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Parathyroid hormone-related protein and its role in pregnancy, lactation, and neonatal growth and development

Since the cloning of the gene for parathyroid hormone (PTH)-related protein (PTHrP) and deduction of the amino acid sequence of the peptide in the late 1980s, extensive research has led to widespread agreement that (a) the peptide is widely distributed in almost all mammalian body tissues, (b) the hormone circulates in insignificant amounts in normal adult humans, (c) the cloned PTH/PTHrP receptor, which binds aminoterminal analogs of both PTH and PTHrP, exists in close proximity to the sites of PTHrP production, and (d) PTHrP therefore functions as a local regulatory, autocrine/paracrine agent rather than a classical, circulating hormone. For a comprehensive recent review of these ideas and of much of the primary literature regarding the distribution and potential physiological roles of PTHrP, the reader is referred to the 1996 publication by Philbrick et al. (1). The present Commentary addresses the key evidence for a role of PTHrP in pregnancy, lactation,