Altered expression of the tachykinins substance P/neurokinin A/hemokinin-1 and their preferred neurokinin 1/neurokinin 2 receptors in uterine leiomyomata

Abstract

Objective: To study the expression levels of tachykinins and tachykinin receptors in uterine leiomyomas and matched myometrium.

Design: Laboratory study.

Setting: University research laboratories and academic hospital.

Patient(s): Women undergoing hysterectomy for symptomatic leiomyomas.

Intervention(s): Quantitative polymerase chain reaction, immunohistochemistry and Western blot.

Main outcome measure(s): Expression and tissue immunostaining of substance P, neurokinin A, hemokinin-1, neurokinin 1 receptor full-length (NK1R-Fl) and truncated (NK1R-Tr) isoforms, and neurokinin 2 receptor (NK2R) in paired samples of leiomyoma and adjacent normal myometrium.

Result(s): TAC1 messenger RNA (mRNA) was significantly up-regulated in leiomyomas, whereas intense immunoreaction for the three peptides was particularly abundant in connective tissue cells. Differential regulation of TACR1 mRNA was observed, and at the protein level there was a significant increased expression of NK1R short isoform (NK1R-Tr). TACR2 mRNA was significantly up-regulated in leiomyomas, although levels of NK2R protein were similar in normal and tumor cells.

Conclusion(s): These and our previous data demonstrate that the whole tachykinin system is differentially regulated in leiomyomas. The increased expression of NK1R-Tr might stimulate leiomyoma growth in a similar way to that observed in other steroid-dependent tumors.

Keywords: Leiomyomas; NK1 receptor short isoform; myometrium; tachykinin receptors; tachykinins.