intro to endo physio
TRANSCRIPT
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Endocrine PhysiologyAn Introduction
Victor L. Mendoza, M.D.
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Regulation of the Functions
of the Body
Nervous system
Endocrine (Hormonal) systemEndocrine (Hormonal) system
Major Control Systems:
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Endocrine vs Nervous Control
both share a role for control and coordination
throughout the body
should not be considered as separate entities
some endocrine glands respond to
nervous stimuli
endocrine system maintains nervous system
both systems involve reflexes
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Wh
at is endocrinologyEndocrinology =
Intercellular Chemical Communication
Endocrinology is about communication systems & information
transfer.
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ENDOCRINE SYSTEM
Uses chemical signals for cell to cell communication
Coordinates the function of cells
Response to an endocrine signal occurs within
minutes toh
ours
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Wh
at is endocrinologyEndocrine Functions
Maintain Internal Homeostasis
Support Cell Growth
Coordinate Development
Coordinate Reproduction
Facilitate Responses to External Stimuli
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Homeostasis & Controls
Successful compensation
Homeostasis reestablished
Failure to compensate Pathophysiology
Illness
Death
Figure: Homeostasis
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Amolecule that functions as a message within an
organism; its only function is to convey information.
Because of this function, physical descriptions of a
chemical thought to be a hormone are not adequate to
indicate the molecule's physiological role. A moleculeis a hormone only when described in the context of its
role in a biological communication system. Definition
of a hormone requires testing of that molecule in a
biological response system, running a bioassay.
Ultimately, the existence of endocrinology is dependenton the existence & use of bioassays. (This is also true
for pharmacology & toxicology.)
What is a hormone?What is a hormone?
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HORMONESH o r m a e i nH o r m a e i n excite; stir up
Endocrine System
chemical substances acting as messengers, produced by
ductless glands, that are transported in the circulation to targetcells
discrete chemical substances which transfer information from
one set of cells to another
chemical substances secreted into body fluids by one cell or achemical substances secreted into body fluids by one cell or agroup of cells and that exert a physiological control effect ongroup of cells and that exert a physiological control effect on
other cells of the bodyother cells of the body
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HormonesHormones
hormones are specialized chemical substances
effective only at specific target cells
hormones are classified according to t
he cells t
heyact upon
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Hormone ClassificationHormone Classification
Endocrines: hormones that are released into the
blood stream and interact with distant target
cells
Paracrines: local hormones that act on nearby
cells
Autocrines: local hormones that act on the cell
that released them
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Signal Chemicals
Made in endocrine cells
Transported via blood
Receptors on target
cells
Long Distance Communication: Hormones
Figure: Long distance cell-to-cell communication
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Figure: Long distance cell-to-cell communication
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Paracrines and Autocrines
Local communication
Signal chemicals diffuse
to target Example: Cytokines
Autocrinereceptor onsame cell
Paracrineneighboring cells
Figure: Direct and local cell-to-cell communication
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What kinds of hormone are there?What kinds of hormone are there?
Known Hormonal Classes
Proteins & peptides
Lipids (steroids, eicosanoids)
Amino acid derived
(thyronines, neurotransmitters)
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PEPTIDEHORMONES
Consist of specific amino acids (at least 3 amino acids)
Synthesized as large precursor proteins
Stored in membrane-enclosed compartments
Hydrophillic
Most abundant
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Protein and Polypeptide Hormones:
Synthesis and Release
Figure : Peptide hormone synthesis, packaging, and release
water soluble, stored in vesicles, secreted by exocytosis triggered
by an increase in cytosolic calcium, fast acting, short half-life
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Steroid Hormones
made from cholesterol
lipophilic (secreted as they are synthesized,
not stored)
specific protein carrier molecules
slow acting - genomic actions
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Endocrine System
HORMONES (peptides vs steroids)
* steroids are small hydrophobic molecules which are protein
bound in plasma while peptides are larger hydrophilic moleculesthat are usually free in plasma
* steroids have longer plasma half-lives than
peptides
* steroids have cytosol or intranuclear receptors while
peptides have membrane receptors
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Endocrine System
HORMONES (peptides vs steroids)
* steroids act directly through a nuclear mechanism, peptides
through a second messenger
* a longer time is required before the effects of steroids are
initiated or terminated because they have to be synthesized
and destroyed
* steroid hormones are synthesized in the smooth ER and are
released without being stored in granules; peptide hormones
are synthesized in the rough ER and are stored in granules
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Amine Hormones
derivatives of single amino acid residues,
primarily TYROSINE (tryptophan)
can behave either like peptides (catecholamines)
or steroids (thyroid hormones)
key characteristics: surface (catecholamines) or intracellular
(thyroid hormones) receptors
fast or slowacting
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Signal Pathways
Signal molecule (ligand)
Receptor
Intracellular signal
Target protein
Response
Figure: Signal pathways
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Hormones
Only target cells will respond to a specific hormone
(but some cells are targets for more than one hormone)
Only target cells possess specific receptors for the
hormone.
