Kuliah biokima hormon
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Transcript of Kuliah biokima hormon
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Hormone
Santoso
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Regulation of homeostasis
Nerves fast governing
Hormones mainly metabolism, growth,
differentiation, reproduction
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Hormone
Substance produced by a specific cell type usually accumulated in one (small) organ
Transport by blood to target tissues
Stereotypical response (receptors)
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Hormone production:“Classic” glands
Hypothalamus:•GHRH, CRH, TRH, GnRH•Somatostatin•ADH
Pituitary:•Growth hormone•Prolactin•ACTH, MSH•TSH•FSH & LH
•Oxytocin•ADH
Pancreas:•Insulin•Glucagon
Ovaries:•Estrogens•Progesterone
Epiphysis:•Melatonin
Thyroid gland:•T3, T4•Calcitonin
Parathyroidglands:
•Parathyroid h.
Adrenal cortex:•Cortisol•Aldosterone•Androgens
Adrenal medulla:•Catecholamines
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Hormone production: Less traditional sources
Placenta:•All hormones
Adipocytes:•Leptin
Cardiocytes:•ANP
Kidney:•Erythropoietin•RAS
GIT:•Gastrin•Cholecystokinin•Secretin,...
Endothelium:•Endothelins•NO•Prostanoids,...
Immune system:•Cytokines
Platelets, mesenchyme:•Growth factors
Gonads:•Inhibins•Activins
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Hormones, cytokines, growth factors
Common aspects: small quantities regulate other cells act through receptors
Tight interactions between immune and endocrine systems
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Hormones Cytokines Growth
factorsProduction Only specialized
cellsMany cell types
Few places Many places
Action Long-range Mostly short -range
Short -range
Pleiotropy Low High Medium
Redundance Low High Medium
Regulation Tight Loose
Function HomeostasisOntogenesis
Defence Remo-deling
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Endocrine and nervous systems
Many common aspects: small quantities regulate other cells & tissues act through receptors functional overlap between some hormones &
neurotransmitters excitability both can secrete into blood
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Types of humoral signalization Endocrine
from gland via blood to a distance
Neurocrine via axonal transport and then via blood
Paracrine neighboring cells of different types
Autocrine neighboring cells of the same type or the secreting
cell itself
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Chemical characteristics of hormones
Amines (from tyrosine) hydroxylation - catecholamines iodination - thyroid hormones
Peptides/proteins Steroids (from cholesterol)
adrenocortikoids sex hormones active metabolites of vitamin D
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Genetic disorders
Peptides/proteins: Often gene coding the hormone
-> activity (e.g. insulin)
Amines & steroids: gene coding enzyme catalyzing the
synthesis-> hormone level and/or precurzor level
e.g. androgens in deficient estrogen synthesis
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Hormone release Proteins & catecholamines:
secretory granules, exocytosis for incorporation into granules often special
sequences cleaved off in granules or after release
stimulus [Ca2+]i (influx, reticulum) granules travel along microtubules towards cell membrane (kinesins, myosins) fusion
QuickTime™ and aVideo decompressor
are needed to see this picture.
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Hormone release Thyroid hormones:
made as part of thyroglobulin stored in folicles T3 & T4 secreted by enzymatic cleavage
• Steroid hormones:• leave the cell across cell membrane right after
synthesis (no storage)
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Regulation of hormone release
Feedback Negative
Gland Target tissue
hormone
product
inhibition
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Regulation of hormone release
Feedback Negative Positive (only narrow dose range)
Gland Target tissue
hormone
product
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Regulation of hormone release
Feedback Negative Positive (only narrow dose range)
Nerve regulation pain, emotions, sex, injury, stress,... e.g. oxytocin with nipple stimulation
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Combined feedback Stress etc.
