Transcript “Basics of Endocrinology” Dietary Cancer

“Basics of Endocrinology”
Dietary Cancer Prevention Course
Rebecca B. Riggins, Ph.D.
[email protected]
202-687-7451
February 12th, 2009
Lecture Outline
• What is endocrinology?
• What are hormones?
– Key types of hormones
– Where are hormones made?
– How are hormones measured?
– What do hormones do?
• Why are hormones important to Dietary Cancer Prevention?
– obesity/diabetes/cancer
– breast cancer
• items highlighted in red are important!
• Many figures are taken from Lehninger’s Principles of
Biochemistry, 4th Edition, Chapter 23 – Dr. Ganganna has an
electronic (PDF) copy of this if you would like to read more
Endocrinology
• The study of the endocrine system and its
secreted products (hormones)
• endocrine is Greek; “endo” = within, “krinein”
= to release, separate
• The endocrine system is a collaborative system
of (small) organs
Organs of the Endocrine System
• Classification of adipose (fat) tissue
as an endocrine organ is recent
• We will focus later on the ovaries
and pancreas
Endocrine System Control
• The endocrine system is controlled by
the nervous system
• Nerve impulses travel to a target cell,
tissue, or organ, and stimulate
hormone release
• Hormones are released into and carried
around the body to their targets via the
bloodstream
Definition of a Hormone
• Hormones are the messengers of the
endocrine system
• 3 common sub-classifications of hormones by
location of action
– Endocrine: act at a distance; released far from
where they act
– Paracrine: act nearby; released next to where they
act
– Autocrine: act on the same cell/tissue/organ from
which they were released
Classification of Hormones by Type
Peptide/Amine
Hormone Receptors
Steroid
• Receptors are SPECIFIC for each hormone
• The presence/absence of a receptor
(“expression”) or its function (“activity”)
dictates the effect of any hormone on a tissue
• Peptide/amine hormones act faster than
steroid hormones
Hormone Synthesis
Peptide Hormone: Insulin
• Peptides, or proteins, are chains of amino acids
• Primary Structure = “beads on a string”
• Quaternary Structure = specific folding creates
domains, or “units” of the protein
Peptide Hormone: Insulin
• Proteolysis, or cleavage/digestion of peptide bonds, produces active insulin
Amine Hormones
• fight-or-flight response
• Tyrosine can be made by the body
(from phenylalanine)
• Also found in nuts/seeds, meats, dairy
Eicosanoid Hormones
• inflammatory/immune responses
• can be made from omega-3 or
omega-6 fatty acids
• Aspirin, Tylenol, Advil prevent
eicosanoid hormone synthesis
Steroid Hormones
• cholesterol is made by the body,
or obtained by eating any animal fats
Vitamin D
• Vitamin D made by your body begins
with a form of cholesterol
•Alternatively, vitamin D is obtained
by eating fortified foods (milk, bread,
orange juice, etc.)
Other Hormones
Focus on Insulin and Steroid
Hormones
• Insulin: regulation of metabolism
• Steroids: sex determination (estrogen,
androgen)
Insulin is produced in the pancreas
Physiology and Blood Glucose
Levels
• fasting blood glucose
Glucose regulates insulin
production by the pancreas
• Glucose enters the bloodstream
after food is digested
• Insulin triggers glucose uptake
by important tissues: liver, muscle,
and adipose (fat)
close
open
Physiology and Blood Insulin
• feeding response of blood insulin levels
•Why/how does this happen?
Glucose, Insulin, and Glucagon
• When you eat, glucose is released following digestion
• Insulin is secreted to lower, or counter-act, high
blood glucose
• Glucagon is another peptide hormone that is
released to lower insulin levels
1.
glucose
3.
insulin
2.
glucagon
4.
• When this system is functioning, energy intake
roughly equals energy output; weight maintenance
Obesity, Type II Diabetes, and
Insulin Resistance
• More than 65% of adult Americans are overweight or
obese
• Determined by body mass index (BMI)
• Insulin resistance: high, unregulated insulin levels
1.
glucose
3.
insulin
2.
glucagon
4.
• Chronic high insulin + high blood glucose = type II
diabetes
Cancer
• Being overweight or obese increases your
cancer risk: endometrial, breast, and colon
• Insulin resistance/high insulin is also linked to
breast cancer risk
• On February 26th – Dr. Hilakivi-Clarke will
lecture on “obesity and cancer risk”
Breast Cancer
• Second-leading cause of cancer death in
women
– ~40,000 in 2008
• >140,000 women in the U.S. were diagnosed
with breast cancer in 2008
– ~1000 men were diagnosed with breast cancer in
2008 too!
Breast Cancer Histology
Cancer
Normal
Invasive
Ductal
Carcinoma
(IDC)
Invasive
Lobular
Carcinoma
(ILC)
Different types of Breast Cancer
• Most common (~70%) are estrogen receptor
positive (ER+)
Estrogen in Pre- vs. PostMenopausal Women
Most active form of estrogen =
17-β-estradiol (E2)
Major site of post-menopausal
estrogen synthesis
Major site of pre-menopausal
estrogen synthesis
The Estrogen Receptor
Active, E2-bound
ER forms a dimer
Inhibiting the Estrogen Receptor
• Selective estrogen receptor modulators –
SERMs
• Tamoxifen – competes with estrogen for
binding to the receptor, preventing its
activation
• Aromatase inhibitors = AIs
• Letrozole, Anastrazole – block estrogen
synthesis in post-menopausal women
Inhibition of Breast Cancer Growth
AIs
SERMs
X
X
Breast Cancer Cell
Estrogen Mimics
On March 5th,
Dr. Warri will lecture
on “ Soy and Cancer
Risk” – Genistein is
a component of soy
On April 16th,
Dr. Hilakivi-Clarke will
lecture on endocrine
disruptors – Cadmium,
BPA, others