Hormone synthesis and the action of hormones

Question 1

Describe peptide and protein hormones

Answer 1

They are water soluble so they don’t need to be bound to proteins to be transported in the blood.

Made from large precursor molecules - prohormones

Question 2

Describe steroid and iodinated tyrosine hormones

Answer 2

Lipid soluble

Made from low molecular weight precursor molecules.

Question 3

What is a pre-prohormone made up of?

Answer 3

Signal sequence + Prohormone

Question 4

What is a prohormone made up of?

Answer 4

Hormone + Redundant sequence

Question 5

Describe synthesis of insulin

Answer 5

Transcription to mRNA

Excision of introns to messenger RNA leaving signal sequence, a, b and c chain

Removal of signal sequence and formation of disulphide bonds in RER

Pre-proinsulin turns into proinsulin

Transfer to Golgi apparatus, excision of C peptide and packaging into secretory granules

Question 6

How is aldosterone made?

Answer 6

Cholesterol - Pregnenolone - Progesterone - Aldosterone

Question 7

How is cortisol made?

Answer 7

Cholesterol - Pregnenolone - 17alphaOH Progesterone

- Cortisol

Question 8

How is oestrogen made?

Answer 8

Cholesterol - Pregnenolone - 17alphaOH Progesterone

- Androgens - (through aromatase) Oestrogens

Question 9

Describe synthesis of thyroid hormones

Answer 9

Active uptake of iodine into a follicular cell

Oxidation of iodide 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

Question 10

What is Goitre?

Answer 10

Enlargement of the thyroid gland

Question 11

What happens with excess thyroid hormones?

Answer 11

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

Question 12

How do peptide and protein hormones induce cell signalling?

Answer 12

They are water soluble so they act on cell surface receptors (can’t pass through the membrane) such as G-protein linked receptors or receptors with or associated with tyrosine kinase domains.

This activates secondary messengers and/or enzymes

Has cytoplasmic and nuclear effects

Question 13

Describe adenyl cyclase and cAMP signalling pathway
Describe phosphoinositide pathway
(both G-protein)

Answer 13

Adenyl cyclase -> cAMP -> Protein kinase A

Phospholipase C -> DAG -> Protein kinase C. or

                         -> IP3 -> Ca2+

Question 14

What are the signalling pathways for receptors with tyrosine kinase activity

Answer 14

RafMEK ERK pathway

PI-3 kinase/Akt pathway

JAK STAT pathway

Question 15

How do steroid hormones induce cell signalling?

Answer 15

They are lipophilic so they affect intracellular receptors in the cytoplasm or nucleus.

The receptors are transcription factors. (proteins that bind to DNA)

Question 16

What are some endocrine disorders associated with mutations in the receptor or the associated G-protein?

Answer 16

Defective G-protein coupled receptor

• Thyroid adenoma - TSH receptor (activating mutation)
• Precocious puberty - LH receptor (activating mutation)

Defective G protein
-McCune Albright syndrome (activating mutations) - fibrous dysplasia of bone and Café au lait syndrome

Question 17

Describe the structural organisation of Steroid hormone nuclear receptors

Answer 17

Steroid hormones receptors are a family of transcriptions factors
Different functional regions of the receptor are defined as domains - A-F
A/B domain is the N terminal domain
C domain is the DNA binding region and is highly conserved
D is the hinge region
E is the ligand binding domain
F is the C-terminal domain
Both A/B and E/F domains have transcriptional activity

Question 18

How do steroid receptors work?

Answer 18

Hormone crosses the cell membrane
Heat shock protein dissociates from the receptor
Hormone binds to receptor and dimerization occurs
Dimerized receptors translocate to the nucleus
Binds to the hormone response element on the DNA
Along with other transcription factors, transcription is initiated
Some receptors located within the nucleus not the cytoplasm

Question 19

WWhat happens when you cannot respond to steroid hormones?

Answer 19

Androgen insensitivity syndrome