Summary: By inducing hot-flash–like responses in both male and female mice, researchers found that activation of Kiss1 neurons triggers a rapid rise in skin temperature followed by a decline in core body temperature, suggesting a neural mechanism linking sex-hormone changes to hot flashes.

Source: Cell Press.

Activation of Kiss1 Neurons Produces Hot-Flash–Like Responses in Mice

Researchers have shown that activating a specific group of neurons in the hypothalamus produces physiological responses in mice that resemble the hot flashes commonly experienced during menopause. Published in Cell Reports, the study implicates Kiss1-expressing neurons—cells already known to respond to sex hormones—as a potential neural link between changing hormone levels and rapid shifts in body temperature.

The research team, led by investigators at the University of Washington, used genetic and viral tools to selectively stimulate Kiss1 neurons that project to brain regions involved in thermoregulation. When these neurons were activated, mice of both sexes exhibited a rapid increase in skin temperature, consistent with the flushing seen during hot flashes, followed by a drop in core body temperature. The effect was stronger in females that had been ovariectomized, indicating that reduced sex hormones enhance the susceptibility to these temperature changes.

Co-author Christopher Johnson, a neuroscience graduate student at the University of Washington, emphasized the potential translational relevance: because Kiss1 neurons exist in humans and perform comparable functions, these results provide specific mechanistic evidence for how hot flashes may be generated in people. The work aligns with a decade of research exploring how sex-hormone–sensitive neural circuits influence thermoregulatory physiology.

Stephanie Padilla, a postdoctoral researcher at the UW School of Medicine and co-author of the study, noted the complexity of hormonal states associated with hot flashes, such as menopause and treatments for prostate cancer. The ability to produce a reliable and robust thermoregulatory response by manipulating a single neuron population in the brain validates prior hypotheses and opens a clearer path for focused investigation.

The authors suggest an evolutionary rationale: in females, the capacity to modulate body temperature beyond normal circadian rhythms might support pregnancy and offspring development. Whether the Kiss1 circuit operates as an independent thermoregulatory pathway directly linking reproduction and temperature control, or whether it is a component within a larger network of temperature-regulating circuits, remains an open question for further research.

Hot flashes in humans often include psychological or emotional components that are difficult to reproduce in animal models. Nevertheless, the physiological response elicited by Kiss1 neuron activation provides a valuable window into the core thermoregulatory mechanisms that underlie hot flashes. These findings may help researchers connect the neuronal activity to broader systems responsible for maintaining homeostasis under changing hormonal conditions.

Clinical and Therapeutic Implications

Currently, estrogen replacement therapy is the most widely used treatment for menopausal hot flashes in the United States, but long-term estrogen use has been associated with increased risks of stroke, blood clots, and heart attack. By identifying a specific neural population that drives hot-flash–like physiology, this study highlights a possible new target for nonhormonal therapeutics. Targeting Kiss1 signaling or its downstream pathways could lead to treatments that reduce hot flashes without the systemic risks associated with hormone replacement.

The discovery also supports ongoing clinical efforts exploring nonhormonal strategies to manage hot flashes. While additional studies in humans will be necessary to confirm the role of Kiss1 neurons in human thermoregulation, the preclinical evidence strengthens the rationale for focused clinical trials and drug development that aim to interrupt the neural cascade behind hot flashes.

Study Details and Funding

The experiments were carried out by researchers in the laboratory of Richard Palmiter, professor of biochemistry at the University of Washington School of Medicine and an investigator with the Howard Hughes Medical Institute. The team used genetic engineering and viral vectors to manipulate Kiss1-expressing neurons and monitor temperature responses in mice.

Funding: The research was supported by the National Institutes of Health.

Source: Joseph Caputo, Cell Press. Organized and reported by Neuroscience News. Original research reported in Cell Reports.

Notes on Further Research

Future studies will need to determine how Kiss1 neurons interact with other thermoregulatory circuits and whether modulating this pathway can safely and effectively reduce hot flashes in humans. Understanding the precise downstream networks and molecular signals involved will be important for developing targeted therapies with minimal side effects.

These findings represent a significant step toward clarifying the neural basis of hot flashes and suggest practical directions for both basic neuroscience and clinical translation in the management of hormone-related thermoregulatory symptoms.