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Endocrinology

Homeostasis through hormonal secretion

Thomas J. Jones Ph.D.


C102 X6219

http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/index.html

Reading
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For a general overview


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http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/index.html

Harrison's Online
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Chapter 332: Principles of Endocrinology


http://www.accessmedicine.com/content.aspx?aid=2863323

Ganongs Review of Medical Physiology


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Chapter 18. Hypothalamic Regulation of Hormonal Function


http://www.accessmedicine.com/content.aspx?aid=5241127

Chapter 24. The Pituitary Gland


http://www.accessmedicine.com/content.aspx?aid=5242234

Current Medical Diagnosis & Treatment 2009


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Endocrine Disorders, Ch 26
http://www.accessmedicine.com/content.aspx?aID=14266

Netter
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Neoapp3, network drive, Physiology

Objectives

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Discuss the chemical structure of hormones Discuss the concept of solubility and how that applies to hormone signaling and transport Know where hormones can exert their effects, and the concept feedback Know the hormones made in the hypothalamus and pituitary glands and their mechanism of release regulation

Endocrinology
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Study of Hormone release and signaling in


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Volume control, Metabolism, immune activities, Growth and Development, Reproduction, Circadian rhythms

vassopression

thyroid

glucocorticoid

Hormones
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Released in one location - effect may be local or at distance May be water (hydrophilic) or lipid soluble (hydrophobic) Act within hours to days to weeks Activity usually achieved through binding to a receptor (lock and key) Can work in an Autocrine or Paracrine fashion

1. Which is an example of a hormone that controls Volume? a) Estrogen b) Glucocorticoid c) Mineralocorticoid d) Testosterone e) Thyroid

aquaporin channels

2. The Thyroid hormone can control which of the following? a) Muscle contraction b) Immune activates c) Metabolism d) Body temperature

metabolism withh cause heat hypothyroid will always be cold!

Endocrine system
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Endocrine glands
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Secrete hormones Effect could be local or systemic (circulated in blood) Examples: Traditional: hypothalamus, anterior pituitary, posterior pituitary, adrenal cortex, adrenal medulla, thyroid, parathyroids, gonads, pancreas Non-traditional: kidney, G.I. tract, liver, thymus, pineal gland, placenta, heart

Endocrine Hormones
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A chemical messenger involved in intracellular and extracellular communication


g-protein ussually

Generally a protein or Ion Functions as a ligand (Key) Binds to a specific receptor (Lock)
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Lock + Key = activity Receptors can be Membrane bound (G-coupled), Cytolsolic (GR), or Nuclear (ER, TR)

3. The endogenous ligand for the glucocortoid receptor is? a) b) c) d)


Corticosterone Cortisol Dexamethasone Prednisone

these 2 are exogenous, synthetic 1000 more potent than endogenous

4. A membrane bound receptor will most likely interact with a _____ hormone? a) Hydrophilic b) Hydrophobic
require carrier protein to make it lipid soluable goes inside

5. Can you give me an example of an extremely fast acting membrane bound receptor that acts through a G coupled receptor? Its action can be seen when you turn on controls the eye's ability to jsut to light the light.

Circulating Hormones
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Secreted into extracellular fluid Transported by the blood (hemocrine) to target cells distance involved Example is thyroid hormone affecting bone growth

6. Which is an example of a circulating hormone known to effect breast tissue? a) b) c) d)


Cortisol Estradiol Estrogen Testosterone

7. Is this hormone a hydrophobic or hydrophilic hormone? a) Hydrophilic b) Hydrophobic


need carrier goes into the cells

8. Can this hormone have a negative effect on breast tissue? a) Yes b) No


some involvemnt in breast cancer

Autocrine Signaling
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Hormone is secreted into extracellular fluid Affects the same cell short or no distance Example
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insulin regulating its own release, insulin-like growth factors

Paracrine Signaling
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Secreted into extracellular fluid Diffuses to adjacent cells and effects them short distance Example
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estrogen produced by cells in the ovary affecting growth of other cells in the ovary

NOTE: Hormones can also work in an autocrine, paracrine, and Hemocrine fashion at the same time

9. Which of the following is a way you can control/ modulate hormone signaling?
a) b) c) d)
Amount released Hormone solubility Receptor antagonism/blockade Trickery

Systemic Control of Hormone signaling


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Downstream hormone effect determined by:


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Number of receptors present Amount of hormone secreted

Can you Block Receptor??


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RU486 (mifepristone)

Regulation of Hormone - Receptor Signaling


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Down-regulation
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! in hormone leads to " in receptor Target cell becomes less sensitive to hormone

Up-Regulation
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" in hormone leads to ! in receptor Target cell becomes more sensitive to hormone

Negative Feedback
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cells can sense the magnitude of the hormones biological effect and decrease the response

Negative Feedback

http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/basics/ control.html

Examples of feedback regulation

http://www.elp.manchester.ac.uk/pub_projects/2000/ mnby7lc2/diabetes.htm#sites

Endocrine and Nervous System Signaling


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Nervous system
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neurons receive information from other neurons via neurotransmitters (paracrine)

Endocrine system
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cells receive information from chemical messengers (ions, hormone) and release their hormone (Autocrine or Paracrine) or produce a product

Water Soluble (Hydrophilic) Hormones


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Amines or Amino Acid Derivatives [Example: Histamine]


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Synthesized by decarboxylating an Amino Acids Stored in vesicles, Stimulus causes release


[Example: Oxytocin, Insulin]

Peptide Hormones
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Polymers of amino acids (3 to 300+ amino acids) Stored in vesicles, Stimulus causes release

Eicosanoid Hormones [Example: Prostaglandins]


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Derived from Arachidonic Acid Not Stored, Stimulus causes secretion and synthesis

Lipid Soluble (Hydrophobic) Hormones


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Steroid Hormones
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[Example: Testosterone]

Derived from Cholesterol Not Stored, Stimulus causes secretion and synthesis
[Example: T3 and T4]

Thyroid Hormone
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Synthesized by attaching Iodine to tyrosine Not Stored, Stimulus causes secretion and synthesis

Neuroendocrine cells

Specialized neuronal cells that can secret hormones


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Neuroendocrine: Conversion of electrochemical signal to hormonal signal

Stimulation by neurotransmitter (neuroendocrine) releases the hormone into circulation

Steroids Derivation from Cholesterol

Features of hormones
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Hormones are effective in nanomolar to picomolar Physiological concentration the amount of hormone ussually a range necessary to elicit a normal response Pharmacological concentration therapeutic amount of hormone may produce exaggeration of physiological effects or noncharacteristic effects or normal response Pathological concentration an abnormally high or low amounts of hormone produced by an endocrine gland
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Produces noncharacteristic effects

Hormone Transport
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Water Soluble Hormones (Amines, Peptides, Eicosanoids)


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Circulate free in blood Plasma

Lipid Soluble Hormones (Steroid, Thyroid Hormones)


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Circulate bound to transport protein Make Lipid soluble proteins water-soluble Retards degradation Provide temporary storage place

This plays a role in route of administration of Hormones

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