BI459 –

ENDOCRINOLOGY
LAND ACKNOWLEDGEMENT

We would like to acknowledge that Wilfrid Laurier University and its campuses are located on the Haldimand tract,
traditional territory of the Neutral, Anishnaabe (Anish-nah-bay) and Haudenosaunee (Hoe-den-no-show-nee) peoples. This
land is part of the Dish with One Spoon Treaty between the Haudenosaunee and Anishnaabe peoples and symbolizes the
agreement to share, protect our resources and not to engage in conflict. From the Haldimand Treaty of Oct. 25, 1784 this
territory is described as: “six miles deep from each side of the river (Grand River) beginning at Lake Erie and extending in the
proportion to the Head of said river, which them and their posterity are to enjoy forever.”
Today, this gathering place is home to many First Nations, Métis and Indigenous peoples from across Turtle Island.
Acknowledging them reminds us of our important connection to this land where we live, learn and work. We recognize,
honour and respect these nations as the traditional stewards of the lands and water on which Laurier is now present.
WELCOME TO BI459 – ENDOCRINOLOGY

http://www.everydayhealth.com/hair-loss/hormone-replacement-therapy-as-a-hair-loss-
treatment.aspx
 People Assessment
BI 459 -
ENDOCRINOLOGY
INTRODUCTION
Course
Reading List
Description
 COURSE INSTRUCTOR

Dr. Cristina Gheorghiu

 Office Hours: by appointment (Zoom – registration required)
 Email: cgheorghiu@myls.wlu.ca (M-F: 9:00 am - 5:00 pm)
 COURSE DESCRIPTION

 An examination of the mechanisms involved

in hormonal control and regulation of
reproduction, growth, development and
metabolism, with a focus on the physiological
consequences of alterations in endocrine
homeostasis.
LECTURE NOTES & COURSE SYLLABUS

 Dr. Gheorghiu’s Lecture Notes will be available on-

line through MyLS before the lecture.

 Course Syllabus & Research Project Guidelines

available through MyLS
 Lecture 50%
 Online Quizzes (6 out of 8) 10% TBA
 Midterm 1 20% Feb. 15
 Midterm 2 20% April 3

 Group Research Project 50%

 Group Enrolment, Contract & Topic choice (group) BONUS Jan. 20
 Seminar Outline/Draft (group) 5% Jan. 27
 Research Seminar (group) 20% TBA
 In-Class Discussions on Seminars (group) 20% TBA
 Peer-Evaluation (individual & confidential) 5% TBA

 Total: 100%
 ONLINE QUIZZES
Lecture Quizzes
• Schedule: Jan. 20, 27, Feb. 10, March 3, 10, 17, 24, 31.
• Non-cumulative: concepts covered in the corresponding Lectures
between quizzes.

LockDown Browser
• make sure you have installed it on your devises.

Format
• MS, FIB, ORD, MATCH.

Deferrals
• NO deferrals.
• 6/8 quizzes for full marks for this component.
 MIDTERMS
REMOTE Midterms – MyLS/Quizzes
• Schedule: Feb. 15, April 3.
• Non-cumulative: concepts covered in the corresponding
chapter.

LockDown Browser
• make sure you have installed it on your devises.

Format
• MS, FIB, ORD, MATCH.
 MIDTERM RULES
 Missed Midterms
 Need approved documentation to justify (doctor’s
note, etc.)
 Email me as soon as possible, preferably the same day
 Provide me with documentation within 1 week of the missed
test

 No DEFERRED Midterm 1
 If missed due to a valid reason and the proper
documentation is provided, you will be able to write a
CUMULATIVE Midterm 2.
 GROUP RESEARCH PROJECT - COMPONENTS
Group Choice
• 5 students/group - self enrolment in Groups of MyLS
• Deadline: Jan. 20; after – autoenrollment.

