Lecture Two: Classes of hormones

Question 1

What are the three classes of hormones lectured in this course;

Answer 1

(There are more than three)

1) Derivatives of AA
2) Peptides + Proteins (most abundant and diverse)
3) Steroids, derivatives of cholesterol (includes vit D)

Question 2

What are the possible derivatives of AA?

Answer 2

Either derived from tyrosine or tryptophan

Question 3

What are the derivatives of tyrosine?

Answer 3

(1,2,3 = Catecholamines)

1) Epinephrine (adrenal medulla secretion)
2) Norepinephrine (SN ending, neurotransmitter)
3) Dopamine = Produced brain + elsewhere

4) Thyroid hormones : Thyroxine (T4), triodothyroninine (T3) (difference in the n. iodine molecules)

Question 4

What are the derivatives of tryptophan?

Answer 4

Melatonin

Question 5

Write some notes on melatonin synthesis and secretion;

Answer 5

Synthesised in the pineal gland, regulates sleep (multiple other roles too)

Melatonin can be converted into serotonin

Question 6

What defines a peptide hormone from a protein?

Answer 6

Peptide = <20AA

Protein = 20+ AA

Question 7

Give some examples of peptide hormones

Answer 7

Oxytonin
ADH
ANG
GnRH

Question 8

Give some examples of protein hormones

Answer 8

Insulin (glucagon too)
ACTH
LH
FSH
Prolactin

Question 9

Describe the synthesis of peptide and protein hormones

Answer 9

• Synthesised on ribosomes as much larger molecules (prohormones and preprohormones)
• Proteins destined for secretion usually have a hydrophobic sequence of AA at the N terminus

Question 10

Describe the whole peptide / protein synthesis process;

Answer 10

1) mRNA on ribosome binds AA into prepropeptide. The chain is directed into the ER by a signal sequence of AA.
2) Enzymes in ER chop off signal sequence creating a prohormone
3) Prohomone passes through ER to Golgi complex
4) Secretory vessles bud off golgi containing enzymes and prohormones. Enzymes chop the prohormone up into one or more active peptides plus additional peptide fragments
5) Secretory vessels release contents via exocytosis.
6) hormones move into the circulation for transportation to target cell.

Question 11

Describe prohormones post translational modification;

Answer 11

This occurs in the golgi complex.

Modification is tissue dependant. So there can be lots of precursors for in lots of places.

Question 12

Describe what clipping does in post synthetic processing;

Answer 12

Clipping the protein may yield more than one biologically important molecule from a single precursor as is seen with ACTH

Question 13

Give an example of prepropeptide post synthetic cleavage;

Answer 13

PreproTRH is clipped to produce:

• x6 TRH (3AA)
• Other peptides
• Signal Sequence (hydrophobic)

Question 14

Give an example of prohormone post synthetic cleavage;

Answer 14

Pro-opiomelancortin is processed into;

• ACTH
• Gama lipotropin
• Beta endorphin
• Other peptide fragment

Question 15

Give another example of prohormone post synthetic cleavage;

Answer 15

Proinsulin has formed a tertiary shape with disulphide bonds.

This is cleaved in insulin (discontinuous, has disulphide bonds) and C-peptide

The disulphide bonds are a result of post translational modification

Question 16

What other post synthetic processing may there be;

Answer 16

Other processing of peptide and protein hormones may include glycosylation (addition of carbohydrate chains to asparagine residues or coupling of sub units)

i.e residue addition may be additional to cleavage

Question 17

Why are peptides and protein hormones stored in vesicles?

Answer 17

Peptides and protein hormones are stored in vesicles ready for the endocrine reflex.

Question 18

What may mutations in prohormones modification lead to?

Answer 18

Can lead to endocrine disease

Question 19

Describe what happens in mutations to POMC (pro-opiomelanocortin)?

Answer 19

AA sequence changes, changed cleavage site of beta MSH, B edorphin, these form a fused protein (instead) resulting in disregulated appetite (obesity)

Question 20

What are steroid hormones derived from?

Answer 20

Cholesterol

Structure is enzymatically modified depending on cells and tissue

i.e different regions of the adrenal gland = different steroid hormones

Question 21

Describe the storage of Amine, peptide and protein hormones;

Answer 21

Peptides, proteins and amine hormones are stored in membrane bound vesicles and are secreted by exocytosis

Question 22

Describe the storage of steroid hormones;

Answer 22

There is little storage of steroid hormones which simply diffuse across the plasma membrane

Question 23

Describe the circulation of hormones;

Answer 23

Many hormones i.e peptides and steroids are in circulation bound to proteins

Question 24

Describe what happens when steroid hormones are bound to carrier proteins;

Answer 24

Carrier proteins i.e albumin, SBH,

Hormones bound are INactive but protected from degredation. They are released when they are near their specific cell receptor as the receptor binding affinity is stronger than the carrier protein affinity.

Question 25

Describe how peptide hormones can be bound to carrier proteins and the effect of this.

Answer 25

Peptide hormones can be bound to thyroid binding proteins and are therefore inactive.

Question 26

What is important biologically in terms of hormones in the blood?

Answer 26

The ratio of bound and unbound hormones

Binding hormones is tightly regulated

Other proteins will bind to protein hormones for protection

Question 27

Describe the regulation of hormone secretion;

Answer 27

• Hormone action must be terminated or limited in duration.
• Hormones are degraded in the circulation and excreted
• Secretion of most hormones is pulsatile.
• Feedback pathways act as regulation

Question 28

Describe the pulsatile manner of hormone secretion;

Answer 28

Lots of different types of pulsatile release, regulated by circadian rhythms i.e high cortisol in the morning, decreases and low melatonin in the morning, increases towards night, Negative feedback.

Must be pulsatile to be biologically active or continuous hormones may result in receptor saturation and lack of effect or receptor downregulation

Question 29

Give an overview of peptide, proteins and catecholamine hormones

Answer 29

Made in advance, stored, dissolved in plasma, short half life, pulsatile release.

Question 30

Give an overview of thyroid hormones

Answer 30

Made in advance, stored in follicles (in vessels) and released into the plasma attached to binding proteins (longer half life)

Unusual in that it is stored in large quantitiesl

Question 31

Describe steroid hormones;

Answer 31

Made on demand, bound to carrier proteins, long half life.