The prokineticins (PK1 and PK2, also known as endocrine gland vascular endothelial growth factor [EG-VEGF] and Bv8 respectively), which bind to two closely homologous G-protein coupled receptors, PKR1 and PKR2, have been identified as novel angiogenic factors in endocrine tissue. However, little information is available on their expression and distribution in the uterus. The objectives of this study were to examine the expression and localisation of prokineticins and their receptors in endometrial tissue across the menstrual cycle. Endometrial tissue (n=35) was obtained from women with regular menstrual cycles. Ethical approval from Lothian Research Ethics Committee and written informed consent were obtained. Temporal expression of PK1, PK2 and their receptors was assessed by real time (Taqman) quantitative RT-PCR. Localisation of PK1 was studied by immunohistochemistry, whilst distribution of PK2, PKR1 and PKR2 were examined by in situ hybridisation. In addition, we examined the effect of progesterone on the expression of PK1. Endometrial tissue (n=5) was incubated with 1 micromolar progesterone for 24 hours and RNA was extracted and subjected to quantitative RT-PCR. PK1 was significantly increased in the secretory phase of the menstrual cycle compared with the proliferative phase (P<0.05), whilst expression of PK2 did not vary with the phase of the cycle. Both PKR1 and PKR2 showed significant upregulation in endometrial tissue during the transition from late secretory to the menstrual phase (P<0.05). PK1, PK2, PKR1 and PKR2 localised to glandular epithelial, stromal and endothelial cells of the endometrium and endothelial cells of the myometrium. Greater intensity of staining was observed for PKR1 compared with PKR2. Treatment of endometrial tissue with progesterone resulted in 2.96plus/minus0.8 fold increase in PK1 expression (P<0.05). In conclusion, these data confirm cyclical regulation of prokineticins and their receptors in the human endometrium and suggest a role for these novel angiogenic factors in endometrial vascular function.
03 - 05 Nov 2003
Society for Endocrinology