Topic Choice
• First come, first served rule
• Post the names of the students enrolled in your
group in the folder corresponding to your preferred
topic already created in the “Topics and groups”,
Discussions folder on MyLS
• Deadline: Jan. 20; after – autoenrollment

Group Contract
• Deadline: Jan. 20
 GROUP CONTRACT
Components:
1. a table with the responsibilities of each member (a suggestion is to base it on their
particular strengths) and the deadlines for when all the work is to be completed
2. the penalties for noncompliance.
3. topics you may want to discuss & consider as a group:
 When will we hold group meetings?
 How will we distribute work? How will we ensure that all group members have equal
contribution to the project?
 How will we handle feedback amongst our group (e.g., what will and will not be
considered constructive criticism)?
 How will we deal with one or more people that have a low motivation to get work
completed, or a person that is not contributing? What about justified reasons to miss a
meeting (will we allow it? If yes, how many times?)
 How will we ensure quality control (checking/reviewing policy) on our work? For
instance, who will be responsible for editing, compiling, and submitting the final project
(these are not trivial responsibilities!)?
 How will we ensure that our work is not plagiarized?
 How will we make sure our group time is enjoyable? (Very important!)
 PROJECT OUTLINE/DRAFT
Project Outline - group
• Focused, clear and concise.
• Main sections with main ideas to be covered.
• Definite steps and deadlines.

Project Draft - group

• Presentation design
• Detailed information for each section, together
with the references.
• Images, videos, etc. to be included

Deadline
• Jan. 27
 GROUP RESEARCH PRESENTATION
Format
• seminar, role playing, interview, animation video, song, game, etc.
• BE CREATIVE!

Guidelines
• posted on the MyLS course page (files in Group Research Project
folder in Content).

Posting
• All presentations together with the scripts should be posted in
BOTH Discussions & Dropbox corresponding folders.
• Posting deadlines: Feb. 5, 26, March 5, 12, 19, 26, April 2
 IN-CLASS DISCUSSIONS ON RESEARCH PRESENTATIONS
Schedule
• Feb. 8, 10, March 1, 3, 8, 10, 15, 17, 22, 24, 29, 31, April 5

Attendance
• You cannot defer any In-class Activities linked to discussions on
Research Projects.
• In order to get full marks, you MUST attend and ACTIVELY PARTICIPATE
in each one of these activities. Attendance will be taken for each class
assessing the student presentations.
a.Irrespective of the group mark, this is a team effort so individuals who
are absent will get a mark of zero for this component (class
discussion).

Activities
• Presenting Groups will give a very brief overview of your research topic
(5 min.)
• Groups in audience: To prepare for the discussions, all students should
watch the presentations that will be discussed during class and prepare
questions and comments for each presentation beforehand.
 PEER EVALUATION
Ranking - individual
• 1 & 2: bellow average proficiency
• 3: the average proficiency
• 4 & 5: above average proficiency

Comments - individual
• to support your individual ranks

Deadlines:
• Feb. 8, 10, March 1, 3, 8, 10, 15, 17, 22, 24, 29, KSAs (Knowledge, Skills, and Abilities)
31, April 5
 ACADEMIC INTEGRITY
 Academic integrity is required to take this
course!

 Academic misconduct limits learning and

disadvantages honest students.

 For University policy on academic

misconduct and penalties see:
www.wlu.ca/academicintegrity
RELIGIOUS ACCOMMODATIONS FOR MID-TERMS, TESTS, LABS
AND OTHER COURSE WORK
Student Obligations

• Alert the instructor within two weeks of the start of the term of
any scheduling conflicts by submitting the Student Request for
Accommodation for Religious Observances form.

Accommodations

• Extending a deadline
• Rescheduling a deadline or test date
• Providing an alternative academic obligation, etc.

More Info

• supports and resources for student religious accommodations.

