We are thrilled to announce that a new Michelson Grant-funded project pursuing a nonsurgical sterilant is underway! The study, led by Dr. Benjamin Renquist of the University of Arizona, is titled, “Enhancing the toxicity of GnRH- and bivalent-targeted RIP conjugates to induce sterility.” This is a continuation of another Michelson Grant-funded project that Dr. Renquist began in 2012 titled, “Increasing the circulating half-life of GnRH-RIP conjugates to improve in vivo efficacy.”
In their newly funded study, the Renquist team will continue their investigation of how to safely destroy gonadotropes. To put this project into context, it’s important to have an understanding of the hypothalamic-pituitary-gonadal (HPG) axis, which controls development, reproduction, and aging in all animals. At the very top of this reproductive cascade is a part of the brain called the hypothalamus, which secretes the peptide gonadotropin-releasing hormone (GnRH). Once it is secreted, GnRH travels to the anterior pituitary at the base of the brain, where it then binds to receptors on cells called gonadotropes. This binding stimulates the gonadotropes to release gonadotropins, which are hormones that travel in the blood stream to the gonads (testes in males, ovaries in females) that trigger the production of testosterone and estrogen. Testosterone release helps trigger spermatogenesis (sperm production) in males, and estrogen is released by growing follicles in females. These two processes, together known as gametogenesis, enable animals to sexually reproduce. When testosterone and estrogen levels in the blood become sufficiently low, the hypothalamus will be triggered to secrete more GnRH, and the whole process will start all over again.
If you visit our Research Findings page, you will see that nearly all of our funded projects involve targeting some part of the HPG axis, and you can see why this makes sense – if one can permanently stop any of the processes that are a part of this cycle, whether in the hypothalamus, the pituitary, or the gonads, one can effectively shut down the reproductive system for good. If this can be achieved non-invasively, we will be able to reach our goal of developing a nonsurgical sterilant for companion animals.
For decades researchers have been attempting gonadotrope ablation, but most have been unsuccessful in completely destroying these cells. Complete gonadotrope destruction will result in sterility, which is why gonadotropes are such an attractive target for our program. Initial findings from Dr. Renquist’s first Michelson Grant-funded project have shown that gonadotropes are resistant to targeted toxins, so in this new project the Renquist team will focus on enhancing the efficacy of internalized toxins. They envision that they will have an optimized cytotoxin ready for testing in mice by the end of this two-year study.
The Michelson Prize & Grants program has approved a total of 35 projects for funding since its inception in 2008 and has committed nearly $15 million to those projects. Every day, our investigators are getting closer to unlocking the key to permanent, nonsurgical sterilization in companion animals. We are proud to support their work and are grateful for their dedication to our cause!