Gonadorelin (GnRH) is a decapeptide gonadotropin-releasing hormone agonist. It stimulates the synthesis and release of luteinizing hormone and follicle stimulating hormone. It is used in human medicine to treat infertility, menstrual cycle irregularities, and hypogonadism. It is also used as a diagnostic agent in assessing pituitary function. Ongoing research has found potential uses for gonadorelin in breast and prostate cancer treatment as well as Alzheimer’s disease.
Research indicates that sex hormones, particularly leuteinizing hormone (LH), act on the brain in ways that are well outside the scope of sexual dimorphism or reproductive capacity. In fact, the associated rise in LH that occurs with menopause has been correlated with an increased incidence of Alzheimer’s disease and decreased memory performance in both humans and animals. Careful research in rats further reveals that LH acts directly on the hippocampus, the primary memory center in the brain. Rats given LH exhibit decreased memory performance and hippocampus dysfunction, a deficit that is reverse by administration of an LH blocking drug[9].
Further research on LH has revealed that higher levels of the hormone are associated with increased neuropathology. In particular, it has been revealed that LH promotes the development of plaques associated with Alzheimer’s[10]. It stands to reason then that reducing LH levels may help to reduce the progression of Alzheimer’s disease. This has been born out, at least partially, in mouse models showing that getting rid of the LH receptor in the brain improves amyloid pathology and helps to preserve the health of cells like astrocytes, which support and protect neurons[11].
As it turns out, testosterone is beneficial to brain health and actually helps to preserve cognitive function. Thus, simply blocking the entire hypothalamic-pituitary-gondal axis is not necessarily an effective means of treating Alzheimer’s disease. That is why scientists have set out to test gonadorelin derivatives to discern if selective interference in LH production is possible and can have potential benefits. This research, while ongoing, has led to the understanding that leuprolide (a common medication used to treat uterine fibroids and a GnRH receptor agonist) is effective in decreasing the risk of Alzhimer’s compared to other gonadorelin analogues[12]. Ongoing research can help to define why this is the case, but it is important to note that men looking to use highly effective CAB treatment against prostate cancer need not choose between cancer and Alzheimer’s disease. Leuprolide can be used in this setting to offset the risks of CAB with regard to Alzheimer’s disease. In particular, the ability of leuprolide to down-regulate levels of serum gonadotrophins (LH in particular) is generally enough to offset the effects of reduced testosterone[13].
New research is seeking to understand how gonadorelin and its analogues affect APOE and MS4A6A expression in Alzheimer’s disease. Both genetic loci are associated with late-onset Alzheimer’s disease, but research suggests that they need to operate in tandem to produce serious problems and that interfering with one gene loci or the other is enough to short-circuit the pathway to pathology. Gonadorelin affects this process of tandem interaction, but it isn’t clear how or why[14]. Right now, researchers are working to understand how the interaction of genes in Alzheimer’s disease can be interrupted to both treat and prevent the condition. Gonadorelin is am important peptide in that research.
Gonadorelin is hardly a new peptide in the treatment of human and mammalian disease, but researchers are constantly uncovering new ways in which GnRH and GnRH analogues operate in both normal physiology as well as the development of disease. The discovery that gonadorelin can play a role in treating prostate cancer was a breakthrough that has allowed doctors to develop a cure so effective that fully 99% of people with prostate cancer can be cured if the disease is caught early enough. It looks like similar breakthroughs are on the horizon with the finding the gonadorelin and its down-stream hormones are substantial players in the pathways that lead to Alzheimer’s disease risk.
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