PARATHYROID HORMONE-RELATED PROTEIN IS EXPRESSED BY PROSTATIC NEUROENDOCRINE CELLS

Objective. Parathyroid hormone-related protein (PTHrP) is a regulatory peptide that has been associated with normal fetal growth and differe ntiation as well as the regulation of fetal calcium. In a variety of c ancers, PTHrP has been implicated in the humoral hypercalcemia of mali gnancy. Recently, we demonstrated that all prostatic adenocarcinomas e xpress PTHrP. In the present study, the localization of PTHrP and its mRNA in nonmalignant prostate tissue was assessed. Methods. Formalin-f ixed, paraffin-embedded prostatic tissues from 23 patients were evalua ted. Immunocytochemistry (ICC) was performed by the streptavidin-perox idase enzyme conjugate method using a monoclonal antibody, 8B12, gener ated against fragment 1-34 of the amino-terminal end of PTHrP. Nonradi oactive in situ hybridization was carried out using a digoxigenin labe led single-stranded cDNA probe complementary to the sequence coding fo r PTHrP(15-120). Results. PTHrP immunoreactivity was observed in the c ytosol of a few epithelial cells. Double labeling and serial section I CC with 8B12 and a monoclonal antibody to chromogranin A (a generic ne uroendocrine [NE] marker) revealed that PTHrP was present in a subpopu lation of prostatic NE cells. In situ hybridization of mirror image se ctions demonstrated positive signals in prostatic NE cells in complete accordance with the ICC findings. Conclusions. The localization and p roduction of PTHrP in prostatic NE cells suggest that this polypeptide may act in an endocrine-paracrine fashion involved in the prostatic g rowth and differentiation as well as the regulation of calcium in seme n and seminal fluid.