The nitric oxide pathway participates in estrous behavior induced by progesterone and some of its ring A-reduced metabolites.

Intracerebral and intravenous administration of progesterone (P) and its ring A-reduced metabolites induces intense sexual behavior (lordosis and proceptivity) in estrogen-primed rats. The present study tested the hypothesis that the nitric oxide-cGMP-protein kinase G pathway is involved in the facilitation of sexual behavior induced by the intracerebroventricular (i.c.v.) administration of P (130 ng) and its ring A-reduced metabolites 5alpha-dihydroprogesterone (5alpha-DHP; 13 ng) and 5alpha,3alpha-pregnanolone (5alpha,3alpha-Pgl; 13 ng). In Experiment 1, we tested the relevance of the nitric oxide/cGMP pathway by infusing a nitric oxide synthase inhibitor or a nitric oxide-dependent, soluble guanylyl cyclase inhibitor icv before progestin administration. The lordosis induced by P, 5alpha-DHP and 5alpha,3alpha-Pgl was significantly reduced at 2 h after progestin infusion by the previous injection of either a nitric oxide synthase inhibitor or by a soluble guanylyl cyclase inhibitor. Lordosis behavior returned to control values by 4 h. In Experiment 2, i.c.v. infusion of the protein kinase G inhibitor KT5823 significantly inhibited the lordosis behavior induced by all three progestins at 2 h. These data support the hypothesis that the nitric oxide/cGMP/protein kinase G pathway is involved in the lordosis induced by P and some of its ring A-reduced metabolites.