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Endocrine system

dr.Swanny, MSc
Physiology Dept.

Endocrine system
Basic Physiologic Concept
General learning objectives.
After studying this IT, you should be able to:
1. Understand the basic concepts applying to all
endocrine system.
2. Understand the control of hormone synthesis,
secretion, blood levels and action.
3. Understand the function of hypothalamo-
pituitary axis.
4. Apply the physiological concepts to recognize
and to manage the patients with endocrine
Endocrine System

Uses chemical signals for cell to cell


Coordinates the function of cells

Response to an endocrine signal occurs

within minutes to hours
Chemical Regulating Systems: Overview

Pheromones: organism to organism

Hormones: cell to cell communication
Made in gland(s) or cells
Transported by blood
Distant or local target tissue receptors
Activates physiological response
Paracrine and Autocrine Hormones

Local communication
Signal chemicals diffuse to target
Example: Cytokines
Autocrinereceptor on same cell
Paracrineneighboring cells

Figure 6-1c: Direct and local cell-to-cell communication

Long Distance Communication: Endocrine Hormones

Signal Chemicals
Made in endocrine cells
Transported via blood
Receptors on target cells

Figure 6-2a: Long distance cell-to-cell communication

Nervous system Endokrin

Functional unit neuron glandula

Chemical Neuro hormon

messenger transmitter
Mode of Action potential Blood stream
Reaction time seconds Minutes -
General concepts
Mayor function of endocrine system :
regulate enzymatic and metabolic
processes (e.g. Molecular transport)
responsible for maintaining the equilibrium
(homeostasis) of the internal environment

To ensure survival
Function of Hormones
2.Growth and development
3.Maintenance of internal
4.Regulation of energy ability
Ad.1. Reproduction
Depend on the interaction of:
Hormones produced by gonads:
Hormones produced by pituitary gland:
Luteinizing Hormones
Follicle Stimulating Hormones
Growth Hormones
Ad.2. Growth And Development
Involves some of Classical Hormones:
Growth Hormones
Thyroid Hormones
Ad.3. Maintenance of internal
The Control of extra cellular fluid
volume and blood pressure
The electrolyte composition of body
The regulation of plasma and tissue
levels of calcium and phosphate ions
Maintenance of bone,Muscle,Body
stores of fat
PTH,ADH,Aldosteron,glukagon, GH,
cathecolamin, sex hormone
Ad.4.Regulation of energy

Played prominently By:

Function: synthesis and release of
messengers (hormones) into the
circulation that act on target tissues
Hormones include: steroids, amino acid
analogues, peptides and proteins
Hormones function to maintain

Fall into 3 Categories:

Comprises hormones derived from single
amino acids
Composed of peptides and proteins
Comprises the steroid Hormones
Life cycle of a hormone
1. Synthesis
2. Secretion
3. Transport
4. Action
5. Metabolism
Peptide and protein hormones:
Uses general enzyme system
Steroid hormones:
Synthesized from cholesterol, uses special
enzyme system.
Derivative of amino acid:
Synthesized from tyrosine, uses special
enzyme system.
Protein and Polypeptide Hormones:
Synthesis and Release

Figure 7-3: Peptide hormone synthesis, packaging, and release


Peptide and protein hormones:


Steroid hormones and thyroid hormones:

diffusion and exocytosis.

May occur in different periodicities

The release pattern of a hormone may
have a much less frequent periodicity
The mechanism underlying the pulsate
release hormones are unknown
Secretory cells, including neurons, have
the intrinsic ability to secrete their product
in discontinuous, episodic manner

Amines, peptides, and proteins circulate in free

form whereas steroids and thyroids hormones are
bound to transport proteins
Binding of hormones to carrier proteins has a
profound impact on the hormone clearance rate
from the circulation
The metabolic clearance rate of hormone defines
quantitively its removal from plasma
The interaction of hormones with their target
tissues is apparently followed by intracellular
degradation of the hormone
Protein hormones water soluble
Circulates as its hormone form.
Steroids, thyroid hormones lipid soluble
1. free : 1 %
2. bound : 99%
To act, hormones need to bind to Receptor.
Receptor located in target cell.
specific binding sites.
confers specificity.
Type of receptors:
a. fixed receptors membrane
b. mobile receptors cytoplasmic, nucleic
Membrane associated receptors
External reactions
Internal reactions
Receptors bind specific ligand
Cell recognition molecules

Figure 5-6: Cell membrane receptor

Receptor locations
Cytosolic or Nuclear
Lipophilic ligand enters cell
Often activates gene
Slower response
Cell membrane
Lipophobic ligand can't enter cell
Outer surface receptor
Fast response

Figure 6-4: Target cell receptors

Protein hormone
Protein and peptide hormones second
messenger hypothesis.
Hormones are water soluble cannot get
through cell membrane (lipid bilayer).
receptor outer cell membrane
fixed receptor
Protein hormone action
1. Hormone (first messenger), binds to its
membrane receptor.
2. Activation of membrane bound adenylate
3. Increased formation of intracellular cAMP
(second messenger)
4. cAMP mediated activation of protein kinase
5. Phosphorylation of intracellular enzymes
6. Physiologic action, such as release or
synthesis of hormones or other products, and
change of membrane permeability to ions.
Steroid hormone
Steroid hormone lipid soluble
able to get cross cell membrane
Its receptors mobile receptors
cytoplasmic, nucleic
Steroid Hormones: Action

Figure 7-7: Steroid hormone action

Steroid hormones
1. Diffusion into cell
2. Binding to cytoplasmic receptor
3. Translocation to nucleus
4. Binding to chromatin
5. Increase protein synthesis
6. New protein physiologic action
a. Inactivation by enzymes in kidney, liver,
blood, target cells.
b. Excretion by kidney.
Aksi 2
Aksi 2 Aksi 1 Aksi 3
Aksi 1 Aksi 3

Hormon Hormon
I 2

Multi hormonal

Aksi 1
Aksi 2
One hormone, Multiple actions
Example: testosterone,
fusion of labioscrotal folds in man embryo during
embryogenesis, induction of differentiation of ductus
wolfii, growth urogenital tract, control spermatogenesis,
growth of beard and hair, retention nitrogen, promote
muscle growth, control of erythropoeitin synthesis,
temporal regression of scalp hair, growth of sebaceous
gland and regulation of sebum production, development
of prostatic hyperplasia in aging males, secretion of
ejaculate, virilization of the hypothalamus, many aspects
of sexually dimorphic behavior.
One function, Multiple hormones.
1. Homeostasis glucose
Insulin, Glucagon, epinephrine, growth
hormone, cortisol.
2. Homeostasis calcium
Parathyroid hormone, calcitonin, cortisol,
growth hormone, sex steroids.
Regulation of hormone action
A. Rate of secretion vs. rate of removal.
B. Target tissue sensitivity
a. number of receptors
b. affinity of receptors
C. Negative feed back mechanism.
Parameter affecting serum
hormone concentration
1. Secretion.
a. endogenous release pattern
e.g. LH, FSH in ovulation
b. exogenous control (via CNS) stress,
circadian rhythm.
e.g. cortisol level: high in morning, low at
2. Serum binding proteins.
H-BP is not active biologically.
e.g. in pregnancy, TBG increase due to
increase of estrogen. TBG increase
level of bound T3, T4. free T3, T4 will
Hypothalamus-pituitary axis
Interaction between nervous and
endocrine system
Hypothalamic pituitary axis
Hypothalamus neuron that secrete
Pituitary anterior adenohypophyse
Pituitary posterior neurohypophyse
The Endocrine Glands and
Their Hormones
Pituitary Gland
A marble-sized gland at the base of the brain
Controlled by the hypothalamus or other neural
Posterior Lobe: Neurohypophyse.
Antidiuretic hormone/ADH: responsible for
fluid retention
Oxytocin: contraction of the uterus
Hypofise posterior
Hormones: sintesa di hypothalamus.
Oxytocin, ADH/ vasopressin.
1. Oxytocin suckling, dilatasi cervix
2. ADH osmoreseptor di hypothalamus
volume reseptor (cardiovascular)
The Endocrine Glands and their
Pituitary Gland
Anterior Lobe: Adenohypophyse.
Adrenocorticotropin/ ACTH
Growth hormone / GH
Follicle-stimulating hormone/FSH
Luteinizing hormone / LH
Hypofise anterior
LH, FSH, TSH, GH, Prolactin, ACTH.
1. Negative feed back
2. CNS(mono-catechol aminergic neuron) dan
hypothalamic peptidergic neuron
-releasing hormones: LHRH, GnRH, TRH, CRH,
-inhibitory hormones : somatostatin : inhibit GH
PIF: inhibit prolactin
Hormonal control of growth
What is growth ?
Growth increase number of cells.
refers to an increase of cell division, not
an increase of size of cells.

