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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

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6 . ENDOCRINE PRINCIPLES

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6 endocrine principles

6. ENDOCRINE PRINCIPLES

V BS 122

2012

Luis A. Bate


Objectives

OBJECTIVES

TO REVIEW BASIC ASPECTS OF ENDOCRINOLOGY TO ESTABLISH A BASELINE KNOWLEDGE

REFERENCE

Review Chapter 5 Senger

Chapter 74 Guyton


Hormones

HORMONES

Potent regulators of biological functions

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

F 6-1


6 endocrine principles

NEURO-ENDOCRINE

NERVOUS

ENDOCRINE

NEURON

SECRETORY

CELL

NEURON

TARGET

TARGET

TARGET

F 6-2


6 endocrine principles

F 6-2


6 endocrine principles

AUTOCRINE

SECRETORY

CELL

ENDOCRINE

PARACRINE

TARGET

TARGET

F 6-3


Classification

CLASSIFICATION

  • Origin

    • Pituitary, thyroid, gonad

  • Activation

    • Direct synthesis, conversion, cleavage

  • Chemical composition

    • Amino acids, lipids, proteins

  • Function/action

    • Neurotransmitters, inhibitors

F 6-4


Type of hormones

TYPE OF HORMONES

Amino acid derivatives

Proteins

Lipid derivatives

F 6-5


Amino acids derivatives

AMINO ACIDS DERIVATIVES

  • Neurotransmitters

    • Catecholamines (Tyrosine derivative)

      • Epinephrine

      • Norepinephrine

      • Dopamine

    • GABA

  • Thyroid hormones

    • Triiodothyronine (T3)

    • Thyroxine (T4)

F 6-6


Proteins

PROTEINS

  • Small peptides

    • TRH 3 aa

  • Polypeptides

    • GnRH 10 aa, ACTH 41 aa

  • Glycoproteins

    • LH, FSH, TSH

F 6-7


Lipids

LIPIDS

  • Steroids

    • Progestogens, glucocorticoids

      • 21 C progesterone, cortisol

    • Androgens

      • 19 C testosterone

    • Estrogens

      • 18 C estrone, estradiol, estriol

  • Prostaglandins

    • PGF2α, PGE, PGH

F 6-8


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Glutamate

HOOC

CH (CH

)

COOH

(CH

)

COOH

2

2

2

3

decarboxylase

NH

NH

2

2

HYPOTHALAMUS

CO

GLUTAMICACID

GABA

2

(

GAMMA-AMINO

BUTYRIC ACID)

F 6-9


6 endocrine principles

O

NH

NH

2

2

CH

CH

CH

CH

HO

2

2

COOH

COOH

O

TYROSINE

PHENYLALANINE

CO

2

2

NH

2

NH

NH

2

2

CH

CH

HO

2

CH

CH

CH

CH

HO

HO

2

2

2

2

COOH

HO

DOPA

DOPAMINE

HO

DOPAMINE

O

B-OXIDASE

H

CH

2

CH

H

N

3

H

NH

2

C

CH

HO

HO

C

CH

2

2

PNMT

O

O

(Phenyl ethanol

H

H

amine N

HO

HO

Methyl transferase)

EPINEPHRINE

NOREPINEPHRINE

ADRENAL GLAND

RATE LIMITINGSTEP

F 6-10


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Cys

OXYTOCIN

Tyr

S

IIe

S

Gln

Cys-Pro-Leu-GlyNH

2

Asn

Cys

Tyr

S

IIe

S

Gln

Cys

Pro-Leu-Gly NH

Asn

2

MIF-I

TOCINOIC

ACID

MIF-II

F 6-11


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INSULIN

INSULIN

PROINSULIN

CPEPTIDE

αCHAIN

βCHAIN

F 6-12


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β

α

Active

hormone

β unit

Inactive

α unit

inactive

F 6-13


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β unit

LH properties

α unit

common

β unit

FSH properties

F 6-14


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GLYCOPROTEINS


6 endocrine principles

NH

2

CH

CH COOH

O

HO

2

T

4

NH

2

CH

CH COOH

HO

O

2

ACTIVE

T

3

NH

2

CH

CH COOH

O

HO

2

INACTIVE

rT

3

NH

2

O

CH

CH COOH

HO

2

THYRONINE

T

CATABOLITE

0

THYROID RELATEDHORMONES

PROHORMONE?

