Luteinizing hormone-releasing hormone (
LHRH) was first isolated in the mammalian hypothalamus and shown to be the primary regulator of the reproductive system through its initiation of pituitary
gonadotropin release. Since its discovery, this form of
LHRH (
LHRH-I) has been shown to be one of many structural variants with a variety of roles in both the brain and peripheral tissues. Enormous interest has been focused on
LHRH-I,
LHRH-II, and their cognate receptors as targets for designing
therapies to treat
cancers of the reproductive system.
LHRH-I is processed by a
zinc metalloendopeptidase EC 3.4.24.15 (EP24.15) that cleaves the
hormone at the Tyr(5)-Gly(6) bond. We have previously reported that the autoregulation of
LHRH gene expression can also be mediated by its processed
peptide,
LHRH-(1-5). Given its importance in the brain, we have investigated the role of the specific processed
peptide of
LHRH-I,
LHRH-(1-5), within Ishikawa cells, a human endometrial cell line. Using real-time polymerase chain reaction, we observed that
LHRH-(1-5) upregulates
LHRH-II mRNA expression in Ishikawa cells but does not exert any influence on
LHRH-I mRNA levels. This is in contrast to the effects of
LHRH-I, which affects the expression of
LHRH-I mRNA. Our findings support a potential role for
LHRH-(1-5) as a processed metabolite in the endometrium. Further investigations are needed to determine the role of this processed metabolite and to identify specific pathways involved in
LHRH-(1-5) signaling.