Insulin-Like Growth Factors and Their Binding Proteins in the Endometrium

Abstract

In mammals and rodents the endometrium undergoes cyclical changes in response to the fluctuations in the circulating levels of ovarian steroid hormones. These changes serve to prime the endometrium for embryo implantation. In rodents, blastocyst attachment to the hormone-sensitized luminal epithelium initiates a process termed decidualization [Psychoyos, 1973]. The blastocyst stimulates a regional differentiation of the underlying stromal cells to form the decidua. The decidua eventually completely surrounds the developing embryo and forms the interface with the trophoblasts of the developing placenta. In humans, blastocyst implantation is not necessary for decidualization and pre-decidual changes can be seen in the stroma in the late secretory phase of the menstrual cycle [Padykula, 1991]. After implantation of the blastocyst the process of decidualization continues with further proliferation and differentiation of stromal cells. This differentiation is accompanied by expression of a variety of biochemical markers such as prolactin, insulin-like growth factor binding protein-1, transforming growth factor-a, adenosine deaminase, metallothionein, desmin and decidual luteotrophin [Croze, et al., 1990; Han et al., 1987; Hong et al., 1991; De et al., 1989; Glasser and Julian, 1986; Gibori et al., 1984]. It is now clearly established that estrogen, progesterone, growth hormone and thyroxine are all required for decidualization of the rodent endometrium [Kennedy and Doktorcik, 1988]. There is also evidence that each of these hormones can enhance IGF-I expression at least in some tissues [Murphy and Friesen, 1988; Murphy et al., 1988a; Norstedt et al., 1989; Wolf et al., 1989]. Although some changes consistent with decidualization can be achieved when human stromal cells are cultured under appropriate conditions, it has not been possible to completely reproduce this process of decidualization in the stromal cells in vitro [Tabanelli et al., 1992]. Suitable in vitro models to address the underlying molecular mechanisms involved in decidualization still remain to be established. The failure to demonstrate in vitro, the same steroid hormone responsiveness in endometrial cells that is observed in vivo, suggests that cell-cell interactions and cell-extracellular matrix interactions are likely to be important in the processes of decidualization and placentation just as they are important in the response of the endometrium to steroid hormones.