Regulation of TNF-alpha MRNA Expression in Endometrial Cells by TNF-alpha and by Oestrogen Withdrawal

During each menstrual cycle, the human endometrium undergoes a series of orchestrated and well controlled changes in anticipation of the arrival of the blastocyst. In the absence of implantation, the endometrium is shed. The underlying basis of the menstrual bleeding is not clear, however, it seems to be related to steroid hormone withdrawal. We showed that tumour necrosis factor-alpha (TNF-alpha) is released by human endometrium and that endometrial epithelial cells are a major source of TNF-alpha mRNA and protein. We show here that TNF-alpha mRNA shows a specific menstrual cycle-dependent expression. The expression of TNF-alpha is mostly minimal throughout the proliferative, early and mid-secretory phases. Expression of TNF-alpha mRNA, however, is increased in the human endometrium in the late secretory phase and during endometrial bleeding. Such a menstrual cycle-dependent expression suggests that specific signals regulate the expression of TNF-alpha mRNA in the human endometrium. In vitro, the expression of TNF-alpha mRNA in endometrial epithelial cells could be regulated by exogenous TNF-alpha. This induced expression was both time- and dose-dependent. In vitro, the TNF-alpha mRNA expression was not altered by oestrogen, progesterone, or both, in the endometrial epithelial cells under conditions that maintain the steroid hormone receptors. However, in vivo, oestrogen withdrawal led to an enhanced expression of TNF-alpha in endometrial epithelial cells. These findings suggest that the up-regulation of TNF-alpha in human endometrium in the late secretory phase may be related to the falling serum oestrogen concentration at the end of the menstrual cycle as well as the potentiating effect of released TNF-alpha on its own mRNA expression.