Hormone

Santoso

Regulation of homeostasis

Nerves fast governing

Hormones mainly metabolism, growth,

differentiation, reproduction

Hormone

Substance produced by a specific cell type usually accumulated in one (small) organ

Transport by blood to target tissues

Stereotypical response (receptors)

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

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

Hormones, cytokines, growth factors

Common aspects: small quantities regulate other cells act through receptors

Tight interactions between immune and endocrine systems

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

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

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

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

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

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

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are needed to see this picture.

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)

Regulation of hormone release

Feedback Negative

Gland Target tissue

hormone

product

inhibition

Regulation of hormone release

Feedback Negative Positive (only narrow dose range)

Gland Target tissue

hormone

product

Regulation of hormone release

Feedback Negative Positive (only narrow dose range)

Nerve regulation pain, emotions, sex, injury, stress,... e.g. oxytocin with nipple stimulation

Combined feedback Stress etc.

CRH secretion in hypothalamus

ACTH secretion in pituitary

plasma ACTH

cortisol secretion in adrenals

plasma cortisol

stimulation

inhibition

Regulation of hormone release

Rhythms circadian

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Cortisol(nM)

Time of day09 0921

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

Pulsatility in GnRH & LH release

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LH (ng/ml)

12:00 16:0014:00Time of day

Hormone action

Receptor specificity of a response to a given hormone

(Second messenger)

∆ activity or concentration of enzymes, transcription factors, or structural proteins

Hormone action

Peptides/proteinsCatecholamines

Steroid & thyroidhormones

Receptor in cellmembrane

Receptor in cytosol ornucleus

Second messengers ² protein activity

² gene expression

Fast Slower

Receptors

∆ affinity or expression modulates hormone action

e.g. phosphorylation, pH, osmolarity,...

down-regulation

up-regulation

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

G proteinsG proteins

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

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)

cAMP cAMP

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

cGMP cGMP

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

Phospholipase C - IP3 & DAG

from cell membrane phospholipids

IP3 activates Ca channel of the endoplasmic reticulum

DAG: PKC affinity to Ca

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

Inhibins, activins & TGF system

Hormone

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)

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

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

Magnitude of response

hormone concentration number of receptor molecules duration of exposure intracellular conditions (second

messengers, kinases,…) synergistic or antagonistic influences

Dose/response

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120

Hormone concentration

Eff

ect

max. response

~sensitivity

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

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Hormone concentration

Eff

ect

Drop in sensitivity

less receptors lower receptor affinity modulating factors faster hormone degradation antagonistic hormones

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Hormone concentration

Eff

ect

Transport of hormones

Freely in blood: Catecholamines Most peptides

Specific transport globulins (from liver): Steroids Thyroid hormones

Transporter binding lengthens hormone halftime

0

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100 99.97 99.7 94 89

Plasma halftime(days)

% bound hormone

Thyroxin

T3 Testosterone

Cortisol

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)

Measuring hormones

Immunoassay (pM)

Bioassay (biol. activity can differ from concentration or immunoreactivity - e.g. mutation of the gene for the hormone)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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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