Rate of growth
1. In utero.
2. Neonatus
3. Children
4. Pubertal growth spurt
5. Adult
What controls growth ?
1. Genome
2. Nutrition
3. Stress fisik dan psikis
4. Growth hormone.
Growth hormon
GH TIDAK mengontrol pertumbuhan :
1.adrenal gland
3.thyroid gland
4.body growth of fetus and infant up to 1
Hormon yg mengatur tumbuh
1. Growth hormon
2. Insulin
3. Thyroid hormone
4. Gonadal steroids estrogen dan
Growth hormone
Disintesa di hypofise anterior.
Plasma level GH :
neonatus paling tinggi, tapi tidak
mengatur pertumbuhan.
anak basal level sama dengan orang
dewasa, namun kadar rerata 24 jam lebih
Sirkulasi GH : dalam beberapa bentuk
produk dari prohormone.

Species specificity :
most abundant hormone in pituitary
recombinant DNA technology produce
human GH (hGH) for treatment.
Mechanism of action cAMP.
Actions of GH
1. Meningkatkan aksi mitosis.
2. Meningkatkan pembentukan kartilago
dan pertumbuhan tulang panjang.
aksi GH pada tulang mediated by
3. Metabolisme organik :
meningkatkan sintesa protein,
meningkatkan glukosa, FFA, benda
keton dalam darah.
Control of GH secretion
1. Hypothalamus via GHRH dan
2. Asam amino via nuclei Ventromedial
3. Stress/trauma meningkatkan GH, tapi
tidak pertumbuhan.
4. Strenuous exercise.
5. Hypoglycemia.
6. Tidur terjadi peningkatan kadar
maximal GH setelah 1 jam tidur dalam
( deep sleep/ slow wave sleep )
peningkatan kadar GH mediated by
limbic system / serotonin.
7. Somatomedin negative feed back.
Disorders caused by abnormal GH
1. Deficiency of GH.
a. Prepubertal dwarfism.
a.1. sexual ateliotic dwarf : decrease of
GH only
a.2. panhypopituitary dwarf.
a.3. Laron dwarf : GH increase, no
a.4. African pygmies : normal GH,
b. Adults no known disease.
2. Excessive GH production.
a. Prepubertal Gigantism
b. In adults Acromegaly.
hormone profile : increase of GH and
Other hormones
Insulin permissive required.
T3 and T4 permissive required.
Gonadal steroids important in puberty.
increase of growth of long bones
high level in adults closure of epiphyse
of long bones stops the length of

Thyroid Gland
Located along the midline of the neck
Secretes two amino acid derivative hormones
Triiodothyronine (T3)
Thyroxine (T4)
Regulates metabolism
increases protein synthesis
promotes glycolysis, gluconeogenesis, glucose
Calcitonin: calcium metabolism
The Thyroid Produces and
Secretes 2 Metabolic Hormones

