A new study led by scientists at King's College London has resolved a long-standing biological debate regarding why females consistently prefer warmer environments than males. Published in The Journal of Physiology, the research identifies that two specific thermosensitive ion channels located in peripheral nerves are molecularly tuned to different activation thresholds based on sex. The team found that TRPM2, which detects warmth, and TRPM8, which senses coolness, activate at significantly higher temperatures in females compared to males.
To investigate this phenomenon, researchers utilized a two-plate choice paradigm with adult mice, allowing them to freely select between temperature-regulated surfaces. Under baseline conditions, female mice demonstrated a strong preference for warmer floors, seeking temperatures around 36°C and readily occupying plates heated to 38°C. In contrast, male mice exhibited heat aversion at these levels, preferring cooler surfaces near 32°C. By employing genetic knockout models and pharmacological blockers, the investigators confirmed that the behavioral differences stem directly from the activity of these two ion channels. Removing the warmth-sensing TRPM2 channel shifted male mice toward warmer plates, while inhibiting the cool-sensing TRPM8 channel pushed females toward cooler temperatures.
The study further explored the role of sex hormones in modulating these sensory thresholds. The researchers discovered that circulating testosterone is a key driver of this divergence. Lowering testosterone levels in male mice shifted their thermal preference toward the warmer ranges typical of females, whereas administering testosterone to females increased their aversion to heat. Conversely, variations in female sex hormones, specifically estrogen and progesterone, showed no direct regulatory effect on the sensors or thermal plate selection. This hormonal influence suggests that testosterone modulates baseline thermosensitivity rather than differences in core body temperature.
Importantly, the study ruled out metabolic differences as the cause of these preferences. Infrared thermography and core rectal thermometry confirmed that male and female mice maintained identical core body temperatures and paw skin temperatures. This indicates that the preference for warmer rooms is a result of peripheral sensory detection rather than differences in basal metabolic heat retention or physical insulation. While the study was conducted on mice, the researchers note that humans possess both TRPM2 and TRPM8 channels and exhibit similar average temperature preferences, suggesting a comparable mechanism is likely at work in people.
Professor Peter McNaughton of the Wolfson Sensory, Pain and Regeneration Centre noted that while it has long been known that females prefer warmer environments across many mammalian species, the molecular basis remained unidentified until now. The findings have potential clinical implications, as both ion channels are implicated in conditions such as neuropathic pain and fibromyalgia, which disproportionately affect women. Future research aims to determine if this sex-specific tuning occurs exclusively within peripheral sensory afferents or involves integration hubs in the spinal cord and hypothalamus.
Sources: Neuroscience News.