Table 1.
Seven-week-old ovariectomized C57Bl/6J mice were subcutaneously injected with vehicle (Ctrl, castor oil), 17β-estradiol (E2, 1, 8, 30, 80, 200 μg/kg) or estetrol (E4, 1, 8, 30, 80, 200 μg/kg, or 1 and 10 mg/kg) and were euthanized 6 h after treatment. mRNA levels of a set of genes from uterus that were up-regulated at least twofold by E2 administration relative to placebo were measured by quantitative PCR and normalized to Hprt1 expression
| GOI | Dose E2 (µg/kg) |
Dose E4 (µg/kg) |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 8 | 30 | 80 | 200 | 1 | 8 | 30 | 80 | 200 | 1,000 | 10,000 | |
| ramp3 | 0.81 ± 0.06 | 30.84 ± 1.48 P < 0.0001 |
21.71 ± 0.45 P < 0.0001 |
22.33 ± 0.42 P < 0.0001 |
29.04 ± 3.11 P < 0.0001 |
0.91 ± 0.10 | 2.01 ± 0.36 P = 0.0005 |
10.09 ± 0.13 P < 0.0001 |
16.22 ± 0.21 P < 0.0001 |
23.20 ± 0.85 P < 0.0001 |
29.87 ± 1.17 P < 0.0001 |
27.75 ± 2.34 P < 0.0001 |
| gadd45g | 1.08 ± 0.15 | 19.87 ± 0.58 P < 0.0001 |
9.05 ± 0.31 P < 0.0001 |
6.89 ± 0.44 P < 0.0001 |
11.96 ± 2.59 P < 0.0001 |
0.91 ± 0.19 | 2.31 ± 0.49 P = 0.0002 |
5.49 ± 0.89 P < 0.0001 |
6.52 ± 0.89 P < 0.0001 |
6.84 ± 0.62 P < 0.0001 |
10.96 ± 0.42 P < 0.0001 |
9.49 ± 0.69 P < 0.0001 |
| mad2l1 | 0.83 ± 0.06 | 19.63 ± 0.33 P < 0.0001 |
7.69 ± 0.54 P < 0.0001 |
5.54 ± 0.56 P < 0.0001 |
7.59 ± 0.56 P < 0.0001 |
0.79 ± 0.16 | 0.46 ± 0.17 P = 0.0014 |
1.42 ± 0.10 P = 0.0058 |
1.82 ± 0.23 P = 0.0009 |
2.80 ± 0.38 P < 0.0001 |
11.03 ± 2.03 P < 0.0001 |
15.52 ± 0.46 P < 0.0001 |
| inhbb | 0.78 ± 0.06 | 18.13 ± 1.62 P < 0.0001 |
8.93 ± 0.36 P < 0.0001 |
7.86 ± 0.41 P < 0.0001 |
10.45 ± 1.29 P < 0.0001 |
0.90 ± 0.03 | 1.44 ± 0.08 P = 0.0024 |
5.36 ± 0.23 P < 0.0001 |
5.76 ± 0.15 P < 0.0001 |
6.81 ± 0.24 P < 0.0001 |
10.55 ± 0.58 P < 0.0001 |
11.44 ± 0.99 P < 0.0001 |
| fam65b | 0.81 ± 0.04 | 12.92 ± 1.07 P < 0.0001 |
10.09 ± 0.33 P < 0.0001 |
8.03 ± 0.97 P < 0.0001 |
9.53 ± 0.86 P < 0.0001 |
0.97 ± 0.11 | 1.65 ± 0.05 P < 0.0001 |
4.42 ± 0.58 P < 0.0001 |
6.53 ± 0.31 P < 0.0001 |
8.08 ± 1.01 P < 0.0001 |
9.85 ± 0.53 P < 0.0001 |
10.77 ± 1.31 P < 0.0001 |
| fos | 0.97 ± 0.14 | 12.36 ± 2.19 P < 0.0001 |
1.42 ± 0.13 | 1.29 ± 0.21 | 3.60 ± 1.39 P = 0.075 |
0.81 ± 0.24 | 0.99 ± 0.22 | 1.64 ± 0.31 | 1.23 ± 0.10 | 3.59 ± 1.37 P = 0.0182 |
6.26 ± 1.61 P = 0.0005 |
2.91 ± 0.54 P = 0.0001 |
| aldh1a2 | 1.08 ± 0.07 | 9.94 ± 0.68 P < 0.0001 |
9.29 ± 0.36 P < 0.0001 |
9.12 ± 0.75 P < 0.0001 |
