![The Nestorone metabolite 3α, 5α-THNES has little effect on GABAARs. (A) Illustrated are the GABA (3 µM)-induced inward currents recorded from a representative WSS-1 cell in the absence (black trace) and presence (gray trace) of the neurosteroid 3α, 5α-THPROG (100 nM). Note the large enhancement of the GABA-evoked response produced by this neurosteroid. (B) The nestorone metabolite 3α, 5α-THNES (100 nM) produced only a modest increase in the GABA (3 µM)-evoked current. (C) Bar chart summarizing the effect of 3α, 5α-THPROG (100 nM; n = 4) and 3α, 5α-THNES (100 nM, n = 10; 1 µM, n = 5) on the peak amplitude of the GABA-evoked response. **P < 0.01; ***P < 0.001 (Student t test). (D, E) The black traces illustrate averaged mIPSCs recorded from representative mouse cortical pyramidal neurons under control conditions. Superimposed upon these control recordings are representative mIPSCs recorded from cortical neurons obtained from brain slices incubated for ∼2 h in 3α, 5α-THPROG (100 nM) (D) and 3α, 5α-THNES (100 nM) (gray traces) (D). (F) Bar chart summarizing the effect of 3α, 5α-THPROG (100 nM; n = 5 neurons) and 3α, 5α-THNES (100 nM, n = 4 neurons; 1 µM, n = 4 neurons) on the control (n = 25 neurons) mIPSC decay time [quantified as the τw the weighted time constant of decay (ms)]. ###P < 0.001 (1-way ANOVA). Note the large prolongation produced by 3α, 5α-THPROG (100 nM), whereas 3α, 5α-THNES (100 nM) was inert in this respect. The data for the control τw and the τw in the presence of 3α, 5α-THPROG (100 nM) is reproduced from Brown et al. (32).](https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/endo/158/1/10.1210_en.2016-1426/3/en.2016-1426f6.jpeg?Expires=1750533095&Signature=ZP0mv5ph8WJDfZ1fktue4wlD0Ax5AOsD6DFy-QRGKkWdV-7uuqF37-SojlDZC8DA7RtNEOhUVbUWaTf73Jg3gC~6CWHb61zk5Xcqj4Vs2vRm6AoI8W7EgdF112zRK6w-z1-YfcbGni-k~08~Af~rgzCAK989bokMBC70Mrx9h~kqKHSYPkCrODdoBRAU7xYvBWwr3pAkOj1fdpb3lfHXZu9zVKfD7~UVu2po3Qbp9~RPBNzHhuKiHQlPrQiVoZIc9OaQfInqEc47i7hMPDtZTjAKQvsfsWgXrxhDn5lFj9Fmb6yUgj5TbhDuzihMSLhSRAwuH-2iZ3HettWtJPz8kw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
The Nestorone metabolite 3α, 5α-THNES has little effect on GABAARs. (A) Illustrated are the GABA (3 µM)-induced inward currents recorded from a representative WSS-1 cell in the absence (black trace) and presence (gray trace) of the neurosteroid 3α, 5α-THPROG (100 nM). Note the large enhancement of the GABA-evoked response produced by this neurosteroid. (B) The nestorone metabolite 3α, 5α-THNES (100 nM) produced only a modest increase in the GABA (3 µM)-evoked current. (C) Bar chart summarizing the effect of 3α, 5α-THPROG (100 nM; n = 4) and 3α, 5α-THNES (100 nM, n = 10; 1 µM, n = 5) on the peak amplitude of the GABA-evoked response. **P < 0.01; ***P < 0.001 (Student t test). (D, E) The black traces illustrate averaged mIPSCs recorded from representative mouse cortical pyramidal neurons under control conditions. Superimposed upon these control recordings are representative mIPSCs recorded from cortical neurons obtained from brain slices incubated for ∼2 h in 3α, 5α-THPROG (100 nM) (D) and 3α, 5α-THNES (100 nM) (gray traces) (D). (F) Bar chart summarizing the effect of 3α, 5α-THPROG (100 nM; n = 5 neurons) and 3α, 5α-THNES (100 nM, n = 4 neurons; 1 µM, n = 4 neurons) on the control (n = 25 neurons) mIPSC decay time [quantified as the τw the weighted time constant of decay (ms)]. ###P < 0.001 (1-way ANOVA). Note the large prolongation produced by 3α, 5α-THPROG (100 nM), whereas 3α, 5α-THNES (100 nM) was inert in this respect. The data for the control τw and the τw in the presence of 3α, 5α-THPROG (100 nM) is reproduced from Brown et al. (32).
