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BY

dr. WIDODO S., MKes


                      1
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
RECEPTORE :
•   HORMONE BIND RECEPTOR OF TARGET CELL
• RECEPTORE ARE PROTEIN
• RECEPTORE CAN CONFLUENCE ACTIVITY OF HORMONE
• HORMONES HAS ONE OR MANY RECEPTORES




                                                 3
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
                                                                  4
   HORMONE IS CALLED FIRST MESSENGER
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

                                                            5
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
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
                                              24
HYPOTHALAMUS AND PITUITARY GLAND
HYPOTHALAMIC HORMONE
HYPOTHALAMIC AND PITUITARY HORMONE INTEGRATION
GROWTH HORMONE (GH), PROLACTIN (PRL)

          AND

CHORIONIC SOMATOMAMOTROPIN (CS)
GROWTH HORMONE = GH

  STRUCTURE : POLIPEPTIDE

► SYNTHESIS :
      SYNTHESZED FROM SOMATOTROPE PF ANTERIOS LOBE PITUITARY
      SITIMULATED BY SLEEP, STRESS , EXERCISE, HYPOGLYCEMIC, SOME OF FOODS




                                                                             29
GROWTH HORMONE




     Sinthesized at somatotrope, pituitary acidophilic cells
     191 aa, 22 kDa
     5-15 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
CHORIONIC SOMATOMAMOTROPIN


           PROLACTIN ACTIONS :
CS ACTIONS :
          LACTATION
      LACTOGENIC ACTIVITY
          LUTEOTROPIC HORMONE

      LUTEOTROPIC ACTIVITY

      METABOLIC EFFECTS PROLACTIN :TO GH
           OVERSECRETION OF SIMILAR

                   INHIBITION GLUCOSE UPTAKE
               AMENORHOE
               GALACTORHOE
                  STIMULATION FATTY ACID RELEASE
               GYNECOMASTY
                  NITROGEN AND CALCIUM RETENTION
               IMPOTENCE
ANTERIOR PITUITARY HORMONE



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
GLYCOPROTEIN HORMONE

   TSH
   GONADOTROPIN (FSH, LH)
TSH, FSH, LH : CONSISTS OF TWO SUBUNIT :      AND

Alfa subunit are same, beta subunit are different

WORKS THROUGH THEIR RECEPTOR AND ACTIVATION OF
ADEYLIL CYCLASE    INCREASE OF cAMP
GONADOTROPIN (FSH, LH)

   RESPONSIBLE FOR GAMETOGENESIS STEROIDOGENESIS
   IN THE GONAD

 FSH
    TARGET : 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
METABOLISME YODIDA dalam FOLIKEL TIROID
                                   RUANG FOLIKULER
                                                                 DIT                             DIT
            Oksid                                                            Perangk
            asi                               Iodinasi     MIT         MIT                  T3           T4
                           I+ +     Tgb
                                                                             aian
       Peroksidase                                       DIT      Tgb DIT                DIT       Tgb    DIT
            H2O2                                         MIT         MIT                  MIT            T4
                                                                 DIT                             DIT
  I-
        O2                                                                                Pagositosis &
                                                                               Tgb
        NADPH NADP+ H+                                                                    Pinositosis




                                                                                               LISOSOM
                                                                                Tgb




                    TIROSIN                                                               Lisosom
                                                                                 Tgb      sekunder
               I-
                                                                 MIT                   Hidrolisa
               I-                                                DIT
POMPA YOD           Kosentrasi *                                             T3 & T4
                     Na-K ATPase                                                  Pelepasan
                                          RUANG EKSTRASELULER                T3 & T4
                                                                                                              45
       I-
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 :        7:1
IOD 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, NONCOVALEN
      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 DEFICIENCY
IODIDE EXESS
IODIDE TRANSPORT DEFECT
IODINATION DEFEXT
COUPLING DEFECT
DEIODINASI DEFICIENCY
PRODUCTION OF ABNORMAL IODINATION PROTEIN
GOITER
ADRENAL HORMONE


             MEDULA      H. KATEKOLAMIN
ADRENAL
                                                    MINERALO-
GLAND                     1. ZONA GLOMERULOSA
                                                    CORTICOID H.
             CORTEX       2. ZONA FASICULATA
                                                    -HGLUCOCOR-
                          3. ZONA RETICULARIS       TICOID H.
                                                    -ANDROGEN H.