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Hormones
Receptor:
The molecular entity (usually a protein or
glycoprotein) either outside or within a cellthat recognizes and binds a particular hormone
When a hormone binds to its receptor, biologic
effects characteristic of that hormone isinitiated
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Endocrine System
RECEPTORS
Receptor proteins have two principal domains:
* hormone binding site
in majority of instances, has high specificity and
affinity
* activity site
couples the HR complex directly or indirectly
to enzyme systems and biological responses
distinguishes receptor from other proteins which
bind hormones but with no known biological activity
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Endocrine System
(conformational change; altered activity)
causes a series of biochemical changes *which produces the physiological responses
* regulation of enzyme
activity
* regulation of biosynthesis and degradationof nucleic acids and proteins
* regulation of the ability of the targets cells to
grow and replicate
R HRH +
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Endocrine System
(conformational change; altered activity)
causes a series of biochemical changes *which produces the physiological responses
R HRH +
Hormones signal cells to start or stop secreting,
contracting, dividing, or differentiating. They may also
accelerate or slow the rates of these processes, or theymay modify responses to other hormones. Function ofhormoneis to modify the physiological activity of a target cell or tissue
The specific response elicited in a given cell is determined by the cell
rather than the hormone; different cell types may respond to the same
stimulus in different ways.
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Can single cells make or sense more thanCan single cells make or sense more thanone hormone at a time?one hormone at a time?
Yes, cellsYes, cells can make multiple hormonescan make multiple hormones, even of differing, even of differingchemical classes, & theychemical classes, & they can sense multiple signalscan sense multiple signals ---- &&integrate themintegrate them ---- all at once.all at once.
Examples:
OvarianOvarian granulosa cellsgranulosa cells makemake inhibininhibin (protein),(protein), estradiolestradiol (steroid),(steroid),&& androstenedioneandrostenedione (steroid) during the follicular phase of the(steroid) during the follicular phase of theovarian cycle. At the same time they respond toovarian cycle. At the same time they respond to FSHFSH && growthgrowthfactorsfactors (proteins),(proteins), estradiolestradiol (steroid), &(steroid), & thyroxinethyroxine (amino acid(amino acidderivative), along with other hormones.derivative), along with other hormones.
Anterior pituitaryAnterior pituitary gonadotropesgonadotropes respond torespond to LHRHLHRH (peptide) &(peptide) &inhibininhibin (protein),(protein), estradiolestradiol,, testosteronetestosterone,, progesteroneprogesterone, &, &glucocorticoidsglucocorticoids (steroids) while they make both(steroids) while they make both FSHFSH && LHLH(proteins).(proteins).
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Receptor locations
Cytosolic orNuclear Lipophilic ligand enters
cell
Often activates gene
Slower response
Cell membrane
Lipophobic ligand can'tenter cell
Outer surface receptor
Fast response
Figure: Target cell receptors
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Membrane associated
enzymes
External reactions
Internal reactions
Receptors bind specific
ligand
Example: Hormones
Cell recognition
molecules
Figure : Cell membrane receptor
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2nd Messenger2nd Messenger
water soluble hormones are denied entrance to the
cell by the lipid bilayer of the plasma membrane
protein receptors embedded into th
e plasmamembrane are able to respond to specific hormones
first messengersin the blood
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2nd Messenger2nd Messenger
Protein hormones bind to specific receptor sites on
the target cells
hormone-protein receptor complex stimulates GG
proteinprotein
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2nd Messenger2nd Messenger
G proteinG protein links the receptors on the outer surface of
the cell to an enzyme (adenylyl clyclase) embedded
on the inner surface of the plasma membrane
adenylyl cyclase converts ATP into cyclic AMP
(cAMP) 2ndmessenger
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2nd Messenger2nd Messenger
cAMPactivatesprotein kinases that trigger a
cascade of enzymatic reactions in the cell
enzymatic reactions cause the cell to carry out its specific
physiological function
a single molecule ofhormone may cause the
production of thousands of molecules ofcAMP
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Cyclic AMPCyclic AMP
cAMP amplifies the signal that causes the cell to
perform its specific function
energy production in liver cells
hormone production in thyroid cells
increased contraction of cardiac muscle
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RECEPTORSPeptide Hormone Receptors
located in the cell membrane with the hormone
binding site expressed on the exterior cell surface
HR complex
alters the activity of membrane bound enzymesand transport processes
acts directly on target siteschange cellular concentration of
regulating molecules which then
function as second messengers(calcium ion, cAMP, DAG, etc)
alteration of enzyme activity
directly modifying
existing enzyme moleculesaltering the synthesis and
concentration of enzyme molecules
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Plasma MembranePlasma Membrane
ReceptorG-protein coupling Signal generator
Second messengers
Ca++, cAMP,cGMP,
phosphoinositides,prostaglandins, etc.
