Proto-oncogenes c-jun and c-fos are down-regulated in human endometrium during pregnancy: relationship to oestrogen receptor status.

Oestrogen is the major stimulatory factor in endometrial cell proliferation. Animal and in-vitro studies have shown that proto-oncogenes c-fos and c-jun are regulated by oestrogen receptor (ER) complex. We have previously shown by Northern blot analysis that proto-oncogenes c-fos and c-jun are strongly expressed in human proliferative and early to mid-secretory endometrium. In this study, we examined the expression of the messenger RNA (mRNA) of the nuclear proto-oncogenes c-fos and c-jun in 10 early (6-10 weeks) and 20 term (30-40 weeks) pregnancy decidua by Northern blotting. In order to investigate the relationship between ER and these proto-oncogenes, the ER and progesterone receptors (PR) were identified in the same tissue samples by immunohistochemistry. When using 30-mer oligonucleotide probes, hardly any signals for c-fos and c-jun could be identified either in early or in late pregnancy decidua. Nuclear ER staining was intense in the epithelium and stroma of proliferative and early to mid-secretory endometrium but was sparsely scattered in stroma and lacking in epithelium during early pregnancy. In late pregnancy decidua, no positive ER staining was detectable. PR were present in abundance both in endometrial epithelium and stroma in proliferative and early secretory phase, and clear positive staining remained in stromal cells in late secretory phase and throughout pregnancy. The temporal association between immunoreactive ERs and the expression of c-fos and c-jun mRNA suggests that the activation of both proto-oncogenes is ER-mediated in human endometrium. The down-regulation of ER is one possible explanation for the repression of these immediate early genes during pregnancy.