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

Abstract

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 microM (micromol/liter(-1)) progesterone for 24 h, and PK1 expression was assessed by quantitative RT-PCR. Treatment with 1 microM ( micromol/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.

Mitogenic functions of endocrine gland-derived vascular endothelial growth factor and Bombina variegata 8 on steroidogenic adrenocortical cells

“…However, the pattern of receptor expression was distinct as endocrine cells expressed both PKR1 and PKR2 whereas capillary endothelial cells expressed only PKR1. In human endometrium, it has also been shown that the endothelial cells coexpressed both factors and both receptors, PKR1 being predominant (Battersby et al 2004). Several studies have reported that PKR1 and PKR2 present similar affinities for both factors and trigger the same signaling cascades in Figure 7 Effect of EG-VEGF/PK1 on ERK1/2 and Akt protein phosphorylation.…”

Role of EG-VEGF in Human Placentation: Physiological and Pathological Implications

“…Prokineticins were originally identified as regulators of intestinal contraction but subsequently shown to affect vascular function, neuronal survival, nociception, immune responses, and gonadotropin releasing hormone systems (Battersby et al, 2004, Dorsch et al, 2005, LeCouter et al, 2003, Maldonado-Perez et al, 2007. Quickly after their discovery, the members of this family showed differential specificities of expression and preferential sites of actions.…”

“…While Bv8/PROK2 was associated to the neuronal system, EG-VEGF was more associated to the reproductive tract. EG-VEGF has been well studied in the ovary, uterus, testis, prostate and placenta (Battersby et al, 2004, Brouillet et al, 2010, Dorsch et al, 2005, Fraser et al, 2005,Hoffmann et al, 2007,2006, Hoffmann et al, 2009, LeCouter et al, 2001, LeCouter et al, 2003, Maldonado-Perez et al, 2007, Pasquali et al, 2006.…”

“…However, we cannot totally exclude that other factors presenting peaks in their expression during the first trimester of pregnancy may also participate in the regulation of EG-VEGF expression. Human chorionic gonadotropin (hCG) and progesterone are two such candidates because they have been recently shown to stimulate EG-VEGF mRNA expression in human luteinized granulosa cells (Fraser et al, 2005) and human endometrial tissue (Battersby et al, 2004), respectively. …”

Cotinine Exposure Increases Fallopian Tube PROKR1 Expression via Nicotinic AChRα-7

“…Reactions were performed using an ABI Prism 7900 (Applied Biosystems) using standard conditions. All primers and probes were previously validated, 20 and the sequences are listed in Table 2. All reactions were performed in triplicate.…”