CRH secretion in hypothalamus
ACTH secretion in pituitary
plasma ACTH
cortisol secretion in adrenals
plasma cortisol
stimulation
inhibition
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Regulation of hormone release
Rhythms circadian
0
100
200
300
400
500
600
Cortisol(nM)
Time of day09 0921
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Regulation of hormone release
Rhythms circadian
light/dark fine/tune endogenous rhythm of cells & suprachiasmatic nucleus of hypothalamus
melatonin, cortisol
monthly seasonal (day length; atavistic) developmental (puberty, menopause)
Pulsations/oscillations gonadotropins
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Pulsatility in GnRH & LH release
0
2
4
6
8
10
12
14 GnRH (pg/10 min)
LH (ng/ml)
12:00 16:0014:00Time of day
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Hormone action
Receptor specificity of a response to a given hormone
(Second messenger)
∆ activity or concentration of enzymes, transcription factors, or structural proteins
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Hormone action
Peptides/proteinsCatecholamines
Steroid & thyroidhormones
Receptor in cellmembrane
Receptor in cytosol ornucleus
Second messengers ² protein activity
² gene expression
Fast Slower
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Receptors
∆ affinity or expression modulates hormone action
e.g. phosphorylation, pH, osmolarity,...
down-regulation
up-regulation
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Membrane receptors
Large glycoproteins, often several subunits
Typically 7x through membrane After activation:
dissociation from the hormone or endocytosis of the complex, then
degradation in lysozomes, recycling
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G proteinsG proteins
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G proteins
a subunit binds activated receptor releases GDP, binds GTP dissociates from its b subunit & the receptor binds & activates/inhibits effector
(adenyl/guanylate cyclase, phospholipase C) hydrolyzes GTP to GDP re-associates with its b-g dimer
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Intracellular signal transduction
(second messengers) cAMP cGMP IP3
Ca/calmodulin tyr kinases Smad MAP kinases One hormone can use several systems (in various cells or
for different functions)
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cAMP cAMP
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Adenylate cyclase - cAMP- protein kinase A
PKA phosphorylates target enzymes (in/activation)
sometimes complementary (e.g. Ca channel activation + Ca pump inhibition)
can affect gene expression cAMP regulatory element (CRE) on DNA binds
transcription factor, CRE binding protein (CREB) cAMP hydrolysis: phosphodiesterases
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cGMP cGMP
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Ca-calmodulin
G proteins activate Ca channels (ROC)
Ca influx stimulates Ca release from endoplasmic reticulum (CICR)
