Parathyroid Hormone-Like Proteins: Biochemical Responses and Receptor Interactions*

作者：John J. Orloff, TERENCE L. WU, ANDREW F. STEWART · 发表于：Endocrine Reviews · 年份：1989 · DOI：10.1210/edrv-10-4-476 · 被引用次数：174 · 研究领域：Bone health and treatments、Fibroblast Growth Factor Research、Cancer Diagnosis and Treatment

HUMORAL hypercalcemia of malignancy (HHM) was first described almost 50 yr ago (1) and is the most common paraneoplastic syndrome. It appears to result in most instances from the production by tumors of a novel class of protein hormones which share amino acid sequence homology with PTH. These PTH-like proteins (PTHLPs)1, purified and amino-terminally sequenced from human HHM-associated tumors, appear to mimic certain of the renal and skeletal actions of PTH, thereby leading to the clinical and biochemical features of the HHM syndrome. The structure, location, and transcriptional pattern of the PTHLP gene have been elucidated and the full complementary DNA-predicted amino acid sequences of three PTHLP translation products have been revealed (2–7). Further, PTHLPs and their mRNA transcripts have been identified in a variety of normal, nonmalignant tissues (8, 9), and may have important regulatory or functional roles in these tissues. The renal tubule and skeletal osteoblast are regarded as the “classical” target tissues for the action of PTH, and recent studies indicate that synthetic amino-terminal PTHLPs interact with the PTH receptor in these “classical” tissues. PTH also induces functional responses in a variety of “non-classical” target tissues, including vascular smooth muscle, dermal fibroblasts, epidermal keratinocytes, lymphocytes, and brain. The role for PTH, if any, in the normal physiology of these tissues remains obscure. The observations that 1) PTHLPs are express...