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Expression and Regulation of the Prokineticins (Endocrine Gland-Derived Vascular Endothelial Growth Factor and Bv8) and Their Receptors in the Human Endometrium across the Menstrual Cycle

MRC Human Reproductive Sciences Unit (S.B., K.M., R.P.M., H.N.J.) and Department of Reproductive and Developmental Sciences (H.O.D.C.), Centre for Reproductive Biology, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom

Address all correspondence and requests for reprints to: Dr. H. N. Jabbour, MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, University of Edinburgh, Chancellor’s Building, 49 Little France Crescent, Edinburgh EH16 4SB, United Kingdom. E-mail: h.jabbour{at}hrsu.mrc.ac.uk.

This study investigated the possible role of the newly discovered endocrine gland-derived vascular endothelial growth factors and their cognate receptors in the human endometrium during the menstrual cycle. Endocrine gland-derived vascular endothelial growth factors are also known as prokineticin (PK) 1 and PK2 and their receptors as PKR1 and PKR2. Expression of PK1 was elevated in the secretory compared with the proliferative phase of the menstrual cycle (P < 0.05). There was no temporal variation in expression of PK2, PKR1, or PKR2.

PK1 and PK2 and their receptors were localized to multiple cellular compartments, including glandular epithelial, stromal, and endothelial cells in the endometrium and endothelial and smooth muscle cells in the myometrium. The elevation in PK1 expression in the secretory phase of the menstrual cycle indicated potential regulation of PK1 by progesterone. To investigate this, endometrial tissue was treated with 1 µM (µmol/liter^–1) progesterone for 24 h, and PK1 expression was assessed by quantitative RT-PCR. Treatment with 1 µM (µmol/liter^–1) progesterone resulted in 2.91 ± 0.75-fold elevation in PK1 expression, compared with controls (P < 0.05). These data identify a paracrine role for the PKs and their receptors in endometrial vascular function.

Abbreviations: FGF, Fibroblast growth factor; FITC, fluoroscein isothiocyanate; PK, prokineticin; PKR, PK receptor; VEGF, vascular endothelial growth factor.

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