Enzyme activity
Enzyme concentration and other
cell proteins
DNA transcription
mRNAs
Substrates
Hormones
Secreted proteins
etc
Metabolic
pathways
Intrinsic kinase
activity
1A
1
23
Peptide +
Catecholamine
hormones
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Steroid Hormones: Action
Figure 7-7: Steroid hormone action
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Plasma MembranePlasma Membrane
ReceptorG-protein coupling Signal generator
Second messengers
Ca++, cAMP,cGMP,
phosphoinositides,prostaglandis, etc.
Enzyme activity
Enzyme concentration and other
cell proteins
DNA transcription
mRNAs
Substrates
Hormones
Secreted proteins
etc
Metabolic
pathways
Intrinsic kinase
activity
1A
1
23
Peptide +
Catecholamine
hormones
Receptor
Steroid Thyroid
Vitamin D Hormones
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HormonesHormones
hormones help regulate the rate of biochemical
reactions
like enzymes, hormones are not changed by the reactions
they regulate
secretion rates ofhormones vary from one gland to
another depending on physiological conditions (may
be episodic, pulsatile, or follow a daily rh
yth
m)
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HormonesHormones
ex: epinephrine (adrenaline) is secreted by the adrenal
glands in response to an emergency that calls for an
immediate increase of blood flow to the muscles
ex: ovarian hormones are secreted cyclically overextended periods of time to regulate the menstrual cycle
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Hormones
Modulation of Responding Systems Concentration ofhormones
Timing of secretion ofhormones
Receptivity of target tissues Sensitivity
Concentration ofhormones
Number of receptors
Capacity to respond Number of competent or differentiated cells Level of development of enzymatic machinery within cells
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Control of Hormone Release
SUBSTRATECONTROL
NERVOUSCONTROL
TROPHICHORMONES
- glucose regulating insulin release
- pituitary hormones
- released by the anterior pituitary
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Regulation of the Endocrine System
The endocrine cell, in addition to synthesizing and
secreting its own hormone products, has the ability to
sense the biologic consequences of secretion of that
hormone. This enables the endocrine cell to adjust itsrate of hormone secretion to produce the desired level
of effect, thereby ensuring maintenance of homeostasis.
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Feedback Loops
Figure: Negative and positive feedback
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Negative Feedback Controls:
Long & Short Loop Reflexes
Figure: Negative feedback
loops in the
hypothalamicanterior pituitary
pathway
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Summary of the Endocrine System
Figure: ANATOMY SUMMARY: Hormones
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HYPOTHALAMUS
Integrates functions that maintain chemical and
temperature homeostasis
Functions with the limbic system
Controls the release ofhormones from the anterior
and posterior pituitary
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Figure: Autonomic control centers in the brain
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HYPOTHALAMUS
Synthesizes & releases hypophysiotropic hormones:
Thyrotropin-releasing hormone (TRH)
Corticotropin-releasing hormone (CRH)
Gonadotropin-releasing hormone (GnRH) Growthhormone-releasing hormone (GHRH)
Growthhormone-inhibiting hormone (GHIH)
Prolactin-releasing factor (PRF)
Prolactin-inhibitn hormone (PIH)
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HYPOTHALAMUS
Synthesizes hypophysiotropic hormones in cell
bodies of neurons located in the hypothalamus
Transports hormones down the axon and stored in
the nerve endings
Secretion ofhormones is in pulses
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HYPOTHALAMUS: Secretion ofHypophysiotropic
Hormones
Is influenced by emotions
Can be influenced by the metabolic state of the
individual
Delivered to the anterior pituitary via the
hypothalamic-hypophyseal portal system
Usually initiates a three-hormone sequence
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Endocrine Control: Three Levels of Integration
Figure: Hormones of the hypothalamic-anterior pituitary pathway
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Sella turcica of the sphenoid bone
Location of the Pituitary
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Structure of the Pituitary Gland
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Structure of the Pituitary Gland
Two distinct lobes:
anterior pituitary
(adenohypophysis; pars distalis)
posterior pituitary
(neurohypophysis; pars nervosa)
- true endocrine tissue
- secretes classic hormones
- neural tissue
- secretes neurohormones
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Anterior PituitaryAnterior Pituitary
