Endocrine Overview

Front 1

Endocrine Organs

Back 1

Front 2

Two major types of endocrine gland systems

Back 2

- ptential for negative or sometimes positive feedback

Front 3

Diurnal Rhythm of cortisol secretion

Back 3

Involvement of clock proteins in suprachiasmatic nucleus of hypothalamus
+
Input from pineal gland melatonin

cortisol lowest at midnight
- and highest just before waking
- bright light is the most useful thing when you are jet lagged

Front 4

Types of Intercellular Communication

Back 4

- paracrine
- synaptic
- endocrine
- autocrine

hypothalamus to pituary ; means the signal is not diluted by being circulated throughout the body

Front 5

Endocrine vs Synaptic Signaling Pathways

Back 5

Front 6

Prohormones

Back 6

EXTRA level of control

= inactive precursors of hormones EXAMPLES:
• proinsulin • vitamin D • testosterone (DHT active at prostate and skin)
•thyroxine

Front 7

PHEROMONES

Back 7

Are also chemical messengers
BUT!
• are carried in AIR
• are produced by one animal to affect
another animal
Thus are not true hormones

Front 8

TYPES OF HORMONES

Back 8

Front 9

Chemical nature of hormone affects

Back 9

•Mechanism of synthesis
•Storage
•Transport in blood
•Mechanism of interaction with target cells

eg Hydrophillic drugs get across cell membranes readily but require transport binding to globulins to get around the body
- peptides can move around no problem but need to bind specific receptors for cell entry

Front 10

PRODUCTION & SECRETION: Peptides

Back 10

Front 11

PRODUCTION & SECRETION: Amines

Back 11

catecholamines – in granules attached to binding protein
hydrophilic

thyroid hormone – as part of thyroglobulin in colloid of thyroid follicles
lipophilic

Front 12

PRODUCTION & SECRETION: Steriods

Back 12

Front 13

Transport in blood:
protein binding

Back 13

Front 14

3 general means by which hormones elicit biological response

Back 14

Front 15

Receptors

Why so complex?

Back 15

Signal amplification
Signal interaction
Signal stabilization

Front 16

Adrenalin MOA

Back 16

Front 17

Growth Hormone Secretion Regulation

Back 17

Front 18

Nuclear receptor
superfamily

Back 18

Front 19

Steroid hormone-receptor
Mechanism of action

Back 19

Front 20

Hormones may bind to more than 1 type of receptor

Back 20

and we can make drugs that only binds to a specific receptors ths eliciting only the required hormonal response

Front 21

Hormone actions may be
- permissive
- Synergistic
- antagonistic

Back 21

Permissive eg thyroid h and catecholamines
Synergistic eg follicle stimulating h & testosterone:
Antagonistic –eg anti-estrogens, anti-androgens

Front 22

Termination of signal

Back 22

1. Hormone metabolised
2. Intracellular signals metabolised eg
cAMP degraded by phosphodiesterases to 5’AMP
phosphatases remove phosphate group
3. Receptor recycling/degradation

Front 23

Pathway of receptor-mediated endocytosis and receptor recycling

Back 23

Front 24

What can go wrong?

Back 24

Front 25

Jansen’s metaphyseal chondrodysplasia

Back 25

Jansen’s metaphyseal chondrodysplasia at age 5 (left) and 22 (right) – due to constitutive activation of parathyroid hormone/PTH- related protein receptor – affects cartilage, especially

- His to arginine in the receptor making it always on

Front 26

Horomonal Responses Overview

Back 26

Front 27

Ix

Back 27

1.Screening – is there hormone over or under-production?
2.Confirmation
1.Stimulation Test (confirm hormone underproduction)
2.Suppression Test (confirm hormone overproduction)
3.Imaging - only once biochemical localization achieved as endocrine organ “incidentalomas” commonly occur

Front 28

Pituitary Disease

Back 28

Structure:
•-Generally pituitary lesions extend upwards and can compress the optic chiasm, causing bitemporal hemianopia
•-However, if they extend laterally (less common), they can involve cranial nerves
•- Rarely, they may invade the sellar floor
•-As part of the mass effect, they can cause headache
•Function:
•Consider the consequences of over or underproduction of the various hormones

Front 29

Pituitary Hormones

Back 29

Front 30

History of pituitary disease

Back 30

Structural effects
•Headache
•Visual disturbance
•Cranial nerve abnormalities
Hormonal effects
Underproduction or overproduction or combination