6 . ENDOCRINE PRINCIPLES
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Transcript of 6 . ENDOCRINE PRINCIPLES
6. ENDOCRINE PRINCIPLES6. ENDOCRINE PRINCIPLES
V BS 122 2012
Luis A. Bate
OBJECTIVESOBJECTIVES
TO REVIEW BASIC ASPECTS OF ENDOCRINOLOGY TO ESTABLISH A
BASELINE KNOWLEDGE
REFERENCE
Review Chapter 5 Senger
Chapter 74 Guyton
HORMONESHORMONES
Potent regulators of biological functions
Their biosynthesis, storage, excretion and metabolism depends on their chemical structure and composition
F 6-1
ENDOCRINE
SECRETORY CELL
TARGET TARGET TARGET
NEURON
NEURON
NEURO-ENDOCRINE NERVOUS
F 6-2
F 6-2
AUTOCRINE
PARACRINE ENDOCRINE
SECRETORY CELL
TARGET TARGET
F 6-3
CLASSIFICATIONCLASSIFICATION
• Origin– Pituitary, thyroid, gonad
• Activation– Direct synthesis, conversion, cleavage
• Chemical composition– Amino acids, lipids, proteins
• Function/action– Neurotransmitters, inhibitors
F 6-4
TYPE OF HORMONESTYPE OF HORMONES
Amino acid derivatives
Proteins
Lipid derivatives
F 6-5
AMINO ACIDS DERIVATIVESAMINO ACIDS DERIVATIVES
– Neurotransmitters• Catecholamines (Tyrosine derivative)
– Epinephrine– Norepinephrine– Dopamine
• GABA
– Thyroid hormones• Triiodothyronine (T3)
• Thyroxine (T4)
F 6-6
PROTEINSPROTEINS
• Small peptides– TRH 3 aa
• Polypeptides– GnRH 10 aa, ACTH 41 aa
• Glycoproteins– LH, FSH, TSH
F 6-7
LIPIDSLIPIDS
• Steroids– Progestogens, glucocorticoids
• 21 C progesterone, cortisol– Androgens
• 19 C testosterone– Estrogens
• 18 C estrone, estradiol, estriol
• Prostaglandins– PGF2α, PGE, PGH
F 6-8
HYPOTHALAMUSHYPOTHALAMUS
HOOC CH (CH2)2 COOH
NH2
GLUTAMIC ACID
Glutamatedecarboxylase
(CH2)3 COOH
NH2
GABA(GAMMA-AMINO BUTYRIC ACID)
CO2
F 6-9
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
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
F 6-11
INSULININSULINPROINSULIN
α CHAIN
C PEPTIDE
β CHAIN
INSULIN
F 6-12
α unitinactive
β unitInactive
β
αActivehormone
F 6-13
α unitcommon
β unitLH properties
β unitFSH properties
F 6-14
GLYCOPROTEINSGLYCOPROTEINS
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
hy
no ph
cl op
Cyclopentanopherhydrophenanthrene
F 6-16
Cy en
ta er
drop
he
nanthrene
2524
H C3
H C3CH
CH3
CH2 CH2 CH2 CH
CH3
CH3
CHOLESTANE
A B
C D
F 6-17
1
2
3
4
5
6
7
89
10
11
12
13
14 15
1617
18
19
20
21
22 23
27
26
H C3
H C3CH
CH3
CH2 CH2 CH2 CH
CH3
CH3
F 6-17
H C3CH
CH3
H C3
2
CH2 CH2 CH2 CH
CH3
CH3
CHOLESTANE TO PREGNANE = 21 C
F 6-18
H C3
H C3CH
CH3
2
PREGNANE TO ANDROSTANE = 19 C
F 6-19
H C3
H C3
ANDROSTANE TO ESTRANE = 18 C
F 6-20
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
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
F 6-22
O
PROSTAGLANDINS
F 6-23
Arachidonic acid
Prostaglandin E
Cyclooxygenase
PROSTAGLANDINS
F 6-24
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)
F 6-25
G protein
β
α
γ
F 6-26
G protein
αβ γ
ATP CAMP
IACAAC
ATPADP
DIRE
PARE
Response: Enzyme act Membrane change Prot Synth.
SECOND MESSENGERSECOND MESSENGER
IPKAPK
F 6-27
CLASSICAL STEROID ACTIONCLASSICAL STEROID ACTION
F 6-28
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
F 6-29
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
F 6-30
RECEPTOR TYPESRECEPTOR TYPES
Nuclearreceptor
Enzyme
G proteinChannel
F 6-31
HORMONE SPECIFICITYHORMONE SPECIFICITY
Specific=Response Non Specific= No Response
Specific=Response
Semi Specific=Some Response
F 6-32
High affinityHigh affinity
Response
Low affinityLow affinity
Response
RECEPTOR AFFINITYRECEPTOR AFFINITY
F 6-33
NUMBER OF SITESNUMBER OF SITES
No response Response
F 6-34
SPECIFICITY OF TISSUESPECIFICITY OF TISSUE
No response Response
F 6-35
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
F 6-36
Full response
Low response
DOWN-REGULATION
F 6-37
UP REGULATIONMaximalresponse
Modest response
F 6-38
HETEROREGULATION
F 6-39
NEGATIVE FEEDBACKNEGATIVE FEEDBACK
F 6-40
POSITIVE FEEDBACKPOSITIVE FEEDBACK
F 6-41
SHORT
LONGULTRA SHORT
FEEDBACK LOOPSFEEDBACK LOOPS
TARGET TISSUE
F 6-42