GROWTH-FACTORS AND GROWTH MODULATORS IN HUMAN UTERINE ENDOMETRIUM - THEIR POTENTIAL RELEVANCE TO REPRODUCTIVE MEDICINE

Objective: To provide an up-to-date, comprehensive review on the prese nce and regulation of growth factors (GFs), GF receptors, and GF regul atory proteins in human endometrium in an effort to understand the pot ential roles of these proteins in endometrial cell mitosis and differe ntiation and in endometrial-trophoblast interactions. Design: Relevant studies were identified through a computerized bibliographic search ( MEDLINE; BRS Information Technologies, a division of Maxwell Online, I nc., McLean, VA) and through manual scanning of recent relevant journa ls. Results: Several GFs, their receptors, and regulatory proteins hav e been identified in endometrium, and cellular localization and steroi d-dependence of these proteins as well as action of several growth mod ulators on endometrial cell function have been studied. Epidermal grow th factor, transforming growth factor (TGF)-alpha, platelet-derived gr owth factor, insulin-like growth factors (IGFs) and their binding prot eins, fibroblast growth factor (FGF), TGF-beta, colony-stimulating fac tor (CSF)-1, and interferon-gamma regulate mitosis of endometrial cell ular components in vitro. Endothelin-l may participate in vasoconstric tion and FGF may participate in angiogenesis in this tissue in vivo. I nterleukins-l and -6 are believed to be involved in endometrial T-cell activation, and TGF-beta, CSF-1, the interleukins, and the IGFs likel y mediate endometrial-trophoblast interactions. The role of tumor necr osis factor in endometrium remains uncertain. Conclusions: Current evi dence supports the thesis that GFs play a central role in cyclic mitos is and differentiation of endometrial cellular components, recruitment of macrophages in decidualizing endometrium, endometrial-trophoblast interactions, early pregnancy maintenance, tissue shedding in the abse nce of implantation, and endometrial functionalis regeneration.