Table 2.
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 down-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 | |
| esr2 | 0.92 ± 0.09 | 0.50 ± 0.04 P = 0.0033 |
0.32 ± 0.05 P = 0.0018 |
0.34 ± 0.04 P = 0.0006 |
0.56 ± 0.08 P = 0.0077 |
0.90 ± 0.22 | 0.41 ± 0.20 P = 0.0056 |
0.32 ± 0.05 P = 0.0019 |
0.13 ± 0.04 P < 0.0001 |
0.26 ± 0.08 P < 0.0001 |
0.36 ± 0.08 P < 0.0001 |
0.34 ± 0.06 P = 0.0006 |
| fgfr1 | 0.98 ± 0.01 | 0.45 ± 0.02 P < 0.0001 |
0.40 ± 0.03 P < 0.0001 |
0.33 ± 0.04 P < 0.0001 |
0.39 ± 0.03 P < 0.0001 |
1.10 ± 0.04 | 0.95 ± 0.08 | 0.68 ± 0.05 P = 0.0020 |
0.44 ± 0.02 P < 0.0001 |
0.42 ± 0.03 P < 0.0001 |
0.40 ± 0.03 P < 0.0001 |
0.44 ± 0.05 P < 0.0001 |
| tgfbr2 | 0.90 ± 0.05 | 0.43 ± 0.01 P < 0.0001 |
0.33 ± 0.02 P < 0.0001 |
0.32 ± 0.02 P < 0.0001 |
0.39 ± 0.03 P < 0.0001 |
0.85 ± 0.04 | 0.87 ± 0.02 | 0.54 ± 0.02 P = 0.0007 |
0.47 ± 0.02 P < 0.0001 |
0.51 ± 0.03 P < 0.0001 |
0.50 ± 0.02 P < 0.0001 |
0.57 ± 0.07 P = 0.0005 |
| esr1 | 0.98 ± 0.03 | 0.41 ± 0.03 P < 0.0001 |
0.27 ± 0.01 P < 0.0001 |
0.29 ± 0.02 P < 0.0001 |
0.38 ± 0.02 P < 0.0001 |
0.90 ± 0.03 | 1.04 ± 0.04 | 0.67 ± 0.02 P = 0.0101 |
0.44 ± 0.02 P < 0.0001 |
0.44 ± 0.02 P < 0.0001 |
0.44 ± 0.02 P < 0.0001 |
0.41 ± 0.02 P < 0.0001 |
| ptov1 | 0.56 ± 0.08 P = 0.0028 |
0.40 ± 0.03 P < 0.0001 |
0.20 ± 0.02 P < 0.0001 |
0.21 ± 0.02 P < 0.0001 |
0.29 ± 0.05 P < 0.0001 |
0.65 ± 0.05 P = 0.0110 |
0.56 ± 0.03 P = 0.0019 |
0.25 ± 0.03 P < 0.0001 |
0.14 ± 0.02 P < 0.0001 |
0.24 ± 0.02 P < 0.0001 |
0.27 ± 0.03 P < 0.0001 |
0.28 ± 0.03 P < 0.0001 |
| sox17 | 1.01 ± 0.05 | 0.40 ± 0.06 P < 0.0001 |
0.43 ± 0.02 P = 0.0006 |
0.35 ± 0.04 P < 0.0001 |
0.40 ± 0.02 P < 0.0001 |
0.90 ± 0.08 | 1.02 ± 0.04 | 0.56 ± 0.04 P = 0.0044 |
0.34 ± 0.01 P < 0.0001 |
0.37 ± 0.01 P < 0.0001 |
0.27 ± 0.02 P < 0.0001 |
0.28 ± 0.03 P < 0.0001 |
| egfr | 1.19 ± 0.04 | 0.38 ± 0.02 P < 0.0001 |
0.53 ± 0.02 P = 0.0062 |
0.52 ± 0.06 P = 0.0022 |
0.63 ± 0.05 P = 0.0064 |
1.53 ± 0.08 P = 0.0011 |
0.77 ± 0.02 | 0.41 ± 0.03 P = 0.0013 |
0.29 ± 0.02 P < 0.0001 |
0.29 ± 0.03 P < 0.0001 |
0.30 ± 0.03 P < 0.0001 |
0.43 ± 0.04 P = 0.0004 |
| ptrf | 0.90 ± 0.03 | 0.34 ± 0.02 P < 0.0001 |
