Evidence of Juxtacrine Signaling for Transforming Growth Factor α inHuman Endometrium

• Published in: Biology of reproduction Vol. 59; no. 6; p. 1522
• Main Authors: Mark R. Bush, Jennifer M. Mele, Grace M. Couchman, David K. Walmer
• Format: Journal Article
• Language: English
• Published: Society for the Study of Reproduction 01.12.1998
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod59.6.1522

To determine the mechanism of signaling for transforming growth factor alpha (TGFα) in human endometrium, uterine luminal fluid proteins were retrieved by lavage followed by collection of the adjacent endometrium at hysterectomy. In the endometrium we observed the presence of the full-length transmembrane TGFα protein and the phosphorylation of its only known receptor, the epidermal growth factor receptor (EGFR), by immunoprecipitation-Western blot; TGFα mRNA via reverse transcription-polymerase chain reaction; and immunolocalization of TGFα to the surface endometrium adjacent to the uterine lumen. Despite this demonstration of TGFα in functional endometrium, we could not detect measurable amounts of TGFα in any of the 16 endometrial washings by either immunoprecipitation-Western blot or by ELISA. Recovery rate for intraluminal fluid spiked with TGFα control peptide was 93.4–97%. The inability to detect TGFα in intraluminal fluid despite its high concentration in cells directly adjacent to the uterine lumen, along with the absence of any cleaved TGFα species identified in the endometrium, suggests that TGFα signals its receptor as a transmembrane ligand. Since the EGFR is present in the endometrium and on the surface of embryos, these data are consistent with a juxtacrine mode of signaling for TGFα between endometrial cells, and between the luminal surface epithelium and preimplantation embryos.