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Evidence of Juxtacrine Signaling for Transforming Growth Factor inHuman Endometrium¹

^a Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Duke University Medical Center, Durham, North Carolina 27710 ^b Laboratory of Molecular Carcinogenesis, and ^c Laboratory of Reproductive and Developmental Toxicology, NIEHS, NIH, Research Triangle Park, North Carolina 27709

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

¹ As presented orally at the 45th annual meeting of the Society for Gynecologic Investigation, Atlanta, Georgia, March 11–14, 1998.

² Correspondence and current address: Mark R. Bush, Division of Reproductive Endocrinology and Infertility, MCHG-OG, Madigan Army Medical Center, Tacoma, WA 98431. FAX: (253) 968-2558; e-mail: MAJ_Mark_Bush;casmtplink.mamc.amedd.army.mil

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