1 BY dr. WIDODO S., MKes
1
BY
dr. WIDODO S., MKes
HORMONE ORGANIC SUBSTANCE PRODUCED BY ENDOCRINE GLAND
SITE OF ACTIVITY HORMONE :
TARGET CELL or TARGET ORGAN
1. AUTOCRINE TISSUE
. H. TESTOSTERON; H. OESTROGEN
2. PARACRINE TISSUE
NEEDS RECEPTOR / MEDIATOR
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RECEPTORE :
• HORMONE BIND RECEPTOR OF TARGET CELL
• RECEPTORE ARE PROTEIN
• RECEPTORE CAN CONFLUENCE ACTIVITY OF HORMONE
• HORMONES HAS ONE OR MANY RECEPTORES
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CLASSIFICATION OF HORMONES BY MECHANISM OF ACTION :
1. HORMONES THAT BIND TO INTRACELLULAR RECEPTOR S :
STEROID HORMONE, THYROID HORMONE. CALCITRIOL
2. HORMONES THAT BIND TO SURFACE RECEPTORS :
II.1. THE SECOND MESSENGER IS c AMP
-. H. ADENOHIPOFISE -. H. HIPOFISE POSTERIOR
-. MSH; etc
II.2. THE SECOND MESSENGER ARE Ca++ / FOSFATIDIL INOSITOL
: ASETIL KOLIN, GASTRIN, VASOPRESIN, ADH
OKSITOSIN.
II.3. SECOND MESSNGER IS KINASE atau PHOSPHATE :
GROWTH HORMONE, PROLAKTIN, INSULIN
MEDIATOR IS CALLED SECOND MESSENGER
HORMONE IS CALLED FIRST MESSENGER
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MEKANISME KERJA HORMON :
KELOMPOK I : HORMON DALAM SEL IKATAN
DENGAN RESEPTOR KOMPLEKS H-R
AKTIVASI IKATAN DENGAN GENE
atau DNA HRE SINTESA PROTEIN
atau TRANSKRIPSI
KELOMPOK II : HORMON MENEMPEL & BERIKATAN
DENGAN RESEPTOR MEDIATOR :
cAMP, Fosfatidil Inositol, Ca++
FUNGSI FISIOLOGIS JARINGAN SASARAN
GROUP I HORMONE : ALTER GENE EXPRESSION
GROUP II HORMONE
- BINDS MEMBRANE RECEPTOR - USE INTRACELLULAR MESSENGERS
EXAMPLE OF INTRACELLULAR MESSENGER : - cyclic AMP - cyclic GMP - CALCIUM - PHOSPHATIDYLINOSITOLS
HORMONE ACTION WITH CYCLIC AMP AS INTRACELLULAR MESSENGERS
HORMONE ACTION WITH CYCLIC GMP AS INTRACELLULAR MESSENGERS
HORMONE ACTION WITH CACIUM AS INTRACELLULAR MESSENGERS
CALCIUM CONCENTRATION :
EXTRACELL : 5 MMOL/L INTRACELL : 0.1 – 10 MICROMOL/L
10,000 FOLD DIFFERENCE
CALMODULIN
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PITUITARY GLAND ( HORMON HIPOFISE )
1. LOBUS / PARS ANTERIOR = ADENOHIPOFISE :
- GH - FSH - LH
- TSH - ACTH - LTH
2. LOBUS / PARS INTERMEDIA : MSH
3. LOBUS / PARS POSTERIOR = NEUROHIPOFISE :
- OKSITOSIN
- VASOPRESIN = ADH
HYPOTHALAMUS AND PITUITARY GLAND
HYPOTHALAMIC HORMONE
HYPOTHALAMIC AND PITUITARY HORMONE INTEGRATION
GROWTH HORMONE (GH), PROLACTIN (PRL) AND
CHORIONIC SOMATOMAMOTROPIN (CS)
