RESUMO
Mating shut down a 2-methoxyestradiol (2ME) nongenomic action necessary to accelerate egg transport in the rat oviduct. Herein, we investigated whether tumour necrosis factor-α (TNF-α) participates in this mating effect. In unmated and mated rats, we determined the concentration of TNF-α in the oviductal fluid and the level of the mRNA for Tnf-a (Tnf) and their receptors Tnfrsf1a and Tnfrsf1b in the oviduct tissues. The distribution of the TNFRSF1A and TNFRSF1B proteins in the oviduct of unmated and mated was also assessed. Finally, we examined whether 2ME accelerates oviductal egg transport in unmated rats that were previously treated with a rat recombinant TNF-α alone or concomitant with a selective inhibitor of the NF-κB activity. Mating increased TNF-α in the oviductal fluid, but Tnf transcript was not detected in the oviduct. The mRNA for TNF-α receptors as well as their distribution was not affected by mating, although they were mainly localized in the endosalpinx. Administration of TNF-α into the oviduct of unmated rats prevented the effect of 2ME on egg transport. However, the NF-κB activity inhibitor did not revert this effect of TNF-α. These results indicate that mating increased TNF-α in the oviductal fluid, although this not associated with changes in the expression and localization of TNF-α receptors in the oviductal cells. Furthermore, TNF-α mimicked the effect of mating on the 2ME-induced egg transport acceleration, independently of the activation of NF-κB in the oviduct. We concluded that TNF-α is the signal induced by mating to shut down a 2ME nongenomic action in the rat oviduct.
Assuntos
Estradiol/análogos & derivados , Tubas Uterinas/efeitos dos fármacos , Transporte do Óvulo/efeitos dos fármacos , Comportamento Sexual Animal/fisiologia , Fator de Necrose Tumoral alfa/fisiologia , 2-Metoxiestradiol , Aceleração , Animais , Líquidos Corporais/química , Líquidos Corporais/metabolismo , Estradiol/farmacologia , Tubas Uterinas/metabolismo , Feminino , Genoma/efeitos dos fármacos , Transporte do Óvulo/fisiologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/fisiologiaRESUMO
Oestradiol (E(2)) accelerates oviductal transport of oocytes in cycling rats through a nongenomic pathway that involves the cAMP-PKA signalling cascade. Here we examined the role of the inositol triphosphate (IP3) and mitogen-activated protein kinase (MAPK) signalling cascades in this nongenomic pathway. Oestrous rats were injected with E(2) s.c. and intrabursally (i.b) with the selective inhibitors of phospholipase C (PLC) ET-18-OCH(3) or MAPK PD98059. The number of eggs in the oviduct assessed 24 h later showed that ET-18-OCH(3) blocked E(2)-induced egg transport acceleration, whereas PD98059 had no effect. Other oestrous rats were treated with E(2) s.c. and 1, 3 or 6 h later oviducts were excised and the levels of IP3 and phosphorylated MAPK p44/42 (activated) were determined by radioreceptor assay and western blot, respectively. Oestradiol administration increased IP3 level at 1 and 6 h after treatment, whereas activated MAPK p44/42 level was unchanged. Finally, we explored whether cAMP-PKA and PLC-IP3 signalling cascades are coupled. Inhibition of adenylyl cyclase by i.b. injection of SQ 22536 blocked the increase of IP3 levels induced by E(2), while inhibition of PLC by ET-18-OCH(3) had no effect on E(2)-induced PKA activity. Furthermore, activation of adenylyl cyclase by Forskolin increased oviductal IP3 levels. Thus, activation of PLC-IP3 by E(2) requires previous stimulation of cAMP-PKA. We conclude that the nongenomic pathway utilised by E(2) to accelerate oviductal transport of oocytes in cycling rats involves successive activation of the cAMP-PKA and PLC-IP3 signalling cascades and does not require activation of MAPK. These findings clearly illustrate a non-genomic pathway triggered by E(2) that regulates a complex physiologic process accomplished by an entire organ.
Assuntos
Estradiol/farmacologia , Tubas Uterinas/metabolismo , Fosfatos de Inositol/fisiologia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Transporte do Óvulo/fisiologia , Transdução de Sinais/fisiologia , Adenina/análogos & derivados , Adenina/farmacologia , Inibidores de Adenilil Ciclases , Adenilil Ciclases/metabolismo , Animais , Colforsina/farmacologia , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Inibidores Enzimáticos/farmacologia , Estro , Feminino , Flavonoides/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Oócitos/citologia , Oócitos/efeitos dos fármacos , Fosfatidilcolinas/farmacologia , Éteres Fosfolipídicos , Ratos , Ratos Sprague-Dawley , Fosfolipases Tipo C/antagonistas & inibidores , Fosfolipases Tipo C/metabolismoRESUMO
Apresenta-se uma revisäo sobre transporte de gametas.