F 6-15


Cyclopentanopherhydrophenanthrene

Cyclopentanopherhydrophenanthrene

ph

ta

no

er

hy

en

Cy

cl

op

dr

op

  • e

he

nt

en

na

hr

F 6-16


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CHOLESTANE

21

CH

CH

27

3

3

18

20

CH

CH

CH

CH

12

CH

H C

2

2

2

22

23

24

25

3

17

11

16

CH

13

D

26

3

C

19

1

H C

3

9

14

15

2

10

8

A

B

3

7

5

4

6

F 6-17


6 endocrine principles

CH

CH

3

3

CH

CH

CH

CH

CH

H C

2

2

2

3

CH

3

H C

3

F 6-17


6 endocrine principles

CH

3

CH

CH

CH

CH

CH

3

2

2

2

CH

CH

H C

2

3

3

HC

3

CHOLESTANE TO PREGNANE = 21 C

F 6-18


6 endocrine principles

CH

3

CH

2

H C

3

HC

3

PREGNANE TO ANDROSTANE = 19 C

F 6-19


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H C

3

H C

3

ANDROSTANE TO ESTRANE = 18 C

F 6-20


Steroid nomenclature

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


6 endocrine principles

CORTISOL

21

OH

CH

2

20

C

O

HC

OH

OH

3

17

11

H C

3

3

O

4

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

F 6-22


Prostaglandins

PROSTAGLANDINS

Arachidonicacid

Cyclooxygenase

Prostaglandin E

F 6-23


Prostaglandins1

PROSTAGLANDINS

F 6-24


Latent period

LATENT 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)

F 6-25


6 endocrine principles

β

α

γ

G protein

F 6-26


6 endocrine principles

SECOND MESSENGER

IAC

AAC

α

β

γ

G protein

DIRE

CAMP

ATP

IPK

APK

Response:

Enzyme act

Membrane change

Prot Synth.

PARE

ATP

ADP

F 6-27


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CLASSICAL STEROID ACTION

F 6-28


Receptor

RECEPTOR

Structure 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

F 6-29


6 endocrine principles

Characteristics of

G Protein- Coupled receptors

Extra cellular amino terminal

variable number of aa

3 extra cellular loops

(exoloops)

7 transmembrane

domains 20-27aa

3 intracellular loops

(introloops)

Intracellular carboxyl terminal

10-700 aa

F 6-30


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G protein

Channel

Enzyme

Nuclear

receptor

RECEPTOR TYPES

F 6-31


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HORMONE SPECIFICITY

Non Specific=

No Response

Specific=Response

Semi Specific=

Some Response

Specific=

Response

F 6-32


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RECEPTOR AFFINITY

Highaffinity

Lowaffinity

Response

Response

F 6-33


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NUMBER OF SITES

Response

No response

F 6-34


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SPECIFICITY OFTISSUE

No response

Response

F 6-35


Regulation of hormone availability and biological activity h r hr

HORMONE

Synthesis

Secretion

Transport

Metabolism

RECEPTOR

Synthesis

Modification

Metabolism

Regulation of hormone availability and biological activity[H] + [R] ↔ [HR]

F 6-36


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DOWN-REGULATION

Full

response

Low

response

F 6-37


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UPREGULATION

Modest

response

Maximal

response

F 6-38


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HETEROREGULATION

F 6-39


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NEGATIVE FEEDBACK

F 6-40


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POSITIVE FEEDBACK

F 6-41


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FEEDBACK LOOPS

SHORT

ULTRASHORT

LONG

TARGETTISSUE

F 6-42


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