Transcript Endocrine Pharmacology - Home

Endocrine Physiology
Bob Bing-You, MD, MEd, MBA
Medical Director
Maine Center for Endocrinology
What is physiology?
• A. Study of function in living matter
• B. Specific characteristics and mechanisms
of the human body that make it a living
being
• C. “The human being is actually an
automaton.”
• D. All of the above.
Learning Objectives
• Explain normal feedback mechanisms for
normal endocrine function
• Describe abnormal pathophysiologic states
• Define treatment approaches for such states
Ground Rules
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Case-based, common examples
Feel to ask questions anytime
Take a few breaks for Q and A
Call or e-mail [[email protected]] with
confused thoughts, concepts, etc.
Major Areas
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Thyroid gland
Adrenal gland function, steroid Rx
Diabetes: glucose monitoring, insulin Rx
Calcium homeostasis, vitamin D
Pheochromocytoma
Diabetes insipidus
Design Exercise
• New heat source for your house in the
basement
• Need monitor system 3 floors above
• Thermostats not invented yet!
• Task= design system to regulate
temperature in your house
Purpose of Endocrine System
• Principally concerned with control of
different metabolic functions of the body
[e.g., transport of substances through cell
membranes]
• Hormonal effects can occur in seconds
while others require days or weeks
What is a hormone?
• A chemical substance secreted into body
fluids by one cell or group of cells
• Exerts a physiological control effect on
other cells in the body
• General vs. local hormones
• General hormones may effect all cells [e.g.
GH] or some effect specific tissues
Major Hormones
• Anterior pituitary
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Growth hormone
Adrenocorticotropin [ACTH]
Thyroid-stimulating hormone [TSH]
Follicle-stimulating hormone [FSH]
Luteinizing hormone [LH]
Prolactin [PRL]
More Hormones
• Posterior pituitary: antidiuretic hormone
[ADH]
• Adrenal
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Aldosterone
Glucocorticoids [cortisol]
Testosterone, estrogen
catecholamines
Even More Hormones!
• Thyroid hormones: thyroxine [T4],
triiodothyronine [T3]
• Pancreatic: insulin, glucagon
• Parathyroid: parathyroid hormone [PTH]
Chemistry of Hormones
• Two types
– Proteins or derivatives of proteins or amino
acids [e.g., anterior pituitary, thyroid]
– Steroid hormones [e.g., adrenal cortex, gonads]
• Circulate in minute quantities [e.g., onemillionth of a milligram]
• Bioassay vs. radioimmunoassay
What describes hormones effecting other local
cells?
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A. Paracrine
B. Endocrine
C. Autocrine
D. None of the above.
Bioassay
• Animal cell tissue system
• Plasma or some extract added to see effect
• E.g., testosterone
Immunoassay
• Sandwich-type
• Very quick [e.g., intra-op PTH]
• Minimal blood or serum required
Mechanisms of Action
• Activation of cyclic AMP system of cells
• Need hormone receptor [key and lock]
• Cyclic AMP forms as an intracellular
hormonal mediator [aka as “second
messenger”]
• ACTH, TSH, FSH, LH, ADH, PTH,
glucagon
• Effects can be instantaneous
2nd mechanism of action
• Activation of genes in target cells, causing
formation of intracellular proteins
• Steroid hormone enters cytoplasm and binds
to receptor proteins
• Enters nucleus to activate genes to form
messenger RNA
• m-RNA promotes new proteins to be made
• Delayed effect of mins [aldosterone] to days
Transport of Hormones
• Biologic effect due to free hormones
• Binding globulins – “the buses”
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Thyroid Binding Globulin [TBG]
Sex-hormone Binding Globulin [SHBG]
Cortisol Binding Globulin [CBG]
Produced in liver
• What is assay measuring? “Total” [I.e.,
bound] vs. “Free”
Sandwich-type assays refer to:
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A. Dialysis method
B. Ham and cheese
C. Two antibodies
D. Live cellular responses
Control of Hormonal System
• Tendency of each gland is to oversecrete
• Need method to prevent oversecretion
• Need method to stimulate production if
undersecreting
• KEY is Negative Feedback
• Some exceptions [e.g., prolactotrophs and
dopaminergic inhibitory fibers]
Key Points
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Hormones effect metabolism all tissues
Instantaneous vs. prolonged effects
Free hormones biologically active
Negative feedback is KEY to normal
homeostasis