For a century, scientists have known that female animals become more active during ovulation, and this behavior has evolved to increase their chances of mating when they are fertile.
Now, a team at the University of California, San Francisco has identified specific neurons and signaling pathways that enable females of many species to run around at this critical moment. The study was done in mice, but the researchers hope it can be confirmed in humans, because this behavior is related to a basic aspect of life. "Why do you want to stand up and walk around?" asked Dr. Holly Ingraham, Herzstein professor of molecular physiology at the University of California, San Francisco. "Well, if you activate circuits in these neurons, maybe thats why."
The discovery also clarified that the loss of estrogen destroyed the activity circuits of menopause, and mice and human females became more sedentary, gaining weight and developing metabolic disorders, such as type 2 diabetes. This study provides a new possibility to treat menopause, avoid estrogen and reactivate the circuit using crispra technology.
When estrogen enters the brain, it interacts with estrogen receptors α (ER α) The interaction activates a gene called MC4R. This produces the melanocortin-4 receptor (MC4R), which is located on the surface of some estrogen sensitive neurons in the brain called the ventrolateral hypothalamic nucleus (vmhvl), which is responsible for regulating the energy use of adult women.
Dr. Jessica tollkuhn, assistant professor and author of the cold spring port laboratory in New York, used the technology established in the brain of living mice to draw an accurate map of the connection between protein and DNA. This technique is called cut & run, that is, targeted cleavage and release using nuclease, which determines er α Two sites that bind to MC4R to regulate its activity, thus establishing a clear link between hormone receptors and genes.
To their surprise, the team also found that vmhvl neurons activated by this circuit entered the part of the hippocampus containing "speed cells", which control the movement speed of mice. These neurons also project to a region of the hindbrain responsible for regulating sexual receptivity and physical activity. MC4R, the central gene of this circuit, is famous for its role in regulating energy, appetite and weight of adult women. The mutant form of this gene leads to obesity, especially in women.
MC4R receptor is also a target of bremelanotide. Bremelanotide is listed under the vyleesi brand for the treatment of acquired and generalized hypolibido (HSDD) in premenopausal women. To determine that these neurons did make mice more active, the researchers used a chemical genetic technique called dreamd (designer receptor exclusively activated by designer drugs) to make vmhvl neurons express a receptor that can only be activated by harmless chemicals added to their water. When their vmhvl neurons were stimulated in this way, both male and female mice became more active, and female mice lost nearly 10% of their body weight after 24 hours of injection. Inhibition of these neurons has the opposite effect, making women more sedentary.
The team also used crispra technology to increase the activity of MC4R. Crispra technology can up regulate gene expression without changing the gene itself. Both male and female mice became more active, but female mice had a stronger effect and their bones became thicker. However, they did not lose weight, probably because they ate more.
These beneficial results increase the debate about hormone replacement therapy for menopausal symptoms. In 2002, an influential study found that it would slightly increase the risk of endometrial cancer, breast cancer, thrombosis and stroke, and many doctors stopped prescribing it.
"Estrogen will affect your health. At least let us know what it is doing, so maybe we can bypass it and obtain the positive effect of estrogen in another way, through another drug, another target."
Learn more about Abebio products
Cindy
Phone: 
E-mail: 
Address: