Examination of Guinea Pig Luteinizing Hormone-Releasing Hormone Gene Reveals a Unique Decapeptide and Existence of Two Transcripts in the Brain*

Abstract

We sequenced the complementary DNA (cDNA) encoding guinea pig LHRH from an expression library derived from the preoptic area-anterior hypothalamus. Data from in situ hybridization and RNase protection assays verified that the cloned cDNA was complementary to guinea pig LHRH messenger RNA. The architecture of the deduced precursor resembles that of LHRH precursors identified in other species. In contrast, the predicted sequence of the decapeptide differs from mammalian LHRH by two amino acid substitutions in positions 2 and 7. This is a novel finding, because the amino acid sequence that comprises LHRH decapeptide is identical in all mammals studied to date. Moreover, the predicted substitution in amino acid position 2 is unique among vertebrates. A second observation of potential significance is the existence of two subspecies of LHRH messenger RNA differing only in the length of their 3′ untranslated regions. These two transcripts were verified by sequence analysis of positive clones from the cDNA library and by RNase protection analysis of preoptic area-anterior hypothalamus extracts, and their presence is consistent with the two polyadenylation signals identified in the untranslated regions of the LHRH gene. Future studies will examine LHRH gene expression in guinea pigs, which like primates but unlike rats, have a true luteal phase as a component of their reproductive cycle.