Gonadorelin

Gonadorelin (GnRH) is a decapeptide gonadotropin-releasing hormone agonist. It stimulates the synthesis and release of luteinizing hormone (LH) and follicle stimulating hormone (FSH). 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.

Formula: C55H75N17O13 Molecular Weight: 1182.29 g/mol Sequence: pyroGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NGonadorelin Effects

Gonadorelin Research and Breast Cancer Prevention

Investigations suggest that a higher lifetime exposure to estrogen may increase a woman's chance of developing breast cancer. Women with prolonged periods of estrogen exposure (e.g., early menarche, late menopause, or use of estrogen-containing therapies) have a higher baseline risk. The use of birth control, while reducing the risk of ovarian cancer, is associated with a temporary increased risk of breast cancer which returns to baseline after cessation.

Since some breast cancer cells require estrogen to grow, minimizing estrogen production or blocking estrogen receptors is an established treatment method. Research shows that gonadorelin can be used to suppress ovarian production of estrogen, which may be an effective primary cancer prevention method. This concept is based on reducing the risk of developing estrogen-receptor-positive breast cancer in high-risk postmenopausal women. The use of gonadorelin in this setting is suggested to be safe and cost-effective. Research indicates that gonadorelin therapy for 10 years could reduce the risk of breast cancer by as much as 60% and 15 years could reduce risk by 70% [1].

The benefits extend beyond primary prevention. Research indicates that adjuvant therapy with anti-estrogen drugs offers disease prevention by as much as 50% in estrogen-sensitive cancer cases. Current treatments often face resistance over time, typically due to increased estrogen receptor expression, which limits their ability to suppress estrogen activity without severe side effects. Gonadorelin could circumvent this problem by reducing estrogen production at the source. Suppressing estrogen generation would boost the efficacy of receptor blocking medications and extend their useful lifespan [4].

Investigations in postmenopausal women with hyperandrogenism (too much estrogen) have demonstrated that those with breast cancer had reduced hormonal levels while minimizing the risk of developing breast cancer. Evidence exists without serious adverse effects and thus offers an alternative approach to estrogen replacement therapy, making it an excellent treatment option.

Gonadorelin a Breakthrough in Prostate Cancer

Despite common belief, prostate cancer is the most hormone-sensitive of all cancers. This sensitivity presents an opportunity for prevention and treatment in men with elevated risk factors. The challenge is to completely cut off hormone flow, which historically involved surgical castration.

The application of GnRH in men with prostate cancer began in 1979 and was termed medical castration. This led to the highly effective therapy known as Combined Androgen Blockade therapy (CAB). Prostate cancer is essentially a mechanically-diagnosed micronucleus [7]. GnRH analogues are most effective when used in tandem with other treatments. Nevertheless, following research on gonadorelin, two new drugs with remarkable safety profiles were developed and accepted by Health Canada, offering a new line of defense against prostate cancer progression and metastases. They even could potentially preserve hormone levels in children [8].

The use of both gonadorelin and newer, localized drugs in treating prostate malignancies is linked to the CAB concept. CAB is a highly effective treatment, especially with early detection. When combined with early detection, CAB makes it possible to cure 99% of all prostate cancer.

Gonadorelin May Reduce Dementia Risk

Investigations indicate that reproductive hormones, particularly luteinizing hormone (LH), influence the neurological system and hippocampal structures, affecting neural capacity. Specifically, the correlation between decreased LH hormone concentrations with menopause has been associated with enhanced mouse cognitive abilities and diminished reproductive capabilities. Contemporary investigations demonstrate that LH influences cognitive functioning directly in the hippocampus, the principal memory center in the brain. Rats given LH demonstrated enhanced spatial memory performance, which was reversed through administration of an LH blocking compound [9].

Additional investigations on LH have demonstrated that elevated levels of the hormone are linked with amyloid-beta (Abeta) pathology. Therefore, reducing LH levels potentially promotes the advancement of plaques correlated with Alzheimer's [10]. It stands to reason that diminishing LH levels (through suppression or deletion) reduces Abeta production and lesions partially, in mouse models demonstrating that eliminating all of the LH associated cells could alleviate amyloid accumulation and beta plaque [11]. Further investigations seek insights from senolytic compounds, which eliminate and preserve neurons [11].

