Answer Happy

This question relates to the biological activity of the
estrogen receptor (ER). You are evaluating the pharmacological
properties of Raloxifene and comparing them to
Estradiol.
The human estrogen receptor has two different isoforms,
alpha and beta. To understand the effect of Raloxifene and
Estradiol and their selectivity, you quantify the expression of a
reporter gene selective to either ER or ER using a luminescence
assay (Figures 1 and 2).
a) Estimate the EC50 and Emax values for estradiol and
raloxifene on ER or ER
b) Explain the pharmacological effect of estradiol and
raloxifene on ER or ER.
c) Compare the selectivity of estradiol and raloxifene
for ER or ER.
Raloxifene action on estradiol activity on ER or ER was
then studied. For this purpose, the reporter gene expression was
monitored in cells treated with 0.5nM estradiol and with increasing
concentrations of Raloxifene (Figure 3).
Figure 3. ER- (black circles) or ER- (red squares)
mediated reporter gene expression of cells treated with 0.5nM
estradiol and increasing concentrations of Raloxifene
180 160 alpha beta 140 120 100 Gene expression (LU) 80 60 40 20 0 1e-11 1e-10 TTTTT 1e-09 1e-08 Estradiol concentration (M) 1e-07 1e-06
30 • alpha beta 25 20 Gene expression (LU) 15 10 5 0 MT 1e-07 MT 1e-06 1e-11 1e-10 1e-09 1e-08 Raloxifene concentration (M)
140 • alpha beta 120 100 Gene expression (LU) 80 60 40 20 TIMIT 1e-06 1e-11 1e-10 1e-09 1e-08 1e-07 Raloxifene concentration (M)