Hormone str bs 1

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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