Fig. 4.

The estrogen receptor (ER)α ligand propyl pyrazole triol (PPT) and the G_q-coupled membrane estrogen receptor (Gq-mER) ligand STX differentially modulate the GABA_B response in NPY/AgRP cells from intact male mice. A–F: representative traces of GABA_B responses before and after application of E₂, PPT, or STX, with or without additional pharmacological manipulations (see below). Experiments were conducted as shown in Fig. 1. Dotted line represents baseline current. V_hold = −50 mV. Vertical scale bars represent 20 pA; all horizontal ones represent 5 min. For illustrative purposes, most of the 15-min vehicle or treatment period between GABA_B responses (R1 and R2) is removed. Other small breaks in the recording signify removal of slightly prolonged return to baseline current following baclofen application. G: bar graphs summarizing effects of E₂, STX, or PPT (all 100 nM) on the GABA_B response (baclofen, 10 μM) in NPY/AgRP neurons from intact males. Baclofen elicited 2 equal-amplitude responses during perfusion of vehicle (n = 7), but E₂ suppressed the response (n = 8). Coperfusing general PI3K inhibitors [wortmannin (WRT), 100 nM, n = 5; LY-294002 (LY), 10 μM, n = 4] or the p110β inhibitor TGX-221 (TGX, 11 nM, n = 6) with E₂ reversed this effect. PPT mimicked the effects of E₂ (n = 4). STX augmented the response (n = 5) but was rendered ineffective by coperfusing an ER antagonist [ICI 182,780 (ICI), 1 μM, n = 4]. **P < 0.01, ***P < 0.001, vs. vehicle control group.