1.anintroductiontoendocrinology
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KOMUNIKASI ANTAR
SEL-SEL
PENGANTAR KULIAH
ENDOKRINOLOGI
SMT IV-A FK UWKS 2006
Paul S. Poli
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What is endocrinology?
Endocrinology =
Intercellular Chemical Communication
Endocrinology is about communication
systems & information transfer.
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What are endocrine systems for?
Endocrine Functions
Maintain Internal Homeostasis
Support Cell Growth
Coordinate Development
Coordinate Reproduction
Facilitate Responses to External Stimuli
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What are the elements of an
endocrine system?
Sender= Sending Cell
Signal= Hormone
Nondestructive Medium = Serum & Hormone Binders
Selective Receiver= Receptor Protein
Transducer= Transducer Proteins & 2 Messengers
Amplifier= Transducer/Effector Enzymes
Effector= Effector Proteins
Response = Cellular Response (2 Hormones)
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What is a hormone?
A molecule 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 molecule is a hormone only
when described in the context of its role in a biologicalcommunication system. Definition of a hormone requires
testing of that molecule in a biological response system,
running a bioassay.
Ultimately, the existence of endocrinology is dependent on
the existence & use of bioassays. (This is also true for
pharmacology & toxicology.)
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What kinds of hormone are there?
Known Hormonal Classes
Proteins & peptides
Lipids (steroids, eicosanoids)
Amino acid derived
(thyronines, neurotransmitters)
Gases (NO, CO)
chem.pdx.edu/~wamserc/ChemWorkshops/ gifs/W25_1.gif
website.lineone.net/~dave.cushman/
epinephrine.gif
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What is a hormone receptor?
Hormone Receptors are cellular proteins
that bind with high affinity to hormones & are
altered in shape & function by binding; they
exist in limited numbers.
Binding to hormone is noncovalent &
reversible.
Hormone binding will alter binding to other
cellular proteins & may activate any receptor
protein enzyme actions.
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What are the main types of receptors?
Membrane Receptors
Imbedded in target cell membrane; integral proteins/glycoproteins; penetrate through membrane
For protein & charged hormones (peptides orneurotransmitters)
3 major groups: Serpentine = 7 transmembranedomains, Growth factor/cytokine = 1 transmembranedomain, Ion channels
Nuclear Receptors
Nuclear proteins that usually act in pairs & bind to
specific Hormone Recognition Elements (HREs) =sequences on the DNA in the promoter regions oftarget genes
For small, hydrophobic molecules (steroids, thyroidhormones)
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What are transducers?Transducers are proteins that convert the
information in hormonal signals into chemicalsignals understood by cellular machinery.
They change their shape & activity when theyinteract directly with protein-hormone complexes.
Usually enzymes or nucleotide binding proteins,they produce 2nd messengers, or change theactivity of other proteins by covalently modifyingthem (adding or removing phosphate, lipid groups,
acetate, or methyl groups), or they interact withother proteins that do these things.
They begin amplifying the energy content of the
original hormone signals.
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How many kinds of
transducers are there?
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What are effectors?
Effectors are the enzymes & otherproteins that convert the transduced
hormonal signal into biochemicalchanges that generate the cellular
response to hormone binding.
Usually amplify the signal further &
allow cellular work to be done: cellmotion, growth, division, altered
metabolism, secretion, depolarization,
etc.
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What are feedback systems?
Feedbacks Generate Control Loops
Negative
These maintain hormonal balance & are often linkedto homeostatic processes.
If the multiplicative effect of the several links in a
control loop is negative, the entire control loop isnegative.
Positive
These cause physiologic changes in the systeminvolved.
If the multiplicative effect of the several links in acontrol loop is positive, the entire control loop is
positive.
--+
++
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How dynamic are these systems?Hormone, receptor, transducer & effector levelsvary with time. Some change over short terms,
others over long terms.
Levels also vary with developmental stage,gender, & health status.
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Can single cells make or sense morethan one hormone at a time?
Yes, cells can make multiple hormones, even ofdiffering chemical classes, & they can sensemultiple signals -- & integrate them -- all at once.
Examples:
Ovarian granulosa cells make inhibin (protein),estradiol (steroid), & androstenedione (steroid)during the follicular phase of the ovarian cycle. Atthe same time they respond to FSH & growth factors(proteins), estradiol (steroid), & thyroxine (amino
acid derivative), along with other hormones.
Anterior pituitary gonadotropes respond to LHRH(peptide) & inhibin (protein), estradiol, testosterone,progesterone, & glucocorticoids (steroids) while
they make both FSH & LH (proteins).
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How do hormone levels vary?
Hormone levels rise & fall due to synthesis ofhormone & due to degradation & clearance ofhormone. Target cell binding accounts for onlya small fraction of removal of hormone fromcirculation.
In addition to hormone levels changing,targetcell receptor, transducer, & effector levels canalso change with age, sex, & physiological ordevelopmental state. These also vary amongcell types giving rise to tissue differences inhormone sensitivity.
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What is the classical
endocrine system?
We now know that
nearly every tissuesecretes chemical
signals that act as
hormones, heart,
immune cells, stomach,intestines, bone cells,
liver, skin, glial cells,
etc.
www.cushin s-hel .com/ ima es/endocrine.
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a248.e.akamai.net/.../pubs/mmanual_home/ illus/i144_1.gifwww.cushings-help.com/ anterior-pituitary.gif
Structural Relationships:
Hypothalamus & Pituitary
Modified from R. Guillemin & R. Burgus (1972)
The hormones of the hypothalamus, Sci Am 227:24-33.
