THE CORTICOTROPIN-RELEASING HORMONE (CRH) IN NORMAL AND TUMORAL EPITHELIAL-CELLS OF HUMAN ENDOMETRIUM

CRH is produced by several intrauterine sites, including placenta and desidua, during pregnancy. However, no data are available regarding the presence of CRH in the nonpregnant uterus. We now report that CRH is produced in the epithelial cells of normally cycling human uterus and in an endometrial epithelial cell-derived tumor. Specifically, we have found that: 1) Northern blot hybridization analysis of normal glandular endometrium as well as of Ishikawa human endometrial adenocarcinoma cells showed the presence of the CRH messenger RNA; the size of the transcript seemed to be identical to that present in human placenta and rat hypothalamus; 2) immunoreactive CRH (ir-CRH) was detectable in normal dispersed glandular endometrial cells as well as in the Ishikawa adenocarcinoma cells; 3) gel filtration chromatography of normal glandular endometrial and Ishikawa cell extracts and their culture media showed that most ir-CRH present had the mel wt of the authentic CRH peptide; in addition, a larger form of ir-CRH was also present in both normal and tumoral endometrial epithelial cell extracts; the latter most probably correspondents to CRH precursor molecules; and 4) immunofluorescence staining of CRH in normal glandular endometrial and Ishikawa cells revealed a cytoplasm rich in granules positive for ir-CRH. Our findings suggest that CRH may play an important role in the physiological events taking place within the uterine cavity, since CRH seems to be present in nonpregnant as well as pregnant uteri. Since CRH is expressed in normal endometrial epithelial cells and in an epithelial tumoral cell Line, we propose the use of the Ishikawa cell line as a convenient model for the in vitro study of endometrial CRH.