Moleculer of Endocrine System

Hormone Receptors

• Receptors: a protein that binds a hormone with high affinity

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HORMONE RESEPTORSHORMONE RESEPTORS

HORMONE RESEPTORSHORMONE RESEPTORS

• Receptors are dynamic • They can respond to rising

levels of hormones by increasing in number (up-regulation)

• Respond to prolonged exposure to high hormone concentrations by reducing the number of receptors (down-regulation)

HORMONE RESEPTORSHORMONE RESEPTORS

In down regulation: receptors are internalized by endocytosis

RESEPTOR INSULINRESEPTOR INSULIN

Kadar insulin rendah dan ikatan pada reseptor yang tinggi latihan fisik dan puasa

Kadar insulin tinggi dengan ikatan yang rendah pada reseptor obesitas, asupan karbohidrat yang tinggi, insulinisasi eksogen kronik yang berlebihan.

RESEPTOR STEROIDRESEPTOR STEROID

Down regulation pada reseptor steroid terjadi dengan menghambat proses transkripsi mRNA protein reseptor penghambatan proses pembentukan protein reseptor konsentrasi molekul reseptor turun.

Berlangsung dengan pendudukan reseptor pada regio khusus pada DNA// response elements (HRE) menghambat transkripsigen

Down regulation reseptor dapat juga melalui proses desensitisasi

Molekul reseptor secara kimia akan mengalami modifikasi sedemikian rupa menjadi kurang responsif

RESEPTOR HORMON DAN OBAT

• Efek obat umumnya timbul karena interaksi obat dengan reseptor pada sel suatu organisme.

• Reseptor dari suatu hormon dapat berperan sebagai reseptor obat tertentu

• Interaksi obat dengan reseptornya ini mencetuskan perubahan biokimiawi dan fisiologis yang merupakan respon khas untuk obat tersebut.

BIOCHEMISTRY MEDICAL FACULTY

USU

Categorized by Categorized by chemical chemical structurestructure

1.1.Proteins or peptides or Proteins or peptides or glycoprotein hormoneglycoprotein hormone

2.2.Amino acid derivatives Amino acid derivatives

3.3.Steroid derivativesSteroid derivatives

4.4.EicosanoidEicosanoid derivates derivates

Classes of Classes of HormonesHormones

Classes of HormonesClasses of Hormones

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Hormone Class of hormone

Location

Amine (epinephrine)

Water-soluble Cell surface

Amine (thyroid hormone)

Lipid soluble Intracellular

Peptide/protein Water soluble Cell surface

Steroids and Vitamin D

Lipid Soluble Intracellular

EICOSANOIDS HORMONE• Produced from arachidonic acid, • Released from phospholipids by action

of phospholipase A2, phospholipase C

• Produced in almost every organ• In one pathway arachidonic acid is

converted to prostanoids by a group of enzymes, the cyclooxygenase system

• A second pathway to produce leukotrienes by the enzyme 5 lipoxygenase

EICOSANOIDS HORMONE

EICOSANOIDS HORMONE

• Roles in inflammation, fever, regulation of blood pressure, blood clotting, control of reproductive processes & tissue growth, sleep/wake cycle regulation

• Most affect other cells by interacting with plasma membrane G-protein coupled receptors. BIOCHEMISTRY

MEDICAL FACULTY USU

Prostaglandins

• Depending on the cell type, the activated G-protein may stimulate or inhibit formation of cAMP (PGE2 and PGI2) by stimulate or inhibit adenylate cyclase

• PGF2 can be activate a phosphatidylinositol signal pathway leading to intracellular Ca++ releaseBIOCHEMISTRY

MEDICAL FACULTY USU

Prostaglandins

• SAIDS inhibit action of phospholipase

• NSAIDs, such as aspirin and derivatives of ibuprofen, inhibit cyclooxygenase activity of PGH2 Synthase

• They inhibit formation of prostaglandins involved in fever, pain, & inflammation

REFERENCES

• Devlin T M, PhD. Text Book of Biochemistry with Clinical Correlations 5thed. Wiley-Liss, New York. 2002 : 906-952, 982-983

• McKee Trudy, McKee James R. The molecular basis of Life. 3rded. McGraw-Hill. Americas, New York. 2003 : 541-559

• Murray R K, et al. Harper’s Biochemistry 26thed. Appleton & Lange. America 2003: 434-473

• Raff A, et al. Moleculer Biology of The Cell. 4thed. Garland Science. New York. 2002: 832-892

• Stryer L. Biokimia. Edisi 4. EGC, Jakarta. 2000.: 340-358