Reproduction Abstracts

Human parturition at term and preterm involves inflammatory and non-inflammatory pathways and includes activation of the intrauterine prostaglandin (PG) cascade, resulting in synchronised membrane rupture, cervical dilation, and myometrial contractility. A key mediator of uterine PG production is the highly inducible enzyme cyclooxygenase 2 (COX2 or PTGS2). We have identified steroid receptor coactivator interacting protein (SIP or KANK2) to be highly expressed in human myometrium and fetal membranes, although its role in the uterus has yet to be investigated. siRNA-mediated knockdown of SIP in primary myometrial cells significantly reduced epidermal growth factor (EGF)-stimulated expression of COX2 mRNA and protein, while it was unable to decrease phorbol ester (PMA)-stimulated induction of COX2. EGF stimulation resulted in rapid and transient phosphorylation of SIP, which was blocked by pharmacological inhibition of the MEK/ERK signalling pathway with PD-184352. Moreover inhibition of ERK signalling decreased EGF-stimulated COX2 expression, suggesting that SIP phosphorylation plays an important role in its ability to regulate transcription of the COX2 gene. The data support a role for SIP in the complex mechanism of human parturition.