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GROWTH HORMONE = GH
► STRUCTURE : POLIPEPTIDE
► SYNTHESIS :
SYNTHESZED FROM SOMATOTROPE PF ANTERIOS LOBE PITUITARY
SITIMULATED BY SLEEP, STRESS , EXERCISE, HYPOGLYCEMIC, SOME OF FOODS
GROWTH HORMONE
Sinthesized at somatotrope, pituitary acidophilic cells191 aa, 22 kDa5-15 mg/g of pituitary
GROWTH HORMONE AND PROLACTIN
GH EFFECT :
PROTEIN SYNTHESIS INCREASE
ANTAGONIZE INSULIN EFFECT
RELEASE FATTY ACID AND GLYCEROL FROM ADIPOSE
RETENSION OF NATRIUM KALIUM AND CHLORIDE
STIMULATE LACTOGENESIS
PROLACTIN ACTIONS
LACTATION LUTEOTROPIC HORMONE
OVERSECRETION OF PROLACTIN
AMENORHOE GALACTORHOE GYNECOMASTY IMPOTENCE
PROLACTIN ACTIONS :
LACTATIONLUTEOTROPIC HORMONE
OVERSECRETION OF PROLACTIN :
AMENORHOEGALACTORHOEGYNECOMASTYIMPOTENCE
CHORIONIC SOMATOMAMOTROPIN
CS ACTIONS :
LACTOGENIC ACTIVITY
LUTEOTROPIC ACTIVITY
METABOLIC EFFECTS SIMILAR TO GH
INHIBITION GLUCOSE UPTAKE STIMULATION FATTY ACID RELEASE NITROGEN AND CALCIUM RETENTION
ANTERIOR PITUITARY HORMONE CLASSIFICATION:
1. GROWTH HORMONE (GH), PROLACTIN (PRL) AND CHORIONIC SOMATOMAMOTROPIN (CS)
2. GLYCOPROTEIN HORMONE TSH, FSH, LH
3. PRO-OPIOMELANOCORTIN PEPTIDE FAMILY (POMC) ACTH, LPH, MSH
ANTERIOR PITUITARY HORMONE
GLYCOPROTEIN HORMONE
TSH GONADOTROPIN (FSH, LH)
TSH, FSH, LH : CONSISTS OF TWO SUBUNIT : a AND b
Alfa subunit are same, beta subunit are different
WORKS THROUGH THEIR RECEPTOR AND ACTIVATION OFADEYLIL CYCLASE INCREASE OF cAMP
GONADOTROPIN (FSH, LH)
RESPONSIBLE FOR GAMETOGENESIS STEROIDOGENESISIN THE GONAD
FSHTARGET : OVARIUM : FOLLICULAR CELLS TESTES : SERTOLI CELLS
LH TARGET : CORPUS LUTEUM, PRODUCE PROGRESTERON LEYDIG CELLS, PRODUCE TESTOSTERON
THYROID HORMONE
HYPERTHYROID
THIROID HORMONE REGULATES :
GENE EXPRESSION
TISSUE DIFFERENTIATION
GENERAL DEVELOPMENT
THYROID HORMONE
T3 : 3,5,3’-TRIIODOTHYRONINE
T4 : 3,5,3’,5’-TETRAIODOTYRONINE (THYROXINE)
NEED TRACE ELEMENT : IODINE
THYROID CELLS
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METABOLISME YODIDA dalam FOLIKEL TIROID
DIT
MIT MIT
DIT DIT
MIT MIT
DIT
Oksidasi
Peroksidase
H2O2
I+ +
DIT
T3 T4
DIT DIT
MIT T4
DIT
IodinasiPerangkaian
I-
Tgb
Tgb
TgbLISOSOM
Pagositosis & Pinositosis
Lisosom sekunder
Hidrolisa
T3 & T4
T3 & T4Pelepasan
MIT DIT
I-
I-
I-
DeiodinasiDeiodinase
Kosentrasi *
Na-K ATPase
RUANG EKSTRASELULER
RUANG FOLIKULER
TgbTgb
O2 NADPH NADP+ H+
TIROSIN
Tgb
POMPA YOD
PRECURSOR OF T3 AND T4 : THYROGLOBULIN
