Hormone Synthesis & Action Flashcards
Describe peptide/protein hormones.
- water-soluble
- made from large precursor molecules - prohormones
Describe steroid/iodinated tyrosine hormones
- Lipid soluble
- Made from low-weight molecular weight precursors
Describe the generalised scheme for the synthesis of protein/peptide hormones.
FLC REVISION
- TRANSCRIPTION: of the DNA to RNA
- POST-TRANSCRIPTIONAL PROCESSING: conversion of RNA to mature RNA with the excision of introns and modifications of the 3’ and 5’ ends
- TRANSLATION: of mature RNA into protein using tRNA to transfer amino acids
- POST-TRANSLATIONAL PROCESSING: cleavage of large-prehormone, folding of proteins, an addition of sugars (glycosylation)
Describe preprohormones.
- Contains the HORMONE
- SIGNAL SEQUENCE - allows the protein to be processed within secretory granules
- REDUNDANT SEQUENCE, both of which will later be cleaved off.
Describe prohormones.
Only contains HORMONE and REDUNDANT SEQUENCE.
Describe the hormonal control of steroid synthesis from cholesterol. PART 1
- Hormone activates GPCR which activates cAMP - increases amount of activated PKA.
- Increases cholesterol ester hydrolase activity - releases cholesterol from cytoplasmic store.
- Increases the synthesis of StAR protein (Steroidogenic Acute Regulatory protein).
Describe the hormonal control of steroid synthesis from cholesterol. PART 2
- Cholesterol is cleaved into pregnenolone by the side chain cleaving enzyme, P450scc
- Pregnenolone is a precursor to other steroid hormones.
- Between the mitochondria and SER, the steroids are synthesised by hydrolase enzymes.
What are the hormones cholesterol can be converted into?
Aldosterone (from progesterone)
Cortisol + Androgens (from hydroxylated progesterone)
What enzymes do androgens need and what do they do?
- Aromatase
- Converts androgens to estrogens
What is aromatase deficiency in men?
- Unable to synthesize estrogens from androgens
- No epiphyseal closure (bone development)
Describe the synthesis of thyroid hormones. PART 1
- Upon the stimulation of TSH, active uptake of iodide into the follicular cell.
- Iodide moves through the apical membrane via a transporter called pendrin
- Iodide oxidised to an iodinated intermediate by thyroid peroxidase (TPO), activated by H2O2.
Describe the synthesis of thyroid hormones. PART 2
- Components iodinate a thyroglobulin molecule (on the tyrosine residues)
- Coupling of the iodinated residues to make T3 or T4.
- T3 /T4 are stored in the colloid.
- When stimulated by TSH , release and secretion of T3 and T4 into the blood circulation.
What is goitre?
Enlargement of the thyroid gland
What is Graves disease?
→ Antibodies to the TSH receptor act on the thyroid gland
→ Stimulates excess thyroid hormones and can cause opthalmopathy
What are properties of peptide and protein hormones?
→ Water soluble → cell surface receptors
→ Activate second messengers/ enzymes with cytoplasmic and nuclear effects