adenohypophysis contains many glandular epithelial
cells
larger of the two lobes (75%)
connected to the hypothalamus by a vascular link
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Posterior PituitaryPosterior Pituitary
neurohypophysis composed of nervous tissue
connected by neuronal tracts to th
eh
ypoth
alamus
neural link of nerve cells and blood vessels called the
infundibulum
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Pituitary and HypothalamusPituitary and Hypothalamus
Hormones secreted by the posterior pituitary are
synthesized and regulated by neuronal centers in the
hypothalamus
nerve impulses link the hypothalamus with the posterior
pituitary
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Hormones of the NeurohypophysisHormones of the Neurohypophysis
posterior pituitary does not actually manufacture
hormones
hormones synthesized in the hypothalamus are
transported through the nerve fibers as secretory
vesicles to the posterior pituitary
hormones are stored until nerve impulses from the
hypothalamus stimulate their secretion
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Hormones of the NeurohypophysisHormones of the Neurohypophysis
Two hormones are secreted in this manner from the
hypothalamus:
antidiuretic hormone (ADH)
oxytocin
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ANTERIOR PITUITARY HORMONES
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ANTERIOR PITUITARY HORMONES
Anterior pituitary produces seven (7) separate hormones
All but two are considered tropic hormones whose primary
target is another endocrine gland
ANTERIOR PITUITARY NON-TROPIC HORMONES
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ANTERIOR PITUITARY NON-TROPIC HORMONES
Growthhormone (GH)
Prolactin
ANTERIOR PITUITARY TROPIC HORMONES
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ANTERIOR PITUITARY TROPIC HORMONES
Gonadotropins:
- Luteinizing hormone (LH)
- Follicle stimulating hormone (FSH)
Adrenocorticotropic hormone (ACTH)
Thyroid stimulating hormone (TSH)
Melanocyte stimulating hormone (MSH)
The Hypothalamic-Hypophyseal Portal System
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The Hypothalamic-Hypophyseal Portal System
2 capillary beds directly joined by blood vessels
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ANTERIOR PITUITARYANTERIOR PITUITARY
ANTERIOR PITUITARY HORMONES
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ANTERIOR PITUITARY HORMONES
Growth Hormone (GH, Somatotropin): primary hormone
responsible for regulating body growth, and is important in
metabolism
Thyroid-stimulating Hormone (TSH): stimulates secretion ofthyroid hormone & growth of thyroid gland
Adrenocorticotropic Hormone (ACTH): stimulates cortisol
secretion by the adrenal cortex & promotes growth of adrenalcortex
ANTERIOR PITUITARY
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ANTERIOR PITUITARY
Follicle-stimulating Hormone (FSH): Females: stimulatesgrowth & development of ovarian follicles, promotes secretion of
estrogen by ovaries. Males: required for sperm
production
Luteinizing Hormone (LH): Females: responsible for ovulation,formation of corpus luteum in the ovary, and regulation of ovarian
secretion of female sexhormones. Males: stimulates cell in the
testes to secrete testosterone
Prolactin: Females: stimulates breast development and milkproduction. Males: involved in testicular function
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ANTERIOR PITUITARY
Synthesis of different anterior pituitary hormone is
by different cell populations.Corticotropes - ACTH
Lactortropes - Prolactin
Somatotropes - GH
Thyrotropes - Thyrotropin
Gonadotropes - FSH, LH
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ANTERIOR PITUITARY
SECRETES TROPIC HORMONES IN PULSATILE FASHION
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Summary of the Endocrine System
Figure: ANATOMY SUMMARY: Hormones
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Summary of the Endocrine System
Figure: ANATOMY SUMMARY: Hormones
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What is the classicalWhat is the classical
endocrine system?endocrine system?
We now know that
nearly every tissue
secretes chemical
signals that act as
hormones, heart,
immune cells,
stomach, intestines,bone cells, liver,
skin, glial cells, etc.
www.cushings-help.com/ images/endocrine.jpg
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How do hormone levels vary?How do hormone levels vary?
Hormone levels rise & fall due toHormone levels rise & fall due to synthesissynthesis of hormone &of hormone &due todue to degradationdegradation & clearance of hormone. Target cell& clearance of hormone. Target cellbinding accounts for only a small fraction of removal ofbinding accounts for only a small fraction of removal ofhormone from circulation.hormone from circulation.