As it currently exists, testosterone demonstrates benefits to neural health and assists in preserving cognitive function. Aging males demonstrate hormonal reductions, which study results indicate result in increased dementia risk. Consequently, research studies advocate that it may be essential to maintain testosterone levels while eliminating LH levels. Research investigations have not yet tested gonadorelin derivatives to discern if selective interference in LH secretion is feasible. Although GnRH and LH have a recognized relationship, this investigation led to the understanding that leuprolide (a common medication used to treat uterine fibroids) generates a lower risk and greater protection level in Alzheimer treatment compared to other gonadorelin analogues [12]. Continuous investigations can help to define why some kinds of agents are more important than others and lead to the development of treatment against prostate cancer that does not choose between cancer and Alzheimer's treatment. Leuprolide, a GnRH analogue, demonstrates lower risk while being an effective agent for managing not only prostate cancer but also the ability of leuprolide to down-regulate levels of natural gonadotropin (LH in particular) through suppressing CAR effects [12]. Evidence suggests reduced testosterone [12].

In Alzheimer's disease, the ability of leuprolide to down-regulate levels of natural gonadotropin (LH particularly) through suppressing CAR represents substantial advantages, especially given indications of CAR being associated with Alzheimer's disease progression. Demonstrating application potential helps prevent prostate cancer and potentially neurodegenerative conditions [13].

Now, investigations in research have discovered how gonadorelin and analogues affect APOE and MS4A4A expression in Alzheimer's disease. Both genetic loci are associated with beta-amyloid and plaques. Application of gonadorelin has potential to regulate each of these tandem to produce serious problems and that interfering with one gene loci or the other is ineffective because there's a compensatory response from the other portion [14] of the process. Tandem interaction, but it isn't clear how or why [14]. Right now, researchers are working to understand better the interaction of the two loci. This information is necessary to develop a test and prevent the condition. Gonadorelin is an important peptide in that research.

Gonadorelin Research

Gonadorelin represents a relatively novel peptide in the management of human and mammalian conditions, yet investigations into gonadotropin-releasing hormone (GnRH) functioning, through which GnRH analogues function in both physiological normality and disease development. The discovery that gonadotropin-releasing hormone potentially fulfills a function in managing breast cancer development was a significant advancement that enabled researchers to establish a therapeutic approach effectively treating 99% of individuals with prostate malignancies and potentially offering benefits if the condition receives early detection through screenings. Despite breakthroughs remaining anticipated regarding the identification of gonadorelin and its downstream hormones functioning as fundamental components in the mechanisms that regulate cognition and dementia. Gonadorelin demonstrates minimal adverse effects, low oral and excellent subcutaneous bioavailability in mice. Per kilogram dosage in mice does not translate to humans. Gonadorelin for human application remains restricted to educational and scientific exploration. Human consumption remains prohibited. Only licensed researchers may obtain Gonadorelin if they are accredited investigators.

Article Author

The referenced literature underwent research, compilation, and organization by Dr. Logan, M.D. Dr. Logan possesses a doctorate qualification from Case Western Reserve University School of Medicine alongside a B.S. in molecular biology.

Scientific Journal Author

Dr. Giorgio Secreto presently conducts studies at the IRCCS National Cancer Institute in Italy. His academic credentials encompass Medicine and Surgery from the Naturalist Claudio de Peid School of Medicine and Surgery, University of Milan, Italy (1974 Degree Specialist in Endocrinology, University of Turin, Italy). Doctor Secreto held administrative positions at the National Cancer Institute of Milan since 1970 until retirement in December 2010. The function of androgens in breast cancer constitutes his primary field of investigation. His affiliation with the Italian School of Senology (1988-1996), Associate Professor in Oncology at L.J.de.S. University, Lugano, Switzerland (1999-2008), and Associate Professor in Endocrinology at National University, School of Medicine, University of Milan (2003-2009). He served as a member of the New York Academy of Sciences and the American Association for Cancer Research. Dr. Secreto has published approximately 150 papers, encompassing a few that relate to GnRH's efficacy on the diminution of ovarian androgen levels while minimizing successive progression.

