Hormone Synthesis & Action Flashcards
Describe the features of protein/peptide hormones
Water soluble, made from large precursor molecules – prohormones
Outline the features of steroid hormones
Steroids + iodinated tyrosines
Lipid soluble, made from low molecular weight precursors
How are protein/peptide hormones synthesised?
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-hormone, folding of proteins, addition of sugars (glycosylation)
What does a preprohormone consist of?
signal sequence + prohormone
What does a prohormone consist of?
active hormone + redundant sequence (inactive form of hormone)
What is teh role of the hormones signal sequence?
Enables hormone to know where to translocate to
Outline the synthesis of Insulin
- Transcription to mRNA
- Excision of introns to messenger RNA
- Removal of signal sequence and formation of disulphide
bonds in RER - Preproinsulin 🡪 proinsulin
- Transfer to Golgi apparatus, excision of C peptide and
packaging into secretory granules
How is the hormone synthesis from cholesterol initiated?
Trophic hormone activates a membrane bound receptor
Initiates conversion of ATP → cAMP → PKA
CEH forms cholesterol
Where does hormone formation from cholesterol occur?
Cholesterol bound to sterol carrier protein - transported to mitochondria
What is a star protein?
StAR = steroidogenic acute regulatory protein
What is the role of the star protein?
transports cholesterol to inner mitochondrial membrane
Outline how the prohomrone is formed from cholesterol once in the mitochondria?
Cholesterol to pregnenolone by side chain cleavage enzyme, P450scc
Hydroxylase enzymes synthesise steroids between mitochondria and smooth endoplasmic reticulum
Which hormones does pregnenolone convert into?
Progesterone –> Aldosterone
17aOH Progesterone –> cortisol
–> Androgens –> oestrogens
via aromatase
What is the consequence of aromatase deficiency?
Unable to synthesise oestrogens from androgens 🡪 no epiphyseal closure 🡪 long stature
- Virilisation of XX fetuses
- Clitoromegaly
- Ambiguous genitalia
Girls develop male-type characteristics and boys show early sexual development due to excess androgens
Outline the process of thyroid hormone synthesis
- Active uptake of iodide into follicular cell
- Oxidation of I- to Iodine by thyroid peroxidase
(TPO) - Iodination of tyrosine residues of thyroglobulin and
apical-colloid interface - Storage in colloid
- Uptake of thyroglobulin droplets into follicle cell
- Release and secretion of T3 and T4 stimulated by TSH
What is Goitre?
Enlargement of thyroid gland
What is the consequence of goitre?
Antibodies to the TSH receptor act on the thyroid gland, stimulate excess thyroid hormones and can cause eye disease – Graves’ disease
Which type of receptors do protein/peptide hormones bind to?
Protein and peptide hormones are water soluble (can’t pass through membrane) and bind to cell surface receptors:
- GPCRs
- Tyrosine Kinase domain associated receptors
What is the effect produced by the binding of protein/peptide hormones to their cell surface receptors?
Activate second messengers/enzymes to cause cytoplasmic and nuclear effects
Which receptors do steroid hormones bind to?
Steroid hormones are lipophilic (pass through membrane) requiring intracellular receptors in cytoplasm / nucleus
Their receptors are Transcription Factors (TF)
What are the 2 major cell signalling pathways of tyrosine kinase receptors?
- Raf/MEK ERK1 pathway
cAMP → PKA → translocation to nucleus and transcription etc.
- mutations in this pathway can lead to cancer as the signalling molecules can act as oncogenes
- PI3 Kinase/AKT pathway
PIP2 → PIP3 leading to Ca2+ release
activated by growth factors (AKT aka PKB) - can also lead to cancer (nTOR is common target for cancer drugs)
Summarise the JAKSTAT pathway
JAK stimulates STAT which is a TF that is translocated to nucleus to increase transcription
Describe the adenyl cyclase secondary messenger pathway of GPCRs
AC -> cAMP -> PKA
What is the effect of protein kinases in signalling pathways?
Kinases activate enzymes or can activate transcription factors