0.31 ± 0.02 P < 0.0001 |
0.29 ± 0.02 P < 0.0001 |
0.35 ± 0.02 P < 0.0001 |
1.13 ± 0.04 | 0.79 ± 0.01 P = 0.0258 |
0.39 ± 0.03 P < 0.0001 |
0.25 ± 0.01 P < 0.0001 |
0.25 ± 0.01 P < 0.0001 |
0.28 ± 0.02 P < 0.0001 |
0.29 ± 0.03 P < 0.0001 |
| igfbp2 | 1.07 ± 0.16 | 0.34 ± 0.06 P < 0.0001 |
0.64 ± 0.13 P = 0.0122 |
0.63 ± 0.11 P = 0.0056 |
0.58 ± 0.06 P = 0.0005 |
2.15 ± 0.42 P = 0.0002 |
2.70 ± 1.84 | 1.15 ± 0.62 | 0.38 ± 0.03 P < 0.0001 |
0.43 ± 0.11 P < 0.0001 |
0.32 ± 0.04 P < 0.0001 |
0.36 ± 0.10 P < 0.0001 |
| tgfb3 | 1.14 ± 0.07 | 0.30 ± 0.02 P < 0.0001 |
0.47 ± 0.03 P = 0.0002 |
0.41 ± 0.03 P < 0.0001 |
0.41 ± 0.04 P < 0.0001 |
1.06 ± 0.05 | 0.86 ± 0.06 | 0.31 ± 0.01 P < 0.0001 |
0.26 ± 0.01 P < 0.0001 |
0.25 ± 0.01 P < 0.0001 |
0.37 ± 0.03 P < 0.0001 |
0.53 ± 0.04 P = 0.0002 |
| vegfb | 0.93 ± 0.02 | 0.28 ± 0.02 P < 0.0001 |
0.22 ± 0.03 P < 0.0001 |
0.20 ± 0.03 P < 0.0001 |
0.27 ± 0.01 P < 0.0001 |
1.06 ± 0.06 | 0.81 ± 0.03 | 0.40 ± 0.04 P = 0.0003 |
0.23 ± 0.01 P < 0.0001 |
0.26 ± 0.01 P < 0.0001 |
0.28 ± 0.02 P < 0.0001 |
0.32 ± 0.02 P < 0.0001 |
| ar | 1.07 ± 0.04 | 0.28 ± 0.01 P < 0.0001 |
0.26 ± 0.01 P < 0.0001 |
0.31 ± 0.02 P < 0.0001 |
0.37 ± 0.02 P < 0.0001 |
0.99 ± 0.03 | 1.01 ± 0.04 | 0.51 ± 0.02 P = 0.0003 |
0.41 ± 0.01 P < 0.0001 |
0.45 ± 0.01 P < 0.0001 |
0.48 ± 0.01 P < 0.0001 |
0.51 ± 0.02 P < 0.0001 |
| igfbp6 | 0.80 ± 0.03 | 0.26 ± 0.02 P < 0.0001 |
0.19 ± 0.01 P < 0.0001 |
0.19 ± 0.02 P < 0.0001 |
0.19 ± 0.01 P < 0.0001 |
0.81 ± 0.03 | 0.75 ± 0.04 | 0.34 ± 0.01 P = 0.0003 |
0.21 ± 0.01 P < 0.0001 |
0.21 ± 0.01 P < 0.0001 |
0.18 ± 0.01 P < 0.0001 |
0.19 ± 0.02 P < 0.0001 |
| egf | 0.93 ± 0.06 | 0.26 ± 0.05 P < 0.0001 |
0.38 ± 0.02 P = 0.0003 |
0.34 ± 0.02 P < 0.0001 |
0.40 ± 0.06 P < 0.0001 |
1.20 ± 0.10 | 0.61 ± 0.04 P = 0.0036 |
0.29 ± 0.02 P < 0.0001 |
0.22 ± 0.02 P < 0.0001 |
0.33 ± 0.01 P < 0.0001 |
0.32 ± 0.03 P < 0.0001 |
0.35 ± 0.02 P < 0.0001 |
| mapk3 | 1.11 ± 0.03 | 0.24 ± 0.01 P < 0.0001 |
0.21 ± 0.02 P < 0.0001 |
0.21 ± 0.01 P < 0.0001 |
0.22 ± 0.01 P < 0.0001 |
1.13 ± 0.04 | 0.78 ± 0.02 P = 0.0497 |
0.34 ± 0.02 P < 0.0001 |
0.19 ± 0.01 P < 0.0001 |
0.19 ± 0.01 P < 0.0001 |
0.19 ± 0.01 P < 0.0001 |
