Hormones That Act Within The Cell

Question 1

What are the two types of hormone that act within the cell?

What is significant about both classes?

Answer 1

1. steroid hormones
2. thyroid hormones

Both classes of hormones are hydrophobic

Question 2

What are steroid and thyroid hormones derived from?

Answer 2

Steroid hormones are derived from cholesterol

Thyroid hormones are derived from tyrosine within the protein thyroglobulin

Question 3

What are the two types of steroid hormones?

Answer 3

1. androgens

2. oestrogens

Question 4

What is the difference between androgens and oestrogens?

Answer 4

Oestrogens have an aromatic ring, introduced by aromatase

Androgens do not

Question 5

How is a receptor-hormone complex formed by a steroid hormone?

Answer 5

1. Steroid hormone enters the cell by simple diffusion
2. It binds to a complementary-shaped receptor in the cytosol or nucleus
3. This forms a receptor-hormone complex

Question 6

What happens to the steroid hormone when it binds to the receptor?

Why is this significant?

Answer 6

The shape of the hormone is changed slightly

This allows it to bind to DNA in the nucleus

Question 7

What will the receptor-hormone complex bind to in the nucleus?

Answer 7

The hormone response element (HRE)

This is a short sequence of DNA within the promoter region of a gene

Question 8

How does the hormone-receptor complex act as a transcription factor?

Answer 8

When it binds to the HRE, the HRE then stimulates binding of DNA polymerase and transcription of mRNA

Question 9

What are the domains that nuclear hormone receptors are divided into?

Answer 9

1. N-terminal domain
2. DNA binding domain
3. Hinge region
4. Ligand binding domain
5. C-terminal domina

Question 10

What is present at the N-terminal domain of the nuclear hormone receptor?

Answer 10

A transcription regulation domain

This interacts with other proteins that regulate transcription

Question 11

What is present at the DNA binding domain of the nuclear hormone receptor?

Answer 11

Zinc fingers which bind to the DNA helix

Question 12

What are zinc fingers?

Answer 12

Loops of protein containing a Zn2+ ion that is coordinated with 4 cysteine residues

Question 13

What is present at the C-terminal domain?

Answer 13

Hormone binding domain

This makes each receptor specific to a particular hormone

Question 14

What are the two closely related versions of the oestrogen receptor?

Answer 14

ER-alpha and ER-beta

Question 15

What is the expression of ER-alpha and ER-beta like in normal healthy breast tissue?

Answer 15

It expresses more ER-beta that ER-alpha

Question 16

What happens if a breast cancer strongly expresses ER-alpha?

Answer 16

It causes the tissue to become more sensitive to oestrogen

Oestrogen promotes rapid division of ER-alpha-positive breast cancer cells

Question 17

How are ER-alpha positive breast cancers detected?

Answer 17

By staining sections of tumour biopsies with antibodies against the oestrogen receptor

ER-alpha positive cells are stained brown

Question 18

How can the growth and spread of ER-alpha positive breast cancers be inhibited?

Answer 18

BY administering anti-oestrogen drugs such as tamoxifen

Question 19

Why is tamoxifen described as a pro-drug?

Answer 19

It gets converted to an active form within the body by being hydroxylated

Question 20

How does tamoxifen work?

Answer 20

1. it binds to the oestrogen receptor
2. the oestrogen receptor does NOT acquire a shape change
3. The oestrogen receptor cannot bind to co-activators as it has not changed shape

Question 21

What are aromatase inhibitors used to treat?

Answer 21

Oestrogen sensitive tumours

Question 22

How do aromatase inhibitors work?

Answer 22

Aromatase introduces an aromatic ring into oestrogens

Aromatase inhibitors block the formation of the aromatic ring in oestrogens

Question 23

In breast cancers that are not ER-positive, how do they increase signalling for cell division?

Answer 23

They do this by changing the amount or properties of HER2

Question 24

What is HER2?

Answer 24

A cell-surface receptor that binds to a growth factor

Question 25

What is used to treat breast cancers that are not ER-positive?

Answer 25

An antibody is given which binds to the HER2 receptor and stops it from signalling

Question 26

How does Trastuzumab work?

Answer 26

It attaches to HER2 so cancer cells cannot grow or divide

Question 27

How do thyroid hormones from a receptor-hormone complex?

Answer 27

They bind to a receptor that is already bound to DNA

Question 28

What is the result of a thyroid hormone binding to a DNA-bound receptor?

Answer 28

The hormone-receptor complex moderates gene expression It stimulates or prevents transcription of certain genes

Question 29

What is T4 and how is it synthesised?

Answer 29

Thyroxine It is synthesised in the thyroid gland by combining tyrosine with iodine

Question 30

How is thyroxine (T4) converted to an active form?

Answer 30

By deiodination in the peripheral tissues It is converted to T3

Question 31

In the nucleus, where are the thyroid hormone receptors bound to?

Answer 31

Thyroid response elements (TRE) in the DNA

Question 32

What does binding of T3 to the TREs lead to?

Answer 32

The release of proteins which will either switch off or activate transcription

Question 33

What happens when transcription is activated by TREs?

Answer 33

The repressors will leave and the activators will bind to the DNA

Question 34

Where are thyroid response elements found?

Answer 34

In the promoter regions of genes involved in heart function and energy metabolism These genes are activated by thyroid hormones

Question 35

How are thyroid hormones synthesised?

Answer 35

1. tyrosine is iodinated on thyroglobulin 2. iodotyrosine molecules on thyroglobulin are crosslinked 3. the thyroxine is cut out to produce the hormone

Question 36

What enzyme do retroviruses contain? What is the function of this enzyme?

Answer 36

Reverse transcriptase It allows them to convert RNA into DNA once entering a cell, so the retroviral DNA can integrate into the host DNA

Question 37

What happens if a retrovirus incorporates host DNA into its sequence?

Answer 37

This produces infectious RNA viruses They carry and express a host gene in the next cell they infect

Question 38

How may a retrovirus become capable of causing cancer?

Answer 38

If the virus captures a version of a protein that is involved in growth control

Question 39

What human protein can act as an oncogene that will cause cancer from a retrovirus?

Answer 39

A mutated version of the thyroid hormone receptor