26 Endocrinology

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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


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Reading

! For a general overview! http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/index.html

! Harrison's Online! Chapter 332: Principles of Endocrinology

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

Ganongs Review of Medical Physiology! 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! Endocrine Disorders, Ch 26

http://www.accessmedicine.com/content.aspx?aID=14266! Netter

! Neoapp3, network drive, Physiology


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Objectives

! 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, andthe concept feedback

! Know the hormones made in the hypothalamus andpituitary glands and their mechanism of release

regulation


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Endocrinology

! Study of Hormone release and signaling in! Volume control, Metabolism, immune activities, Growth and

Development, Reproduction, Circadian rhythms

! Hormones! 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 (lockand key)

! Can work in an Autocrine or Paracrine fashion

vassopression thyroid glucocorticoid


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1. Which is an example of a hormone that controls Volume?a)Estrogenb)Glucocorticoidc)Mineralocorticoidd)Testosteronee)Thyroid

2.The Thyroid hormone can control which of the following?a)Muscle contractionb)Immune activatesc)Metabolismd)Body temperature

aquaporin channels

metabolism withh cause hea t

hypothyroid will always be cold!


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Endocrine system

! Endocrine glands! 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


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Endocrine Hormones

! A chemical messenger involved in intracellular andextracellular communication

! Generally a protein or Ion

! Functions as a ligand (Key)

! Binds to a specific receptor (Lock)! Lock + Key = activity! Receptors can be Membrane bound (G-coupled),

Cytolsolic (GR), or Nuclear (ER, TR)

g-protein ussually


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3. The endogenous ligand for the glucocortoid receptor is?a) Corticosteroneb) Cortisolc) Dexamethasoned)

Prednisone

4. A membrane bound receptor will most likely interact with a_____ hormone?

a) Hydrophilicb) Hydrophobic

these 2 are exogenous, synthetic

1000 more potent than

endogenous

require carrier protein to make it lipid

soluable

goes inside


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5. Can you give me an example of an extremely fast actingmembrane bound receptor that acts through a G coupled

receptor? Its action can be seen when you turn onthe light. controls the eye's ability to jsut to light


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Circulating Hormones

! Secreted into extracellular fluid

! Transported by the blood (hemocrine) to target cells distance involved

! Example is thyroid hormone affecting bone growth


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6. Which is an example of a circulating hormone known toeffect breast tissue?

a) Cortisolb) Estradiolc) Estrogend) Testosterone

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

need carrier

goes into the cells


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

some involvemnt in breast cancer


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Autocrine Signaling

! Hormone is secreted into extracellular fluid

! Affects the same cell short or no distance

! Example! insulin regulating its own release, insulin-like growth

factors


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Paracrine Signaling

! Secreted into extracellular fluid

! Diffuses to adjacent cells and effects them shortdistance

! Example! 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


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9. Which of the following is a way you can control/modulate hormone signaling?

a) Amount releasedb) Hormone solubilityc) Receptor antagonism/blockaded) Trickery


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Systemic Control of Hormone signaling

! Downstream hormone effect determined by:! Number of receptors present! Amount of hormone secreted

! Can you Block Receptor??! RU486 (mifepristone)


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Regulation of Hormone - Receptor Signaling

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

!Up-Regulation! " in hormone leads to ! in receptor

! Target cell becomes more sensitive to hormone

! Negative Feedback! cells can sense the magnitude of the hormones

biological effect and decrease the response


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

control.html

Negative Feedback


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Examples of feedback regulation

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


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Endocrine and Nervous System Signaling

! Nervous system! neurons receive information from other neurons via

neurotransmitters (paracrine)

! Endocrine system! cells receive information from chemical messengers (ions,

hormone) and release their hormone (Autocrine or

Paracrine) or produce a product


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Water Soluble (Hydrophilic) Hormones

! Amines or Amino Acid Derivatives [Example: Histamine]! Synthesized by decarboxylating an Amino Acids

! Stored in vesicles, Stimulus causes release

! Peptide Hormones [Example: Oxytocin, Insulin]! Polymers of amino acids (3 to 300+ amino acids)

! Stored in vesicles, Stimulus causes release

!Eicosanoid Hormones

[Example: Prostaglandins]

! Derived from Arachidonic Acid

! Not Stored, Stimulus causes secretion and synthesis


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Lipid Soluble (Hydrophobic) Hormones

! Steroid Hormones [Example: Testosterone]! Derived from Cholesterol


! Thyroid Hormone [Example: T3 and T4]! Synthesized by attaching Iodine to tyrosine



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Neuroendocrine cells

! Specialized neuronal cells that can secret hormones! Neuroendocrine: Conversion of electrochemical signal to

hormonal signal

! Stimulation by neurotransmitter (neuroendocrine)releases the hormone into circulation


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Steroids Derivation from Cholesterol


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Features of hormones

!Hormones are effective in nanomolar to picomolar

! Physiological concentration the amount of hormonenecessary to elicit a normal response

! Pharmacological concentration therapeutic amount ofhormone may produce exaggeration of physiological effectsor noncharacteristic effects or normal response

! Pathological concentration an abnormally high or lowamounts of hormone produced by an endocrine gland

! Produces noncharacteristic effects

ussually a range


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Hormone Transport

!Water Soluble Hormones

(Amines, Peptides, Eicosanoids)

! Circulate free in blood Plasma

! Lipid Soluble Hormones (Steroid, Thyroid Hormones)! 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 ofHormones


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