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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
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

slide4
NEURO-ENDOCRINE

NERVOUS

ENDOCRINE

NEURON

SECRETORY

CELL

NEURON

TARGET

TARGET

TARGET

F 6-2

slide6
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

slide12
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

slide13
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

slide14
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

slide15
INSULIN

INSULIN

PROINSULIN

CPEPTIDE

αCHAIN

βCHAIN

F 6-12

slide16
β

α

Active

hormone

β unit

Inactive

α unit

inactive

F 6-13

slide17
β unit

LH properties

α unit

common

β unit

FSH properties

F 6-14

slide19
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

slide22
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

slide23
CH

CH

3

3

CH

CH

CH

CH

CH

H C

2

2

2

3

CH

3

H C

3

F 6-17

slide24
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

slide25
CH

3

CH

2

H C

3

HC

3

PREGNANE TO ANDROSTANE = 19 C

F 6-19

slide26
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
slide28
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

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

slide32
β

α

γ

G protein

F 6-26

slide34
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

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

slide39
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

slide40
G protein

Channel

Enzyme

Nuclear

receptor

RECEPTOR TYPES

F 6-31

slide41
HORMONE SPECIFICITY

Non Specific=

No Response

Specific=Response

Semi Specific=

Some Response

Specific=

Response

F 6-32

slide42
RECEPTOR AFFINITY

Highaffinity

Lowaffinity

Response

Response

F 6-33

slide43
NUMBER OF SITES

Response

No response

F 6-34

slide44
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

slide46
DOWN-REGULATION

Full

response

Low

response

F 6-37

slide47
UPREGULATION

Modest

response

Maximal

response

F 6-38

slide51
FEEDBACK LOOPS

SHORT

ULTRASHORT

LONG

TARGETTISSUE

F 6-42

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