7.01 Overview of Endocrine Control

Question 1

Define endocrinology

Answer 1

The study of the homeostatic mechanisms that are controlled by hormones

Question 2

Define Hormone

Answer 2

A blood‐borne chemical mediator released from endocrine glands that act on distant target cells

Question 3

What is the main group of hormones released by the hypothalamus?

Describe its main target and effect

Answer 3

Tropic hormones (hormones that affect the activity of other hormones)

They target the anterior pituitary to release or inhibit pituitary hormones

(Note: many of them are also trophic meaning that they elicit a growth effect on their target cells causing hyperplasia and hypertrophy)

Question 4

What is the major guide for classification of hormones?

Answer 4

The structure of a hormone

Question 5

Define the following:

• Endocrine
• Neurocrine
• Autocrine
• Paracrine

Answer 5

• Endocrine: a chemical mediator that travels through the blood strem to act on a distant target (ie. a hormone)
• Neurocrine: a chemical mediator that acts on adjacent cells with a nervous input (action potential (ie. neurotransmitters)
• Autocrine: a chemical messenger that acts on the same cell that secreted it (self-reacting)
• Paracrine: a chemical messenger that acts on the cells very locally

Question 6

Compare and contrast the nervous system with the endocrine system by filling in the following table:

Answer 6

Question 7

There is a lot of overlap in the endocrine system. What are four general principles that relate to this?

Answer 7

1. One particular endocrine gland may produce multiple hormones (eg. pituitary)
2. Hormones may be produced by multiple endocrine glands (eg. sex steroids)
3. Hormones may have more than one target and function (sex steroids, GH)
4. A single cell/ organ may be influenced by more than one hormone (pancreas, reproductive)

Question 8

Is the rate of hormone secretion always tonic?

Answer 8

No

• Rate of secretion is highly controlled and stimualated by many sources and trophic hormones
• Rate of secretion of some hormones varies over time in a cyclic pattern (sex steroids)

Question 9

What is an example of a chemical messenger that may be hormone or neurotransmitter?

Answer 9

Noradrenaline

Question 10

Are hormones specific for targets or do they act globally to where they can access via the bloodstream?

Answer 10

Hormones will only have affect on target cells that express specific receptors for them (ie. if they are able to be recognised by cells)

A cell without a receptor, will have no response

Question 11

How does the solubility profile of a hormone impact on its action?

Answer 11

Lipophilic/Hydrophobic

• Means that it is able to easily diffuse through membranes and thus often have intracellular receptors
• Also means it requires protein carriers in the blood

Hydrophilic = Lipophobic

• Means that it requires endocytosis in the cells requiring an extracellular/membrane bound receptor

Question 12

What is a neurohormone?

Answer 12

Chemical messengers that are released by neurons directly into the bloodstream to act on distant targets - neurocrine action

Question 13

What are the three main groups of neurohormones?

Answer 13

1. Hypothalamus neurohormones acting on the Anterior Pituitary.
2. Hypothalamus neurons acting on the Posterior Pituitary.
3. Catecholamines (made by modified adrenal medulla neurons).

Question 14

What is a tropic hormone?

Answer 14

A hormone that controls the secretion of another hormone (trophic usually stimulates growth & development)

– Often (not always) have names that end with tropin Eg. Thyrotropin (TSH), Corticotropin, ACTH, etc.

Question 15

Draw the simple neural reflex

Answer 15

Question 16

Draw a simple neurohormonal reflex

Answer 16

Question 17

Make sure you understand the following images (neuroendocrine pathways)

Answer 17

These are all varying complexities of neuroendocrine reflexes

Question 18

What makes the simple endocrine pathways unique? How common are they?

Answer 18

They have no neuronal involvement at all

They are quite rare

Question 19

What are the four main schemes of classifying hormones? Give examples

Answer 19

1. Source of Hormone

•eg. pituitary

1. Hormone Structure

• eg. Peptides, Amines, Steroids

2. Hormone Solubility

• eg. hydrophilic or lipophilic

3. Binding of Receptor Type

• eg. G protein‐coupled receptors, tyrosine kinase‐linked receptors etc

Question 20

What are the three main classifications based on the structure?

Answer 20

1. Peptide
2. Steroid
3. Amine (catecholamines and thyroid hormones)

Question 21

Hydrophobic/lipophillic hormones travel through the blood often bound to protein carriers. What does this achieve?

Answer 21

• It enables a specificity to the hormones
• Increases half-life

Question 22

Describe the synthesis pathway of a peptid hormone

Answer 22

1. Messenger RNA on ribosomes bind amino acids into a peptide chain = preprohormone that is directed to the ER
2. Enzymes in the ER cleave off the signal sequence creating an inactive prohormone
3. The prohormone passes through the golgi complex
4. They are packed and stored in secretory vesicles that contain the enzymes and the prohormone. The enzymes cleave the prohormone into one or more active peptides
5. A release signal comes in causing exocytosis of vesicle contents into the extracellular space
6. Hormones move into the circulation for transport to the target

Question 23

Fill in the following table about peptide hormones

Answer 23

Question 24

What is common to all steroid hormones in terms of their synthesis?

Give examples of steroid hormones

Answer 24

All steroid hormones start from cholesterol (it is the background structure). Depending on the enzymes in various tissues, gives the final steroid hormone:

• Adrenal cortex: aldosterone and cortisol
• Ovaries: oestrogen

Question 25

Describe the location of receptors for steroid hormones. What action does binding normally elicit?

