Nuclear hormone receptors

Question 1

What are steroid hormones and vitamin D derived from?

Answer 1

Cholesterol

Question 2

What are thyroid hormones and aromatic amines derived from?

Answer 2

Amino acids e.g. thyroxine

Question 3

What are prostaglandins derived from?

Answer 3

Fatty acids

Question 4

Where do peptide hormones and catecholamines bind to?

Answer 4

Bind to cell surface receptors

Question 5

Where do steroid and thyroid hormones bind to?

Answer 5

Intracellular receptors

Question 6

Do steroid hormones and T3 act within the nucleus?

Answer 6

YES

Question 7

What happens to the receptor-hormone complex after the hormone binds in the nucleus?

Answer 7

Binds to specific DNA sequences to affect transcription

Question 8

Why can steroid hormones pass through the membrane easily?

Answer 8

They are lipophilic because they are derived from cholesterol

Question 9

Give some examples of the roles of steroid hormones

Answer 9

Carbohydrate regulation
mineral balance
reproductive function

inflammatory response, stress response, bone metabolism, cardiovascular fitness, cognition, mood & behaviour

Question 10

What are most steroid hormones bound to?

Answer 10

Plasma protein carriers

Question 11

What does the hormone receptor complex act as?

Answer 11

Transcription factor

Question 12

Where are thyroid hormones synthesised?

Answer 12

Thyroid gland (T4) and peripheral tissues (T3)§ through deiodination of T4

Question 13

How are thyroid hormones synthesised?

Answer 13

An iodine is attached to tyrosine residue son a protein called thyroglobulin. Iodotyrosine molecules in thyroglobulin are cross linked and thyroxine (T4) is cut out.

Question 14

How do thyroid hormones know where to bind?

Answer 14

The thyroid hormone recognition element (RE) is in front of various genes of energy metabolism and heart function

Question 15

What can thyroid hormone receptor mutation lead to?

Answer 15

Thyroid hormone resistance, and symptoms of hypothyroidism

Question 16

Can you live without either thyroid hormone nuclear receptors?

Answer 16

YEs

Question 17

What are nuclear receptors?

Answer 17

Sequences upstream of the minimal promoter region in transcription that affect transcription. Some are binding sites for nuclear hormone receptors.
Can include small sequences of 6-10 nucleotides, sometimes with a spacer of a few nucleotides between them. Can be direct repeats (TTAAGGCCXXXTTAAGGCC) or palindrome repeats (TTAAGGCCXXXGTCCTTAA)

Question 18

Is the most efficient response element palindrome or direct repeat? Where is it found?

Answer 18

Palindrome

Upstream of an egg protein in Xenopus (frog)

Question 19

What does a steroid hormone receptor consist of?

Answer 19

Variable domain (interacts with other transcription factors)
DNA binding domain (Zinc finger)
Domain for dimerisation (two receptor hormone complexes)
Hormone binding domain

Question 20

How are nuclear receptors activated?

Answer 20

Ligand binding which causes conformational change. An inhibitory protein dissociates from the structure and co-activators bind to the complex , forming the hormone receptor complex

Question 21

What is the zinc finger on the nuclear hormone receptor?

Answer 21

A zinc atom surrounded by 4 cysteine residues in the groove of the DNA helix stabilises the structure

Question 22

What do thyroid hormones bind to in the nucleus? What do these in turn bind to?

Answer 22

thyroid hormone receptors

thyroid response elements

Question 23

What is a homodimer? heterodimer?

Answer 23

Thyroid hormone receptors can pair with each other or pair with other nuclear receptors

Question 24

What are the two oestrogen receptors?

Can we live without these?

Answer 24

o ERα
o ERβ

Yes

Question 25

What is the difference between thyroid and steroid hormones in terms of DNA binding?

Answer 25

Steroid nucelar recpetors wont bind to DNA in the non-activated state

Question 26

How do some retroviruses carry oncogenes? (can cause cancer in organisms they infect)

Answer 26

They are often mutated versions of the host cell genes The retrovirus captures part of a host gene which happens to be a porto-oncogene (important roles in growth but doesnt cause cancer). The partial gene has some biological activity but isn't subject to normal control.

Question 27

How do oncogenes cause cancer?

Answer 27

Proto-onco genes produce proteins that function to stimulate cell division, inhibit differentiation, halt cell death. Oncogenes cause increased production of these proteins = cancer

Question 28

What is androgen sensitivity syndrome? What does it show?

Answer 28

Results in the cell's partial or complete inability to respond to androgens People are genetically male but have female physical traits Shows that androgen nuclear signalling is not essential for life

Question 29

How can the hormone progesterone be used in medical therapy?

Answer 29

For contraceptives and abortion

Question 30

How can the hormone androgen be used in medical therapy?

Answer 30

Prostate cancer

Question 31

How can the hormone oestrogen be used in medical therapy?

Answer 31

Breast cancer (tamoxifen)

Question 32

Which oestrogen receptor does breast tissue normally express more of? Which oestrogen receptor does breast cancer express?

Answer 32

ERβ | ERα

Question 33

How can breast cancer biopsies be identified

Answer 33

Stained with antibodies against the oestrogen receptor (ERα cells are brown)

Question 34

What is the active metabolite of tamoxifen?

Answer 34

4-hydroxy tamoxifen

Question 35

What is the normal role of oestrogen?

Answer 35

Causes cellular proliferation by binding to oestrogen receptors, causing conformational change and meaning oestrogen receptors can bind to co-activators and bind to DNA

Question 36

How does tamoxifen work?

Answer 36

Mimics the shape of oestrogen and binds to oestrogen receptors. No conformational change occurs and the tamoxifen receptor cannot bind to co-actiators so no transcription occurs, tumour shrinks

Question 37

Why is it known that tamoxifen is an agonist in bone and an antagonist in breast?

Answer 37

It increases bone density because there is a different receptor (potentially Erβ)

Question 38

What do aromatase inhibitors (MOA) do?

Answer 38

They block the formation of the aromatic ring in oestrogen to stop it binding to receptors

Question 39

How can breast cancers become unresponsive to anti-oestrogens?

Answer 39

Kinases (e.g. ERK) phosphorylate oestrogen receptor Erα which can activate gene transcription in the absence of oestrogen. This is not blocked by anti-oestrogens. Developing breast cancers also appear to up-regulate ERK pathways to restore oestrogen-like signalling even in the presence of anti-oestrogens