Nitric oxide and ERK/MAPK mediation of estrous behavior induced by GnRH, PGE2 and db-cAMP in rats

Abstract

We tested the hypothesis that GnRH, PGE 2 and db-cAMP act via the nitric oxide (NO)-cGMP and MAPK pathways to facilitate estrous behavior (lordosis and proceptivity) in estradiol-primed female rats. Estradiol-primed rats received intracerebroventricular (icv) infusions of pharmacological antagonists of NO synthase (L-NAME), NO-dependent soluble guanylyl cyclase (ODQ), protein kinase G (KT5823), or the ERK1/2 inhibitor PD98059 15 min before icv administration of 50 ng of GnRH, 1 μg of PGE 2 or 1 μg of db-cAMP. Icv infusions of GnRH, PGE 2 and db-cAMP enhanced estrous behavior at 1 and 2 hr after drug administration. Both L-NAME and ODQ blocked the estrous behavior induced by GnRH, PGE 2 and db-cAMP at some of the times tested. The protein kinase G inhibitor KT5823 reduced PGE 2 and db-cAMP facilitation of estrous behavior but did not affect the behavioral response to GnRH. In contrast, PD98059 blocked the estrous behavior induced by all three compounds. These data support the hypothesis that the NO-cGMP and ERK/MAPK pathways are involved in the lordosis and proceptive behaviors induced by GnRH, PGE 2 and db-cAMP. However, cGMP mediation of GnRH-facilitated estrous behavior is independent of protein kinase G.

Lack of functional GABAB receptors alters GnRH physiology and sexual dimorphic expression of GnRH and GAD-67 in the brain

“…GnRH neurons in the OB have been shown to participate in olfaction in land vertebrates and mammals such as the prairie vole (72,98), as well as in lordosis behavior in mice and rats (34,49). In addition, the presence of GABA B Rs in neurons in the OB also has been demonstrated in rats (47).…”

Dose-dependent effects of the antiprogestin, RU486, on sexual behavior of naturally cycling Fischer rats

“…Clearly, various agents (e.g. progesterone metabolites, neurotransmitters) can substitute for progesterone in facilitating lordosis behavior of rats primed with estrogen doses that are insufficient for facilitation of the behavior [13, 75–77]. Other reproductive events, such as the preovulatory LH surge, may also be increased by estrogen independently of intracellular progesterone receptors.…”

“…Since rat and mouse strains show differences in levels and/or receptors of neurotransmitters which may be able to substitute for progesterone in reproductive behavior [75, 79–83], it is possible that strain differences in ligand-independent mechanisms might account for the apparent greater sensitivity of Fischer females for estradiol-induced lordosis behavior. Fischer rats have a high sensitivity to stress [81, 84–86] and differ from other strains on several measures of serotonergic and/or dopaminergic functioning [81, 87–91], two neurotransmitters known to influence progesterone action and/or to be influenced by progesterone [13, 92–94].…”

Activation of progestin receptors in female reproductive behavior: Interactions with neurotransmitters

“…This facilitation appears to involve the activation of MAPK pathway, since MAPK inhibitors decreased the display of proceptive and receptive responses in female rats [99–100, 103]. The behaviors were also inhibited by the administration of PR antagonist RU486, indicating functional interactions between the rapid, membrane-mediated pathways and nuclear PRs [102].…”

“…A number of second messenger molecules, including cAMP, 3′-5′-cyclic guanosine monophosphate (cGMP) and nitric oxide (NO) can also substitute for P in the facilitation of reproductive behavior in female rats [56–57, 103]. NO has been demonstrated to be a mediator of GnRH release and a facilitator of female reproductive behavior [164].…”