Inositol triphosphate participates in an oestradiol nongenomic signalling pathway involved in accelerated oviductal transport in cycling rats

Pedro A. Orihuela, Alexis Parada-Bustamante, Lidia M. Zuñiga, Horacio B. Croxatto

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

Oestradiol (E2) 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 E2 s.c. and intrabursally (i.b) with the selective inhibitors of phospholipase C (PLC) ET-18-OCH3 or MAPK PD98059. The number of eggs in the oviduct assessed 24h later showed that ET-18-OCH3 blocked E2-induced egg transport acceleration, whereas PD98059 had no effect. Other oestrous rats were treated with E2 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 E2, while inhibition of PLC by ET-18-OCH3 had no effect on E2-induced PKA activity. Furthermore, activation of adenylyl cylase by Forskolin increased oviductal IP3 levels. Thus, activation of PLC-IP3 by E2 requires previous stimulation of cAMP-PKA. We conclude that the nongenomic pathway utilised by E2 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 E2 that regulates a complex physiologic process accomplished by an entire organ.

Original languageEnglish
Pages (from-to)579-588
Number of pages10
JournalJournal of Endocrinology
Volume188
Issue number3
DOIs
Publication statusPublished - Mar 2006

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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