0.19 ± 0.01 P < 0.0001 |
| tnxb | 0.98 ± 0.02 | 0.21 ± 0.02 P < 0.0001 |
0.30 ± 0.01 P < 0.0001 |
0.27 ± 0.03 P < 0.0001 |
0.30 ± 0.02 P < 0.0001 |
1.04 ± 0.02 | 0.89 ± 0.03 | 0.31 ± 0.01 P < 0.0001 |
0.17 ± 0.01 P < 0.0001 |
0.19 ± 0.01 P < 0.0001 |
0.23 ± 0.01 P < 0.0001 |
0.24 ± 0.03 P < 0.0001 |
| bcl2 | 1.10 ± 0.01 | 0.21 ± 0.02 P < 0.0001 |
0.24 ± 0.02 P < 0.0001 |
0.23 ± 0.01 P < 0.0001 |
0.23 ± 0.01 P < 0.0001 |
1.12 ± 0.08 | 0.59 ± 0.03 P = 0.0002 |
0.17 ± 0.02 P < 0.0001 |
0.10 ± 0.01 P < 0.0001 |
0.12 ± 0.01 P < 0.0001 |
0.16 ± 0.01 P < 0.0001 |
0.18 ± 0.01 P < 0.0001 |
| igf1r | 1.00 ± 0.04 | 0.20 ± 0.01 P < 0.0001 |
0.15 ± 0.01 P < 0.0001 |
0.11 ± 0.01 P < 0.0001 |
0.12 ± 0.01 P < 0.0001 |
1.04 ± 0.02 | 0.59 ± 0.01 P = 0.0005 |
0.21 ± 0.02 P < 0.0001 |
0.09 ± 0.01 P < 0.0001 |
0.08 ± 0.01 P < 0.0001 |
0.09 ± 0.01 P < 0.0001 |
0.09 ± 0.01 P < 0.0001 |
| pik3r2 | 0.83 ± 0.02 | 0.18 ± 0.01 P < 0.0001 |
0.14 ± 0.01 P < 0.0001 |
0.15 ± 0.02 P < 0.0001 |
0.20 ± 0.02 P < 0.0001 |
0.84 ± 0.05 | 0.82 ± 0.03 | 0.31 ± 0.02 P < 0.0001 |
0.16 ± 0.01 P < 0.0001 |
0.20 ± 0.02 P < 0.0001 |
0.21 ± 0.01 P < 0.0001 |
0.18 ± 0.02 P < 0.0001 |
| sox4 | 0.83 ± 0.03 | 0.17 ± 0.01 P < 0.0001 |
0.16 ± 0.01 P < 0.0001 |
0.16 ± 0.02 P < 0.0001 |
0.20 ± 0.01 P < 0.0001 |
0.73 ± 0.04 | 0.61 ± 0.11 P = 0.0139 |
0.19 ± 0.02 P < 0.0001 |
0.13 ± 0.01 P < 0.0001 |
0.18 ± 0.01 P < 0.0001 |
0.23 ± 0.01 P < 0.0001 |
0.22 ± 0.02 P < 0.0001 |
| lepr | 1.13 ± 0.03 | 0.16 ± 0.01 P < 0.0001 |
0.17 ± 0.01 P < 0.0001 |
0.12 ± 0.02 P < 0.0001 |
0.13 ± 0.01 P < 0.0001 |
1.26 ± 0.04 P = 0.462 |
0.79 ± 0.06 | 0.28 ± 0.03 P = 0.0001 |
0.12 ± 0.01 P < 0.0001 |
0.10 ± 0.01 P < 0.0001 |
0.07 ± 0.01 P < 0.0001 |
0.07 ± 0.01 P < 0.0001 |
| gpr30 | 1.04 ± 0.04 | 0.16 ± 0.01 P < 0.0001 |
0.20 ± 0.04 P < 0.0001 |
0.16 ± 0.01 P < 0.0001 |
0.17 ± 0.01 P < 0.0001 |
1.10 ± 0.05 | 0.74 ± 0.08 | 0.23 ± 0.03 P < 0.0001 |
0.11 ± 0.01 P < 0.0001 |
0.11 ± 0.01 P < 0.0001 |
0.11 ± 0.01 P < 0.0001 |
0.12 ± 0.02 P < 0.0001 |
| fgfr2 | 1.25 ± 0.07 | 0.15 ± 0.02 P < 0.0001 |
0.17 ± 0.01 P = 0.0001 |
0.17 ± 0.04 P < 0.0001 |
0.13 ± 0.01 P < 0.0001 |
1.03 ± 0.05 | 0.95 ± 0.02 | 0.25 ± 0.03 P = 0.0003 |
