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  • Title: Parathyroid hormone-related peptide.
    Author: Kaiser SM, Goltzman D.
    Journal: Clin Invest Med; 1993 Oct; 16(5):395-406. PubMed ID: 8261693.
    Abstract:
    Parathyroid hormone-related peptide (PTHRP) was discovered through its ability to cause parathyroid hormone (PTH)-like effects in malignancy-associated hypercalcemia (MAH). It shares limited amino-terminal sequence homology with PTH and can thus interact with PTH receptors. It was originally isolated, cloned, and sequenced from tumors of patients with MAH. The human PTHRP gene is complex and can generate 3 peptide isoforms of 139, 141, and 173 amino acids. The gene encoding PTHRP in other species is somewhat simpler and generally results in only a single isoform; however, there is marked interspecies amino acid sequence homology in the protein product up to residue 111. PTH and PTHRP genes have similar structural organizations and it is believed that these 2 genes have a common ancestral origin and may have arisen through an ancient gene duplication. There are now several region specific radioimmunoassays, as well as immunoradiometric assays, which have been developed and which have all demonstrated elevated circulating levels of PTHRP in patients with MAH. PTHRP is expressed in a wide variety of tissues and, in addition to its classical PTH-like activities, it may have a local or systemic role in calcium regulation in the fetus and perhaps in the neonate. It may also act locally as a smooth muscle relaxant and a vasorelaxant. Its local role in some fetal tissues and in keratinocytes may take the form of a regulator of cell growth and/or differentiation. Thus when antisense RNA technology was used to inhibit endogenous PTHRP production in an established human keratinocyte cell line, PTHRP was found to inhibit growth and enhance differentiation. Irrespective of its precise normal role however, PTHRP provides a potential therapeutic target in MAH and, with improved methods of detection, may also be useful as a tumor marker.
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