Endocrine Disease in the White House

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Transcript Endocrine Disease in the White House

Chapter 18 Part 2
• Thyroid Gland
– Synthesis and function of Thyroid hormone
Calcitonin and Calcium regulation
• Parathyroid Gland
– PTH and Calcium regulation
• Adrenal Gland
– The corticosteroids
• Pancreas
– Regulation of blood glucose
Thyroid Gland
Hyoid Bone
• Covers anterior
surface of trachea
• 2 lobes with isthmus
lobe of
thyroid
lobe of thyroid
Isthmus
Trachea
Thyroid gland
• Tissue consists of follicles
• Follicles are hollow spheres
lined with epithelial cells
(follicle cells)
• Follicular cells take up Iodine
from circulation and produce
thryoglobulin (the precursor
to thyroid hormone)
• Thyroglobulin is stored in the
colloid of follicle
• C cells produce calcitonin
(CT)
Thyroid Gland
An elusive C-cell is indicated
Here thyroglobulin, a
glycoprotein, is stained
hot pink
Synthesis of thyroid hormone
Synthesis of thyroid hormone
• A funky, multistep process
• Iodine selectively pumped into the membrane of
follicular cells
• Iodine bound to tyrosine molecules, forming
thyroid hormone, incorporated into thyroglobulin
• Thyroglobulin is stored in follicle
• Upon TSH stimulation, thyroglobulin is
endocytosed back into follicle cell, diffuses across
cell, and released into bloodstream
T4 versus T3
• What is the difference?
• The thyroid releases 90%
T4, 10% T3
• T3 is the active form!
Functions of Thyroid Hormone
• Actively transported into all cells of body
• Binds mitochondria, increases rate of mitochondrial
ATP production
• Binds nuclear receptors and increases transcription
of Na+/K+ ATPase
• Also activates genes that code for enzymes involved
in glycolysis and ATP production
• PUNCHLINE: Thyroid hormone increases basal
metabolic rate
Thyroid Hormone Regulation
Misregulation and Goiters
• TSH causes
thyroid
hormone
release AND
growth of
thyroid tissue
C cells and Calcitonin
• C cells respond directly to
high levels of Ca2+ in
body fluids
• Release Calcitonin (CT),
works to reduce Ca2+
concentration in body
fluids
• How??
Calcitonin and Ca2+ regulation
• Inhibition of osteoclasts
(the bone breaker-downer
cells)
• Stimulation of Ca2+
excretion at kidneys
CT
osteoclast
Parathyroid Glands
• Located on the posterior
aspect of the thyroid gland
• Chief cells produce and
release parathyroid
hormone (PTH) directly in
response to low
circulating Ca2+ levels
• PTH works to increase
Ca2+ levels
Parathyroid Glands
• Stimulates osteoclasts
• Inhibit osteoblasts
(decreases rate of Ca2+
deposition)
• Increases Ca2+ resorption
at kidnes
• Stimulates formation of
calcitriol at kidneys
(works at gut)
Chomp, chomp!
PTH
osteoclast
PTH and Calcitonin regulate Ca2+ levels
Adrenal Gland
cortex
medulla
•The cortex has three cellular
regions (zones), each that makes
specific hormones
–Zona glomerulosa (outermost)
–Zona fasciculata (middle)
–Zona reticularis (innermost)
Adrenal Gland
medulla
250uM
Adrenal Cortex
• Endocrine tissue that produces a variety of
corticosteroids (general term for steroids from the
cortex)
• All affect gene transcription
• This collection of steroids are vital to life
• The cortex has three cellular regions (zones), each
that makes specific hormones
– Zona glomerulosa: Mineralocorticoids
– Zona fasciculata: Glucocorticoids
– Zona reticularis: Androgens
Adrenal Cortex
Zona glomerulosa
-Mineralocorticoids
• Aldosterone, the “Na+ saver”
• Its release is triggered by a drop in blood
Na+, blood volume or blood pressure
• Aldosterone works at: kidneys, sweat glands,
salivary glands and pancreas to decrease
Na+ secretion/release
• Effect: water follows Na+, so water is saved,
as well
Adrenal Cortex
• Zona fasciculata
– Glucocorticoids
• When stimulated by ACTH, cortisol
and corticosterone secreted (and
cortisone is converted from cortisol
by the liver)
• Glucocorticoids exhibit negative
feedback at both the hypothalamus
and anterior pituitary
Effects of Glucocorticoids
• Accelerate rates of glucose synthesis and
glycogen formation, especially at liver
• Adipose breaks down TG into Fas
• Anti-inflammatory effects
– Inhibit WBC and other immune system
fuction
– Slow migration of phagocytic cells into
injury site, and decrease activity
– Negative effects on wound healing
Adrenal cortex
• Zona Reticularis
– Produces androgens
Adrenal Medulla
• What is the composition of this part of the
gland?
• What triggers the release?
• What hormones are produced?
Adrenal Medulla
Sympathetic division
Parasympathetic division
Effects of Adrenal Medulla Stimulation
• @ skeletal muscles: mobilize glycogen reserves,
increase beakdown of glucose into ATP
• @ adipose tissue: stored fats are broken down,
fatty acids into circulation
• @ liver: glycogen breakdown (the brain needs
glucose!)
• @ heart, 1 receptors stimulated, increase in
cardiac force and rate
Pancreas
• A unique gland with both exocrine and
endocrine functions
– Exocrine: produces enzymes for digestion
– Endocrine: produces hormones for blood
glucose regulation
Histology of the
Pancreas
A single islet containing 
and  cells
Endocrine Islets in a sea
of exocrine cells (acinar
cells)
Regulation of Blood Glucose
 cells release glucagon
 cells release insulin
Nutshell version:
Normal blood glucose levels = 70-110 mg/dL
--When blood glucose is low, glucagon stimulates glycogen
breakdown and glucose release from liver
--When glucose levels are elevated, insulin encourages the
uptake use, and storage of glucose
Regulation of blood glucose
gluconeogenesis
One example in detail
• How does insulin actually increase glucose
uptake by cells?
• This process is not totally understood and is an area of
intensive research.
• Glucose transporter discovered in mid 1980’s
http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/pancreas/insulin_phys.html
http://research.imb.uq.edu.au/~l.rathbone/glut4/
Diabetes
• 17 million Americans have Type 2 (adultonset) diabetes, a disorder in which cells
lose their ability to absorb glucose from the
blood stream.
• This is different from Type 1 (juvenile
onset) diabetes, in which the immune
system attacks insulin-producing,  cells.
What tissues, organs suffer in diabetic state? Why?