The parathyroid hormone-related protein as a regulator of normal tissue functions

Abstract

The parathyroid hormone-related protein (PTHrP) was originally identified as a humoral factor secreted by cancer cells to cause hypercalcemia in association with malignant tumors Recent work has begun to uncover a set of physiologic functions for the protein. PTHrP appears to regulate both chondrogenesis and the mineralization of cartilage, and deletion of a functional PTHrP gene is an embryonic lethal mutation in homozygotes. PTHrP is also expressed in lactating mammary tissue and secreted in extremely high levels into milk, serving an as yet unidentified function. In the skin, PTHrP appears to regulate hair follicle function and the differentiation of epidermal keratinocytes. PTHrP may also act as a local regulator of smooth muscle tone in vascular, bladder, and other smooth muscle beds. Expressed in the myometrium of rodents and in the human amnion, the protein has been proposed to function in the regulation of parturition. Finally, it has been proposed that PTHrP is a humoral regulator of placental calcium transport. Although many of these actions may involve activation of the common receptor parathyroid hormone or PTHrP, there is both direct and indirect evidence to suggest the existence of additional PTHrP receptors, some of which may recognize different regions of the PTHrP sequence from the classic parathyroid hormone receptor.