An Inverse Relation Between the Expression of Tumor Necrosis Factor Alpha (TNF‐α) and TNF‐α Receptor in Human Endometrium

PROBLEM: To determine whether the expression of tumor necrosis factor (TNF-alpha) correlates with TNF-alpha receptor expression in human endometrium. METHOD OF STUDY: A multiprimer synthetic cDNA standard template containing complimentary sequences for several cytokines including TNF-alpha and TNF-alpha receptor type 2 was constructed and used in quantitative reverse transcription polymerase chain reaction (Q-RT-PCR). RESULTS: Endometrium from proliferative phase of the menstrual cycle expresses higher levels of TNF-alpha mRNA (2.35 +/- 0.2 x 10(5) copies/microg of total cellular RNA) than secretory phase ([1.3 +/- 0.08 x 10(5) copies] P < 0.05), with a significant reduction during menses (1.2 +/- 0.1 x 10(4) copies) and postmenopausal period (8.1 +/- 1.6 x 10(4) copies [P < 0.05]). In contrast, TNF-alpha type 1 receptor mRNA expression was higher in endometrium from the secretory phase (6.6 +/- 0.6 x 10(7) copies) compared to the menses (5.1 +/- 0.5 x 10(6) copies), proliferative phase (1.9 +/- 0.1 x 10(6) copies) and postmenopausal period (5.8 +/- 0.7 x 10(4) copies [P < 0.05]). Comparatively, TNF-alpha receptor type 2 is expressed 10 to 100 fold higher in the endometrium than TNF-alpha (P < 0.05). CONCLUSION: The data confirm that human endometrium expresses TNF-alpha; and provide the first evidence that TNF-alpha expression is inversely related to TNF-alpha type 1 receptor expression during the menstrual cycle. Such an inverse relation between TNF-alpha and TNF-alpha receptor expression may provide a regulatory mechanism necessary to overcome the detrimental effect of high levels of TNF-alpha on various endometrial cell types.