6 . ENDOCRINE PRINCIPLES

52
6. ENDOCRINE PRINCIPLES V BS 122 2012 Luis A. Bate

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6 . ENDOCRINE PRINCIPLES. V BS 122 2012 Luis A. Bate. OBJECTIVES. TO REVIEW BASIC ASPECTS OF ENDOCRINOLOGY TO ESTABLISH A BASELINE KNOWLEDGE REFERENCE Review Chapter 5 Senger Chapter 74 Guyton. HORMONES. Potent regulators of biological functions - PowerPoint PPT Presentation

Transcript of 6 . ENDOCRINE PRINCIPLES

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6. ENDOCRINE PRINCIPLES6. ENDOCRINE PRINCIPLES

V BS 122 2012

Luis A. Bate

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OBJECTIVESOBJECTIVES

TO REVIEW BASIC ASPECTS OF ENDOCRINOLOGY TO ESTABLISH A

BASELINE KNOWLEDGE

REFERENCE

Review Chapter 5 Senger

Chapter 74 Guyton

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HORMONESHORMONES

Potent regulators of biological functions

Their biosynthesis, storage, excretion and metabolism depends on their chemical structure and composition

F 6-1

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ENDOCRINE

SECRETORY CELL

TARGET TARGET TARGET

NEURON

NEURON

NEURO-ENDOCRINE NERVOUS

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F 6-2

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AUTOCRINE

PARACRINE ENDOCRINE

SECRETORY CELL

TARGET TARGET

F 6-3

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CLASSIFICATIONCLASSIFICATION

• Origin– Pituitary, thyroid, gonad

• Activation– Direct synthesis, conversion, cleavage

• Chemical composition– Amino acids, lipids, proteins

• Function/action– Neurotransmitters, inhibitors

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TYPE OF HORMONESTYPE OF HORMONES

Amino acid derivatives

Proteins

Lipid derivatives

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AMINO ACIDS DERIVATIVESAMINO ACIDS DERIVATIVES

– Neurotransmitters• Catecholamines (Tyrosine derivative)

– Epinephrine– Norepinephrine– Dopamine

• GABA

– Thyroid hormones• Triiodothyronine (T3)

• Thyroxine (T4)

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PROTEINSPROTEINS

• Small peptides– TRH 3 aa

• Polypeptides– GnRH 10 aa, ACTH 41 aa

• Glycoproteins– LH, FSH, TSH

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LIPIDSLIPIDS

• Steroids– Progestogens, glucocorticoids

• 21 C progesterone, cortisol– Androgens

• 19 C testosterone– Estrogens

• 18 C estrone, estradiol, estriol

• Prostaglandins– PGF2α, PGE, PGH

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HYPOTHALAMUSHYPOTHALAMUS

HOOC CH (CH2)2 COOH

NH2

GLUTAMIC ACID

Glutamatedecarboxylase

(CH2)3 COOH

NH2

GABA(GAMMA-AMINO BUTYRIC ACID)

CO2

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ADRENAL GLANDADRENAL GLAND

CH2 CH

NH2

COOH

PHENYLALANINE RATE LIMITING STEP

CH2

PNMT(Phenyl ethanol

amine NMethyl transferase)

