Arthur Eastwood Broadus MD, PhD
Ensign Professor of Medicine (Endocrinology)
Parathyroid hormone-related peptide; Mineral metabolism; Cartilage and bone regulation, Regulation of periosteal bone and ligament/tendon insertion sites
The parathyroid hormone-related peptide (PTHrP) was initially discovered at Yale as the tumor product that is responsible for the humoral hypercalcemia that complicates many types of cancer. It is now known that the PTHrP gene is a member of a small gene family that includes parathyroid hormone (PTH) and that PTH and PTHrP share not only homologous sequences but a common receptor. Yet the functions of PTH and PTHrP are remarkably different. The PTHrP gene turns out to be widely expressed in both adult and fetal tissues, and all evidence to date indicates that PTHrP functions predominantly as an autocrine/paracrine regulatory molecule. In the adult, functions include the control of placental calcium transport, regulation of smooth muscle tone in accommodative smooth muscle structures such as the uterus, and participating in the regeneration of peripheral nerves. In the fetus as well as in postnatal development, PTHrP serves as a developmental regulatory molecule. Such functions include PTHrP control of the differentiation of the mammary epithelium, the development of endochondral bone, and the eruption of teeth. Most recently, we have found PTHrP in the insertion sites of tendons and ligaments into cortical bone (in which PTHrP may mediate the bone formation that tethers these insertions to bone) and in the fibrous layer of the periosteum that covers cortical bone surfaces. PTHrP mediates the modeling of these surfaces driven by mechanical loading.