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Li Endocrine Glands
Li Endocrine Glands
Li Endocrine Glands
of Hormone Action
April 6, 2002
“Classical” Endocrine Glands
A more complete listing of the endocrine glands
Bioassay
Chemical assay
Radioimmunoassay (1977 Nobel prize)
% *Hormone bound
[hormone] (ng/ml)
↑ Blood glucose
↓
β cells in the pancreas
↓ ↓ blood glucose
↑ Insulin secretion
↓
↑Uptake of blood glucose
Liver
Muscle Fat
Glucose Glucose
↓ ↓
Glycogen Triglyceride
Structure of an islet
How glucose and therapeutic drugs cause insulin secretion
Two general principles of hormone action
150 _
120 _
33%
90 _
60 _ 28% ?
30 _
0
1980 1990 2000 2010
Leptin: a new hormone from fat
R105 (CGA→TGA)
167
Leptin Receptor Isoforms
Short OB-Ra
894
OB-Rc 892
OB-Rd
900
Soluble OB-Re
805
Tissue distribution of the leptin receptor
Sk. Muscle
Kidney
Spleen
Testis
Heart
Brain
Liver
Lung
Probe Length (kb)
Common 0.60
Ob-Ra 0.25
Ob-Rb 0.20
Actin 2.00
Rodent Mutations at the db Locus
db3J/db3J
625
dbPas/dbPas
281
Rat Q269P
fa/fa
1162
fak/fak
762
Leptin Levels in Lean and Obese Rodents
Leptin northern
β-actin
Leptin levels in lean and ZDF rats
14
12
Leptin (ng)
10
0
Plasma (µl) 1 2 5 10 25 50 50
ZDF Lean
Soluble Leptin Receptor Levels in Lean and ZDF Rats
Lean ZDF
Plasma (µl) 100 1 2 5 10 20
M.W. (kDa)
203
OB-Re
116
Jak-STAT Pathway of Leptin Receptor
Signal Transduction
Ob-Ra Ob-Rb
Leptin
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
SUMMARY
• 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