 STAY INFORMED

Brightspace Pulse app - mobile devices

 Course calendars
 Readings
 Assignments
 Evaluations
 Grades
 News
 READING LIST
 Endocrine Physiology
(2018), P.E. Molina
 5th ed.
 McGraw Hill Professional
 ISBN-13: 9781260019360

 Integrated
Endocrinology (2012), J.
Laycock & K. Meeran
 2nd ed.
 John Wiley & Sons Canada,
Limited.
 ISBN-13: 9780470688120
 INTRODUCTION TO
ENDOCRINOLOGY

 Anatomy & Physiology –

Overview of Main
Concepts
 Endocrine vs. Exocrine
Glands
 Modes of Secretion
 Overview of the
Endocrine System
 General Organization
 Main Functions
  CELL: Basic element (unit) of living organism

 TISSUES: Group of cells having same functions

 ORGANS: Functional units composed of tissues (e.g. glands)

 Parenchyma vs. stroma
ANATOMY  SYSTEMS: Group of organs with related functions
- MAIN CONCEPTS -
 PHYSIOLOGY - MAIN CONCEPTS

Secretion vs. Excretion

 both are involved in the passage or movement of materials

 both involved in homeostasis

 “Excretion”: removal of material from a living thing

 (mostly body wastes; e.g.: tears, urine, carbon dioxide, feces)

 “Secretion”: movement of materials (that can be metabolized

and used by our bodies) from one point to another
 e.g. hormones, saliva
 ENDOCRINE VS.
EXOCRINE GLANDS
Gland: organ that releases certain
substances for use in the body
or for discharge into the
surroundings
a) Endocrine
• separated from surface (no
ducts)
• secretions (usually) transported
via circulatory system
Pancreas
b) Exocrine
• maintain connection to surface
• secretions empty to surface
through ducts
 Cellular Patterns of Secretion
Secretory Pattern Description Example

Endocrine Secretion into the blood for transport internally to Hormones

______________
target tissues

Exocrine Secretion into a duct that opens onto an external or Sweat

______________
internal surface

Merocrine Secretion without visible damage to the secretory ______________

Peptide hormones
cell (involves exocytosis)

Apocrine Release by sloughing of “outer” or apical portion of Mammary gland - milk

______________
secretory cell

Holocrine Release through cell death and lysis Sebaceous gland secretion
______________
(skin)

Cytogenous Release of whole, viable cells Spermatozoa

______________
 ENDOCRINOLOGY - OVERVIEW
▪ Endocrinology: study of endocrine glands/tissues &
their products (hormones)
▪ endocrine (‘internal secretion’)

▪ Hormone: A chemical signal/messenger synthesized

by an endocrine organ (gland) or tissue
▪ secreted in the bloodstream to act on specific target
cells and elicit a specific physiological response
▪ Water-soluble: via exocytosis (vesicles)
▪ Lipid-soluble: via diffusion (simple or facilitated)
 ENDOCRINE SYSTEM
- GENERAL ORGANIZATION -

▪ Includes a number of different cells, tissues, and

organs (glands)
▪ Components are ONLY functionally related
▪ Synthesizes & secretes hormones that:
▪ Regulate
▪ Coordinate
functions of target cells (in most cases
long-distance targets)
▪ Integrate
 ENDOCRINOLOGY -
OVERVIEW
▪ Not ALL vertebrates have the same
glands/endocrine tissues!!

▪ E.g. Mammals:
▪ Glands: pituitary, thyroid, parathyroid,
adrenal, pineal

▪ Tissues: (structures/organs with

some endocrine function):
hypothalamus, thymus, pancreas,
gonads, kidneys, stomach, liver,
small intestine, adipose tissue
 ENDOCRINE SYSTEM
- CELLULAR ORGANIZATION -

▪ Cords (most common)

▪ linear arrangement
▪ e.g. pituitary gland; adrenal cortex

▪ Follicles
▪ spherical masses → product (h) inside (lumen)
▪ e.g. thyroid gland
 ENDOCRINE SYSTEM
- CELLULAR ORGANIZATION -

▪ Scattered clumps or clusters

▪ e.g. I. of Langerhans (pancreas; Leydig cells in
testes)

▪ Single cells (unicellular gland)

▪ e.g. cells within the epithelial lining of digestive and
respiratory tract
 HORMONE DELIVERY - OVERVIEW
▪ Endocrine - via circulation (distant delivery)