          CORTEX ADRENALIS

CORTICOSTEROID H. :   1. GLUCOCORTIKCOID
                      2. MINERALOCORTIKCOID
                      3. ANDROGEN ( SEX HORMON E)             55
CORE OF STEROID  SIKLO PENTANO PERHIDRO PENENTREN
                                    (              17 ATOM C )
                          12            17
                     11        13            16
                           C        D
            1    9             14        15                21 C   C    C       C
        2       10        8                                 20 C OHC       C
                                                                  OH
        3   A   5 B       7                                18
                                                                               C
            4        6
                              CH2                  19
                              C=O
                                                                CHOLESTEROL
                                              HO




HO

                                                                                   56
            PREGNENOLON
BIOSINTESIS H. STEROID
 KOLESTEROL

                              17-HIDROKSI            DEHIDROEPIANDRO
PREGNENOLON
                              PREGNENOLON            STERON ( DHEA )
3β-HIDROKSI STEROID DEHIDROGENASE : ∆5,4 ISOMERASE

POGESTERON             17-HIDROKSI PROGESTERON          ∆4ANDROSTENE-
                                                        3,17-DION
   21 - HIDROKSILASE


11-DEOKSIKORTI-                                         TESTOSTERON
                                11-DEOKSIKORTISOL
KOSTERON ( DOC )

   11-β-HIDROKSILASE
                                                       17-α-ESTRADIOL
KORTIKOSTERON                   KORTISOL

18-HIDROKSILASE-18-HIDROKSI
DEHIDROGENASE

                                                                      57
ALDOSTERON
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 LYPOLYSIS
   4.   PROMOTE PROTEIN AND RNA METABOLISM

   5. SUPPRESS IMMUNE RESPONS
   6. SUPPRESS INFLAMATORY RESPONS

   7. MAINTENANCE BLOOD PRESSURE AND CARDIAC OUTPUT
   8. MAINTENANCE WATER AND ELECTROLITE BALANCE
   9. RESPONS TO STRESS
GLUCOCORTICOID INSUFFICIENCY :

PRIMER : ADDISON’S DESEASE
HYPOGLYCEMIA, STRESS INTOLERANCE, ANOREXIA, WEIGHT LOSS,
NAUSEA , WEAKNESS, LOW BLOOD PRESSURE,
LOW GROMELURAL FILTRATION RATE, LOW PLASMA NATRIUM, HIGH
PLASMA KALIUM, LYPHOCYTE AND EOSINOPHIL INCREASE
HYPERPIGMENTATION (ACTH INCREASE POMC INCREASE)

SECONDARY : DECREASE ACTH (TUMOR INFARCTION OR INFECTION)


GLUCOCORTICOID EXCESS :

CUHSHING SYNDROME
HYPERGLYCEMIA, 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


AFFECTED ORGANS:       BRAIN, MUSCLE, CARDIOPULMONARY, LIVER
                       SKIN , GI TRACT, LYMPHOID
CATECHOLAMINES
  BIOSYNTHESIS




PNMT : phenylethanolamine
N-methyltransferase
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




