Enhancing pharmacokinetics of PRL, GH and their antagonists

Human prolactin (PRL) and growth hormone (GH) are pituitary hormones that regulate the survival, proliferation and differentiation of cells in a variety of tissues and endocrine glands. Owing to their relatively low molecular weight and protein nature, these hormones and hormone antagonists are removed from the circulation by renal clearance and proteolytic degradation within responsive tissues. Until now, there have been no attempts to enhance the pharmacokinetics of PRL or its antagonist. With regard to GH, the absorption half-life of hGH has been extended by using sustained release formulations and extending its elimination half-life by using polyethylene glycol (PEG) modification to reduce renal clearance. However this process decreases receptor binding thereby reducing their efficacy. Another strategy has been to fuse it with a large carrier protein. However, this process is difficult and may sterically hinder the ability of the ligand to interact with its receptor.

Langenheim and Chen report that the genetic fusion of a serum albumin-binding peptide to the amino terminus of hPRL, hGH and their antagonists appear to be an economically feasible alternative to strategies of fusion to a large carrier protein or modification with PEG to reduce clearance and enhance half-life. This strategy required no alterations to the standard procedures for producing and purifying proteins; had minimal deleterious effects upon signal transduction and bioactivity in vitro; resulted in favourable tissue distribution of hPRL and hGH and is amenable to further modifications such as sustained release formulations to further enhance the effectiveness of these proteins by reducing the frequency of injections. Langenheim and Chen, Journal of Endocrinology, DOI:10.1677/JOE-09-0211