
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 Pituitary gland

sphenoid bone

Lateral
•Copyright © 2010 Pearson Education, Inc. plane
 1. What is the name of the stalk that connects
the hypothalamus to the pituitary?
MRI
Coronal
A. sphenoid stalk
B. nephron
C. corpus callosum
8
D. infundibulum
E. cerebral cortex
?

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 2. The posterior pituitary is an extension of the brain that
secretes neurohormones made in the hypothalamus.
Ÿ Neurohormones: Hormones produced by specialized nerve cells and
secreted into the circulation. In this example, the neurohormones are
synthesized by two clusters of neuronal cell bodies in the hypothalamus.
1. The supraoptic nuclei extend
axons down the infundibulum to the 2. The
posterior pituitary and synthesize paraventricular
the neurohormone, Vasopressin. nuclei extend
axons to the
posterior pituitary
and synthesize
the
neurohormone,
Oxytocin.
* Note that a
cluster of nerve
cell bodies in
the central
nervous system
is called a
nucleus.
•Copyright © 2010 Pearson Education, Inc.
 The two posterior pituitary neurohormones are
composed of nine amino acids each.
• In women, Oxytocin is • Vasopressin, also
involved in two reflexes: called antidiuretic
hormone (ADH), acts
i) In response to on the kidneys to
stimulation of the nipples regulate water balance
during nursing, sensory in the body.
information is sent to the
brain resulting in activation
of the paraventricular
nuclei.
The released oxytocin
stimulates ejection of milk
from the mammary
glands.
ii) During labor, stretch receptors
in the cervix send signals back to
the brain and hypothalamus,
which releases oxytocin.
Oxytocin then stimulates
contraction of uterine smooth
muscle cells until birth.
•Copyright © 2010 Pearson Education, Inc.
 2. You have consumed a six-pack of beer in the
course of an evening. The combination of fluid
intake and alcohol act to inhibit the secretion of:

A. Adrenocorticotropic hormone (ACTH)

B. Thyrotropin-releasing hormone (TRH)
C. Vasopressin (ADH)
D. Insulin
E. Thyroid-stimulating hormone (TSH)
F. Parathyroid hormone
G. Oxytocin
H. Corticotropin-releasing hormone (CRH)
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•Copyright © 2010 Pearson Education, Inc.
 Vasopressin and oxytocin are stored and released
by the posterior pituitary.

1. Neurohormone is made and

packaged in cell body of neuron.

2. Vesicles are transported down

long extensions of the neurons
called axons.

3. Vesicles containing
D
neurohormone are stored in the
axon terminals where they wait
for a release signal.

4. When a signal (in the form of

an action potential) passes down
the neuron, the neurohormones
are released into the blood.
•Copyright © 2010 Pearson Education, Inc.
3. Where are the posterior pituitary hormones
manufactured? The posterior pituitary hormones
are made by:
A. endocrine cells located in the
posterior pituitary.
B. endocrine cells located in the
anterior pituitary. Posterior
C. endocrine cells located in the pituitary
medulla of the adrenal gland.
&
D. neurosecretory cells that originate
in the hypothalamus.
E. neurosecretory cells that originate
in the thalamus.
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 Key points:
• The hypothalamus is considered a master control center of
the endocrine system.

infundibulum

anterior
pituitary gland

• The pituitary gland, comprising the anterior pituitary gland

and the posterior pituitary, is connected to the hypothalamus by
an infundibulum, or stalk, containing neurons and blood
vessels.
 Key points:
• Specific axons, whose cell bodies are in the hypothalamus,
terminate in the posterior pituitary and release oxytocin and
vasopressin.

Posterior pituitary
 3. Structure of the anterior pituitary gland.
Several hypothalamic nuclei The hypothalamic
send axons whose terminals hormones that
end in the median eminence. regulate anterior
pituitary gland
function are called
Median hypophysiotropic
eminence hormones or
hypothalamic
Note that non- inhibiting/releasing
hypothalamic hormones hormones.
also influence the anterior
pituitary gland (including
some involved in
feedback inhibition).

•Copyright © 2010 Pearson Education, Inc.

 Neurohormones from the hypothalamus reach the
anterior pituitary through a specialized circulatory region
called the hypothalamic-hypophyseal portal system.

•Copyright © 2010 Pearson Education, Inc.

