RESUMEN
The effect of genital stimulation, either by vaginocervical stimulation (VCS) using a calibrated vaginal probe combined with manual flank stimulation (FS), or by mounts performed by the male, on the hypothalamus and preoptic area concentration of the progesterone receptors A (PR-A) and B (PR-B) was assessed in ovariectomized (ovx) estrogen-primed rats. VCS/FS or stimulation provided by male mounts, even without intromission, significantly decreased PR-B concentration in the hypoythalamus. Down regulation of PR produced by genital stimulation was quantitatively similar to that elicited by progesterone (P) administration. Bilateral or unilateral transection of the pelvic or the pudendal nerves prevented down regulation elicited by VCS/FS. Repeated VCS/FS elicited lordosis behavior in most ovx estrogen primed rats, but the lordosis intensity was lower than that observed in response to P. P administered to ovx estrogen primed rats, induced sequential inhibition, i.e., failure to display estrous behavior in response to a second P injection (24h after the initial P injection). VCS/FS failed to elicit sequential inhibition, since rats responded with normal estrous behavior to the second injection of P. This suggests that down regulation by VCS, by contrast with P, failed to inhibit the subpopulation of PR involved in the facilitation of estrous behavior by P.
Asunto(s)
Encéfalo/metabolismo , Estro/efectos de los fármacos , Progesterona/farmacología , Receptores de Progesterona/metabolismo , Vagina/inervación , Animales , Encéfalo/anatomía & histología , Encéfalo/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Ovariectomía , Estimulación Física/métodos , Ratas , Ratas Sprague-Dawley , Conducta Sexual Animal/efectos de los fármacos , Conducta Sexual Animal/fisiología , Estadísticas no Paramétricas , Factores de Tiempo , Vagina/efectos de los fármacosRESUMEN
We tested the hypothesis that GnRH, PGE2 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 microg of PGE2 or 1 microg of db-cAMP. Icv infusions of GnRH, PGE2 and db-cAMP enhanced estrous behavior at 1 and 2 h after drug administration. Both L-NAME and ODQ blocked the estrous behavior induced by GnRH, PGE2 and db-cAMP at some of the times tested. The protein kinase G inhibitor KT5823 reduced PGE2 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, PGE2 and db-cAMP. However, cGMP mediation of GnRH-facilitated estrous behavior is independent of protein kinase G.
Asunto(s)
AMP Cíclico/metabolismo , Dinoprostona/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Hormona Liberadora de Gonadotropina/metabolismo , Óxido Nítrico/metabolismo , Conducta Sexual Animal/fisiología , Análisis de Varianza , Animales , Carbazoles/farmacología , AMP Cíclico/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Ciclo Estral/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Femenino , Flavonoides/farmacología , Guanilato Ciclasa/antagonistas & inhibidores , Guanilato Ciclasa/metabolismo , Inyecciones Intraventriculares , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/antagonistas & inhibidores , Ratas , Ratas Sprague-Dawley , Sistemas de Mensajero Secundario/efectos de los fármacos , Sistemas de Mensajero Secundario/fisiología , Conducta Sexual Animal/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Estadísticas no ParamétricasRESUMEN
In estrogen-primed female rats, vaginal cervical stimulation (VCS) provided by male intromissions or by an experimenter enhances estrous behaviors exhibited by females during subsequent mating with a male. We tested the hypothesis that alpha(1)-adrenergic receptors, acting via the nitric oxide-cGMP-protein kinase G pathway, mediate VCS-induced facilitation of female reproductive behaviors. Ovariectomized, estradiol-primed rats received intracerebroventricular (icv) infusions of vehicle or pharmacological antagonists 15 or 60min before VCS. Estrous behaviors (lordosis and proceptivity) in the presence of a male were recorded immediately (0min), and 120min following VCS. First we verified that VCS, but not manual flank stimulation alone, enhanced estrous behaviors when females received icv infusion of the vehicles used to administer drugs. Increased estrous behavior was apparent immediately following VCS and persisted for 120min. We then infused prazosin, phenoxybenzamine (alpha(1)-adrenergic receptor antagonists), yohimbine, idaxozan (alpha(2)-adrenergic receptor antagonists), or propranolol (beta-adrenergic receptor antagonist) 15min prior to the application of VCS in females primed with 5mug estradiol benzoate. Only alpha(1)-adrenergic antagonists inhibited VCS facilitation of estrous behavior, apparent 120min after VCS. Finally, we administered specific inhibitors of soluble guanylyl cyclase, nitric oxide synthase or protein kinase G icv 15 or 60min before VCS. All three agents significantly attenuated VCS facilitation of estrous behavior. These data support the hypothesis that endogenously released norepinephrine, acting via alpha(1)-adrenergic receptors, mediates the facilitation of lordosis by VCS, and are consistent with a mechanism involving alpha(1)-adrenergic activation of the nitric oxide/cGMP/protein kinase G pathway.
Asunto(s)
Ciclo Estral/fisiología , Óxido Nítrico/metabolismo , Receptores Adrenérgicos alfa 1/fisiología , Conducta Sexual Animal/fisiología , Transducción de Señal/fisiología , Vagina/inervación , Adrenérgicos/farmacología , Animales , Conducta Animal/efectos de los fármacos , Anticonceptivos/farmacología , Interacciones Farmacológicas , Inhibidores Enzimáticos/farmacología , Estradiol/análogos & derivados , Estradiol/farmacología , Ciclo Estral/efectos de los fármacos , Femenino , Masculino , Ovariectomía/métodos , Estimulación Física/métodos , Ratas , Transducción de Señal/efectos de los fármacos , Factores de TiempoRESUMEN
The aim of this work was to study the ontogeny of chondrocyte cell division using embryo, adult and osteoarthritic (OA) cartilage. We searched for mitosis phases and performed a comparative evaluation of mitotic index, basic fibroblast growth factor b (FGFb), transforming growth factor beta1 (TGF-beta1) receptors, cyclin dependent kinase (CDK1) and Cyclin-B expression in fetal, neonate, 3, 5, 8 weeks old rats and experimental OA. Our results showed that mitosis phases were observed in all normal cartilage studied, although, we found a decrease in mitotic index in relation to tissue development. No mitosis was detected in OA cartilage. We also found a statistical significant reduction in cell number in OA cartilage, compared with the normal tissue. Furthermore, FGFb and TGF-beta1 receptors diminished in relation to tissue development, and were very scarce in experimental OA. Western blot assays showed CDK-1 expression in all cases, including human-OA cartilage. Similar results were observed for Cyclin-B, except for 8 weeks, when it was not expressed. Our results suggest that cell division seems to be scarce, if not absent within the OA cartilage studied. Nevertheless, the existence of factors essential for cell division leaves open the question concerning chondrocyte proliferation in OA cartilage, which is likely to be present in the early stages of the disease.