PRODUCED BY FOLLICULAR CELLS OF THYROID GLAND
PRODUCTION STIMULATED BY TSH
PROTEIN 660 KDA, 5000 AMINO ACID
CONTAIN 115 TYROSINE RESIDUES FOR IODINATION
T4:T3 RATIO IN THYROBLOBULIN : 7:1IOD DEFISIENSI : RATIO T4:T3 DECREASE
IODIDE METABOLISM
-CONCENTRATION OF IODIDE : IOD PUMP
-OXIDATION OF IODIDE : I- TO I+
-IODINATION OF TYROSINE : 3 AND 5 POSITION
-COUPLING OF IODOTYROSIS : DIT+DIT : T4 MIT+DIT : T3
THYROID HORMONE ARE TRANSPORTED BY THYROID-BINDING GLOBULIN
TBG : THYROXIN-BINDING GLOBULIN GLICOPROTEIN, 50 KDA 100X AFFINITY OF TBPA, NONCOVALENT BINDS T3 AND T4 100 TIMES AFFINITY TO TBPA MORE IMPORTANT THAN TBPA
PRODUCE IN THE LIVER STIMULATES BY ESTROGEN (PREGNANT AND PILS) DECREASE DURING ANDROGEN OR GLUCOCORTICOID TX
ONLY SMALL AMOUNT OF FREE T3 AND T4
FREE T3 T4 : IMPORTANT FOR BIOLOGIC ACTIONS
RATIO T3:T4 IN BLOOD PLASMA: 1:1
80% T4 CONVERTED TO T3 IN CIRCULATION (DEIODINATION)
T3 BINDS RECEPTOR 10 TIMES OF T4
T3 MORE IMPORTANT FOR BIOLOGIC ACTIVITY
THYROID HORMONE ACTION
ENHANCE PROTEIN SYNTHESIS
INDUCE GH TRANSCRIPTION IMPORTANT FOR DEVELOPMENT
ELEVATED TSH :
CAUSED BY :
IODIDE DEFICIENCYIODIDE EXESSIODIDE TRANSPORT DEFECTIODINATION DEFEXTCOUPLING DEFECTDEIODINASI DEFICIENCYPRODUCTION OF ABNORMAL IODINATION PROTEIN
GOITER
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ADRENAL HORMONE
ADRENAL GLAND
CORTEX
MEDULA H. KATEKOLAMIN
1. ZONA GLOMERULOSA
2. ZONA FASICULATA
3. ZONA RETICULARIS
MINERALO-CORTICOID H.
-HGLUCOCOR-TICOID H. -ANDROGEN H.
CORTEX ADRENALIS
CORTICOSTEROID H. : 1. GLUCOCORTIKCOID
2. MINERALOCORTIKCOID
3. ANDROGEN ( SEX HORMON E)
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CORE OF STEROID SIKLO PENTANO PERHIDRO PENENTREN
( 17 ATOM C )
1 9 14 15
2 10 8
3 5 7
4 6
12 17
11 13 16
C C C C
C C C
C
OH OH
HO
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18
21
20
CHOLESTEROL
CH2
C=O
HO
PREGNENOLON
A B
C D
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BIOSINTESIS H. STEROIDKOLESTEROL
PREGNENOLON
3β-HIDROKSI STEROID DEHIDROGENASE : ∆5,4 ISOMERASE
POGESTERON
21 - HIDROKSILASE
11-DEOKSIKORTI- KOSTERON ( DOC )
11-β-HIDROKSILASE
KORTIKOSTERON KORTISOL
18-HIDROKSILASE-18-HIDROKSI DEHIDROGENASE
ALDOSTERON
17-HIDROKSI PREGNENOLON
DEHIDROEPIANDRO STERON ( DHEA )
17-HIDROKSI PROGESTERON ∆4ANDROSTENE-3,17-DION
11-DEOKSIKORTISOLTESTOSTERON
17-α-ESTRADIOL
HORMONES OF ADRENAL CORTEX
INTRACELLULAR RECEPTOR