 Stimulus The hypophysiotropic hormones typically
act in a 3-hormone sequence.
Hypothalamus
Increase in Hormone 1 secretion.

Increase in Hormone 1 plasma concentration.

(in hypothalamo-pituitary portal vessels)

Anterior pituitary
Increase in Hormone 2 secretion.

Increase in Hormone 2 plasma concentration.

Third endocrine gland

Increase in Hormone 3 secretion

Increase in Hormone 3 plasma concentration.

Target cells of Hormone 3

Response to Hormone 3
 The anterior pituitary secretes six characterized peptide
hormones. Adrenocorticotropic
Follicle-stimulating
hormone (FSH) and hormone (ACTH)
Luteinizing hormone stimulates the
(LH) are gonadotropic adrenal cortex to
hormones that secrete cortisol.
stimulate the gonads.
Growth
Prolactin controls milk hormone (GH)
production in the breast. stimulates the
liver to
Thyroid-stimulating secrete the
hormones (TSH) induces growth
the thyroid to secrete promoting
thyroxine and hormone,
triiodothyronine. insulin-like
growth factor.

•Copyright © 2010 Pearson Education, Inc.

 An easy mnemonic to remember the anterior
pituitary hormones is “FLAT PiG.”

Exclusively
F(SH) = Follicle-Stimulating Hormone
tropic
L(H) = Luteinizing Hormone hormones—are
A(CTH) = Adrenocorticotropic Hormone hormones that
stimulate other
T(SH) = Thyroid Stimulating Hormone endocrine glands.

P(rolactin) = stimulates milk in female Stimulate

another part of
i(gnore) mammary glands. the body
G(H) = Growth Hormone directly.
•Copyright © 2010 Pearson Education, Inc.
4. Which of the following anterior pituitary hormones
is NOT a tropic hormone?

A. Follicle-Stimulating Hormone (FSH)

B. Adrenocorticotropic Hormone (ACTH)
C. Thyroid Stimulating Hormone (TSH)
D. Prolactin
E. Luteinizing Hormone (LH)
anterior
pituitary gland

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 Key points:

•Copyright © 2010 Pearson Education, Inc.

4. Several hypophysiotropic hormones are named for the anterior
pituitary gland hormone whose secretion they control.
Ÿ For example, corticotropin–releasing hormone (CRH) and growth hormone
releasing hormone (GHRH) stimulate release of corticotropin (ACTH) and
growth hormone.
Ÿ Two of the hypophysiotropic hormones inhibit, release of anterior pituitary
hormones, including somatostatin (SS) and dopamine (DA).
Ÿ Release of growth hormone is under dual-control of stimulatory GHRH and
inhibitory SS. Release of other anterior pituitary hormones may also be
dependent upon exposure to relative amounts of hypothalamic hormones.
 5. Hormonal feedback control of the
hypothalamus and anterior pituitary gland
• Each of the hormonal sequences initiated by
a hypophysiotropic hormone feature negative
feedback exerted upon the hypothalamo-
pituitary system by one or more of the
hormones in its sequence.

• In short-loop feedback, pituitary hormones

feed back to decrease hormone secretion by
the hypothalamus.

• In long-loop feedback, the last hormone in

a pathway feeds back to suppress secretion of
hormones by the hypothalamus.

•Copyright © 2010 Pearson Education, Inc.

 5. Which of the following statements regarding the
regulation of pituitary hormone secretion by the
hypothalamus is CORRECT?

A. All anterior and posterior pituitary hormones are

regulated by tropic hormones from the
hypothalamus.
B. All anterior pituitary hormones are regulated by a
releasing hormone and a release inhibiting
hormone from the hypothalamus.
C. All posterior pituitary hormones are regulated by
a releasing hormone from the hypothalamus.
D. All anterior pituitary hormones are tropic
hormones.
O
E. None of the above.
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6. Which of the following statements concerning the
hypothalamus and anterior pituitary gland is FALSE?

A. Hypothalamic releasing hormones are True

synthesized and secreted by neurons.
⑧
B. Blood flows from the anterior pituitary to the
hypothalamus in portal vessels.
C. The hypophysiotropic hormones produced by the
hypothalamus typically act in a 3 hormone Tire
sequence to generate a response.
D. Hypophysiotropic hormones are released into a
capillary bed called the median eminance. True

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 Key points:
• The anterior pituitary gland secretes a number of hormones,
including the tropic hormones (FSH, LH, ACTH, and TSH) and
the direct-acting hormones Growth Hormone (GH) and Prolactin.

