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 th e 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 hav e found that: 1) Northern blot hybridization analysis of normal glandu lar endometrium as well as of Ishikawa human endometrial adenocarcinom a cells showed the presence of the CRH messenger RNA; the size of the transcript seemed to be identical to that present in human placenta an d rat hypothalamus; 2) immunoreactive CRH (ir-CRH) was detectable in n ormal dispersed glandular endometrial cells as well as in the Ishikawa adenocarcinoma cells; 3) gel filtration chromatography of normal glan dular endometrial and Ishikawa cell extracts and their culture media s howed that most ir-CRH present had the mel wt of the authentic CRH pep tide; in addition, a larger form of ir-CRH was also present in both no rmal and tumoral endometrial epithelial cell extracts; the latter most probably correspondents to CRH precursor molecules; and 4) immunofluo rescence staining of CRH in normal glandular endometrial and Ishikawa cells revealed a cytoplasm rich in granules positive for ir-CRH. Our f indings suggest that CRH may play an important role in the physiologic al events taking place within the uterine cavity, since CRH seems to b e present in nonpregnant as well as pregnant uteri. Since CRH is expre ssed in normal endometrial epithelial cells and in an epithelial tumor al cell Line, we propose the use of the Ishikawa cell line as a conven ient model for the in vitro study of endometrial CRH.