Marcjanna Bartkiewicz, Ph.D. Associate Research Scientist Endocrinology and Cell Biology Department of Internal Medicine 333 Cedar Street P.O. Box 208020 New Haven, CT 06520-8020 USA Email: marcjanna.bartkiewicz@yale.edu Telephone: (203) 785-5457 Fax: (203)785-6015

The parathyroid hormone-related peptide (PTHrP) was initially discovered as the tumor product that is responsible for the hypercalcemia that complicates many types of cancer. It subsequently became clear that the PTHrP gene is a member of a small gene family that includes parathyroid hormone (PTH), but the functions of PTH and PTHrP are remarkably different. The PTHrP gene turns out to be widely expressed in both adult and fetal tissues, as is its receptor, and all evidence to date indicates that PTHrP functions in an autocrine/paracrine fashion. In the adult, functions include the regulation of placental calcium transport, the regulation of smooth muscle tone in accommodative smooth muscle structures such as the uterus, and neuropeptidergic signaling in the CNS. The most intense present interest is focused on PTHrP as a developmental regulatory molecule. Recent experiments in gene-targeted and transgenic mice clearly reveal that PTHrP controls the differentiation of mammary epithelium, the development of endochondral bone and the eruption of teeth. Most recently, we have found an age-related neurodegenerative process in the PTHrP-null CNS and have shown that PTHrP is an endogenous neuroprotective protein by virtue of regulation of L-type calcium channels.