RESUMO
An injection of unesterified oestradiol (E2 ) facilitates receptive behaviour in E2 benzoate (EB)-primed, ovariectomised female rats when it is administered i.c.v. or systemically. The present study tested the hypothesis that inhibitors of protein kinase A (PKA), protein kinase G (PKG) or the Src/mitogen-activated protein kinase (MAPK) complex interfere with E2 facilitation of receptive behaviour. In Experiment 1, lordosis induced by i.c.v. infusion of E2 was significantly reduced by i.c.v. administration of Rp-cAMPS, a PKA inhibitor, KT5823, a PKG inhibitor, and PP2 and PD98059, Src and MAPK inhibitors, respectively, between 30 and 240 minutes after infusion. In Experiment 2, we determined whether the ventromedial hypothalamus (VMH) is one of the neural sites at which those intracellular pathways participate in lordosis behaviour induced by E2 . Administration of each of the four protein kinase inhibitors into the VMH blocked facilitation of lordosis induced by infusion of E2 also into the VMH. These data support the hypothesis that activation of several protein kinase pathways is involved in the facilitation of lordosis by E2 in EB-primed rats.
Assuntos
Antagonistas de Estrogênios/farmacologia , Lordose/fisiopatologia , Inibidores de Proteínas Quinases/farmacologia , Núcleo Hipotalâmico Ventromedial/fisiologia , Animais , Carbazóis/farmacologia , AMP Cíclico/análogos & derivados , AMP Cíclico/farmacologia , Estradiol/fisiologia , Feminino , Flavonoides/farmacologia , Infusões Intraventriculares , Lordose/induzido quimicamente , Masculino , Microinjeções , Inibidores de Proteínas Quinases/administração & dosagem , Pirimidinas/farmacologia , Ratos , Tionucleotídeos/farmacologia , Núcleo Hipotalâmico Ventromedial/efeitos dos fármacosRESUMO
The present study tested the hypothesis that the Janus kinase 2, Src tyrosine kinases, and mitogen-activated protein kinase interact to regulate lordosis behavior induced by leptin in ovariectomized, estrogen-primed rats. The role of protein kinase A and protein kinase C in lordosis facilitation by leptin was also assessed. In experiment 1, the intracerebroventricular administration of leptin to ovariectomized, estradiol-primed rats significantly stimulated lordosis behavior at 1, 2 and 4 h post-injection tests. In experiment 2, the Janus kinase 2 inhibitor AG490, the Src tyrosine kinase inhibitor PP2 and the mitogen-activated protein kinase inhibitor PD98059 were administered into the right lateral ventricle before leptin. The lordosis quotient and the lordosis score induced by leptin were significantly decreased by each of these kinase inhibitors. In experiment 3, we examined the effects of RpcAMPS and bisindolylmaleimide, protein kinase A and protein kinase C inhibitors on the lordosis elicited by leptin administration. Lordosis behavior induced by leptin was significantly decreased by both the protein kinase A and protein kinase C inhibitors at 1 h post-leptin injection. The results confirm that multiple intracellular pathways participate in the expression of lordosis behavior in estrogen-primed rats elicited by leptin.
Assuntos
Dorso/fisiologia , Estrogênios/administração & dosagem , Leptina/fisiologia , Ovariectomia , Proteínas Quinases/metabolismo , Comportamento Sexual Animal , Animais , Feminino , Infusões Intraventriculares , Leptina/administração & dosagem , Ratos , Ratos Sprague-DawleyRESUMO
Intracerebroventricular (icv) administration of leptin facilitates lordosis behavior in ad libitum-fed, estrogen-primed rats. The cellular mechanism involved in this response is unknown. The present study tested the hypothesis that the nitric oxide-guanylyl cyclase, cGMP-dependent protein kinase (PKG) pathway is involved in the facilitation of lordosis behavior induced by the central administration of leptin. We tested the importance of the nitric oxide/cGMP pathway for lordosis stimulation by either icv infusion of a nitric oxide synthase inhibitor (L-NAME) or a nitric oxide-dependent, soluble guanylyl cyclase inhibitor (ODQ) 30 min before leptin administration (1 µg). This dose of leptin reliably induced lordosis behavior in ovariectomized estradiol benzoate treated rats. The lordosis induced by leptin at 1 and 2h after infusion was significantly reduced by the previous injection of either L-NAME or by ODQ. Intracerebroventricular infusion of the PKG inhibitor (KT5823) 30 min before leptin infusion, also significantly inhibited the lordosis behavior induced by leptin at 1 and 2h after hormone administration. These data support the hypothesis that the nitric oxide/cGMP/PKG pathway is involved in the facilitation of lordosis by leptin in estrogen-primed female rats.