▪ Autocrine - act on the same cell that secreted it

▪ Paracrine - act on neighboring cells

▪ Intracrine – act within the same cell that made it

▪ Neuroendocrine - “neurohormones” released via

synapses (neurosecretory cells) into bloodstream
 NEUROENDOCRINE SYSTEMS
▪ Allow the nervous system to coordinate
endocrine systems and to communicate with
peripheral tissues

▪ Neurosecretory cells are different from regular

neurons: Eckert Fig 9.15

▪ secrete neurohormones
▪ large size of secretory vesicles
▪ terminals on blood vessels (Release hormones into
interstitial space close to bed of capillaries
(neurohemal organ)
 NEUROSECRETORY CELLS &
NEUROHORMONES

Magnocellular (large neurons) of hypothalamus

 Axons in neurohypophysis
 Secrete ADH (vasopressin) & oxytocin
 Vasopressin (ADH)
 vasoconstriction
 water reabsorption (kidney)
 Oxytocin
 contraction of smooth muscle of uterus
 contraction of myoepithelial cells (milk ejection)
 ENDOCRINE SYSTEM
- MAIN FUNCTIONS -
▪ Maintains the internal environment in the body
(optimum biochemical environment; “homeostasis”).
(W. Cannon; 1929)
▪ Regulates growth, development, and metabolism

▪ Controls sexual reproduction, including gametogenesis,

fertilization, fetal growth and development, and
nourishment of the newborn
▪ Regulates the response to stimuli (e.g. stress and/or
injury)
Claude Bernard (1813-1878):….
“The stability of the internal
environment [the milieu intérieur] is
the condition for the free and
independent life”
 ENDOCRINE VS. NERVOUS SYSTEM
 Nervous & endocrine systems share
responsibility for maintaining body health
 Nervous system sends nerve impulses
(action potentials) & responds to stimuli to
adjust body processes
 Endocrine system sends hormones but
responds more slowly.

Nolte, 2009
over long distances point-to-point
 EXPERIMENTS ON
ENDOCRINE FUNCTION OF
A GLAND/ORGAN/TISSUE
 Removal of tissue should
produce deficiency/effect
(can be difficult if it has
more than one function, e.g.,
heart)

 Replacement should reverse

deficiency/effect
First recorded endocrine
experiment (~1849):
 Deficiency/effect relieved demonstrated that the combs of
when suspected hormone is Arnold Berthold roosters is androgen dependent
injected (most important
criterion)
German physiologist / zoologist Testosterone (purified ~1935)
PHEROMONES

Organic compound
(CH-skeleton)
Different types of
transmission (diffusion;
current-borne; contact)

Medium: air or water

Invertebrates &
vertebrates

Differ in size, shape,

composition & polarity
 HORMONE DELIVERY
 Endocrine hormones
 Intracrine, autocrine, and paracrine
hormones, neurohormones
 (endohormones)

 Pheromones
 exocrine signals released externally to
initiate response in another organism
 (ectohormones)
 Example: Fish use pheromones to assist social
HORMONE DELIVERY: behavior:
• schooling
PHEROMONAL • identification of conspecifics
COMMUNICATION • potential mates & in reproduction.
• Prostaglandins (i.e., PGF2a) are released by
female fish around the time of ovulation
and influences male spawning behavior.
▪ Pheromones= exocrine • Biol Reprod. 1988 Dec;39(5):1039-50.
signals released
externally to initiate
response in another
organism; odorless;
well studied in wildlife
 BI459 –
ENDOCRINOLOGY
• Classification of hormones
• Characteristics of different
hormone types
• Life history of a hormone
• Regulation of secretion and
delivery
• Modes of action
• Metabolism

42
CLASSIFICATION OF
HORMONES
ACCORDING TO
THEIR SOLUBILITY
 CLASSIFICATION OF HORMONES
▪ Four main groups based on chemical nature:
(A) Peptides and proteins
(most) water soluble
(B) Amino-acid derivatives
(C) Steroids
lipid soluble
(D) Fatty acid derivatives – Eicosanoids
▪ In general:
▪ water-soluble hormones have cell surface receptors
▪ lipid-soluble hormones have intracellular receptors
CLASSIFICATION OF HORMONES
 PEPTIDE/PROTEIN HORMONES