HO

HO

C CH2

HNH

OH

CH3

EPINEPHRINE

CH2 CH

NH2

COOHO

TYROSINE

HO

O

DOPAMINEB-OXIDASE

HO

HO

C CH2

NH2H

OH

O

NOREPINEPHRINE

CO

CH2 CH2

NH2

HO

HO DOPAMINE

2

CH2 CH2

NH2

HO

2

F 6-10

HO

CH2 CH

NH2

HO

COOHDOPA

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OXYTOCINOXYTOCINTyrCys

IIe

Cys-Pro-Leu-Gly NH 2Gln

Asn

Pro-Leu-Gly NH 2

MIF-ITOCINOICACIDMIF-II

S

S

TyrCys

IIe

Gln

Asn

S

S

Cys

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INSULININSULINPROINSULIN

α CHAIN

C PEPTIDE

β CHAIN

INSULIN

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α unitinactive

β unitInactive

β

αActivehormone

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α unitcommon

β unitLH properties

β unitFSH properties

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GLYCOPROTEINSGLYCOPROTEINS

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THYROID RELATED HORMONES

PROHORMONE?HO O CH2 CH COOH

NH2

T4

HO O CH2 CH COOH

NH2

ACTIVET3

HO O CH2 CH COOH

NH2

INACTIVErT3

HO O CH2 CH COOH

NH2

T0

THYRONINE CATABOLITE

F 6-15

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hy

no ph

cl op

Cyclopentanopherhydrophenanthrene

F 6-16

Cy en

ta er

drop

he

nanthrene

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2524

H C3

H C3CH

CH3

CH2 CH2 CH2 CH

CH3

CH3

CHOLESTANE

A B

C D

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1

2

3

4

5

6

7

89

10

11

12

13

14 15

1617

18

19

20

21

22 23

27

26

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H C3

H C3CH

CH3

CH2 CH2 CH2 CH

CH3

CH3

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H C3CH

CH3

H C3

2

CH2 CH2 CH2 CH

CH3

CH3

CHOLESTANE TO PREGNANE = 21 C

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H C3

H C3CH

CH3

2

PREGNANE TO ANDROSTANE = 19 C

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H C3

H C3

ANDROSTANE TO ESTRANE = 18 C

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STEROID NOMENCLATURE

• Prefix Suffix Indicates

• Hydroxy -ol Hydroxyl group (-OH)• β-OH - Hydroxyl above plane • α-OH - Hydroxyl below plane

• Oxo one Keto or carbonyl group (C=O)

• - al Aldehyde (-CHO)• Carboxy -oic acid Carboxylic acid (COOH)• - -ene Double bond (-C=C-)• - -yne Triple bond (-C=C-)• - -ane Saturated ring

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H C3

H C3C

CH

O

OH OH

OH2

3

4

1117

20

21

PREGN-4-ENE-3, 20 DIONE, 11β, 17α, 21 TRIOL

CORTISOLCORTISOL

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O

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PROSTAGLANDINS

F 6-23

Arachidonic acid

Prostaglandin E

Cyclooxygenase

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PROSTAGLANDINS

F 6-24

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LATENT PERIODLATENT PERIOD• Ultra short Pre-existing , Enzymes (Seconds) Permeability• Very short Enzymatic cascades (Minutes)• Short Peptide assembly (½-1 hour)• Long Protein induction (Hours)• Very long Growth, cell proliferation (Days)• Ultra long Cell enhancement (Weeks)

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G protein

β

α

γ

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G protein

αβ γ

ATP CAMP

IACAAC

ATPADP

DIRE

PARE

Response: Enzyme act Membrane change Prot Synth.

SECOND MESSENGERSECOND MESSENGER

IPKAPK

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CLASSICAL STEROID ACTIONCLASSICAL STEROID ACTION

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RECEPTORStructure to which a hormone binds to trigger a biological

response

It is composed of a binding site joined by a transduction or coupling mechanism to an

effector site

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Extra cellular amino terminalvariable number of aa

Intracellular carboxyl terminal10-700 aa

7 transmembrane domains 20-27aa

3 intracellular loops(introloops)

3 extra cellular loops(exoloops)

Characteristics of G Protein- Coupled receptors

Characteristics of G Protein- Coupled receptors

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RECEPTOR TYPESRECEPTOR TYPES

Nuclearreceptor

Enzyme

G proteinChannel

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HORMONE SPECIFICITYHORMONE SPECIFICITY

Specific=Response Non Specific= No Response

Specific=Response

Semi Specific=Some Response

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High affinityHigh affinity

Response

Low affinityLow affinity

Response

RECEPTOR AFFINITYRECEPTOR AFFINITY

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NUMBER OF SITESNUMBER OF SITES

No response Response

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SPECIFICITY OF TISSUESPECIFICITY OF TISSUE

No response Response

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Regulation of hormone availability and biological activity

[H] + [R] ↔ [HR]

Regulation of hormone availability and biological activity

[H] + [R] ↔ [HR]

• HORMONE– Synthesis– Secretion– Transport– Metabolism

• RECEPTOR– Synthesis– Modification– Metabolism

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Full response

Low response

DOWN-REGULATION

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UP REGULATIONMaximalresponse

Modest response

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HETEROREGULATION

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NEGATIVE FEEDBACKNEGATIVE FEEDBACK

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POSITIVE FEEDBACKPOSITIVE FEEDBACK

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SHORT

LONGULTRA SHORT

FEEDBACK LOOPSFEEDBACK LOOPS

TARGET TISSUE

F 6-42

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