Endocrine Glands and the General Principles of Hormone Action
Cai Li, Ph.D.
Assistant professor
Touchstone Center for Diabetes Research
Departments of Physiology and Internal Medicine
The University of Texas Southwestern Medical Center
Dallas, TX 75390-8854
April 6, 2002

“Classical” Endocrine Glands

Endocrine gland
Adipose tissue
Adrenal cortex
Adrenal medulla
Heart
Hypothalamus
Small intestine
Islets of Langerhans
Kidneys
Liver
Ovaries
Parathyroid glands
Pineal gland
Pituitary, anterior
Pituitary,posterior
Skin
Stomach
Testes
Thymus
Throid gland
A more complete listing of the endocrine glands
Major hormones
Leptin
Glucocorticoids
Aldosterone
Epinephrine
Atrial natriuretic hormones
Releasing and inhibiting hormones
Secretin, cholecystokinin
Insulin glucagon erythropoietin
Somatomedins estradiol, progesterone
Parathyroid hormone
Melatonin
Trophic hormones
Antidiuretic hormone oxytocin
1,25-dihydroxy vitamin D
3
Gastrin
Testosterone
Thymosin
T3, T4, calcitonin
Primary target organs hypothalamus liver, muscle kidneys heart, blood vessels kidneys pituitary stomach, liver, pancreas fat, muscle, brain liver, fat bone marrow cartilage repro. tract, mammary glands bone, small intestine, kidneys hypothalamus, ant. Pituitary endocrine glands kidney, blood vessels uterus, mammary glands small intestine
Stomach prostate, seminal vesicles lymph nodes
Many

Exocrine and Endocrine Glands

Exocrine Glands and Endocrine glands
Exocrine Glands:
Examples:
Secrete into a duct and to the outside of a body surface sweat, tear, saliva
Endocrine Glands: Secrete (hormone) into the blood
Hormone circulates in blood and acts
Examples: at target organs where hormone receptor is expressed insulin
Exocrine and Endocrine glands:
Liver:
Pancreas
Endocrine Exocrine
IGF Bile
Pancreatic juice insulin, glucagon, PP

Chemical Structure of Hormones
1. Amines (amino acid derivatives)
Tyrosine derived: epinephrine, thyroid hormones
Tryptophan derived: melatonin
2. Polypeptides
Insulin, leptin, ADH
3. Glycoproteins
FSH, LH
4. Steroids (cholesterol derived)
Glucocorticoids, testosterone, vitamine D

Mechanisms of Actions of Hormones
•
•
•
All hormones act by binding to their receptors
Some receptors are located on the cell surface
ƒ Polar hormones (insulin, leptin)
Some receptors are located in the cytoplasm
ƒ Lipophilic hormones (steroids, thyroid hormones)
Some receptors are located in the nucleus
ƒ Lipophilic hormones (TZDs, Fibrates)

Assay and Measurement of Hormones
Bioassay
Chemical assay
Radioimmunoassay (1977 Nobel prize)
#
[hormone] (ng/ml)
Receptor binding assay (Scatchard plot)

Action of nuclear hormones

Actions of PPAR γ , a nuclear hormone receptor

Regulation of hormone secretion:
A simple feedback loop
↑ Blood glucose
↓
β cells in the pancreas
↓
↑ Insulin secretion
↓
↑ Uptake of blood glucose
Liver
Muscle
Glucose
↓
Glycogen
Fat
Glucose
↓
Triglyceride
↓ blood glucose

Structure of an islet

How glucose and therapeutic drugs cause insulin secretion

Two general principles of hormone action
Acts on cells containing the receptor
Action is regulated by a feedback mechanism

180
_
150
_
120
_
90
_
60
_
30
_
28%
33%
54%
60%
?
0
1980 1990 2000 2010

Leptin: a new hormone from fat
• Made in the adipose tissues
• A polypeptide of 167 amino acids
• Product is secreted into blood
• Its receptor is found in many tissues
• Leptin deficiency causes obesity, infertility, and many other
• complications

Tissue distribution of leptin

Leptin gene mutation in ob/ob mouse ob/ob
R105 (CGA → TGA)
R105 (CGA → TGA)
167

Leptin Receptor Isoforms
Long OB-Rb
Short OB-Ra
OB-Rc
OB-Rd
Soluble OB-Re
Extracellular TMR Intracellular
1162
894
892
900
805

Tissue distribution of the leptin receptor
Common
Probe Length (kb)
0.60
Ob-Ra 0.25
Ob-Rb 0.20
Actin 2.00

db
Mouse
Ob-Rb
C57BL/KsJ db/db db3J/db3J dbPas/dbPas
Rat fa/fa fak/fak
Extracellular TMR Intracellular
1162
894
625
281
Q269P
1162
762

Leptin Levels in Lean and Obese Rodents
+/+ db/db +/+ fa/fa
Leptin western
Leptin northern
β -actin

Leptin levels in lean and ZDF rats
14
12
10
8
6
4
2
0
Plasma ( µ l)
1 2 5 10 25 50 50
ZDF Lean

Soluble Leptin Receptor Levels in Lean and ZDF Rats
Plasma ( µ l)
Lean ZDF
100 1 2 5 10 20
203
116
OB-Re

Jak-STAT Pathway of Leptin Receptor
Signal Transduction
Ob-Ra Ob-Rb
Leptin
Jak2 Jak2
Y
Y
Y
Y
Y
Y
P
P
P
Y
Y
Y
Jak2 Jak2
Y
Y
P
Y
P
P
SHP-2
P
P
STAT3
P
P
Jak2 Jak2 P
P
P
Y
Y
Y
Y
Y
P
Y
P
Moves to Nucleus

Hypothalamic signaling pathways regulating energy homeostasis

Severe postnatal obesity of a child with leptin mutation
Age (years)

One example of human leptin mutation

Leptin treatment of a girl with leptin deficiency

• Most tissues are endocrine glands and have the capacity to secrete molecules that act on other tissues
• All hormones act by interaction with their receptors
• The action of most hormones are regulated by a negative feedback mechanism