• Secretion of the anterior pituitary gland hormones is

controlled mainly by hypophysiotropic hormones secreted
into capillaries in the median eminence of the hypothalamus.

• The hypophysiotropic hormones reach the anterior pituitary via

the portal vessels connecting the hypothalamus and anterior
pituitary gland.

• In three-hormone sequences beginning with a

hypophysiotropic hormone, the third hormone exerts negative
feedback effects on the secretion of the hypothalamic and/or
anterior pituitary gland hormone.
6. Thus far, we have referred to Cortisol simply as
an example of a steroid hormone.

Cortisol,
secreted from the
adrenal cortex, is
often referred to
as the body’s
stress hormone
as cortisol plays a
direct role in the
mediation of long-
term (chronic)
stress.
Emory Counseling and Psychological Services (CAPS):
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The term stress as used in biology has been defined as any
change in the environment that changes or threatens to
change an existing optimal state.
• Most, if not all, of these stresses activate processes at the
molecular, cellular, or systemic level that tend to restore the
previous state, that is, they are homeostatic reactions.

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 Stress refers to an environmental
change that must be adapted to if
health and life are to be maintained.
On Feb 18th we’ll
examine the role of
the Autonomic
Nervous System in
the Fight or Flight
response.

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The control pathway for cortisol secretion is known as
the hypothalamic-pituitary-adrenal (HPA) pathway.

• The HPA pathway begins with

hypothalamic corticotropin-
releasing hormone (CRH) being
secreted into the hypothalamic-
hypophyseal portal system.

• CRH stimulates release of

adrenocorticotropic hormone
(ACTH or corticotropin) from the
anterior pituitary.

• ACTH acts on the adrenal

cortex to promote synthesis and
release of Cortisol. Cortisol then
acts as a negative feedback
signal, inhibiting ACTH and CRH
secretion.
 7. Cortisol exerts many important actions in both
stress and non-stress conditions.
Ÿ The most important metabolic effect of Cortisol is protection
against hypoglycemia.
When blood glucose levels
drop, α-cells of the pancreas
secretes glucagon to
promote gluconeogenesis and
glycogen breakdown.

In the absence of cortisol,

glucagon is unable to respond
adequately to a hypoglycemic
challenge.

Cortisol has a permissive

effect on glucagon and
catecholamine activity.

• Cortisol is essential for life—animals whose adrenal glands have

been removed die if exposed to any significant environmental stress.
The permissive action on reactivity to catecholamines
by cortisol also affects blood pressure.

Cortisol has permissive

action on the reactivity to
catecholamines by smooth
muscle cells that surround
arterioles.

As a result, basal levels

of cortisol help
maintain normal blood
pressure.
 Cortisol suppresses the immune system through
multiple pathways.
A. Cortisol prevents
cytokine release and
antibody production
by white blood cells.

B. Cortisol inhibits
the inflammatory
response by
decreasing leukocyte
mobility and migration.

• Consequently, Cortisol had been used as an anti-inflammatory drug

for treating a variety of conditions that ranged from bee stings and
pollen allergies to the prevention of rejection of transplanted organs.
• An animation of the normal inflammation response is found here:
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ory.html
 Key points:
• Cortisol is released from the
adrenal cortex upon
stimulation with
adrenocorticotropic hormone
(ACTH).

ACTH, in turn, is stimulated by

the release of corticotropin-
releasing hormone (CRH)
from the hypothalamus.

• The physiological functions of cortisol are to maintain the

responsiveness of target cells to epinephrine and
norepinephrine, to provide a “check” on the immune system,
and to participate in energy homeostasis.
 Key points:
• In response to stress, the usual physiological functions of
cortisol are enhanced as cortisol concentrations in the plasma
increase (see below). Thus, gluconeogenesis, lipolysis, and
inhibition of insulin actions increase. This results in increased
blood concentrations of energy sources (glucose, fatty acids)
required to cope with stressful conditions.

• High cortisol
concentrations
also inhibit
“nonessential”
processes, such
as reproduction,
during stressful
situations and
inhibit immune
function.
 8. Cortisol pathologies result from too much or too little
hormone.

