Evidence of Juxtacrine Signaling for Transforming Growth Factor α inHuman Endometrium1

Abstract

To determine the mechanism of signaling for transforming growth factor alpha (TGFalpha) 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 TGFalpha protein and the phosphorylation of its only known receptor, the epidermal growth factor receptor (EGFR), by immunoprecipitation-Western blot; TGFalpha mRNA via reverse transcription-polymerase chain reaction; and immunolocalization of TGFalpha to the surface endometrium adjacent to the uterine lumen. Despite this demonstration of TGFalpha in functional endometrium, we could not detect measurable amounts of TGFalpha in any of the 16 endometrial washings by either immunoprecipitation-Western blot or by ELISA. Recovery rate for intraluminal fluid spiked with TGFalpha control peptide was 93.4-97%. The inability to detect TGFalpha in intraluminal fluid despite its high concentration in cells directly adjacent to the uterine lumen, along with the absence of any cleaved TGFalpha species identified in the endometrium, suggests that TGFalpha 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 TGFalpha between endometrial cells, and between the luminal surface epithelium and preimplantation embryos.

Endometriotic Cells Exhibit Metaplastic Change and Oxidative DNA Damage as Well as Decreased Function, Compared to Normal Endometrium

“…TGF b-1 is known to function as a juxtacrine signalling molecule between endometrial cells, and between the luminal surface epithelium and preimplantation embryos (Bush et al 1998). The normal functioning of TGF b-1 is important for normal implantation (Das et al 1997) and it is an essential growth factor for the normal functioning of the endometrium (Polli et al 1996).…”

Structural Dynamics and Function of Early Embryonic Coats

“…Reports that implantation can be blocked in mice by an IL-1 antagonist [Simó n et al, 1994;Karagouni et al, 1998] received particular attention. The EGF-like growth factor family is of special interest since it shows evidence of very local signal exchange within the implantation chamber [Das et al, 1994[Das et al, , 1997Bush et al, 1998]. …”

Proteomics Methods for Probing Molecular Mechanisms in Signal Transduction

“…However, transmembrane forms of TGFα have been identified (Luetteki and Lee, 1990). Juxtacrine actions of these forms of TGFα have been suggested (Bush et al, 1998;Xiao and Majumder, 2001). In addition, dimerization of transmembrane TGFα molecules with anti-TGFα induces protein phosphorylation reminiscent of receptor activation (Shum et al, 1994).…”