Ca, mainly by binding calmodulin, modulates many enzymes, often via protein kinase C
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Phospholipase C - IP3 & DAG
from cell membrane phospholipids
IP3 activates Ca channel of the endoplasmic reticulum
DAG: PKC affinity to Ca
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Tyrosin kinases Receptor autophosphorylation upon hormone
binding unmasks tyr-kinase activity typically insulin (& growth factors)
Or conformational change of the receptor upon hormone binding attracts & activates cytoplasmic tyr-kinases
e.g. growth hormone
tyr-kinases phosphorylate cascades of tyr & ser kinases & phosphatases
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Inhibins, activins & TGF system
Hormone
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Intracellular receptors
Lipophilic hormones: Thyroid Steroid Vitamin D
Enter the cell or all the way to nucleus, where they bind the receptor (large oligomeric protein)
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Intracellular receptors
C-terminal domain binds hormone hormone specificity
Central domain binds DNA (HRE, hormone regulatory unit, 8-15 bases) gene specificity
N-terminal domain activates RNA polymerase
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Function of intracellular receptors
Hormone displaces inhibitory protein (e.g. HSP) translocation to nucleus, DNA binding
corticoids
Or hormone binding displaces the receptor from resting, inhibitory association with DNA
thyroid hormones
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Magnitude of response
hormone concentration number of receptor molecules duration of exposure intracellular conditions (second
messengers, kinases,…) synergistic or antagonistic influences
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Dose/response
0
20
40
60
80
100
120
Hormone concentration
Eff
ect
max. response
~sensitivity
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Decrease in max. response
less target cells less receptors less/lower activity of enzymes activated
by hormone less substrate for final product more non-competitive inhibitor
0
20
40
60
80
100
120
Hormone concentration
Eff
ect
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Drop in sensitivity
less receptors lower receptor affinity modulating factors faster hormone degradation antagonistic hormones
0
20
40
60
80
100
120
Hormone concentration
Eff
ect
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Transport of hormones
Freely in blood: Catecholamines Most peptides
Specific transport globulins (from liver): Steroids Thyroid hormones
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Transporter binding lengthens hormone halftime
0
1
2
3
4
5
6
7
100 99.97 99.7 94 89
Plasma halftime(days)
% bound hormone
Thyroxin
T3 Testosterone
Cortisol
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Inactivation of hormones
Target tissue uptake Metabolic degradation (plasma, liver,
kidney) Excretion in urine
( by transporter binding; low for proteins - also re-absorbtion & degradation in kidneys)