 They comprise the largest group

 Synthesized in the ER (pre (ER) signal)

 They vary considerably in size (3-100s of Aas)

and post-translational modifications

 Many protein hormones are synthesized as

prohormones, then proteolytically clipped to
generate their mature form
 PEPTIDE/PROTEIN HORMONES –
SECRETION
 ER (synthesis) → Golgi → secretory granules (for secretion)
 Regulated secretion: Granules stored and released upon
cell stimulation (most common; allows cells to secrete
large amounts of H in little time)
 Constitutive secretion: H in secretory vesicles is secreted
as it is synthesized
 The half-life of most circulating peptide Hs is only a few
minutes
 Some may circulate bound to other proteins (e.g. insulin-like
growth factor-1 (IGF-1)
 Amino Acid Derivatives
• Precursors = tyrosine, tryptophan, histidine

Two groups of hormones derived from tyrosine:

1) Thyroid hormones (double tyrosine with incorporation of 3 or 4 iodine atoms)
2) Catecholamines (catechol ring structure; E, NE, DA)
 Amino Acid Derivatives –
Thyroid Hormones
▪ Produced by the thyroid gland
▪ Two forms: T4 and T3
▪ (In most cases, T4 = main circulating form and is converted in
the liver or in target cells to T3)

▪ Mostly bound to thyroxin binding globulin for transport

in the blood (circulating half-life = a few days)
hydrophobic at normal blood pH
▪ Enter cells by facilitated diffusion (special transporters)
▪ They are inactivated primarily by intracellular
▪ deiodinases
Where is the R??
AMINO ACID DERIVATIVES –
CATECHOLAMINES
 Epinephrine (E), norepinephrine (NE),
Dopamine (DA)
 Function as both neurohormones and
neurotransmitters:
 E and NE produced by the adrenal
medulla
 Dopamine released by
hypothalamus
 Secreted by exocytosis (vesicles)
 Rapidly degraded by liver monoxidase
(MAO) and aldehyde oxidase
 circulating half-lives of only a few
minutes)
 Catecholamines may be synthesized
from either phenylalanine or tyrosine What determines which one is released??
 OTHER AMINE ACID
DERIVATIVES

 Tryptophan- precursor
for:
 Serotonin
 Melatonin

 Histidine - converted to
histamine
Amine Acid Derivatives – Catecholamines

http://www.epipen.co.uk/hcp/anaphylaxis-treatment/adrenaline/moa/#
 STEROID
HORMONES

 Derived from cholesterol

(mostly from liver; released
into the blood as lipid
droplets coated with
protein)

 Steroid H. are not packaged!

→ synthesized and released

Copyright © 2013 Elsevier Inc. All rights reserved.

 STEROID
Cholesterol
HORMONES
Different steroid hormones have
different ring structure and side
chains
▪ Glucocorticoids - e.g. cortisol (stress)
▪ Mineralocorticoids - e.g. aldosterone
(Na, water retention)
Estradiol
▪ Androgens - e.g. testosterone
(reproduction/development)
▪ Estrogens - e.g. estradiol and estrone
(reproduction/development)
▪

▪ Progestogens (aka progestins) -

e.g. progesterone
(reproduction/development)

Copyright © 2013 Elsevier Inc. All rights reserved.

