Strategies for construction of luteinizing hormone beta subunit analogs with carboxyl terminal extensions in non-primate, non-equid mammalian species

Chorionic gonadotropins (CG) are unique because they have a carboxyl terminal peptide (CTP) extension on their beta subunits that prolongs circulatory survival. CGβ genes from the human being and horse have evolved from ancestral luteinizing hormone (LH) beta genes by different pathways that involve deletions that change the reading frames and yield a CTP. Here we further review our previous analysis, aimed at determining whether LHβ genes in non-primate, non-equid species inherently possess DNA sequences that encode CTP-like domains. In multiple mammalian species, simple frame-shift mutations using either the human or equine CGβ gene as a model can be used to construct LHβ analogs with putative CTP domains. Furthermore, DNA sequences from mammalian LHβ genes can be aligned to maximize similarity with CGβ genes in order to devise more refined strategies for construction of CTP-bearing LHβ analogs as exemplified in the bovine case. Thus, mammalian LHβ genes have DNA sequences that can be potentially expressed in order to construct CTP-bearing glycoprotein hormone analogs.