ENDOTHELIN-CONVERTING ENZYME-1 IS EXPRESSED ON HUMAN OVARIAN FOLLICLES AND CORPORA-LUTEA OF MENSTRUAL-CYCLE AND EARLY-PREGNANCY

We have previously reported that membrane-bound amino- and carboxypept idases were expressed on the human follicles and corpora lutea (CL), a nd we proposed that these peptidases are involved in ovarian functions , probably by regulating the extracellular peptide concentrations. In this study, we examined the expression of endothelin-converting enzyme -1 (ECE-1) on human follicles and CL, which is a membrane-bound endope ptidase and is known to convert big endothelin-l to endothelin-l. In t he preovulatory follicles, immunohistochemical study showed that ECE-1 was expressed, with moderate intensity, on the theca. interna cells a nd weakly on the granulosa cells. In the menstrual and pregnant CL, EC E-1 was highly expressed on both large and small luteal cells, indicat ing that ECE-1 expression increases during luteinization. Western blot ting analysis revealed that the molecular mass of the ECE-1 extracted from the menstrual CL was 130 kDa and that ECE-1 was more strongly exp ressed on the CL in early and midluteal phases than the CL in late lut eal phases. In the isolated luteinizing granulosa cells obtained from patients undergoing in vitro fertilization, ECE-1 was immunohistochemi cally detected on their cell surface. The activity of ECE-1 was also d etected on cultured luteinizing granulosa cells by measuring endotheli n-l production from its precursor. The activity of ECE-1 was significa ntly enhanced by the treatment of human CG (10 U/mL) and interleukin ( IL)-1 (10 ng/mL) during 4-day culture, whereas no significant alterati on was observed by IL-4 (10 ng/mL) and IL-10 (10 ng/mL) treatment. The se results indicate that ECE-1 is a cell surface differentiation-relat ed molecule of human granulosa and of theca interns cells and suggest that the expression of ECE-1 is regulated by LH/human CG and cytokines .