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Measuring hormones
Immunoassay (pM)
Bioassay (biol. activity can differ from concentration or immunoreactivity - e.g. mutation of the gene for the hormone)
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KELENJAR APA SAJA YANG DAPAT MENGHASILKAN HORMON
HIPOFISA HIPOFISA ANTERIOR, MEDULA, POSTERIOR THYROID PARATHYROID ADRENAL KORTEKS & MEDULA PANKREAS SEL ALPHA, SEL BETA, SEL DELTA, SEL F LAMBUNG (GASTER) DUODENUM (USUS HALUS = INTESTINUM TENUE) OVARIUM TESTIS THYMUS
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KELENJAR HIPOFISA (PITUITARI)
TERDIRI DARI HIPOFISA ANTERIOR (DEPAN), MEDULA (TENGAH) & POSTERIOR (BELAKANG)
ANTERIOR & MEDULA ADENOHIPOFISA POSTERIOR NEUROHIPOFISA ADA SINYAL SYARAF
BARU DISEKRESIKAN KELENJAR HIPOFISA MASTER GLAND KARENA DPT
MENGHASILKAN HORMON & HORMON YANG DIHASILKAN DAPAT MERANGSANG KELENJAR LAIN UNTUK MENGHASILKAN HORMON LAIN hipofisa anterior TSH = tyrosomatotropic hormone merangsang kelenjar thyroid untuk menghasilkan thyroksin thyroksin digunakan untuk metabolisme tubuh (kh, protein, lipid) berarti jln menuju hipofisa anterior akan terhambat dst
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HIPOFISA ANTERIOR
HORMON PERTUMBUHAN = GROWTH HORMONE = SOMATOTROPIN = GH HORMON INI BEKERJA PD TULANG, OTOT, RAWAN, KULIT & BEKERJANYA SANGAT TERBATAS PD PRIA LHR 21 THN PERTMBUHAN DRASTIS 13-16 THN; SDGKAN PD WANITA LHR 18 THN PERTUMBUHAN DRASTIS 9-12 THN
GH SANGAT DIPENGARUHI KADAR GLUKOSA DLM DRH BILA SELESAI MAKAN KDR GULA DLM DRH AKAN MENING-KAT, GH TDK MAU BEKERJA; BILA KDR GULA DLM DRH MENU-RUN, GH BEKERJA SECARA MAKSIMAL
BILA GH BEKERJA NORMAL TBH AKAN NORMAL, BILA HI-PERSEKRESI MANUSIA RAKSASA (GIANT), BILA HIPOSEKRE-SI MANUSIA KERDIL/CEBOL LORAIN PENDEK & KURUS; FROLICH PENDEK, GENDUT, PERUT BUNCIT
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LANJUTAN HIPOFISA ANTERIOR
THYROTROPIC HORMONE = THYROSOMATOTROPIC HORMONE = TSH MEMPENGARUHI KEL THYROID MENG-HASILKAN THYROKSIN (T4), LIOTIRONIN (T3) & KALSITONIN
ADRENO CORTICO TROPIC HORMONE (ACTH) ADA 3 KELOMPOK BESAR 1. GLUKOKORTIKOID PENGHASIL GULA; 2. MINERALOKORTIKOID MENGATUR KESEIMBANGAN CAIRAN ANTARA ION Na & ION K; 3. GONADO-KORTIKOID UTK WANITA ESTRONE & PROGESTRONE; UTK PRIA TESTRONE
PROLACTINE = LACTOGENIC HORMONE = LUTEOTROPIC HORMONE = LTH PERSIAPAN PRODUKSI AIR SUSU IBU (ASI) PD SAAT SEORANG WANITA DINYATAKAN MENIKAH & HAMIL; MSH GADIS TDK KELUAR ASI KRN ADA HORMONE YG MENGHAMBAT ESTROGEN
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LANJUTAN HIPOFISA ANTERIOR
GONADOTROPIN HORMONE (GTH) tdd:
FSH FOLLICLE STIMULATING HORMONE & LH (LUTEINIZING HORMONE) = ICSH = INTERSTITIAL CELL STIMULATING HORMONE
PDWANITA FSH MEMATANGKAN TELUR DALAM FOLIKEL OVARIUM MULAI DR FOLIKEL AWAL – PRIMER – SEKUNDER – TERSIER – DE GRAAF (MATANG) ; LH MENEBALKAN DDG RAHIM & MEMPERTAHANKAN IMPLANTASI JANIN
PD PRIA FSH MEMATANGKAN SPERMATOGONIUM SPERMATOZOA MELALUI SPERMATOGENESIS, SPERMIOGENE-SIS, TRANSFORMASI; LH = ICSH MENGHASILKAN SEL LEYDIG YANG MEMPRODUKSI HORMON TESTOSTERON