Two principal hormones

Thyroxine (T4 ) and triiodothyronine (T3)

Required for homeostasis of all cells

Influence cell differentiation, growth, and


Considered the major metabolic hormones

because they target virtually every tissue
Thyroid-Stimulating Hormone

Regulates thyroid hormone

production, secretion, and growth

Is regulated by the negative

feedback action of T4 and T3
Hypothalamic-Pituitary-Thyroid Axis
Negative Feedback Mechanism
Biosynthesis of T4 and T3

The process includes

Dietary iodine (I) ingestion
Active transport and uptake of iodide (I -) by thyroid
Oxidation of I- and iodination of thyroglobulin (Tg)
tyrosine residues
Coupling of iodotyrosine residues (MIT and DIT) to
form T4 and T3
Proteolysis of Tg with release of T 4 and T3 into the
Iodine Sources

Available through certain foods

(eg, seafood, bread, dairy products),
iodized salt, or dietary supplements,
as a trace mineral

The recommended minimum intake is

150 g/day
Production of T4 and T3
T4 is the primary secretory product of the thyroid
gland, which is the only source of T4

The thyroid secretes approximately 70-90 g of T4

per day

T3 is derived from 2 processes

The total daily production rate of T3 is about 15-30 g
About 80% of circulating T3 comes from deiodination of T4 in
peripheral tissues
About 20% comes from direct thyroid secretion
T4: A Prohormone for T3

T4 is biologically inactive in target

tissues until converted to T3
Activation occurs with 5' iodination of the
outer ring of T4

T3 then becomes the biologically

active hormone responsible for the
majority of thyroid hormone effects
Sites of T4 Conversion

The liver is the major extrathyroidal

T4 conversion site for production of

Some T4 to T3 conversion also occurs

in the kidney and other tissues
T4 Disposition
Normal disposition of T4
About 41% is converted to T3
38% is converted to reverse T3 (rT3), which is metabolically
21% is metabolized via other pathways, such as
conjugation in the liver and excretion in the bile
Normal circulating concentrations
T4 4.5-11 g/dL
T3 60-180 ng/dL (~100-fold less than T4)
Thyroid Hormone Plays a Major Role
in Growth and Development

Thyroid hormone initiates or sustains

differentiation and growth
Stimulates formation of proteins, which exert trophic
effects on tissues

Is essential for normal brain development

Essential for childhood growth

Untreated congenital hypothyroidism or chronic
hypothyroidism during childhood can result in
incomplete development and mental retardation
Thyroid Hormones and the Central
Nervous System (CNS)

Thyroid hormones are essential for neural

development and maturation and function
of the CNS
Decreased thyroid hormone concentrations
may lead to alterations in cognitive function
Patients with hypothyroidism may develop
impairment of attention, slowed motor function, and
poor memory
Thyroid-replacement therapy may improve cognitive
function when hypothyroidism is present
Thyroid Hormone Influences
Cardiovascular Hemodynamics
Thyroid hormone Local
Release Metabolic
Mediated Thermogenesis Vasodilitation
(Peripheral Tissues)

T3 Systemic
T3 Vascular
Elevated Blood Resistance

Cardiac Decreased
Chronotropy and Diastolic Blood
Cardiac Output
Inotropy Pressure

Laragh JH, et al. Endocrine Mechanisms in Hypertension. Vol. 2. New York, NY: Raven Press;1989.
Thyroid Hormone Influences the
Female Reproductive System

Normal thyroid hormone function

is important for reproductive
Hypothyroidism may be associated with
menstrual disorders, infertility, risk of
miscarriage, and other complications of

Doufas AG, et al. Ann N Y Acad Sci. 2000;900:65-76.

