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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
! Not Stored, Stimulus causes secretion and synthesis
! Thyroid Hormone [Example: T3 and T4]! Synthesized by attaching Iodine to tyrosine
! Not Stored, Stimulus causes secretion and synthesis
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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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