In addition to hormone levels changing,In addition to hormone levels changing, target celltarget cellreceptor, transducer, & effector levels can also changereceptor, transducer, & effector levels can also change
with age, sex, & physiological or developmental state.with age, sex, & physiological or developmental state.These also vary among cell types giving rise to tissueThese also vary among cell types giving rise to tissuedifferences in hormone sensitivity.differences in hormone sensitivity.
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Hypothalamic stimulationfrom CNS
Pituitary stimulationfrom hypothalamic trophic Hs Endocrine gland stimulationfrom pituitary trophic Hs
Endocrine Control: Three Levels of Integration
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Pathologies: Over orUnder Production
Figure : Negative feedback by exogenous cortisol
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Pathologies: Due to Receptors
Figure : Primary and secondary hypersecretion of cortisol
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Hormones
Hormone Interactions Synergistic
Ex.: FSH & LH stimulate different stages of spermatogenesis at puberty
Ex.: Estrogen, Cortisol, Prolactin and Oxytocin complimentary action in regards
milk production Ex.: Epinephrine and norepinephrine increase heart rate
Permissive Ex.: Uterus exposed to estrogen induces formation progesterone
Ex.: Glucocorticoids permissive on catecholamines
Ex.: PTHhas a permissive effect on actions of vitamin D3
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Hormone Interactions Antagonistic
Ex.: Estrogen during pregnancy inhibits prolactin
Ex.: Insulin and glucagon
Hormones
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Growthhormone
Prolactin
Gonadotropins:
Luteinizing hormone (LH)
Follicle stimulating hormone (FSH)
Adrenocortocotropic hormone (ACTH)
Thyroid stimulating hormone (TSH)
Melanocyte stimulating hormone (MSH)
Anterior Pituitary Hormones
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peptide hormone
both a hormone and a trophic factor
- stimulates release of insulin-like growth
factors (IGFs; somatemedins)
chemical structure different between species
GROWTHHORMONE
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also called somatotropin
affects all parts of the body associated with growth
rather than targeting specific organs
increases tissue mass by stimulating cell division
GROWTHHORMONE
GROWTH HORMONE
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GH is only one necessary factor for normal
development
thyroid hormone
androgens
estrogens
insulin
IGFs
GROWTHHORMONEEffect on Growth
GROWTH HORMONE
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GH stimulates long bone growth
- increases length prior to epiphyseal closure
- increases width after epiphyseal closure
IGFs stimulate both bone and cartilage growth
GROWTHHORMONEBone Development
GROWTH HORMONE
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GH stimulates growth by increasing formation of RNA
- increased RNA causes increased protein synthesis
G
Hdecreases t
he breakdown of protein
GH causes a shift from the use of carbohydrates for energy to use of
fats
overall effect --> a change in the body's composition to increased
muscle mass and decreased fat deposition
GROWTHHORMONEAction
GROWTH HORMONE
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GH stimulates growth by increasing formation of RNA
- increased RNA causes increased protein synthesis
GH decreases the breakdown of protein
GH
causes a sh
ift from th
e use of carboh
ydrates for energy to use of fats
blood glucose levels rise resulting in hyperglycemia
*ifhyperglycemia is prolonged, it may lead to excessive
stimulation and early "burnout" of the beta cells, eventuallyleading to diabetes mellitus
GROWTHHORMONEAction
GROWTH HORMONE
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released in a pulsatile fashion in response to GHRH release
from the hypothalamus; inhibited by GHIH
also released by:
- hypoglycemia and fasting
- sleep
- stress
- exercise- increased amino acids in plasma
GROWTHHORMONERegulation of Secretion
GROWTH HORMONE
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Release of GH is controlled by 2hormones produced by the
hypothalamus:
- Growth-hormone releasing hormone (GHRH)
- stimulates GH release- Growth-hormone inhibiting hormone (GHIH)
- "somatostatin"
- inhibits release of GH
GROWTHHORMONERegulation of Secretion
GROWTH HORMONE
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in childhood, results in pituitary dwarfism
- complete deficiency
- partial deficiency
both respond to GH therapies
GROWTHHORMONEDeficiency
GROWTH HORMONE
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direct effect of GH is to maintain the epiphyseal disks of long bones
dwarfism is the result of deficient GH and
premature closure of the epiphyseal plates
cretinism (also dwarf) is caused by the
deficiency of thyroid hormone, not
pituitary hormone
gigantism is the result of continued release of GH
at the end of adolescence
GROWTHHORMONERegulation of Secretion
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