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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-09-0211v1 203/3/375    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Langenheim, J. Articles by Chen, W. PubMed PubMed Citation Articles by Langenheim, J. Articles by Chen, W.

J Langenheim, Biological Sciences, Clemson University, Greenville, United States
W Chen, Biological Sciences, Clemson University, Greenville, United States

Wen Chen, Email: wchen{at}ghs.org

To prolong the circulation half-life of human prolactin (hPRL), human growth hormone (hGH), and their competitive antagonists, hPRL-G129R and hGH-G120R, we examined the effects of fusing a serum albumin binding peptide (SA20) to their amino- or carboxyl-terminus. Fusion of the SA20 peptide to the amino-terminus of the ligands was less detrimental upon their ability to induce or inhibit signal transduction and cell proliferation in vitro than fusion to the carboxyl-terminus. Pharmacokinetic (PK) studies in mice revealed that the half-life of SA20-hPRL and SA20-hGH were as prolonged about 5-fold and their its clearance was reduced approximately 6-fold in comparison to hPRL and hGH. Pharmacodynamic (PD) studies in 8-week-old female mice revealed that lobuloalveolar development in mammary glands was greater in all three groups (daily, every two days, or every third day over a 12-day period) of mice treated with SA20-hPRL (4 mg/kg) compared to hPRL (3.59 mg/kg). Similarly, daily administration (i.p.) of SA20-hGH (8 mg/kg) or hGH (7.15 mg/kg) to 23 day old female mice over a 40-day period revealed the superiority of SA20-hGH over hGH as measured by weight gain, body length, and lobuloalveolar development in the mammary glands. These findings indicate that SA20 modification of hPRL, hGH, and their respective antagonists improves their PK/PD properties.