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From the time of its discovery and isolation in the mammalian hypothalamus, the decapeptide, gonadotropin-releasing hormone (GnRH), has also been found to be expressed in non-hypothalamic tissues and can elicit a diverse array of functions both in the brain and periphery. In cancer, past studies have targeted the gonadotropin-releasing hormone receptors (GnRHR) as a way to treat reproductive cancers due to its anti-tumorigenic effects. On the contrary, its metabolite, GnRH-(1-5), behaves divergently from its parental peptide through putative orphan G-protein coupled receptor (oGPCR), GPR101. In this review, we will focus on the potential roles of GnRH-(1-5) in the periphery with an emphasis on its effects on endometrial cancer progression.

The rising incidence and mortality of endometrial cancer (EC) in the United States calls for an improved understanding of the disease's progression. Current methodologies for diagnosis and treatment rely on the use of cell lines as models for tumor biology. However, due to inherent heterogeneity and differential growing environments between cell lines and tumors, these comparative studies have found little parallels in molecular signatures. As a consequence, the development and discovery of preclinical models and reliable drug targets are delayed. In this study, we established transcriptome parallels between cell lines and tumors from The Cancer Genome Atlas (TCGA) with the use of optimized normalization methods. We identified genes and signaling pathways associated with regulating the transformation and progression of EC. Specifically, the LXR/RXR activation, neuroprotective role for THOP1 in Alzheimer's disease, and glutamate receptor signaling pathways were observed to be mostly downregulated in advanced cancer stage. While some of these highlighted markers and signaling pathways are commonly found in the central nervous system (CNS), our results suggest a novel function of these genes in the periphery. Finally, our study underscores the value of implementing appropriate normalization methods in comparative studies to improve the identification of accurate and reliable markers.

The effect of eating on the transit of radiolabelled particles through the small intestine has been monitored in eight healthy subjects dosed after an overnight fast. Each subject participated on three occasions and either remained fasting for 9 h after dosing or consumed a meal at 1.5 h or 4 h. The mean +/- 1 S.D. small intestinal transit time during the fasting study was 5.5 +/- 2.1 h and during the 1.5h and 4 h fed studies 4.8 +/- 2.9 h and 4.7 +/- 2.2 h, respectively. These times were not significantly different, nor were the rates of entry of the particles into the colon. These findings indicate that once in the small intestine the efficacy of orally administered pharmaceutical preparations is unlikely to be affected by eating.