Principles of cellular physiology 4

Question 1

State the difference between cell surface receptors and intracellular receptors

Answer 1

• CELL SURFACE Membrane receptors for: hydrophilic signalling molecules activate a wide variety of intracellular ‘signal transduction’ pathways e.g. gene regulation
• INTRACELLULAR: most receptors for hydrophobic signalling molecules act as transcription factors in nucleus to regulate gene transcription

Question 2

What are hormones?

Answer 2

• First messengers and are classified as ‘steroid’ or ‘nonsteroid’

Question 3

Describe steroid hormones.

Answer 3

• Lipid soluble - derived from cholesterol
• Relatively small so can pass through the plasma membrane
• Enter target cells and bind to intracellular receptor and activate genes that produce new proteins
• Slower acting than non steroid hormones

Question 4

Describe non steroid hormones.

Answer 4

• Water soluble - derived from amino acid
• Binds to receptors on target cell membranes and activates signal transduction pathways that produces a chemical called a second messenger
• Work through intermediate mechanisms to activate existing enzymes; small amount of hormone can produce a significant cellular change
• Faster action than steroid hormones

Question 5

Describe the hormone receptors pathway (steroid hormones)

Answer 5

Hormone - nuclear receptors - activate genes - synthesise new proteins or enzymes - cell responds

Question 6

Describe the hormone receptors pathway (non steroid)

Answer 6

Hormone - membrane-bound receptors - receptors alter the activity of G proteins which opens or closes ion channels and activates existing enzymes - cell responds OR receptors alter the activity of intracellular enzymes which activates existing enzymes - cell responds

Question 7

Name the ligands for intracellular-nuclear receptors

Answer 7

• Androgens, Oestrogens and progesterone - produced by gonads
• Corticosteroids, Glucocorticoids, Mineralocorticoids - produced by adrenal gland
• Thyroid hormone
• Vitamin D3
• Retinoic acid

Question 8

Where are corticosteroids produced?

Answer 8

Adrenal gland

Question 9

Where are glucocorticoids (GR) produced and what does it stimulate?

Answer 9

Adrenal gland
Act to stimulate glucose production

Question 10

Where are mineralocorticoids (MR) produced and what does it act on?

Answer 10

Adrenal gland
Act on kidney to regulate salt and water balance

Question 11

Where are thyroid (TR) hormones produced and state its role

Answer 11

Synthesised from tyrosine in thyroid gland
Has an important role in development and regulation of metabolism

Question 12

Describe the role of vitamin D3

Answer 12

Regulated Ca2+ metabolism, bone growth

Question 13

What is retinoic acid (RAR) synthesised from and what is its role?

Answer 13

• Synthesised from vitamin A
• Play important roles in vertebrate development

Question 14

Where is the receptor GR localised?

Answer 14

cytoplasm

Question 15

Where is the receptor MR localised?

Answer 15

Cytoplasm

Question 16

Where is the receptor Estrogen localised?

Answer 16

Nuclear

Question 17

Where is the receptor progesterone localised?

Answer 17

Nuclear

Question 18

Where is the receptor TR localised?

Answer 18

Nuclear

Question 19

Where is the receptor RAR localised?

Answer 19

Nuclear

Question 20

Describe the structure of nuclear receptors.

Answer 20

• Transactivation domain (A/B & E)
• DNA-binding/dimerization domain (C)
• Nuclear localisation domain (D)

Question 21

What is the role of transactivation domain (A/B & E)?

Answer 21

Contains the ligand binding domain (E) which causes a change of conformation to the DNA, initiating transcription

Question 22

What is the role of DNA-binding/dimerisation domain (C)

Answer 22

Allows dimerisation of receptors and
binding to the DNA

Question 23

What is the role of nuclear localisation domain (D)?

Answer 23

Allows the receptor to enter the nucleus or to maintain the nuclear localisation

Question 24

Describe the mechanism of CYTOPLASMIC receptor activation.

Answer 24

• Receptor located in cytoplasm
• Ligand enters cell and causes receptor activation
• Ligand binding dislodges regulatory/repressor protein
• Ligand-Receptor complex enters nuclear and binds to specific DNA sequence (in promoter region)
• Gene transcribed and translated, protein produced
• Or gene expression inhibited
• Can have latent period of several hours due to production of mRNA and protein

Question 25

Describe the mechanism of action of NUCLEAR receptor activation.

Answer 25

1. lipid soluble hormones diffuse through the plasma membrane
2. Lipid-soluble hormones bind to nuclear receptors
3. The hormone-receptor complex binds to hormone response element on the DNA - acts as transcription factor
4. The binding of the hormone-receptor complex to DNA stimulates the synthesis of mRNA - codes for specific proteins
5. The mRNA leaves the nucleus, passes into the cytoplasm of the cell and binds to ribosomes - directs the synthesis of specific proteins
6. Newly synthesised proteins produce the cell’s response to the lipid-soluble hormones

Question 26

Describe the intracellular regulation of gene expression.

Answer 26

1. Steroid hormone binds to intracellular receptor
2. Inhibitor is released to expose DNA binding site of receptor
3. Receptor binds to DNA and activates gene expression

Question 27

Name two hormones that also cause transcriptional activation.

Answer 27

• glucocorticoid
• thyroid hormone

Question 28

Give an example of steroid signalling.

Answer 28

• Na+ reabsorption depends upon epithelial Na+ channel (ENaC) in cortical collecting duct in the kidney
• These cells express a protein called Nedd4-2 which can bind to ENaC and causes channels to be internalised
• This limits rate of Na recovery allowing Na+ to be lost in urine

Question 29

What happens if our body needs more Na+?

Answer 29

Aldosterone induces expression of protein kinase called serum - glucocorticoid- inducible kinase 1 (SGK1)

Question 30

What is the role of SGK1 and state what this leads to.

Answer 30

• phosphorylates Nedd4-2
• Prevents protein binding to ENaC so it remains in membrane
• Leads to increased Na+ retention