                                                               72
Hormone str bs 1
Hormone str bs 1
Hormone str bs 1
Hormone str bs 1

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Hormone str bs 1

  • 2. 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
  • 3. RECEPTORE : • HORMONE BIND RECEPTOR OF TARGET CELL • RECEPTORE ARE PROTEIN • RECEPTORE CAN CONFLUENCE ACTIVITY OF HORMONE • HORMONES HAS ONE OR MANY RECEPTORES 3
  • 4. 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 4 HORMONE IS CALLED FIRST MESSENGER
  • 5. 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 5
  • 6.
  • 7. GROUP I HORMONE : ALTER GENE EXPRESSION
  • 8.
  • 9.
  • 10.
  • 11. GROUP II HORMONE - BINDS MEMBRANE RECEPTOR - USE INTRACELLULAR MESSENGERS EXAMPLE OF INTRACELLULAR MESSENGER : - cyclic AMP - cyclic GMP - CALCIUM - PHOSPHATIDYLINOSITOLS
  • 12. HORMONE ACTION WITH CYCLIC AMP AS INTRACELLULAR MESSENGERS
  • 13.
  • 14.
  • 15.
  • 16.
  • 17. HORMONE ACTION WITH CYCLIC GMP AS INTRACELLULAR MESSENGERS
  • 18. HORMONE ACTION WITH CACIUM AS INTRACELLULAR MESSENGERS CALCIUM CONCENTRATION : EXTRACELL : 5 MMOL/L INTRACELL : 0.1 – 10 MICROMOL/L 10,000 FOLD DIFFERENCE
  • 20.
  • 21.
  • 22.
  • 23.
  • 24. 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 24
  • 27. HYPOTHALAMIC AND PITUITARY HORMONE INTEGRATION
  • 28. GROWTH HORMONE (GH), PROLACTIN (PRL) AND CHORIONIC SOMATOMAMOTROPIN (CS)
  • 29. GROWTH HORMONE = GH STRUCTURE : POLIPEPTIDE ► SYNTHESIS : SYNTHESZED FROM SOMATOTROPE PF ANTERIOS LOBE PITUITARY SITIMULATED BY SLEEP, STRESS , EXERCISE, HYPOGLYCEMIC, SOME OF FOODS 29
  • 30. GROWTH HORMONE Sinthesized at somatotrope, pituitary acidophilic cells 191 aa, 22 kDa 5-15 mg/g of pituitary
  • 31. GROWTH HORMONE AND PROLACTIN
  • 32. GH EFFECT : PROTEIN SYNTHESIS INCREASE ANTAGONIZE INSULIN EFFECT RELEASE FATTY ACID AND GLYCEROL FROM ADIPOSE RETENSION OF NATRIUM KALIUM AND CHLORIDE STIMULATE LACTOGENESIS
  • 33. PROLACTIN ACTIONS LACTATION LUTEOTROPIC HORMONE OVERSECRETION OF PROLACTIN AMENORHOE GALACTORHOE GYNECOMASTY IMPOTENCE
  • 34. CHORIONIC SOMATOMAMOTROPIN PROLACTIN ACTIONS : CS ACTIONS : LACTATION LACTOGENIC ACTIVITY LUTEOTROPIC HORMONE LUTEOTROPIC ACTIVITY METABOLIC EFFECTS PROLACTIN :TO GH OVERSECRETION OF SIMILAR INHIBITION GLUCOSE UPTAKE AMENORHOE GALACTORHOE STIMULATION FATTY ACID RELEASE GYNECOMASTY NITROGEN AND CALCIUM RETENTION IMPOTENCE
  • 35. ANTERIOR PITUITARY HORMONE 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
  • 36. GLYCOPROTEIN HORMONE TSH GONADOTROPIN (FSH, LH)
  • 37. TSH, FSH, LH : CONSISTS OF TWO SUBUNIT : AND Alfa subunit are same, beta subunit are different WORKS THROUGH THEIR RECEPTOR AND ACTIVATION OF ADEYLIL CYCLASE INCREASE OF cAMP
  • 38. GONADOTROPIN (FSH, LH) RESPONSIBLE FOR GAMETOGENESIS STEROIDOGENESIS IN THE GONAD FSH TARGET : OVARIUM : FOLLICULAR CELLS TESTES : SERTOLI CELLS LH TARGET : CORPUS LUTEUM, PRODUCE PROGRESTERON LEYDIG CELLS, PRODUCE TESTOSTERON
  • 41. THIROID HORMONE REGULATES : GENE EXPRESSION TISSUE DIFFERENTIATION GENERAL DEVELOPMENT
  • 42. THYROID HORMONE T3 : 3,5,3’-TRIIODOTHYRONINE T4 : 3,5,3’,5’-TETRAIODOTYRONINE (THYROXINE) NEED TRACE ELEMENT : IODINE
  • 43.
  • 45. METABOLISME YODIDA dalam FOLIKEL TIROID RUANG FOLIKULER DIT DIT Oksid Perangk asi Iodinasi MIT MIT T3 T4 I+ + Tgb aian Peroksidase DIT Tgb DIT DIT Tgb DIT H2O2 MIT MIT MIT T4 DIT DIT I- O2 Pagositosis & Tgb NADPH NADP+ H+ Pinositosis LISOSOM Tgb TIROSIN Lisosom Tgb sekunder I- MIT Hidrolisa I- DIT POMPA YOD Kosentrasi * T3 & T4 Na-K ATPase Pelepasan RUANG EKSTRASELULER T3 & T4 45 I-
