31 - Sex Steroid Receptors

Question 1

What are response elements?

Answer 1

Response elements are specific sequences of nucleotides recognised by the specific receptor

Question 2

ERE (oestrogen response element) nucleotide sequence

Answer 2

The nucleotide sequence of the ERE will be significantly different from that of the ARE (androgen response element)
o These sequences are usually palindromic
o Any structural gene that is activated by the oestrogen receptor will have at least one ERE
o Some oestrogen activated genes have more than one ERE, though the reason for this is not clear

Question 3

What has information about ERE lead to?

Answer 3

This has led to the development of SERMS or Selective Estrogen Response Modifiers

Question 4

SERMs

Answer 4

These can, during and after the menopause, prevent osteoporosis, they:
o Lower plasma cholesterol
o Prevent neural decay in the brain
o Stabilise vaso-motor activity
o Restore skin condition
Without causing potential damage to the reproductive tract

Question 5

Example of a SERM

Answer 5

o Polycystic ovary syndrome can lead to female infertility due to anovulation
o This can be treated with clomifene, a selective oestrogen receptor modulator (SERM)
o Clomifene acts by inhibiting the action of oestrogen on the gonadotroph cells in the anterior pituitary gland
o “sensing” low oestrogen levels, LH and FSH release is increased, leading to a higher rate of ovulation and hence pregnancy

Question 6

What does Clomiphene do?

Answer 6

o Clomiphene blocks the negative feedback the oestrogen has on the anterior pituitary during the first half of the menstrual cycle
o This switches to positive feedback at the midpoint of the menstrual cycle, causing a surge is LH and FSH production
o This stimulates ovulation in the ovary
o The pituitary thinks that the oestrogen levels are low in the presence of clomiphene therefore it stimulates LH and FSH to compensate

Question 7

Other examples of SERMs

Answer 7

o Progesterone receptor agonists- contraceptive
o Oestrogen receptor agonists- hormone replacement therapy
o Oestrogen receptor antagonists- for the prevention and treatment of breast cancer (tamoxifen)
o Androgen receptor antagonists- treatment of prostate cancer (Bicalutamide/Casodex)