Glinoer D. Trends Endocrinol Metab. 1998; 9:403-411.
Glinoer D. Endocr Rev. 1997;18:404-433.
Thyroid Hormone is Critical for Normal
Bone Growth and Development

T3 is an important regulator of
skeletal maturation at the growth
T3 regulates the expression of factors and other
contributors to linear growth directly in the
growth plate

T3 also may participate in osteoblast

differentiation and proliferation, and chondrocyte
maturation leading to bone ossification
Thyroid Hormone Regulates
Mitochondrial Activity
T3 is considered the major
regulator of mitochondrial
A potent T3-dependent transcription factor
of the mitochondrial genome induces early
stimulation of transcription and increases
transcription factor (TFA) expression

T3 stimulates oxygen consumption by the

Thyroid Hormones Stimulate
Metabolic Activities in Most Tissues

Thyroid hormones (specifically T3) regulate rate

of overall body metabolism
T3 increases basal metabolic rate

Calorigenic effects

T3 increases oxygen consumption by most peripheral


Increases body heat production

Metabolic Effects of T3

Stimulates lipolysis and release of free fatty acids and


Induces expression of lipogenic enzymes

Effects cholesterol metabolism

Stimulates metabolism of cholesterol to bile acids

Facilitates rapid removal of LDL from plasma

Generally stimulates all aspects of carbohydrate metabolism

and the pathway for protein degradation
Clinical Exam. of Thyroid
Have patient seated on a stool / chair
Inspect neck before & after
Examine with neck in relaxed position
Palpate from behind the patient
Remember the rule of finger tips
Use the tips of fingers for palpation
Palpate firmly down to trachea
Where to look for Thyroid ?
Clinical Anatomy of Thyroid
Clinical Exam of Thyroid
Clinical Exam of Thyroid
Parathyroid gland

Secretes parathyroid hormone

regulates plasma calcium (osteoclast activity)
regulates phosphate levels
Parathyroid hormone
Essential for life.
Cell of origin : parathyroid glands
Chemical nature : 84-amino acids peptide
Biosynthesis : continuous production, little
Transport : dissolved in plasma
Half life : less than 20 minutes
Parathyroid hormone
Factor affecting release : decrease plasma
Target cell : Kidney, bone, intestine
Target receptor : membrane receptor acts
via cAMP
Whole body or tissue action : increase
plasma Ca++
Actions of
hormone (PTH) on
the kidney and
Parathyroid hormone
Action at cellular level :
Increase vit.D3 synthesis
Increase renal reabsorption of Ca++
Increase bone resorption

Action at molecular level :

Rapidly alters Ca++ transport but also initiates
protein synthesis in osteoclasts.
Activation of vitamin D (25 (OH) vitamin D3, 25 -
hydroxyvitamin D3; 1,25(OH)2 vitamin D3, 1,25-
dihydroxyvitamin D3)
Parathyroid hormone
Onset of action :
2 3 hours for bone, with increased
osteoclast activity requiring 1 2 hours; 1
2 days for intestinal absorption; within
minutes for kidney transport.

Feed back regulation : Negative feed back

by increasing plasma Ca++
Other information
Osteoclast have no PTH receptors, so are
affected by PTH induced paracrines.


Absence of PTH causes hypocalcemic
tetany, which may lead to death.
How PTH raises Ca++
1. PTH mobilizes calcium from bone.
Increased bone resorption by osteoclasts takes
about 12 hours to become measurable.
Osteoclasts do not have PTH receptors.
PTH effects are mediated by paracrines, such as
osteoprotegerin (OPG) and osteoclast
differentiation factor called RANKL.
PTH raises Ca++
2. PTH enhances renal reabsorption of
Takes place in the distal nephron.
PTH simultaneously enhances renal
excretion of phosphate by reducing its
PTH raises Ca++

3. PTH indirectly increases intestinal

absorption of calcium by its influence on

There are 2 adrenal glands.