8.61 ± 0.45 P < 0.0001 |
1.25 ± 0.06 P = 0.0241 |
1.07 ± 0.13 | 5.38 ± 0.38 P < 0.0001 |
8.33 ± 0.36 P < 0.0001 |
7.62 ± 0.45 P < 0.0001 |
7.91 ± 0.39 P < 0.0001 |
7.22 ± 0.45 P < 0.0001 |
| p21 | 1.01 ± 0.06 | 9.17 ± 0.66 P < 0.0001 |
9.37 ± 0.34 P < 0.0001 |
6.49 ± 0.54 P < 0.0001 |
8.62 ± 1.04 P < 0.0001 |
1.01 ± 0.07 | 1.83 ± 0.27 P = 0.0002 |
5.57 ± 0.37 P < 0.0001 |
6.09 ± 0.60 P < 0.0001 |
6.89 ± 0.38 P < 0.0001 |
7.80 ± 0.67 P < 0.0001 |
6.33 ± 0.82 P < 0.0001 |
| aars | 0.98 ± 0.05 | 6.95 ± 0.30 P < 0.0001 |
10.50 ± 0.05 P < 0.0001 |
9.00 ± 0.75 P < 0.0001 |
9.24 ± 1.06 P < 0.0001 |
1.04 ± 0.03 | 1.33 ± 0.10 P = 0.0062 |
7.12 ± 0.04 P < 0.0001 |
7.03 ± 0.50 P < 0.0001 |
7.84 ± 0.73 P < 0.0001 |
7.94 ± 0.77 P < 0.0001 |
7.77 ± 0.62 P < 0.0001 |
| lcn2 | 1.04 ± 0.11 | 6.68 ± 0.48 P < 0.0001 |
4.93 ± 0.51 P < 0.0001 |
5.61 ± 0.96 P < 0.0001 |
9.42 ± 1.18 P < 0.0001 |
0.98 ± 0.02 | 0.81 ± 0.03 | 5.86 ± 0.56 P < 0.0001 |
8.12 ± 0.69 P < 0.0001 |
10.21 ± 0.90 P < 0.0001 |
9.04 ± 1.36 P < 0.0001 |
6.12 ± 0.42 P < 0.0001 |
| errfi1 | 1.06 ± 0.14 | 6.62 ± 0.84 P < 0.0001 |
3.41 ± 0.18 P < 0.0001 |
3.13 ± 0.12 P < 0.0001 |
4.25 ± 0.96 P < 0.0001 |
1.16 ± 0.14 | 1.94 ± 0.35 P = 0.0002 |
2.86 ± 0.56 P < 0.0001 |
2.04 ± 0.25 P < 0.0001 |
2.45 ± 0.32 P < 0.0001 |
3.10 ± 0.27 P < 0.0001 |
2.30 ± 0.16 P < 0.0001 |
| sprr2f | 0.89 ± 0.12 | 6.25 ± 1.36 P < 0.0001 |
1.37 ± 0.09 | 4.48 ± 1.35 P = 0.0002 |
4.87 ± 1.43 P = 0.0007 |
0.98 ± 0.26 | 0.41 ± 0.21 P = 0.0129 |
2.36 ± 0.55 P = 0.0007 |
3.02 ± 0.18 P < 0.0001 |
3.88 ± 0.80 P = 0.0001 |
10.70 ± 1.49 P < 0.0001 |
10.01 ± 0.75 P < 0.0001 |
| rasd1 | 1.13 ± 0.07 | 5.97 ± 0.35 P < 0.0001 |
4.18 ± 0.19 P < 0.0001 |
3.28 ± 0.23 P < 0.0001 |
3.47 ± 0.19 P < 0.0001 |
1.06 ± 0.11 | 1.42 ± 0.22 P = 0.0134 |
1.61 ± 0.32 P = 0.0035 |
1.18 ± 0.19 | 1.42 ± 0.37 | 2.49 ± 0.23 P < 0.0001 |
3.18 ± 0.13 P < 0.0001 |
| vegfa | 0.86 ± 0.10 | 5.04 ± 0.51 P < 0.0001 |
4.23 ± 0.28 P < 0.0001 |
3.06 ± 0.37 P < 0.0001 |
3.61 ± 0.29 P < 0.0001 |
0.97 ± 0.04 | 1.11 ± 0.09 | 2.13 ± 0.09 P < 0.0001 |
1.43 ± 0.12 P = 0.0037 |
1.63 ± 0.14 P < 0.0001 |
2.91 ± 0.32 P < 0.0001 |
3.60 ± 0.51 P < 0.0001 |
| cebpb | 0.92 ± 0.03 | 4.54 ± 0.23 P < 0.0001 |
2.82 ± 0.19 P < 0.0001 |
2.37 ± 0.29 P < 0.0001 |
2.72 ± 0.08 P < 0.0001 |
1.21 ± 0.04 | 0.86 ± 0.10 | 1.54 ± 0.10 P = 0.0011 |
1.08 ± 0.09 | 1.20 ± 0.13 | 1.59 ± 0.11 P < 0.0001 |