  • 46.
  • 47. 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 : 7:1 IOD DEFISIENSI : RATIO T4:T3 DECREASE
  • 48. 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
  • 49. THYROID HORMONE ARE TRANSPORTED BY THYROID-BINDING GLOBULIN TBG : THYROXIN-BINDING GLOBULIN GLICOPROTEIN, 50 KDA 100X AFFINITY OF TBPA, NONCOVALEN 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
  • 50.
  • 51. 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
  • 52. THYROID HORMONE ACTION ENHANCE PROTEIN SYNTHESIS INDUCE GH TRANSCRIPTION IMPORTANT FOR DEVELOPMENT
  • 53. ELEVATED TSH : CAUSED BY : IODIDE DEFICIENCY IODIDE EXESS IODIDE TRANSPORT DEFECT IODINATION DEFEXT COUPLING DEFECT DEIODINASI DEFICIENCY PRODUCTION OF ABNORMAL IODINATION PROTEIN
  • 55. ADRENAL HORMONE MEDULA H. KATEKOLAMIN ADRENAL MINERALO- GLAND 1. ZONA GLOMERULOSA CORTICOID H. CORTEX 2. ZONA FASICULATA -HGLUCOCOR- 3. ZONA RETICULARIS TICOID H. -ANDROGEN H. CORTEX ADRENALIS CORTICOSTEROID H. : 1. GLUCOCORTIKCOID 2. MINERALOCORTIKCOID 3. ANDROGEN ( SEX HORMON E) 55
  • 56. CORE OF STEROID  SIKLO PENTANO PERHIDRO PENENTREN ( 17 ATOM C ) 12 17 11 13 16 C D 1 9 14 15 21 C C C C 2 10 8 20 C OHC C OH 3 A 5 B 7 18 C 4 6 CH2 19 C=O CHOLESTEROL HO HO 56 PREGNENOLON
  • 57. BIOSINTESIS H. STEROID KOLESTEROL 17-HIDROKSI DEHIDROEPIANDRO PREGNENOLON PREGNENOLON STERON ( DHEA ) 3β-HIDROKSI STEROID DEHIDROGENASE : ∆5,4 ISOMERASE POGESTERON 17-HIDROKSI PROGESTERON ∆4ANDROSTENE- 3,17-DION 21 - HIDROKSILASE 11-DEOKSIKORTI- TESTOSTERON 11-DEOKSIKORTISOL KOSTERON ( DOC ) 11-β-HIDROKSILASE 17-α-ESTRADIOL KORTIKOSTERON KORTISOL 18-HIDROKSILASE-18-HIDROKSI DEHIDROGENASE 57 ALDOSTERON
  • 58.
  • 59. HORMONES OF ADRENAL CORTEX INTRACELLULAR RECEPTOR REGULATE GENE EXPRESSION ALTERRED PROTEIN SYNTHESIS METABOLIC PROCESSES GLUCONEOGENESIS NATRIUM KALIUM BALANCE
  • 61.
  • 62. 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
  • 63. GLUCOCORTICOID ACTION : 1. INCREASE GLUCOSE PRODUCTION {GLUCONEOGENESIS) 2. INCREASE GLYCOGEN DEPOSITION 3. PROMOTE LYPOLYSIS 4. PROMOTE PROTEIN AND RNA METABOLISM 5. SUPPRESS IMMUNE RESPONS 6. SUPPRESS INFLAMATORY RESPONS 7. MAINTENANCE BLOOD PRESSURE AND CARDIAC OUTPUT 8. MAINTENANCE WATER AND ELECTROLITE BALANCE 9. RESPONS TO STRESS
  • 64. GLUCOCORTICOID INSUFFICIENCY : PRIMER : ADDISON’S DESEASE HYPOGLYCEMIA, STRESS INTOLERANCE, ANOREXIA, WEIGHT LOSS, NAUSEA , WEAKNESS, LOW BLOOD PRESSURE, LOW GROMELURAL FILTRATION RATE, LOW PLASMA NATRIUM, HIGH PLASMA KALIUM, LYPHOCYTE AND EOSINOPHIL INCREASE HYPERPIGMENTATION (ACTH INCREASE POMC INCREASE) SECONDARY : DECREASE ACTH (TUMOR INFARCTION OR INFECTION) GLUCOCORTICOID EXCESS : CUHSHING SYNDROME HYPERGLYCEMIA, PROTEIN CATABOLISM, THINNING SKIN, MUSCLE WASTING, OSTOPOROSIS, FULL MOON FACE, EDEMA , HYPERTENSION, INFECTION
  • 66. 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
  • 67. MINERALOCORTICOID EXCESS PRIMERY : CONN’S SYNDROME HYPRTENSION, HYPOKALEMIA, HYPERNATREMIA, ALKALOSIS SECONDARY
  • 68. ANDROGEN ANDROGEN : DHEA (DEHYDROEPIANDROSTERONE), ANDROSTENEDIONE, TESTOSTERONE
  • 70. CHROMAFFIN CELLS OF ADRENAL MEDULLA PRODUCE CATECHOLAMINES: DOPAMINE, EPINEPHRINE, NOREPINEPHRINE IMPORTANT FOR STRESS RESPONS AFFECTED ORGANS: BRAIN, MUSCLE, CARDIOPULMONARY, LIVER SKIN , GI TRACT, LYMPHOID
  • 71. CATECHOLAMINES BIOSYNTHESIS PNMT : phenylethanolamine N-methyltransferase
  • 72. 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 72