Modified from R. Guillemin & R. Burgus (1972)
The hormones of the hypothalamus, Sci Am 227:24-33.
Hormone A Hypop Hypoth alamic Regulator(s) Hormo nal Functio n(s)
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What are the regulary products of
the hypothalamus?
Hormone A
c
r
o
n
y
m
Hypop
hysia l
Cell
Type
Hypoth alamic Regulator(s) Hormo nal Functio n(s)
Corticotropin,
Adrenocortic
otropin
A
C
T
H
Cortic
otrope
+Corticotropin Releasing Hormone,
Corticoliberin (CRH); + Interleukin 1 ; -
Glucocortical Steroids (via CRH); +
Vasopressin; + PACAP
Stimulates glucocorticoid production by
adrenal fasiculata & reticularis
Thyrotropin,
Thyroid
Stimulating
Hormone
T
S
H
Thyrot
rope
-Thyroxine (T4); +Thyroid Releasing Hormone,
Thyroliberin (TRH); -Somatostatin (SS)
Stimulates thyroxine production by thyroid
Prolactin,
Mammotropin, Luteotropin
P
RL
Lactot
rope;Mamm
otrope
-Dopamine; + TRH; - SS; + Estrogens; +
Oxytocin
Stimulates milk synthesis by secretory
epithelium of breast; supports corpus luteumfunction
Somatotropin
, Growth
Hormone
G
H
Somat
otrope
+ Growth Hormone Releasing Hormone,
Somatoliberin (GHRH); - SS; + PACAP
Stimulates somatic growth, supports
intermediary metabolism
Follitropin,
Follicle
StimulatingHormone
F
S
H
Gona
dotro
pe
+ Gonadotropin Releasing Hormone,
Luteinizing Hormone Releasing Hormone,
Gonadoliberin (GnRH, LHRH); - Inhibin; - Sexsteroids (via LHRH)
Supports growth of ovarian follicles &
estradiol production; Supports Sertoli cell
function & spermatogenesis
Lutropin,
Luteinizing
Hormone
L
H
Gona
dotro
pe
+ GnRH (LHRH); - Sex steroids (via LHRH in &
); + Estradiol in near midcycle
Supports late follicular development,
ovulation, & corpus luteum function
(especially progesterone synthesis); Supports
testosterone synthesis, Leydig cell
Melanotropin,
Melanocyte
Stimulating
Hormone
M
S
H
Melan
otrope
+ CRH Supports dispersal & synthesis of pigment in
melanocytes; may alter adrenal response to
ACTH
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Where do these come from?
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How is the thyroid controlled?
Kenneth L. Campbell, 1997.
All rights reserved.
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How is the adrenal cortex
controlled?
Kenneth L. Campbell, 1997. All rights reserved.
Th d l/ t i
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The adrenal/stress axis& blood pressure
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How is growth hormone
controlled?
Kenneth L. Campbell, 1997. All rights reserved.
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Pancreatic endocrine physiology
After meals gl cose
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After meals glucose
from liver is mainly
stored as glycogen in
liver & muscle & as fat
in fat cells. When more
energy is needed
between meals,
glycogen, fat & protein
(last) are broken down
& liver uses the parts to
make glucose.
Hormones (insulin,
glucagon, adrenalin,
cortisol) signal the
change from storage to
synthesis.
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H C t l th
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Glucagon acts on liver tostimulate glucose production& release, & on fat to causefat breakdown.Glucagon
rises when glucose falls.
Adrenaline, cortisol, &
growth hormonealso
make blood glucoserise. Butinsulin-like-
growth factor I acts
like insulin.
Pancreas
Hormones Control theGlucose Balance
Insulin acts on body cells
to allow them to take incirculating glucose.Insulin levels rise whenglucose rises.
InsulinGlucagon
Islets of Langerhans
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Body Mass
Homeostasis:
Our New
Understanding
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The satiety axis
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A Little More About the CentralPlayers
C
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Calcium Homeostasis
H th d t ll d?
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How are the gonads controlled?
LH
Kenneth L. Campbell, 1997. All rights reserved.
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How are the gonads controlled? FSH
Kenneth L. Campbell, 1997. All rights reserved.
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How is prolactin controlled?
Kenneth L. Campbell, 1997. All rights reserved.
What questions remain open?
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Examples:
Molecular discovery Exploration of molecular interactions Definition of the genetics of endocrine
molecules & their interactions Description of dynamics & kinetics of
cellular interactions Impacts of environmental variables on
molecular or cellular interactions Impacts of toxicants on molecular or
cellular interactions Discovery & exploration of chemical
modifiers of the endocrine system
What questions remain open?
Wh t i li ti i l d?
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Genomics, Proteomics, Transgenics,
Pharmacology, Toxicology, Clinical &
Veterinary Medicine, Nursing,Diagnostics, Forensics, Epidemiology,
Statistics, Biomedical Engineering,
Informatics, Basic EndocrineResearch
What specializations are involved?
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Communication among cells & organisms &between organisms & their environment isabsolutely central to life & reproduction. Whilemany of the basics of endocrine communication areknown, we are continually surprised by newfindings that revise our existing knowledge. Many,of the details of endocrine molecular biology,genetics, cell biology, & development remain to bedefined. As one of the most dynamic & central ofthe biomedical sciences for practitioners,paramedical professions, & basic scientists,endocrinology will continue to be a vital science formany years to come.
Conclusions: