Hormone synthesis and action of hormones

Question 1

Peptides and proteins

Answer 1

Water-soluble, mostly made from large precursor molecules - prohormones

Question 2

Steroids and iodinated tyrosines

Answer 2

Lipid soluble, made from low molecular weight precursors

Question 3

A generalized scheme for the synthesis of protein/peptide hormones

Answer 3

• Transcription of DNA to RNA
• Post transcriptional processing RNA - mRNA - excision of introns, modifications of 3’ and 5’ ends
• Translation of mRNA into protein using tRNA to transfer amino acids
• Post-translational processing cleavage of large pre hormone, folding of proteins, the addition of sugar (glycosylation)

Question 4

Synthesis of insulin

Answer 4

• Transcription to mRNA
• Excision of introns to messenger RNA
• Removal of the signal sequence and formation of disulfide bonds in RER
• Pre-proinsulin - proinsulin
• Transfer to Golgi apparatus, excision of C peptide and packaging into secretory granules

Question 5

Control of steroid synthesis from cholesterol

Answer 5

Cholesterol bound to sterol carrier protein - transported to mitochondria
StAR protein transported cholesterol to inner mitochondrial membrane
Cholesterol to pregnenolone by side-chain cleavage enzyme (rate-limiting)
Between mitochondria and smooth endoplasmic reticulum steroids synthesized by hydroxylase enzymes

Question 6

Abnormalities in steroid synthesis

Answer 6

Aromatase deficiency in men
unable to synthesis estrogens from androgens - no epiphyseal closure - long stature
Girls develop male type characteristics and boys show early sexual development due to excess androgens

Question 7

Synthesis of thyroid hormones

Answer 7

1) Active uptake of iodide into follicular cell
2) Transport across the apical membrane
3) oxidation of iodide to iodinated intermediate by thyroid peroxidase (TPO) which is activated by H2O2
4) Iodination of tyrosine residues of thyroglobulin
5) coupling of iodinated tyrosine residues
6) Storage of T3 and T4 in colloid
7) Uptake of thyroglobulin droplets into follicle cell
8) release and secretion of T3 and T4 stimulated by TSH

Question 8

Goiter - enlargement of the thyroid gland

Answer 8

Antibodies to the TSH receptor act on the thyroid gland, stimulate excess thyroid hormones and cause eye disease - graves’ disease

Question 9

Signaling pathways for receptors with tyrosine kinase activity

Answer 9

Rat/MEK ERK pathway
PI3- kinase/Akt pathway
JaAK STAT pathway

Question 10

Defective G protein-coupled receptor

Answer 10

Thyroid adenoma -TSH receptor (activating mutation)

Precocious puberty - LH receptor (activating mutation)

Question 11

C domain

Answer 11

DNA binding region

Question 12

A/B and E/F

Answer 12

Transcriptional activity