PTH and hyperinsulinemic hypoglycemia, familial, 4: Although both PTH and PTHrP signal via the same receptor, the biological functions of the two ligands are distinct, as PTH acts in an endocrine manner on bone and kidney cells to regulate blood levels of calcium and phosphate, enhancing bone remodeling, as evidenced by slow bone turnover in individuals with PTH deficiency (38), whereas PTHrP, in normal physiology, acts in a paracrine manner within developing tissues, such as the skeletal growth plate, to regulate osteoblast and chondrocyte differentiation and proliferation, but also in breast cells and skin (37, 39).