Each gland weighs about 4 grams.
Location : superior poles of the two kidneys.
1. Adrenal cortex : a true endocrine gland.
secretes hormone corticosteroid.
2. Adrenal medulla : 20% central of gland.
a modified sympathetic ganglion.
functionally related to sympathetic nervous
secretion : catecholamine ( epinephrine, and
norepinephrine ) in response to sympathetic
stimulus. Effect : same as direct stimulation of
sympathetic nervous to body.
1563 : Eustachius ; first described this gland
1885 : T. Addison ; established that adrenal
glands are necessary for life.
1917 : really demonstrated that adrenal
cortex, not the medulla is essential for life.
Three layers :
1. Zona glomerulosa ( surface ); secretes
2. Zona fasciculata (middle ) : secretes
cortisol and adrenal androgen.
3. Zona reticularis ( deep ) : secretes cortisol
and adrenal androgen.
Multiple hormone release. (adrenals and gonads).
1. Several hormones have a common synthetic
2. A specific enzyme deficiency can dramatically
alter gland function
3. Some overlap of function due to structural
similarities among the hormones ( at high
level, aldosterone can act as cortisol )
Synthesis :
From cholesterol absorbed directly from the
circulating blood by endocytosis through
cell membrane.
All the adrenocortical hormones are
STEROID compounds.
Cortisol = Glucocorticoid
Actions of cortisol
1. Effects on organic metabolism.
a. increase blood glucose : due to stimulation of
gluconeogenesis and decreased glucose
utilization by cells.
b, increase blood fatty acids : mobilization of
fatty acids from adipose tissue.
c. increase blood amino acids ; reduction in
cellular protein ( protein wasting effect )
d. permissive effects : indirectly increase
gluconeogenesis, lipolysis & glycogenolysis by
GH, glucagon and epinephrine.
2.Cardiovascular effects.
a. increase peripheral resistance.
b. decrease capillary resistance
c. increase cardiac contractility
3. Resistance to stress.
In stress situation , CRF increases ACTH
increases cortisol increases.
Type of stress : trauma, infection, intense heat or
cold, surgery, injection of norepinephrine and
other sympathetic drugs, injection of
necrotizing substances beneath skin,
restraining an animal so that it cannot move,
and almost any debilitating disease.
4. Anti inflammatory and anti allergic effects.
5. Immunosuppression ( at pharmacologic
- decrease lymphocyte number
- decrease antibody production
- atrophy of thymus, lymph nodes, spleen.
6. Essential for normal :
a. CNS function
b. muscle tone
c. connective tissue integrity
d. bone formation and growth
e. erythropoiesis
f. loss of water load
Transport of cortisol
A. Free : 4% in plasma.
B. Bound : 96%.
1. albumin :15%, non specific, low
affinity, reversible
2. cortisol binding protein (CBG)
Control of cortisol secretion
1. ACTH ( via CRH ).
Effect of ACTH on adrenal glands :
-increase size of adrenal cortex
-increase blood flow to adrenal cortex
-increase synthesis and secretion of
2. Negative feed back.
Cortisol has direct negative feed back
effects on :
a. Hypothalamus to decrease CRF/CRH.
b. Anterior pituitary to decrease ACTH.
3. Diurnal rhythms.
The secretory rates of CRF, ACTH and cortisol are
high in the early morning but low in the late