Ÿ The most common HPA pathologies result from hormone

deficiency (for e.g. – hypocortisolism) and hormone excess (for
e.g. - hypercortisolism, also called “Cushing’s syndrome”).

Ÿ Abnormal tissue responsiveness is an uncommon cause of adrenal

steroid disorders.

In Poll Everywhere:
Take a minute to:
7. Predict the signs of hypercortisolism based on the normal
actions of Cortisol.
8. Write down any possible cause(s) of hypercortisolism.
 Symptoms of hypercortisolism
Excess
gluconeogenesis- >
hyperglycemia ,
which

mimics diabetes

Muscle protein breakdowns lyposis >

-
 Hypercortisolism has three common causes:
1. Primary hypercortisolism: caused by adrenal
-

tumor
-
that autonomously secretes cortisal
not
z
under control of
pirnitary ACTH

2. Secondary hypercortisolism:
pituitary tumor
autonomously secretes ACT .
Tumor does not
respond to
negative feedback

3. Iatrogenic (physician-caused) hypercortisolism:

occurs
secondary to cortisol
therapy for some

other condition.
 Hyposecretion of cortisol is much less common than
hypersecretion
Ÿ Primary adrenal Ÿ Addison’s disease results in
insufficiency, also known the hyposecretion of all adrenal
as Addison’s disease,
results from the steroid hormones including
autoimmune destruction of aldosterone, resulting in an
the adrenal cortex. imbalance in Na+, K+, and water
in the blood possibly leading to
hypotension (low blood
pressure).

Ÿ A characteristic of Addison’s
disease is the elevation of serum
ACTH (and CRH) levels due to
the loss of negative feedback
by Cortisol.
Josh is a mixed martial arts fighter. In a recent match he was
crescent kicked in the head and briefly lost consciousness.

Now, a month later, he has come to your clinic complaining of

nausea, vomiting, weakness, and fatigue. Your clinical exam
establishes that he is experiencing hypoglycemia, though blood
pressure and coloration of the skin are normal.

9. What is your preliminary diagnosis given Josh’s

symptoms and injury?

A) Primary hypocortisolism
B) Secondary hypocortisolism
C) Tertiary hypercortisolism
D) Primary hypercortisolism
E) Secondary hypercortisolism
Josh is a mixed martial arts fighter. In a recent match he was
crescent kicked in the head and briefly lost consciousness.

Now, a month later, he has come to your clinic complaining of

nausea, vomiting, weakness, and fatigue. Your clinical exam
establishes that he is experiencing hypoglycemia, though blood
pressure and coloration of the skin are normal.

10. To confirm your diagnosis in Question # 7 above, you

order a blood panel examining hormone levels. What would you
expect given the patient’s symptoms and injury?

A) ↓CRH ↑ACTH ↑Cortisol

B) ↓CRH ↓ACTH ↑Cortisol
C) ↑CRH ↓ACTH ↓Cortisol
D) ↑CRH ↑ACTH ↓Cortisol
E) ↑CRH ↑ACTH ↑Cortisol
Josh is a mixed martial arts fighter. In a recent match he was
crescent kicked in the head and briefly lost consciousness.

Now, a month later, he has come to your clinic complaining of

nausea, vomiting, weakness, and fatigue. Your clinical exam
establishes that he is experiencing hypoglycemia, though blood
pressure and coloration of the skin are normal.

11. How would you recommend treating Josh, the patient

above?

A) Surgical removal of the pituitary gland

B) Prescription of cortisol injections
C) Surgical removal of a portion of the adrenal cortex
D) Discontinuance of steroidal anti-inflammatories
E) Prescription of insulin injections
 Key points:
• Adrenal insufficiency may result from adrenal destruction
(primary adrenal insufficiency, or Addison’s disease) or from
hyposecretion of ACTH (secondary adrenal insufficiency).

• Adrenal insufficiency is associated with decreased ability to

maintain blood pressure (due to loss of aldosterone) and blood
sugar. It may be fatal if untreated.

• Cushing’s syndrome is the result

of chronically elevated plasma
cortisol concentration.

Cushing’s syndrome is associated

with hypertension, high blood sugar,
redistribution of body fat, obesity,
and muscle and bone weakness. If
untreated, it can also lead to
immunosuppression.