RELATIVE OVEREXPRESSION OF THE PARATHYROID HORMONE-RELATED PROTEIN GENE IN HUMAN LEIOMYOMAS

Uterine leiomyomas or fibroids are common among women of reproductive age, but their biology is poorly understood. The PTH-related protein ( PTHrP) has been identified in a number of sites throughout the reprodu ctive tract. We, therefore, examined whether fibroids express PTHrP mR NA and compared their level of expression with that in normal myometri um. Total RNA prepared from fibroid tissue and corresponding normal my ometrium from seven patients was examined by RNase protection analysis . In all cases, fibroid and myometrial tissue expressed PTHrP, and in six of seven cases, PTHrP expression was higher in fibroids than in no rmal myometrium. Cultured fibroid cells from four patients also expres sed higher levels of PTHrP mRNA than corresponding cultured normal myo metrial cells. Tissue extracts from eight patients and conditioned med ium from cultured cells from nine patients were examined for PTHrP imm unoreactivity using a two-site immunoradiometric assay. In tissue extr acts and conditioned medium, the mean PTHrP concentration was signific antly higher in fibroids than normal myometrium. Immunohistochemical s taining of fibroid and myometrial tissue was positive for PTHrP. Final ly, PTHrP-(1-34) induced a dose-dependent increase in cAMP in fibroid and myometrial cells in vitro. These findings suggest that PTHrP may h ave an autocrine/paracrine function in regulating myometrial physiolog y and may play a role in regulating fibroid growth or differentiation.