Measurement of blood cortisol is meaningful only

when expressed in terms of time in the cycle at
which the measurement is made.
4. Stress.
Can override the negative feed back.
Superimpose with diurnal rhythms.
Controls sodium balance.
Aldosterone/ mineralocorticoid increases
reabsorption of sodium in the distal tubule
and collecting duct of the kidney.
Also causes K+ secretion.
Control of aldosterone secretion
Three primary stimuli :
1. Increased K+
2. Increased osmolarity.
3. Angiotensin II.
Factors affecting aldosterone
1.Direct at adrenal cortex.
Increased extracellular K+
Increased osmolarity inhibits
2. Indirect, through the RAAS pathway.
Decreased blood pressure stimulates
Decreased flow past the macula densa
Adrenal androgen
Male sex hormone :
dehydroepiandrosterone (DHEA ) :
continually secreted, especially during
fetal life.
Female sex hormone :
progesterone and estrogens are secreted
in minute quantities.
Effect of adrenal androgen
Normally, has weak effects.
It is possible that part of the early
development of the male sex organs
results from childhood secretion of adrenal
In female, exerts mild effects before puberty
and throughout life, such as growth of
pubic and axillary hair.
The fate of adrenal androgens
Adrenal androgens are converted to
testosterone, the major male sex
hormone, in extra-adrenal tissues, such as
testes, which accounts for much of their
androgenic effects.
Hormones of adrenal medulla
Adrenal medulla secretes : catecholamine
hormones : Epinephrine and
Norepinephrine , on stimulation of
sympathetic nerve.
Epinephrine and norepinephrine are derived
from amino acid tyrosine
Function of adrenal medulla
Secretion of epinephrine : 80% and 20%
secretion is norepinephrine.
The effects of circulating catecholamine are
almost the same as by direct sympathetic
stimulation, except that the effects last 5 to
10 times as long because
these hormones are removed from blood
1. Constriction of essentially all blood
2. Increased activity of heart.
3. Inhibition of GI tract.
4. Dilation of pupil.
Value of adrenal medulla to the function of
sympathetic nervous system
1. Supporting function.
2. Substitute.
3. The capability of epinephrine and
norepinephrine to stimulate structures
that are not innervated by direct
sympathetic fibers.

Located slightly behind the stomach

Insulin: reduces blood glucose
Facilitates glucose transport into the cells
Promotes glycogenesis
Inhibits gluconeogensis
Glucagon: increases blood glucose

Endocrine Islands of Langerhans

secretes 3 hormones:
Exocrine Glucagon (alpha
Insulin (beta cells)
Delta cells - somatostatin
Sintesa : sel beta pankreas.
Stimulasi sekresi : glukosa darah.
Tipe hormon protein.
Disekresikan dalam bentuk pro insulin
dlm darah dipecah jadi Insulin (aktifitas
hormon) dan C-peptide ( tidak mempunyai
aktifitas hormonal).
Aksi fisiologis Insulin
1. Meningkatkan up take glukosa ke dalam
2. Meningkatkan pembentukan glycogen
3. Menurunkan gluconeogenesis
4. Menurunkan Lipolysis
5. Meningkatkan up take asam amino ke
dlm sel
6. Menurunkan kadar glucagon
Normal Insulin Production
Pancreas releases
insulin into the

Blood carries it to
all cells in the
Normal Insulin Profiles
Basic Requirements What happens
when you eat

After a meal
Just to function normally

the body needs a constant level of sugar in the blood the blood sugar rises

and a background level of insulin and extra insulin is needed

Normal Insulin Profiles
Daily Requirements

Breakfast Lunch Evening Meal

Blood sugar

Mealtime insulin
Background insulin
Kontrol sekresi Insulin
1. Glukosa darah
2. Asam amino
3. Hormon tractus digestivus : Gastrin, CCK
4. Parasimpatis: meningkatkan insulin
5. Simpatis ; menurunkan insulin
6. Glucagon dosis tinggi: meningkatkan insulin
7. Somatostatin dosis tinggi: menurunkan insulin
Insufisiensi Insulin
1. Metabolisme Karbohidrat.
up take glukosa menurun
gluconeogenesis meningkat
pemecahan glycogen meningkat
di hati, glycogen di ubah jadi glukosa.
di otot, glycogen di ubah jadi asam laktat
dibawa ke hati glukosa
2. Metabolisme Lemak.
meningkatkan pemecahan lipid
free fatty acid meningkat
glycerol phosphat menurun.
efek sekunder FFA yang tinggi
meningkatnya pembentukan keton
bodies di hepar
3. Protein.
sintesa protein menurun
katabolisme meningkat
kadar asam amino darah meningkat
up take asam amino ke dalam sel
Net Result
Insulin menurun
meningkatnya glukosa, FFA, keton bodies
dalam darah.
glycogen menurun
toleransi glukosa ginjal menurun
glukosa keluar di urine

