Serum Human Hepatocyte Growth Factor in Human Menstrual Cycle and Pregnancy: A Novel Serum Marker of Regeneration and Reconstruction of Human Endometrium

Abstract

Serum concentrations of human hepatocyte growth factor (hHGF) were measured in normal menstrual cycles and during uncomplicated pregnancies. In the normal menstrual cycle, the concentrations of hHGF increased through the mid and the late luteal phases to reach the highest peak during the menstrual phases, followed by a gradual decline during the follicular phase toward the trough levels seen in the ovulatory and the very early luteal phases. During pregnancy, serum hHGF concentrations increased continuously from the late luteal levels and constituted 4 distinct peaks. By immunostaining, c-Met protein, a receptor for hHGF, was localized not in the stromal but in the epithelial layer of the endometrium. In cultured isolated endometrial cells, hHGF stimulated the proliferation of both the epithelial and the stromal cells. It is likely that hHGF is involved in the repair or reconstruction process of the endometrium after menstrual shedding and implantation.

Intercellular Adhesion Molecule-1 and Hepatocyte Growth Factor in Human Endometriosis: Original Investigation and a Review of Literature

“…Bottaro and colleagues identified the proto-oncogene c-met encoded protein as the receptor for HGF [12]. Finally, Negami and colleagues have shown that HGF stimulates the proliferation of endometrial epithelial cells, induces superficial epithelialization in three-dimensional cell culture systems, and is involved in the reconstruction and growth of the endometrium [13]. These studies disclose various defects in the cell-mediated immune system and their possible relationship to the progression of endometriosis.…”

Expression and action of hepatocyte growth factor in bovine endometrial stromal and epithelial cells in vitro*

“…It might be due to an effect of calf serum contained in the culture medium. HGF has also been shown to act on human endometrial epithelial cells as a mitogen, motogen and morphogen (Negami et al, 1995;Sugawara et al, 1997a). Furthermore, expression of c-met mRNA has been observed in human (Sugawara et al, 1997a), as well as murine and ovine endometrial epithelial cells (Yang and Park, 1995;Chen et al, 2000).…”

“…It is primarily produced by mesenchymal-derived cells in many types of tissues and acts as an epithelial cell-speci®c mitogen (Nakamura, 1991;Matsumoto and Nakamura, 1993). Recent studies demonstrated that HGF stimulated the proliferation of human endometrial epithelial cells (Negami et al, 1995;Sugawara et al, 1997a). In addition, the protooncogene c-met, also named c-met, has been identi®ed as the receptor for HGF (HGFR) (Bottaro et al, 1991).…”

Innate Immunity in the Female Reproductive Tract: Role of Sex Hormones in Regulating Uterine Epithelial Cell Protection Against Pathogens

“…The synthesis of HGF by stromal fibroblasts, together with its reported effects on epithelia, suggests a paracrine mode of action and a role in stromal fibroblast-epithelial interactions [69][70][71]. Negami et al have demonstrated that during the normal menstrual cycle, HGF concentrations fluctuate, with peak levels detected during the mid-and late secretory phase [72]. During pregnancy, HGF concentrations increase in the late secretory phase and remain high until parturition [72].…”

“…Negami et al have demonstrated that during the normal menstrual cycle, HGF concentrations fluctuate, with peak levels detected during the mid-and late secretory phase [72]. During pregnancy, HGF concentrations increase in the late secretory phase and remain high until parturition [72]. Collectively, this suggests that HGF may influence endometrial repair and reconstruction after menstrual shedding and implantation.…”