“Basics of Endocrinology”Dietary Cancer Prevention Course

Rebecca B. Riggins, Ph.D.rbr7@georgetown.edu

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