DIFFERENTIAL EXPRESSION OF MESSENGER-RNAS FOR ENDOTHELIN-RELATED PROTEINS IN HUMAN ENDOMETRIUM, MYOMETRIUM AND LEIOMYOMA

The expression of mRNAs encoding endothelin-1 (ET-1) and its receptors (ET(A)-R and ET(B)-R) as well as the ET degrading enzyme, neutral end opeptidase 24.11 (NEP), was determined in tissue samples of endometriu m, myometrium and leiomyoma by using a reverse transcriptase polymeras e chain reaction (RT-PCR) technique. ET-1 mRNA was detected in all sam ples studied. The level of ET-1 mRNA was higher in endometrium than in myometrium (p < 0.01) and Ieiomyoma (p < 0.001). The ET(A)-R mRNA was more abundant in endometrium than in myometrium (p < 0.001). For ET(B )-R mRNA there was no difference between these tissues. In contrast to ET(A)-R mRNA, which was more abundant in leiomyoma than in myometrium (p < 0.01), the ET(B)-R mRNA was less abundant in leiomyoma (p < 0.01 ). The NEP mRNA was detected in all endometrial samples but not in myo metrium and leiomyoma. Our results show that the expression and relati ve levels of mRNAs encoding ET-1, ET(A)-R, ET(B)-R, and NEP vary in di fferent tissue compartments of the human uterus. Since the net biologi cal action of ET-1 in a particular cell type presumably depends on the balance between the peptide itself, its receptors and degrading enzym es, these results suggest different roles for ET-1 action in uterine e ndometrium, myometrium and leiomyoma. The difference in relative abund ance of ET(A)-R and ET(B)-R mRNAs between myometrium and leiomyoma sug gests that an altered ET-R gene expression may be a contributing facto r in myomal growth.