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HIPOFISA MEDULLA
MENGHASILKAN MSH = MELANOCYTE STIMULATING HORMONE AKAN MENGHASILKAN PIGMEN MELANIN UNTUK WARNA KULIT
MAKIN BANYAK MELANIN MAKIN HITAM PIGMEN KULIT, MAKIN SEDIKIT MELANIN MAKIN PUTIH PIGMEN KULIT
ORANG BULE MENJEMUR KULIT TUBUH PD SAAT ULTRA VIOLET MATAHARI TIDAK BAIK (DIATAS JAM 9 PG S/D 15 SORE, SEHINGG PIGMEN KULIT PECAH SHG MENIMBULKAN BERCAK PECAH BER-WARNA COKLAT SPT NODA PADA KULIT
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HIPOFISA POSTERIOR = NEUROHIPOFISA
OXYTOSIN REGULASI KONTRAKSI RAHIM SETIAP 3 JAM, 2,5 JAM, 2 JAM, 1,5 JAM, 1 JAM SEKALI S/D 10 MENIT SEKALI; SELAIN ITU JG MEMBANTU DALAM PROSES PENGELUARAN AIR SUSU IBU BILA SETELAH MELAHIRKAN KELENJAR MAMMAE IBU DIHISAP OLEH BAYI
RELAXIN MEMBUKANYA SIMPHISIS PUBIS (TLG KEMALUAN) SEHINGGA BAYI MUDAH DILAHIRKAN
KEDUA HORMON DI ATAS HARUS BEKERJA SAMA AGAR BAYI MUDAH DILAHIRKAN
ADH = ANTI DIURETIKA HORMONE = PITRESSIN = VASOPRES- SIN MENCEGAH AGAR URIN YANG KELUAR TIDAK TERLALU BANYAK ( IN PUT = OUT PUT) BILA TIDAK AKAN MENYE-BABKAN DIABETES INCIPIDUS
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KELENJAR THYROID
1. THYROKSIN UNTUK METABOLISME TUBUH BAIK META-BOLISME KH, PROTEIN MAUPUN LIPID
2. LIOTIRONIN MERUPAKAN BAHAN BAKU THIROKSIN DGN SYARAT HARUS ADA ION IODIUM DEKAT LAUT ATAU HASIL DARI LAUT IKAN, GARAM YG BERIODIUM
3. KALSITONIN MERUPAKAN BAHAN BAKU PEMBENTUKKAN PARATHORMON YANG JUGA DISEKRESIKAN OLEH KELENJAR PARATHYROID -- > BERFUNGSI UNTUK MENGATUR KADAR CALCIUM (ION Ca2+) DALAM DARAH
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KELENJAR PARATHYROID
MENEMPEL PD KELENJAR THYROID SEBANYAK 2 PASANG SEPASANG PD BAGIAN ATAS & SEPASANG PD BAGIAN BAWAH
MENGHASILKAN PARATHORMONE = HORMON PARATHYROID YG BERFUNGSI MENGATUR KADAR CALCIUM DALAM DARAH
CALCIUM DIBUTUHKAN TUBUH:
1. DALAM PROSES MEMPERCEPAT PEMBEKUAN DARAH APA-BILA TERDAPAT LUKA
2. DALAM PROSES PEMBENTUKAN & MEMPERKUAT TULANG & GIGI
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KELENJAR ADRENAL (ANAK GINJAL)
DISEBUT KELENJAR SUPRARENALIS ADA BAGIAN KORTEKS (TEPI) & MEDULLA (TENGAH) BAGIAN KORTEKS MEMPUNYAI 3 (TIGA) KELOMPOK
BESAR:
1. GLUKOKORTIKOID MENGHASILKAN KORTISON & HIDRO-KORTISON UNTUK PEMBENTUKAN GULA BILA TUBUH KEKURANGAN GULA
2. MINERALOKORTIOD ALDOSTERON KESEIMBANGAN CAIRAN TUBUH ANTARA ION Na (NATRIUM = SODIUM) & ION K (KALIUM=POTASIUM)
3. GONADOKORTIKOID PEMBENTUKAN HORMON PD WANITA ESTRONE & PROGESTRONE SERTA PD PRIA TESTRONE
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LANJUTAN KELENJAR ADRENAL
BAGIAN MEDULA (TENGAH) ADRENALIN & EPINEPHRIN SERTA DERIVATNYA YAITU:
NORADRENALIN & NOREPINEPHRIN DILATASI (PELEBARAN) PEMBULUH DARAH CORONARIA
JANTUNG DILATASI PEMBULUH DARAH & OTOT-2 BRONKIOLUS
AGAR RESPIRASI BERJALAN NORMAL KONSTRIKSI (PENYEMPITAN) PEMBULUH DARAH PD
DAERAH MUKA (TERUTAMA BILA KITA DIPERMALUKAN) AKIBAT LAIN TERJADINYA HIPERTENSI (TEKANAN DARAH TINGGI)
