Cyclic GMP may potentiate lordosis behaviour by progesterone receptor activation

The purpose of this study was to test the hypothesis that cGMP acts as a pr ogesterone substitute to facilitate lordosis in oestrogen-primed rats. Fema le Sprague-Dawley rats underwent stereotaxic surgery to place a 26-gauge gu ide cannula into the third ventricle. Bilateral ovariectomy was done at the same time as stereotaxic surgery. Five days later ovariectomized rats were primed with 2 mu g estradiol benzoate 24 and 48 h prior to behaviour testi ng. Some animals were further injected with 200 mu g progesterone 4 h befor e behaviour testing. A nitric oxide synthase inhibitor infused into the thi rd ventricle before progesterone administration significantly reduced lordo sis performance, 8-Bromo-cGMP, a cell permeable cGMP analogue, or saline ve hicle was infused into the third ventricle of hormone-primed animals approx imate to 4 h prior to the first of 3-h behaviour tests. This cGMP analogue facilitated lordosis behaviour. We next used KT5823, a highly specific inhi bitor of protein kinase G (PKG), to test the hypothesis that cGMP action is mediated by this kinase. In this experiment, KT5823 was infused 15 min bef ore progesterone. KT5823 significantly decreased lordosis behaviour. RU486, a progesterone receptor antagonist, was used to assess whether the stimula tory effects of cGMP are mediated through the progesterone receptor, Oestro gen-primed animals were injected with 5 mg of RU486 or vehicle 60 min befor e infusion with 8-bromo-cGMP. RU486 significantly attenuated cGMP-facilitat ed lordosis behaviour. These data show that cGMP facilitates lordosis throu gh activation of PKG and the progesterone receptor.