Hormone synthesis and action of hormones Flashcards
Describe the solubility of peptide and protein hormones and what they are made from
Water soluble, mostly made from large precursor molecules – prohormones
Describe the solubility of Steroids and iodinated tyrosines hormones and what they are made from
Lipid soluble, made from low molecular weight precursors
Describe the synthesis of an active hormone from a large precursor protein
What does a pre-prohormone consist of?
What does prohormone consist of?
Pre-prohormone (signal sequence + prohormone + peptide sequnce)
Prohormone (hormone + peptide sequence(s)
What is the generalised scheme for the synthesis of protein/peptide hormone?
Transcription of DNA to RNA
Post transcriptional processing RNA -> mature RNA – excision of introns, modifications of 3’ and 5’ ends
Translation of mature RNA into protein using tRNA to transfer amino acids
Post translational processing cleavage of large pre-prohormone, folding of proteins, addition of sugars (glycosylation)
How it insulin synthesised?
Transcription to mRNA
Excision of introns to messenger RNA
Removal of signal sequence and formation of disulphide bonds in RER.
Pre-proinsulin -> proinsulin
Transfer to Golgi apparatus, excision of C peptide and packaging into secretory granules
Describe how a trophic hormone is converted to pregnenolone
How is pregnenolone produced (used to produce steroid hormones)?
- Trophic hormones bind to a receptor
- Converts Atp to cAMP
- Produced Protein kinase A
- This PKA cause ps activating StAR and of the release of cholesterol from lipid stores
- Cholesterol enters the mitochondria and is cleaved by a cytochrome enzyme to produce pregnenolone
What is aromatase?
What is a consequence of not being able to produce oestrogen in men?
Converts Androgens to Oestrogens
Unable to synthesise oestrogens from androgens -> no epiphyseal closure -> long stature
Girls develop male-type characteristics and boys show early sexual development due to excess androgens
How is thyroid hormones synthesised?
- Active uptake of iodide into follicular cell
- Transport across the apical membrane
- Oxidation of iodide to iodinated intermediate by thyroid peroxidase (TPO) which is activated by H2O2
- Iodination of tyrosine residues of thyroglobulin
- Coupling of iodinated tyrosine residues
Storage of T3 and T4 in colloid - Uptake of thyroglobulin droplets into follicle cell
- Release and secretion of T3 and T4 stimulated by TSH
What is Goitre?
What happens if antibodies act on the TSH receptor on the thyroid gland constantly?
enlargement of thyroid gland
stimulate excess thyroid hormones and can cause eye disease – Graves’ disease
What receptors do protein and peptide hormones act upon?
What do they activate?
Where in the cell do they cause effects?
Water-soluble = cell surface receptors
Activate second messengers and/or enzymes
Cytoplasmic and nuclear effects
What receptors do steroid hormones act upon?
What do they activate?
Where in the cell do they cause effects?
Lipophilic = intracellular
receptors in cytoplasm or nucleus. Receptors are transcription factors
What 2 receptors do protein and peptide hormones activate?
- G-protein
2. Tyrosine kinase domains
What signalling pathways do protein and peptide hormones activate?
1. Adenyl cyclase and cAMP pathway On image 2. Phosphoinittide signalling pathway On image 3. Raf/ Mek/ ERK1/2 On image 4. Phosphatidylinositol kinase/ AKT signalling pathway On image 5. JAK/ STAT signalling pathway
What secondary messengers are produced from adenyl cyclase and phospholipase C?
- cAMP and Protein Kinase A
2. DAG and IP3 produces protein kinase C and Ca2+
Why is it important to know about receptors and their signalling pathways?
To understand endocrine disorders and to provide targets for the development of new drugs
