Role of glycoprotein hormones in endometrial cancer

In vitro investigations into the reported anticancer activity of gonadotropin-releasing hormone (GnRH) in endometrial cancer have provided new information on the role of the glycoprotein hormones in this disease. GnRH analogs had no discernable effects on cell growth or on GnRH receptor activation in HEC-1A and Ishikawa cells. Rather, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), glycoprotein hormones whose levels are greatly suppressed by GnRH analogs in vivo, significantly enhanced cell numbers by up to 70% in 6 days of culture. Despite these results, the cells do not express appreciable levels of respective receptor mRNA; consequently, it seems likely that the hormones may be acting on another target. Comparisons are drawn between the actions of LH and FSH in these cell lines and the similar activity of a related glycoprotein hormone, namely human chorionic gonadotropin free P-subunit (hCGbeta), in bladder carcinoma cells. This molecule is thought to be able to block transforming growth factor (TGF)-beta-mediated apoptosis by acting as an antagonist at TGF-beta receptors. Further evidence for this hypothesis is provided by the discovery that not only LH and FSH, but also hCGbeta can increase HEC-1A and Ishikawa cell numbers in vitro. The results are discussed in the light of the knowledge that TGF-beta is structurally related to the glycoprotein hormones in that they are all members of the cystine knot growth factor superfamily, thus providing a possible mechanism for the observed results.