REGULATE GENE EXPRESSION
ALTERRED PROTEIN SYNTHESIS
METABOLIC PROCESSES GLUCONEOGENESIS NATRIUM KALIUM BALANCE
GLUCOCORTICOID : CORTISOL
SECRETION OF CORTISOL : DIURNAL RHYTHM BY ACTH STIMULATION
HIGH : AM, SHORTLY AFTER AWAKENING LOWEST : LATE AFTERNOON, EARLY EVENING
PLASMA TRANSPORT : TRANSCORTIN / CBG (CORTICOSTEROID BINDING GLOBULIN)
EXCRETION : 70% URINE, 20% FECES, 10% SKIN
GLUCOCORTICOID ACTION :
1. INCREASE GLUCOSE PRODUCTION {GLUCONEOGENESIS)2. INCREASE GLYCOGEN DEPOSITION 3. PROMOTE LYPOLYSIS4. PROMOTE PROTEIN AND RNA METABOLISM
5. SUPPRESS IMMUNE RESPONS6. SUPPRESS INFLAMATORY RESPONS
7. MAINTENANCE BLOOD PRESSURE AND CARDIAC OUTPUT8. MAINTENANCE WATER AND ELECTROLITE BALANCE9. RESPONS TO STRESS
GLUCOCORTICOID INSUFFICIENCY :
PRIMER : ADDISON’S DESEASEHYPOGLYCEMIA, STRESS INTOLERANCE, ANOREXIA, WEIGHT LOSS, NAUSEA , WEAKNESS, LOW BLOOD PRESSURE, LOW GROMELURAL FILTRATION RATE, LOW PLASMA NATRIUM, HIGHPLASMA KALIUM, LYPHOCYTE AND EOSINOPHIL INCREASE HYPERPIGMENTATION (ACTH INCREASE POMC INCREASE)
SECONDARY : DECREASE ACTH (TUMOR INFARCTION OR INFECTION)
GLUCOCORTICOID EXCESS :
CUHSHING SYNDROMEHYPERGLYCEMIA, PROTEIN CATABOLISM, THINNING SKIN, MUSCLE WASTING, OSTOPOROSIS, FULL MOON FACE, EDEMA , HYPERTENSION,INFECTION
MINERALOCORTICOID : ALDOSTERONE
MINERALOCORTICOID : ALDOSTERONE
SECRETION : INDUCED BY ANGIOTENSIN, POTASIUM, ACTH , SODIUM
WEAK BINDING WITH ALBUMIN
EXCRESSION : CLEARANCE BY LIVER, EXCRETED IN THE URINE
ACTION
Na RETENTION, K, H, NH4 SECRETION
MINERALOCORTICOID EXCESS
PRIMERY :CONN’S SYNDROME HYPRTENSION, HYPOKALEMIA, HYPERNATREMIA, ALKALOSIS
SECONDARY
MINERALOCORTICOID EXCESS
PRIMERY :CONN’S SYNDROME HYPRTENSION, HYPOKALEMIA, HYPERNATREMIA, ALKALOSIS
SECONDARY
ANDROGEN
ANDROGEN : DHEA (DEHYDROEPIANDROSTERONE), ANDROSTENEDIONE, TESTOSTERONE
HORMONES OF ADRENAL MEDULA
CHROMAFFIN CELLS OF ADRENAL MEDULLA PRODUCE CATECHOLAMINES:
DOPAMINE, EPINEPHRINE, NOREPINEPHRINE
IMPORTANT FOR STRESS RESPONS
BRAIN, MUSCLE, CARDIOPULMONARY, LIVERSKIN , GI TRACT, LYMPHOID
AFFECTED ORGANS:
CATECHOLAMINES BIOSYNTHESIS
PNMT : phenylethanolamineN-methyltransferase
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LANGERHANS α CELL : GLUCAGON HORMONE
β CELL : INSULIN HORMONE
INSULIN HORMONE
INSULIN STRUCTURE IS PROTEIN, THAT IS CONSIST OF α – POLIPEPTIDE AND β = POLIPEPTIDAE , HAVE TWO DIPEPTIDE BOND and ONE DISULFIDE BOND IN THE α = PO LIPEPTIDE