Parathyroid hormone-related protein in teleost fish

A brief description is given of the discovery of PTHrP and the roles of the peptide in mammalian physiology. Next, the occurrence of PTHrP in the earliest vertebrates, sharks, skates and fishes, is reviewed and the calciotropic functions of PTHrP are addressed more specifically in fishes. Parathyroid hormone-related protein (PTHrP) is a hypercalcemic hormone in teleostean fishes, but also has para- and autocrine functions. After the isolation and identification of fish PTHrP and PTHrP receptors and the subsequent development of recombinant protein and a real-time quantitative PCR, a calciotropic role of PTHrP in fish physiology could be assessed. PTHrP influences calcium physiology via regulation of calcium mobilisation from internal sources (bone and scales) and via calcium uptake from the environment (water and diet). Continuous variations in the need for calcium and in the availability of environmental calcium require fast calciotropes to guarantee calcium balance, in which PTHrP is pivotal for the fish. PTHrP is essential in fish bone physiology, e.g. in mineralisation and calcium reabsorption from the scales. Moreover, PTHrP plays a role in vitellogenesis, cortisol production, regulation of renal Mrp2 activity and melatonin synthesis. The plethora of functions of PTHrP in fish concern endocrine, paracrine and autocrine (and possibly intracrine) functions; calciotropic actions of PTHrP at the organismal and cellular level are prominent in fish. The strong conservation of the pthrp gene in the vertebrate lineage and the N-terminal similarity of the coded proteins relates to the important role of PTHrP in calcium physiology that is of paramount importance to all physiological processes. Recent and ongoing studies will contribute to our rapidly expanding knowledge of the original physiological functions of PTHrP in teleost fish.