Cellular biology of myomas: interaction of sex steroids with cytokines and growth factors

Abstract

Many investigators who have been trying to delineate the pathophysiology of leiomyomata believe in the autocrine-paracrine model of tumor growth,where ovarian hormones act as regulators of gene expression in cells. These affected cells overproduce the stimulatory and fibrogenic cytokines and growth factors to which they respond, resulting in sustained, self-stimulated proliferation and fibrogenesis. A number of cytokines and growth factors have been investigated in leiomyomata to determine which cytokines or factors may be responsible for mediating the growth-promoting effects of ovarian hormones. A review of the literature reveals that TGF-3 is the only growth factor shown to be overexpressed in leiomyomata versus myometrium, hormonally regulated both in vivo and in vitro, and both mitogenic and fibrogenic in these tissues. The authors believe that, given the extent and depth of the current research on the cellular biology of leiomyoma, the cellular mechanisms responsible in the pathogenesis of leiomyoma will be identified clearly within the foreseeable future. This will enable researchers to develop therapy directed against the molecules and mechanisms at the cellular level, which undoubtedly will have a major impact on the number of hysterectomies being performed for a"fibroid uterus."