MENGHASILKAN GULA DARI GLIKOGEN OTOT
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KELENJAR PANKREAS
BERFUNGSI GANDA DAPAT MENGHASILKAN EKSOKRIN BGN ACINI (ACINUS) SERTA ENDOKRIN BGN PULAU-2 LANGERHANS
1. SEL A = ALPHA GLUKAGON MENGHASILKAN GULA BILA TUBUH KEKURANGAN GULA
2. SEL B = BETA INSULIN MENGURAIKAN GULA BILA BERLEBIHAN MENJADI GLIKOGEN DALAM OTOT
3. SEL D = DELTA SOMATOSTATIN TERGANTUNG DR KE-BUTUHAN TUBUH MEMBANTU SEL A BILA KEKURANGAN GULA & MEMBANTU SEL B BILA KELEBIHAN GULA
4. SEL F PANKREOPEPTIDA MEMBANTU DALAM PROSES PENCERNAAN MAKANAN TERUTAMA PROTEIN
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KELENJAR LAMBUNG (GASTER)
MENGHASILKAN GASTRIN
MEMBANTU DALAM PROSES GERAK PERISTALTIK YANG TERATUR SEHINGGA MAKANAN DIANTAR ANTARA LAMBUNG MULAI DARI ESOPHAGUS, KARDIA LAMBUNG, FUNDUS LAMBUNG DAN PYLORUS LAMBUNG
MEMBENTUK MAKANAN YANG PADAT MENJADI LUNAK ATAU DALAM BENTUK CAIR (KHIME) SEHINGGA MUDAH DICERNA OLEH INTESTINUM TENUE (USUS HALUS) YG TDD: DUODENUM, JEJENUM, ILEUM
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KELENJAR DUODENUM
MENGHASILKAN SEKRETIN
MEMBANTU DALAM PROSES GERAK PERISTALTIK DALAM USUS HALUS MULAI DARI DUODENUM, JEJENUM KEMUDIAN KE ILEUM KE USUS KASAR/BESAR (INTESTINUM CRASSUM)
MEMPERCEPAT PENGANTARAN NUTRISI KE JARINGAN DAN SEL-SEL SETELAH DALAM BENTUK KHIME
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KELENJAR THYMUS
MENGHASILKAN THYMOSIN BERFUNGSI UNTUK KEKEBALAN TUBUH MANUSIA KEKEBALAN ADA 2 (DUA) MACAM: 1. KEKEBALAN SELULER KEKEBALAN YANG
DIBERIKAN PD SAAT KITA DALAM KANDUNGAN IBU IBU MAKAN PROTEIN ATAU DISUNTIK AKAN TERBENTUK ANTIBODI YANG AKAN DIBERIKAN KE ANAK SHG ANAK MENJADI KEBAL
2. KEKEBALAN HUMORAL KEKEBALAN YANG DIBERIKAN SETELAH ANAK DILAHIRKAN MELALUI VAKSINASI/IMUNISASI MULAI DARI BCG; DPT 1, 2, 3; POLIO 1, 2, 3, CAMPAK, RUBELLA, HEPATITIS DAN DILAKUKAN PENGULANGAN SETELAH 1 THN, 3 THN, 6 THN
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KELENJAR OVARIUM
MENGHASILKAN ESTROGEN & PROGESTERON ESTROGEN BERFUNGSI UNTUK MEMATANGKAN
TELUR DALAM FOLIKEL-2 TELUR (FOLIKEL AWAL, PRIMER, SEKUN-DER, TERSIER, DE GRAAF), MENEBALKAN DINDING RAHIM UTK PERSIAPAN BILA OVUM KETEMU DG SEL SPERMA
MENGEMBANGKAN PAYUDARA SECARA MAKSIMAL, MULAI DARI PUTING & AEROLA (bgn berwarna coklat yg mengelilingi puting)
TANDA SEKS SEKUNDER PD WANITA MENSTIMULI PERTEMUAN OVUM DG SEL SPERMA PADA
SALURAN TELUR (OVIDUCT) PROGESTERON BERFUNGSI MEMPERTAHANKAN
KETEBA-LAN DDG RAHIM SHG BILA TERJADI PERTEMUAN OVUM DG SEL SPERMA AKAN DI IMPLANTASIKAN
MENGHAMBAT PERTEMUAN OVUM DG SEL SPERMA BILA MELEBIHI KAPASITAS YANG SEHARUSNYA
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KELENJAR TESTIS (TESTES)
MENGHASILKAN HORMON TESTOSTERON
SETIAP 3 (TIGA) TUBULUS SEMINIFERUS DLM TESTIS KETEMU AKAN MENGHASILKAN HORMON TSB
MENINGKATKAN HASRAT LIBIDO PRIA
SEBAGAI TANDA SEKS SEKUNDER PRIA SUARA BERAT, TUMBUH JAKUN (ADAM APPLE’S), BAHU MELEBAR, PINGGANG TETAP RAMPING
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Terima Kasih