Answer 25

Receptor is either in the cytoplasm or nucleus. Binding causes the **altering gene expression** and production of new proteins. Thus the **pathway takes time**

Question 26

Fill in the following table about steroid hormones

Answer 26

Question 27

What is the basic building block of the amine hormones? What are the 2 main subgroups of the amines?

Answer 27

All amine hormones are derived from the amino acid tyrosine. 1. Catecholamines (dopamine, noradrenaline, adrenaline) 2. Thyroid Hormones (T3, T4)

Question 28

Describe the binding and mechanism of action of steriod hormones

Answer 28

1. Most hydrophobic steroids are bound to plasma protein carriers (only unbound can diffuse into the target) 2. Receptors in the cytoplasm or nucleus * Although some steroid hormones also bind to membrane receptors that cause rapid responses by activating second messenger cascades 3. Receptor-hormone complex binds to DNA and activates or represses one or more genes 4. Activated genes create new mRNA that moves back into the cytoplasm 5. Translation produces new proteins for cell processes

Question 29

Fill in the following table in regards to the amine hormones (catecholamines and thyroid hormones)

Answer 29

Question 30

Which two types/classes of hormones are hydrophilic? What is their mechanism of hormone action?

Answer 30

Peptide and catecholamines They bind to extracellular receptors and elicit an intracellular signal or “second messenger”

Question 31

What is the mechanism of action of thyroid hormones?

Answer 31

They behave like steroids (alter gene expression)

Question 32

What is the role of plasma proteins in the endocrine system? [3]

Answer 32

1. Transport of lipophilic and hydrophilic hormones 2. Act as a reservoir to maintain equilibrium of unbound plasma hormones 3. Facilitate solubility of lipophilic hormones

Question 33

What are the three major influences on the **plasma concentration** of a hormone at any one time?

Answer 33

1. Rate of **secretion** of the hormone 2. Rate of **metabolic activation** of hormones (for only a few hormones) 3. Extent of **binding to plasma proteins** (for lipophilic proteins) 4. Rate of **metabolic inactivation and excretion**

Question 34

What is the general flow of hormone removal? (what organs)

Answer 34

Liver --\> Kidney --\> Urine

Question 35

How are each of the hormone classifications removed from the body?

Answer 35

Steroid Hormones: – Conjugation→Urine (and Bile) Amines: – Specific circulating degrading enzymes Large Peptides: most get recycled – Receptor‐mediated endocytosis Smaller peptides (most) = Kidneys

Question 36

Describe the major means of feedback in hormone regulation

Answer 36

The role of feedback systems is to supress or increase activity of endocrine glands and create a stable environment and homeostasis The negative feedback loops * Short loops for fine tuning * Long loops from peripheral hormones to earlier parts of the pathway as a back up feedback

Question 37

Give examples of positive feedback control of hormone regulation

Answer 37

* LH surge triggered by oestrogen to cause ovulation * Cervix: production of higher levels of oxytocin to aid deliver of the baby

Question 38

What is another means of negative feedback to hormone regulation?

Answer 38

Neuroendocrine reflexes offer fine tuning of hormone release

Question 39

# Define the following terms in regards to hormone regulation: * Down regulation * Antagonism * Synergism * Permissive regulation

Answer 39

**Down‐regulation** * Endocytosis * Target cell desenitisation **Antagonism** * Act together but act in opposite directions (insulin & glucagon) * Allows fine tuning **Synergism** * Multiple stimuli and effect is more than additive (glucagon, cortisol & adrenaline regulating blood glucose; reproductive) **Permissive** * First hormone cannot exert effects without presence of second hormone (cortisol & adrenaline)

Question 40

What is the difference between a primary and a secondary endocrine disorder?

Answer 40

Primary: gland abnormal Secondary: gland is normal but the secretion is abnormal

Question 41

Describe the causes of endocrine disorder when there is a decrease in hormone activity? = **Hyposecretion**

Answer 41

Primary (gland abnormal) Secondary (normal gland; abnormal tropic hormone) * Removal from blood * Abnormal tissue response: Lack of receptorsor Lack of enzyme for cell response

Question 42

What would the treatment by for hyposecretion?

Answer 42

hormone administration for most cases

Question 43

Describe the causes of endocrine disorder when there is an increase in hormone activity? ## Footnote **= Hypersecretion**

Answer 43

Primary (gland abnormal eg. tumour) Secondary (normal gland; excessive stimulation) * 􏰄Plasma protein binding * Removal from blood: by inactivation or 􏰄Excretion

Question 44

What would the treatment by for hypersecretion?

Answer 44

Tumor removal, inhibiting drugs

Question 45

How would you make a differential diagnosis between primary and secondary causes?

Answer 45

Based on the levels of secretion of the different hormones (and trophic hormones) that are involved in the pathway.

Question 46

Draw the normal pathway for cortisol secretion starting from the hypothalamus to the target tissue

Answer 46

* Corticotrophine hormone is released by the hypothalamus * This goes to the anterior pituitary gland to the target cell and causes it to release Adrenocorticotropic hormone (ACTH) * ACTH (also called corticotrophin) then travels to the adrenal cortex to lead to cortisol release

Question 47

Now draw pathways that would help differentiate hypersecretion due to... * Hypothalamic problem * Pituitary Problem * Adrenal cortex which of these is primary and which is secondary?

Answer 47

* Hypothalamic problem (secondary) * Pituitary Problem (secondary) * Adrenal cortex (primary) if can't read image: see slide 36