1.87 ± 0.08 P < 0.0001 |
| psat1 | 1.18 ± 0.08 | 4.31 ± 0.23 P < 0.0001 |
8.98 ± 0.45 P < 0.0001 |
9.95 ± 0.70 P < 0.0001 |
8.26 ± 1.22 P < 0.0001 |
1.15 ± 0.09 | 0.81 ± 0.05 | 5.09 ± 0.38 P < 0.0001 |
5.49 ± 0.45 P < 0.0001 |
4.96 ± 0.65 P < 0.0001 |
5.07 ± 0.51 P < 0.0001 |
5.30 ± 0.70 P < 0.0001 |
| gadd45a | 1.02 ± 0.03 | 3.70 ± 0.40 P < 0.0001 |
4.88 ± 0.35 P < 0.0001 |
4.09 ± 0.64 P < 0.0001 |
3.77 ± 0.56 P < 0.0001 |
0.81 ± 0.05 P = 0.0436 |
1.21 ± 0.12 | 3.09 ± 0.20 P < 0.0001 |
2.22 ± 0.24 P < 0.0001 |
2.54 ± 0.47 P = 0.0003 |
3.33 ± 0.40 P < 0.0001 |
3.16 ± 0.21 P < 0.0001 |
| hspa5 | 1.04 ± 0.01 | 3.28 ± 0.19 P < 0.0001 |
3.03 ± 0.18 P < 0.0001 |
3.71 ± 0.31 P < 0.0001 |
4.95 ± 0.84 P < 0.0001 |
1.01 ± 0.01 | 1.18 ± 0.04 | 2.23 ± 0.15 P < 0.0001 |
4.90 ± 0.32 P < 0.0001 |
5.17 ± 0.48 P < 0.0001 |
5.58 ± 0.54 P < 0.0001 |
5.64 ± 0.35 P < 0.0001 |
| igf1 | 1.07 ± 0.03 | 3.27 ± 0.15 P < 0.0001 |
2.82 ± 0.08 P < 0.0001 |
3.52 ± 0.23 P < 0.0001 |
3.67 ± 0.30 P < 0.0001 |
1.11 ± 0.09 | 1.07 ± 0.08 | 3.18 ± 0.15 P < 0.0001 |
4.19 ± 0.24 P < 0.0001 |
3.72 ± 0.18 P < 0.0001 |
4.01 ± 0.18 P < 0.0001 |
5.23 ± 0.89 P < 0.0001 |
| cars | 1.07 ± 0.11 | 3.16 ± 0.04 P < 0.0001 |
3.55 ± 0.27 P < 0.0001 |
3.73 ± 0.37 P < 0.0001 |
4.26 ± 0.32 P < 0.0001 |
0.96 ± 0.10 | 1.06 ± 0.08 | 3.19 ± 0.09 P < 0.0001 |
3.62 ± 0.35 P < 0.0001 |
3.47 ± 0.23 P < 0.0001 |
4.27 ± 0.54 P < 0.0001 |
3.96 ± 0.37 P < 0.0001 |
| cyr61 | 0.91 ± 0.12 | 2.73 ± 0.16 P < 0.0001 |
0.96 ± 0.07 | 1.11 ± 0.18 | 2.08 ± 0.81 P = 0.0560 |
0.73 ± 0.19 | 0.56 ± 0.07 P = 0.0442 |
0.75 ± 0.12 | 0.94 ± 0.13 | 2.65 ± 0.92 P = 0.0245 |
4.23 ± 0.57 P < 0.0001 |
3.08 ± 0.15 P < 0.0001 |
| dio2 | 0.79 ± 0.06 | 2.49 ± 0.47 P = 0.0002 |
2.05 ± 0.07 P < 0.0001 |
3.67 ± 0.33 P < 0.0001 |
4.60 ± 0.71 P < 0.0001 |
1.03 ± 0.10 | 0.73 ± 0.07 | 1.33 ± 0.08 P = 0.0036 |
2.68 ± 0.21 P < 0.0001 |
4.60 ± 0.40 P < 0.0001 |
6.30 ± 0.66 P < 0.0001 |
5.12 ± 0.38 P < 0.0001 |
| pgr | 0.87 ± 0.04 | 2.47 ± 0.17 P < 0.0001 |
1.80 ± 0.03 P < 0.0001 |
1.67 ± 0.09 P < 0.0001 |
1.90 ± 0.07 P < 0.0001 |
0.88 ± 0.05 | 1.25 ± 0.04 P = 0.0163 |
1.58 ± 0.06 P < 0.0001 |
1.55 ± 0.09 P = 0.0002 |
1.74 ± 0.11 P < 0.0001 |
2.31 ± 0.13 P < 0.0001 |
2.20 ± 0.09 P < 0.0001 |
Results were expressed as mean ± SEM (n = 4–8 mice/group). Significance of the observed effects was evaluated using Student's t-test. Gray highlight represents the maximum of regulation