Lecture Two: Classes of hormones Flashcards
What are the three classes of hormones lectured in this course;
(There are more than three)
1) Derivatives of AA
2) Peptides + Proteins (most abundant and diverse)
3) Steroids, derivatives of cholesterol (includes vit D)
What are the possible derivatives of AA?
Either derived from tyrosine or tryptophan
What are the derivatives of tyrosine?
(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)
What are the derivatives of tryptophan?
Melatonin
Write some notes on melatonin synthesis and secretion;
Synthesised in the pineal gland, regulates sleep (multiple other roles too)
Melatonin can be converted into serotonin
What defines a peptide hormone from a protein?
Peptide = <20AA
Protein = 20+ AA
Give some examples of peptide hormones
Oxytonin
ADH
ANG
GnRH
Give some examples of protein hormones
Insulin (glucagon too) ACTH LH FSH Prolactin
Describe the synthesis of peptide and protein hormones
- 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
Describe the whole peptide / protein synthesis process;
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.
Describe prohormones post translational modification;
This occurs in the golgi complex.
Modification is tissue dependant. So there can be lots of precursors for in lots of places.
Describe what clipping does in post synthetic processing;
Clipping the protein may yield more than one biologically important molecule from a single precursor as is seen with ACTH
Give an example of prepropeptide post synthetic cleavage;
PreproTRH is clipped to produce:
- x6 TRH (3AA)
- Other peptides
- Signal Sequence (hydrophobic)
Give an example of prohormone post synthetic cleavage;
Pro-opiomelancortin is processed into;
- ACTH
- Gama lipotropin
- Beta endorphin
- Other peptide fragment
Give another example of prohormone post synthetic cleavage;
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
What other post synthetic processing may there be;
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
Why are peptides and protein hormones stored in vesicles?
Peptides and protein hormones are stored in vesicles ready for the endocrine reflex.
What may mutations in prohormones modification lead to?
Can lead to endocrine disease
Describe what happens in mutations to POMC (pro-opiomelanocortin)?
AA sequence changes, changed cleavage site of beta MSH, B edorphin, these form a fused protein (instead) resulting in disregulated appetite (obesity)
What are steroid hormones derived from?
Cholesterol
Structure is enzymatically modified depending on cells and tissue
i.e different regions of the adrenal gland = different steroid hormones
Describe the storage of Amine, peptide and protein hormones;
Peptides, proteins and amine hormones are stored in membrane bound vesicles and are secreted by exocytosis
Describe the storage of steroid hormones;
There is little storage of steroid hormones which simply diffuse across the plasma membrane
Describe the circulation of hormones;
Many hormones i.e peptides and steroids are in circulation bound to proteins
Describe what happens when steroid hormones are bound to carrier proteins;
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.
Describe how peptide hormones can be bound to carrier proteins and the effect of this.
Peptide hormones can be bound to thyroid binding proteins and are therefore inactive.
What is important biologically in terms of hormones in the blood?
The ratio of bound and unbound hormones
Binding hormones is tightly regulated
Other proteins will bind to protein hormones for protection
Describe the regulation of hormone secretion;
- 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
Describe the pulsatile manner of hormone secretion;
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
Give an overview of peptide, proteins and catecholamine hormones
Made in advance, stored, dissolved in plasma, short half life, pulsatile release.
Give an overview of thyroid hormones
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
Describe steroid hormones;
Made on demand, bound to carrier proteins, long half life.