 STEROID
HORMONES
 Hydrophobic → need to be carried in
blood complexed to carrier proteins
(globulins)
 Examples: Corticosteroid binding
globulin (CBG) carries cortisol;
Sex steroid binding globulin
(SSBG) (SSBH) carries
testosterone and estradiol
 H generally inactive when bound to
carrier
 Binding capacity of the carrier protein
influences the clearance rate of the
hormone
 → specific (high affinity) or non-
specific (i.e. albumins-low affinity)
Fatty Acid Derivatives
- Eicosanoids -
▪ Include prostaglandins,
prostacyclins, leukotrienes
and thromboxanes
▪ Derived from
polyunsaturated fatty acids
(main precursor: arachidonic
acid (DAG derivative)
▪ not stored → synthesized
as required
▪ Rapidly inactivated
(metabolized) → active for
only a few seconds
Type of eicosanoids synthesized determined by
enzyme type present in the cell
Copyright © 2013 Elsevier Inc. All rights reserved.
 Fatty Acid Derivatives
- Prostaglandins -
▪ The most commonly occurring prostaglandins
are PGE1, PGE2, and PGF2a
▪ Functions:
▪ smooth muscle contraction in the intestine
▪ vasodilation (but may cause vasoconstriction)
▪ inhibition of blot clotting
▪ Reproduction: induction of ovulation, lactation, anti- inflammatory and antipyretic
labor (fever-decreasing) action of aspirin
▪ Immune function: induction of inflammation & fever is due to its inhibition of PG
synthesis
 Cellular Morphology of
Endocrine Cells
▪ Steroid secreting cells contain extensive sER, contain
numerous mitochondria with tubular cristae, and often
contain numerous lipid droplets
▪ Protein secreting cells contain extensive rER, have well-
Figure 1-6 Cytology of hormone-secreting
developed Golgi bodies, and frequently accumulate cells. (A) Microscopic appearance of a steroid-
acidophilic secretory granules in their peripheral secreting cell (adrenocortical cells from
juvenile salmon), (B) A growth-hormone
cytoplasm secreting cell from the coho salmon
(Oncorhynchus kisutch) showing dense
▪ Amino acid derived H-secreting cells contain small secretory granules - Copyright © 2013 Elsevier
secretory or storage granules similar to synaptic vesicles Inc. All rights reserved.
found in axonal endings in neurons, but lack extensive
sER or rER
 Why Is Important To Understand
Hormone Structure/Chemical Nature?

▪ It determines how the H is synthesized,

secreted, and transported in blood
▪ It determines how it interacts with target cells
(i.e. where its receptors are located) and how
it produces its effects
▪ It determines how is metabolized or
inactivated
▪ It determines the specificity for receptors
 Life History of A
Hormone
1. Synthesized and secreted by
an endocrine cell
• In some cases: H secreted
in an inactive form
2. Spends its life in the blood
• bound or not to binding
proteins
3. Binding to target cell
• causing a particular effect)
4. It may be metabolized
and/or excreted before or
after it binds to a target cell
• Liver and kidney → major
sites for metabolism and
excretion

Copyright © 2013 Elsevier Inc. All rights©reserved.

Copyright 2013 Elsevier Inc. All rights reserved.
 Regulation of Endocrine Activity

Control at different levels:

1) Synthesis and secretion of the hormone
- e.g. positive and negative feedback mechanisms, seasonal/daily cycles, age and
stage of development, sleep, etc.
2) Delivery of hormone to target cell
- Regulating concentration of H in blood and extracellular fluid
3) Binding to receptors on target cell
- Number and type of receptors on target cells
4) Termination of the response
 Feedback Hypothalamic-pituitary axis (neuroendocrine reflexes)
Mechanisms
Commonly used to regulate secretion example of close integration between
of hormones the nervous and endocrine systems!!
A) Positive feedback loops: increase (controller)
in hormone levels stimulates further
secretion
- important for short-term events or
rapid response but is detrimental over
longer time periods E1 (effector 1)

B) Negative feedback loops: Increase

in hormone levels has an inhibitory
effect on release or synthesis of the
(adrenal
hormone
- most common
gland, ovaries,
- helps maintain homeostasis testes) E2 (effector 2)
- contributes to pulsatile secretion of
hormones
 Feedback
Mechanisms
Commonly used to regulate secretion
of hormones
A) Positive feedback loops: increase
Positive Feedback:
in hormone levels stimulates further Oxytocin Release
secretion
- important for short-term events or
rapid response but is detrimental over
longer time periods

B) Negative feedback loops: Increase

in hormone levels has an inhibitory
effect on release or synthesis of the
hormone
- most common
- helps maintain homeostasis
- contributes to pulsatile secretion of
hormones
 AMOUNT OF HORMONE
DELIVERED
 The physiological effects of hormones depend largely on their
concentration in blood and extracellular fluid
 Hormones are normally present at very low concentrations
in circulation