0.13 ± 0.01 P < 0.0001 |
0.12 ± 0.01 P < 0.0001 |
0.10 ± 0.01 P < 0.0001 |
0.12 ± 0.02 P < 0.0001 |
| ctsf | 1.02 ± 0.02 | 0.14 ± 0.02 P < 0.0001 |
0.11 ± 0.01 P < 0.0001 |
0.08 ± 0.01 P < 0.0001 |
0.10 ± 0.01 P < 0.0001 |
1.03 ± 0.04 | 0.71 ± 0.04 P = 0.0068 |
0.19 ± 0.02 P < 0.0001 |
0.07 ± 0.01 P < 0.0001 |
0.07 ± 0.01 P < 0.0001 |
0.06 ± 0.01 P < 0.0001 |
0.06 ± 0.01 P < 0.0001 |
| kgf | 1.28 ± 0.15 | 0.14 ± 0.01 P < 0.0001 |
0.16 ± 0.01 P < 0.0001 |
0.18 ± 0.02 P < 0.0001 |
0.24 ± 0.02 P < 0.0001 |
1.12 ± 0.07 | 1.02 ± 0.04 | 0.41 ± 0.02 P = 0.0007 |
0.31 ± 0.01 P < 0.0001 |
0.36 ± 0.03 P < 0.0001 |
0.29 ± 0.01 P < 0.0001 |
0.28 ± 0.020 P < 0.0001 |
| igfbp3 | 1.10 ± 0.06 | 0.14 ± 0.01 P < 0.0001 |
0.15 ± 0.01 P = 0.0003 |
0.13 ± 0.02 P < 0.0001 |
0.13 ± 0.02 P < 0.0001 |
1.18 ± 0.11 | 0.65 ± 0.05 P = 0.0379 |
0.21 ± 0.01 P = 0.0005 |
0.12 ± 0.01 P < 0.0001 |
0.10 ± 0.01 P < 0.0001 |
0.09 ± 0.01 P < 0.0001 |
0.11 ± 0.01 P < 0.0001 |
| hdac5 | 0.74 ± 0.06 P = 0.0438 |
0.13 ± 0.02 P < 0.0001 |
0.09 ± 0.01 P < 0.0001 |
0.08 ± 0.01 P < 0.0001 |
0.09 ± 0.01 P < 0.0001 |
0.88 ± 0.07 | 0.58 ± 0.05 P = 0.0023 |
0.19 ± 0.03 P < 0.0001 |
0.06 ± 0.01 P < 0.0001 |
0.07 ± 0.01 P < 0.0001 |
0.08 ± 0.01 P < 0.0001 |
0.06 ± 0.01 P < 0.0001 |
| vegfc | 1.06 ± 0.08 | 0.11 ± 0.01 P < 0.0001 |
0.11 ± 0.01 P < 0.0001 |
0.11 ± 0.01 P < 0.0001 |
0.13 ± 0.01 P < 0.0001 |
1.02 ± 0.05 | 0.78 ± 0.06 | 0.30 ± 0.01 P < 0.0001 |
0.18 ± 0.01 P < 0.0001 |
0.15 ± 0.01 P < 0.0001 |
0.16 ± 0.01 P < 0.0001 |
0.16 ± 0.01 P < 0.0001 |
| txnip | 1.29 ± 0.05 P = 0.0246 |
0.08 ± 0.01 P < 0.0001 |
0.09 ± 0.01 P < 0.0001 |
0.08 ± 0.01 P < 0.0001 |
0.10 ± 0.01 P < 0.0001 |
1.32 ± 0.06 P = 0.0160 |
0.68 ± 0.03 P = 0.0144 |
0.15 ± 0.01 P < 0.0001 |
0.09 ± 0.01 P < 0.0001 |
0.09 ± 0.01 P < 0.0001 |
0.07 ± 0.01 P < 0.0001 |
0.07 ± 0.01 P < 0.0001 |
| ccng2 | 0.99 ± 0.03 | 0.08 ± 0.01 P < 0.0001 |
0.08 ± 0.01 P < 0.0001 |
0.06 ± 0.01 P < 0.0001 |
0.06 ± 0.01 P < 0.0001 |
1.11 ± 0.02 | 0.58 ± 0.03 P = 0.0003 |
0.10 ± 0.02 P < 0.0001 |
0.04 ± 0.01 P < 0.0001 |
0.04 ± 0.01 P < 0.0001 |
0.05 ± 0.01 P < 0.0001 |
0.06 ± 0.01 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