maintenance of blood glucose concentration

brain depends on glucose; >50% of total
prolonged starvation has <25% decline in glucose
hyperglycemia too little insulin
hypoglycemia too little intake or too much insulin
The Endocrine Glands
testes (testosterone) = sex characteristics
muscle development and maturity
ovaries (estrogen) = sex characteristics
maturity and coordination
Kidneys (erythropoietin)
regulates red blood cell production
hormone excess

hormone deficiency

hormone resistance
Endocrine pathology
1.Subnormal hormone production.
2. Hormone overproduction
3. Production of abnormal hormone
4. Disorder of hormone receptors.
5. Abnormalities of hormone transport or
6. Multiple hormone abnormalities
7. Benign or malignant tumors that produce
Subnormal hormone production
Etiologi :
1. Absense or malformation of endocrine organs
due to defects in embryogenesis.
2. Lacking some enzyme essential for hormone
3. Normal gland destroyed by a secondary
process ( tuberculosis, infarct, autoimmune
disorders, chemotheraphy, surgical, thermal,
4. Unknown primary hypothyroidism without
Hormone excess
1. Tumors of endocrine gland
2. Tumors of non endocrine gland
3. Homeostatic mechanism that control
normal secretion is set at abnormal level.
Production of abnormal hormone
1. A single gene mutation DM caused
by abnormal insulin molecule
2. Hormone precursors or incompletely
processed peptide hormones may be
released into circulation.
3. Some of genes are not expressed
Disorders of hormone receptors
Can cause decrease or absence of
hormone function.
example: hormone resistance hereditary
Hormone resistance :
1. pre receptor
2. receptor
3. post receptor
Abnormalities of hormone transport
or metabolism
In normal condition, will not cause any
abnormality feed back mechanism
Abnormal condition : exogenous dose of
corticosteroid in cirrhosis hepatis
Cushing syndrome, because free
hormone increase, meanwhile catabolism
Multiple hormone abnormalities
Hyperfunction ( multiple endocrine neoplasia
Mixed pattern of hypo and hyperfunction of
various endocrine glands ( polyglandular
autoimmune syndrome)
Tumors of endocrine gland
Functional tumor pheochromocytoma or
adrenocortical adenoma clinical
Non functional tumor tumor of thyroid

Endocrine glands throughout body are key

to chemical integration and homeostasis
Protein, polypeptide, amine and a few
steroid hormones are plasma soluble and
target membrane
Surface receptors transduce signals into
cell and activate via second messengers

Most steroid and some amine hormones

are lipophilic, can pass into cell, bind on
cytoplasmic or nuclear receptors and
activate DNA for protein synthesis
Hypothalamus, pituitary trophic hormone
pathways coordinate endocrine regulation
Summary of the Endocrine System

Figure 7-2-1: ANATOMY SUMMARY: Hormones

Summary of the Endocrine System

Figure 7-2-2: ANATOMY SUMMARY: Hormones

Summary of the Endocrine System

Figure 7-2-3: ANATOMY SUMMARY: Hormones

1. Essential of Anatomy and Physiology.
Valerie C. Landau & Tina sanders.
2. Understanding Human anatomy and
Silvia S. Mander.
3. Human physiology, an integrated approach
Dee Unglaub Silverthorn
4. Text book of Medical physiology
Guyton and Hall.
Further readings
1. Essential human anatomy and physiology.
Barbara R. Landau.
2. Anatomy and Physiology in health and
Anne Waugh & Allison Grant.