 Factors that affect the [hormone] delivered to target:

 Rate of production
 Rate of delivery (related to regulation of blood flow to the
target organ)
 Rate of degradation and elimination (metabolized for
excretion)
 RECEPTOR BINDING

[Hormone] required to achieve

response will depend on:
 Receptor properties (or
characteristics of Hormone-
Receptor Interactions):
 Affinity (Kd; tendency to bind
the H)
 Specificity
 Typically: high affinity, specificity
→ bind tightly, low receptor
numbers needed
 Abundance of receptors
 RECEPTOR BINDING

Agonists = molecules that bind

the receptor for a particular
ligand and mimics its action

Antagonists = molecules that

block binding of the agonist by
binding the receptor, but do not
activate it

Inverse agonists = molecules that

bind the receptor but produce
the opposite effect on the target
cell
Cell Surface vs. Intracellular Receptor Activation
Principle Mechanism
Location of Receptor Classes of Hormones
of Action

Generation of second
messengers which
Proteins and peptides,
Cell surface receptors alter the activity of
catecholamines, and
(plasma membrane) other molecules -
eicosanoids
usually enzymes -
within the cell

Intracellular Alter transcriptional

Steroids and thyroid
receptors (cytoplasm activity of responsive
hormones
and/or nucleus) genes
 Breakdown of Glycogen by Liver Cells
Signal Transduction
Pathways Amplify
Cellular Response
to a Signal
▪ Very small quantities of
ligand are often sufficient
to elicit a response
▪ In most steps, a signaling
intermediate stimulates
the production of many
molecules for the next
step ➔ amplification
Cell Surface vs. Intracellular Receptor Activation - Summary
Eicosanoids
 TURNING OFF THE RESPONSE
TO HORMONES

 H-R internalization and degradation

 Receptor phosphorylation and inactivation
 Degradation of 2nd messengers
 Metabolism (Inactivation/degradation) of 1st
messengers (hormones) in blood and target cells
 Metabolism of Hormones

Circulating hormone
▪ Mainly metabolized in the liver and eliminated by
kidneys (some via feces OR bile)

In target cells
▪ protein and amine hormones bound to receptors are
internalized and degraded by the cell (peptidases, or
deamination in lysosomes)
▪ steroid and thyroid hormones are degraded after H-R
complex binds to DNA
 Biological Half-Life
Hormone Source Half Life
of Hormones
(min)
Biological Half-Life = The time Polypeptides Mammalian 3-50 min
required to remove or clear half
of the amount of biologically
active hormone from the blood Proteins Mammalian 10-200 min
▪ usually determined by following
the rate of removal of
radioactively labeled molecules
Amines Mammalian 2-3 min
▪ in general: the larger the peptide
the longer its biological half-life
▪ exceptions: some small Thyroid Mammalian 1 (T3)-7 (T4) days
peptides have post-
translational modifications hormones
that slows their enzymatic
degradation
Steroids Mammalian 5-150 min
 Cross-Talks
Among
Hormonal
Pathways

▪ Many ways in which Hs

interact with other
pathways such that one
H system may influence
the effectiveness of
another Copyright © 2013 Elsevier Inc. All rights reserved.

Copyright © 2013 Elsevier Inc. All rights reserved.

A FINAL INTRODUCTORY
THOUGHT…

 All pathophysiologic events are

influenced by hormone
signaling

 Many physiologic effects are

mediated by multiple
hormones acting in concert
(cross-talk)

 There are many hormones

known and little doubt that
others functions or new
hormones remain to be
discovered
 Hormones are classified into protein, amino acid–
derived, and steroid based on their chemistry.
 Binding proteins regulate hormone availability and
prolong hormone half-life.
 Physiologic effects of hormones require binding to
specific receptors in target organs.
 Hormone release is under neural, hormonal, and
product regulation.
 Hormones can control their own release through
feedback regulation.