29 - Type 1 Nuclear Receptors

Question 1

Different classes of nuclear receptors?

Answer 1

Type I and Type II

Question 2

Type II receptors

Answer 2

Type II receptors generally are the receptors for the steroid hormones, including the mineralocorticoids, glucocorticoids and the sex steroids as well

Question 3

Type I nuclear receptors

Answer 3

o Androgen receptor
o (O)estrogen receptors
o Glucocorticoid receptor
o Mineralocorticoid
o Progesterone receptor

Question 4

Type I HRE sites

Answer 4

o Type I HREs consist of two half-sites separated by a variable length of DNA
o The second half-site has a sequence inverted from the first (inverted repeat)

Question 5

Type I HRE sequences

Answer 5

o There is an inverted repeat on the second strand, which makes each hormone response element to each binding site for nuclear receptors palindromic
o In the figure, there is the binding site for the glucocorticoid receptor family and the oestrogen receptor
o Nuclear receptors of the type I family bind to these palindromic sequences as homodimers

Question 6

Type I receptors and heat shock proteins

Answer 6

o The empty receptors form a large complex with heat shock protein-90, hsp-56, and hsp-27
o Only the function of hsp-90 is known
o It acts as a dimer and binds to both the DNA- binding sit and the ligand binding site
o This prevents the empty receptor from accidentally dimerising and binding to DNA

Question 7

Ligands activate type I receptors in the cytosol resulting in:

Answer 7

1. Dissociation of heat shock proteins
2. Homo-dimerisation
3. Translocation into the cell nucleus
4. Binding to specific sequences of DNA known as hormone response elements (HREs)
5. The nuclear receptor/DNA complex then recruits other proteins that transcribe DNA downstream from the HRE

Question 8

What happens when a steroid hormone enters the cell?

Answer 8

o When the steroid hormone enters the cell, it passes straight through the cell membrane and docks with the ligand binding site, allowing the association of heat shock proteins
o There is then dimerization and translocation to the nucleus and direct interaction with hormone response elements, leading to the recruitment of coactivator proteins and RNA polymerase
o Allows transcription of target DNA which gets translated into proteins in the cytoplasm
- These proteins change cell function

Question 9

Type II HRE sequences?

Answer 9

o Type II HREs consist of two half-sites separated by a variable length of DNA
o The second half is a direct repeat of the first sequence

o vitamin D response element, thyroid hormone response element, and the retinoic acid response element