PRESENCE OF MESSENGER-RIBONUCLEIC-ACID FOR ENDOTHELIN-1, ENDOTHELIN-2, AND ENDOTHELIN-3 IN HUMAN ENDOMETRIUM AND A CHANGE IN THE RATIO OF ETA AND ETB RECEPTOR SUBTYPE ACROSS THE MENSTRUAL-CYCLE

The aim of the present study was to determine whether MRNA for the three endothelin peptides (endothelin-1, endothelin-2, and endothelin-3) and the two known receptor subtypes (ET(A) and ET(B)) was present in human endometrium at different stages of the menstrual cycle (menstrual, early and mid-proliferative, and early, mid-, and late secretory). Endometrium was obtained from women undergoing surgery for benign disease, and total RNA was extracted using a guanidinium isothiocyanate method. MRNA for endothelin peptide and receptor was detected using the reverse transcriptase-polymerase chain reaction with nested oligonucleotide primers. MRNA for endothelin-1, endothelin-2, and endothelin-3 was demonstrated throughout the menstrual cycle, and three splice variants of MRNA encoding endothelin-3 were found in all samples. The ratio of ET(A) to ET(B) receptor MRNA was found to change throughout the menstrual cycle. In the proliferative phase, amplified CDNA product was almost exclusively confined to the ET(A) receptor, whereas an increase in the amplified product of the ET(B) receptor CDNA was seen in the secretory and menstrual phases. These studies show that MRNA for endothelin-1, endothelin-2, and endothelin-3 is present in human endometrium at all stages of the menstrual cycle and suggest that different physiological actions of the endothelin peptides may be mediated through changes in the ratio of the ET(A) and ET(B) receptor subtypes.