PONUGOTI, B.; PAPASANI, M.R.; LAYMAN, J.A.; GENSURE, R; JUPPNER, H; RUBIN, D.A.*; Illinois State University, Normal; Mass. General Hospital & Harvard University, Boston: Molecular isolation and evolution of teleost parathyroid hormones (PTH), PTH-related peptides (PTHrP) and tuberoinfundibular peptides of 39 residues (TIP39).

Since the isolation of human and bovine PTHrP, it has been assumed that fishes used other factors and hormones (teleocalcin, hypocalcin, parathyrin of the CS, stanniocalcin, or prolactin) to regulate serum calcium and bone physiology because mammals, birds, reptiles, and amphibians contain parathyroid glands, however these glands appear to be absent in fishes. None of these substances when purified, however, showed any resemblance to PTH with respect to amino acid composition or sequence. Although Rosenberg and Kronenberg showed sequence for a PTH-like molecule in fishes, comparative studies on calcium regulation for over a decade have not focused research efforts to obtain a teleost PTH-like hypercalcemic factor. Instead, researchers have focused upon the isolation of PTHrP which was assumed to be the ancestral ligand of tetrapod PTH, because fishes being ancestral to the tetrapods would express PTHrP since they did not contain PTH glands. Data will be presented which clearly nullify the above hypothesis. The isolation of pairs of teleost PTH molecules from two disparate orders of teleosts (Cypriniformes and Perciformes) provides significant sequence information to validate that not only do teleosts express orthologous PTH molecules, but that they have a high efficacy in stimulating their cognate receptors. Thus, with the gDNA identification and subsequent molecular isolation of the cDNAs for PTH, a hypothetical argument can not be made that the apparent identification of teleost PTH pairs are paralagous forms of PTHrP since these species also express PTHrP and TIP39 transcripts. Supported by NIH DK60513 to DAR.