Dr. Giorgio Secreto receives acknowledgment as a prominent scientist engaged in the investigation and advancement of Gonadorelin. The involvement of this doctor/scientist in endorsing or promoting the acquisition, distribution, or application of this compound for any purpose is categorically denied. No association, affiliation, or connection exists between Peptide Sciences and this researcher. The citation of this doctor serves to recognize, appreciate, and acknowledge the significant investigative and developmental contributions undertaken by scientists researching this peptide. Doctor Secreto receives identification in [1] and [3] under the referenced citations.

Referenced Citations

G. Secreto et al., "A novel approach to breast cancer prevention: reducing excessive ovarian androgen production in elderly women," Breast Cancer Res. Treat., vol. 158, no. 3, pp. 553–561, 2016. D. V. Spicer and M. C. Pike, "Sex steroids and breast cancer prevention," J. Natl. Cancer Inst. Monogr., no. 16, pp. 139–147, 1994. G. Secreto, P. Muti, M. Sant, E. Meneghini, and V. Krogh, "Medical ovariectomy in menopausal breast cancer patients with high testosterone levels: a further step toward tailored therapy," Endocr. Relat. Cancer, vol. 24, no. 11, pp. C21–C29, 2017. E. S. Volleard, A. P. van Beck, F. A. J. Verburg, A. Rozs, and J. A. Land, "Gonadotropin releasing hormone agonist treatment in premenopausal women with hyperandrogenism of ovarian origin," J. Clin. Endocrinol. Metab., vol. 96, no. 5, pp. 1197–1201, May 2011. F. Labrie, "Hormonal therapy of prostate cancer," Prog. Brain Res., vol. 182, pp. 321–341, 2010. F. Labrie, "GnRH agonists and the rapidly increasing use of combined androgen blockade in prostate cancer," Endocr. Relat. Cancer, vol. 21, no. 4, pp. R301–317, Aug. 2014. F. Labrie, "Combined blockade of testicular and locally made androgens in prostate cancer: a highly significant medical progress based upon intracrinology," J. Steroid Biochem. Mol. Biol., vol. 145, pp. 144–156, Jan. 2015. F. Labrie, "Keynote of endocrinology in the victory against prostate cancer," Bull. Cancer (Paris), vol. 93, no. 9, pp. 849–868, Sep. 2006. V. Burnham, C. Sundby, A. Laman-Maharg, and J. Thornton, "Luteinizing hormone acts at the hippocampus to dampen spatial memory," Horm. Behav., vol. 89, pp. 55–63, 2017. C. V. Rao, "Involvement of Luteinizing Hormone in Alzheimer Disease Development in Elderly Women," Reprod. Sci. Thousand Oaks Calif, vol. 24, no. 3, pp. 355–368, 2017. J. Lin et al., "Genetic ablation of luteinizing hormone receptor improves the amyloid pathology in a mouse model of Alzheimer disease," J. Neuropathol. Exp. Neurol., vol. 69, no. 3, pp. 253–261, Mar. 2010. R. L. Bowen, T. Butler, and C. S. Atwood, "Nad All Androgen Deprivation Therapies Are Created Equal: Leuprolide and the Decreased Risk of Developing Alzheimer's Disease," J. Clin. Oncol., vol. 34, no. 23, p. 2800, Aug. 2016. M. A. Smith, P. L. Bowen, R. O. Nguyen, G. Perry, C. S. Atwood, and A. A. Rimm, "Putative Gonadorelin Releasing Hormone Against Therapy and Dementia: An Application of Medicare Hospitalization Claims Data to PLA JAD, vol. 63, no. 4, pp. 1259–1277, 2018. A. Clelems, J. E. Vargas, and J. R. Gonzalez, "APOE and MS4A4A interact with GnRH signaling in Alzheimer's disease: Disrupting in mab and Alzheimer Dement. J. Alzheimers Assoc., vol. 13, no. 4, pp. 493–497, Apr. 2017.