“basics of endocrinology” dietary cancer prevention course rebecca b. riggins, ph.d....
TRANSCRIPT
“Basics of Endocrinology”Dietary Cancer Prevention Course
Rebecca B. Riggins, [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) tissueas an endocrine organ is recent
• We will focus later on the ovariesand pancreas
Endocrine System Control• The endocrine system is controlled bythe nervous system
• Nerve impulses travel to a target cell, tissue, or organ, and stimulatehormone release
• Hormones are released into and carriedaround 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
Hormone Receptors
• 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 thansteroid hormones
Peptide/Amine Steroid
Hormone Synthesis
Peptide Hormone: Insulin
• Primary Structure = “beads on a string”
• Quaternary Structure = specific folding creates domains, or “units” of the protein
• Peptides, or proteins, are chains of amino acids
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 oromega-6 fatty acids• Aspirin, Tylenol, Advil preventeicosanoid 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 beginswith a form of cholesterol •Alternatively, vitamin D is obtainedby 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
close
open
• Glucose enters the bloodstreamafter food is digested
• Insulin triggers glucose uptakeby important tissues: liver, muscle,and adipose (fat)
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
• When this system is functioning, energy intake roughly equals energy output; weight maintenance
glucose insulin glucagon1.
2.
3.
4.
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
• Chronic high insulin + high blood glucose = type II diabetes
glucose insulin glucagon1.
2.
3.
4.
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
IInvasiveDDuctalCCarcinoma(IDC)
IInvasiveLLobularCCarcinoma(ILC)
NormalCancer
Different types of Breast Cancer
• Most common (~70%) are estrogen receptor positive (ER+)
Estrogen in Pre- vs. Post-Menopausal Women
Major site of pre-menopausalestrogen synthesis
Major site of post-menopausalestrogen synthesis
Most active form of estrogen = 17-β-estradiol (E2)
The Estrogen Receptor
Active, E2-boundER 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
X
SERMs X
AIs
Breast Cancer Cell
Estrogen MimicsOn March 5th, Dr. Warri will lectureon “ Soy and CancerRisk” – Genistein isa component of soy
On April 16th, Dr. Hilakivi-Clarke will lecture on endocrinedisruptors – Cadmium,BPA, others