Summary:
A molecular neurobiology study led by researchers at King’s College London’s Institute of Psychiatry, Psychology & Neuroscience (IoPPN) reveals the cellular mechanism behind why females consistently prefer warmer environments than males.
Published in The Journal of Physiology, the team discovered that two key thermosensitive ion channels in peripheral nerves, TRPM2 (which detects warmth) and TRPM8 (which detects coolness), are tuned to activate at significantly higher temperatures in females. This physiological calibration explains a conserved thermal preference observed across mammals and birds, while demonstrating how circulating testosterone modulates baseline thermosensitivity.
Key Facts:
- Higher Activation Thresholds: In female mice, both the warmth-detecting ion channel TRPM2 and the cold-sensing channel TRPM8 activate at warmer thermal ranges compared to males, causing environments that feel comfortably warm to females to feel uncomfortably hot to males.
- Testosterone-Driven Modulation: Lowering testosterone in males shifted their preference toward warmer ambient temperatures, whereas administering testosterone to females increased heat aversion; female sex hormones (estrogen and progesterone) showed no direct regulatory effect on the sensors.
- Sensory, Not Core Metabolic: Baseline core body temperature and paw skin temperature were identical between sexes, confirming that preference differences stem directly from peripheral sensory detection rather than differences in basal metabolic heat retention.
Source: King’s College London
The recurring domestic and office debate over the thermostat setting, where women typically favor ambient temperatures around 25°C (77°F) while men prefer cooler rooms near 22°C (71.6°F), is not merely psychological. Across nearly every mammalian species studied to date, as well as in avian lineages, females consistently select warmer environmental temperatures than their male counterparts.
While evolutionary biologists have long noted this behavioral dichotomy, the precise molecular sensors responsible for sex-specific thermal comfort have remained unidentified.
Now, an experimental investigation led by researchers at the Wolfson Sensory, Pain and Regeneration Centre within the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London, published in The Journal of Physiology, identifies the cellular culprit: two distinct thermosensitive ion channels embedded within peripheral nerve endings that are inherently tuned to higher temperature thresholds in females.
Thermosensation on the Two-Plate Arena
To dissect thermal preference under controlled behavioral settings, the researchers evaluated adult mice using a two-plate choice paradigm. Animals freely explored two adjacent temperature-regulated metal surfaces: one plate remained anchored at an indifferent baseline of 33°C, while the adjacent test plate was systematically adjusted.
Under baseline conditions, female mice demonstrated a sharp preference for warmer surfaces, seeking out floor temperatures of 36°C and readily occupying plates heated to 38°C. In contrast, male mice exhibited pronounced heat aversion, avoiding surfaces at 38°C and preferring cooler floor temperatures around 32°C.
The team focused on two transient receptor potential (TRP) ion channels—specialized microscopic pores embedded in sensory nerve membranes that gate the influx of positively charged ions when external temperatures change, sending depolarizing electrical spikes to the central nervous system:
- TRPM2: The primary neural sensor detecting mild, gentle warmth.
- TRPM8: The principal neural channel responsible for registering coolness and innocuous cold.
By applying targeted pharmacological blockers alongside selective genetic knockout models, the investigators isolated the channels’ behavioral roles. Genetically ablating the warmth-sensing TRPM2 channel shifted male mice toward warmer plates.
Conversely, knocking out or pharmacologically inhibiting the cool-sensing TRPM8 channel pushed females toward cooler temperatures. Because both systemic pharmacological inhibition and genetic deletion yielded identical behavioral shifts, the researchers confirmed that the behavioral differences stem directly from the activity of these two ion channels.
“It has long been known that in many mammals, including humans, females prefer a warmer environment than males, but the molecular basis for this difference had not been identified until now,” said Peter McNaughton, PhD, Professor of Pharmacology at the Wolfson Sensory, Pain and Regeneration Centre at IoPPN.
“In mice, we found that the thermal ranges of activation of the two ion channels that detect warmth and coolness, TRPM2 and TRPM8, are shifted towards warmer temperatures in females, and it is this shift that causes the difference in how males and females sense and react to temperature. This study did not look at humans, but humans have both of these types of ion channels, and similar differences in average temperature preference so it is likely that a similar mechanism is at work.”
The Influence of Sex Hormones
The researchers investigated whether systemic core temperatures or circulating endocrine signals drove the divergence.
Infrared thermography and core rectal thermometry confirmed that male and female mice maintained identical core body and cutaneous paw skin temperatures, proving that the behavioral split was not caused by differences in body heat production or physical insulation.
However, endocrine manipulation exerted a clear regulatory effect:
- Testosterone Depletion: Reducing circulating testosterone in male mice shifted their thermal choices toward the higher warmth thresholds typical of females.
- Testosterone Administration: Elevating testosterone levels in female mice made them significantly more averse to elevated temperatures.
- Female Sex Hormones: Variations in estrogen and progesterone produced no measurable impact on thermal plate selection, though testosterone alone did not fully account for the baseline phenotypic gap.
“Much of the earlier work on temperature sensing, including our own, was carried out only in male mice,” explained Dr. Bruno Vilar, co-investigator at the Wolfson Centre. “However, genetically removing the warmth sensor TRPM2, which had a large effect on how males responded to warmth, had almost no effect in females. We wanted to understand why, and that led us to discover that both sensors are shifted towards warmer temperatures in females.”
Unresolved Questions and Clinical Horizons
Because TRPM2 and TRPM8 were deleted throughout the entire body in the knockout lines, the team cannot yet determine whether the sex shift operates exclusively within peripheral sensory afferents in the skin or involves secondary integration hubs in the spinal cord and preoptic hypothalamus.
Furthermore, when primary sensory neurons were cultured and isolated in vitro, the sex-specific activation shifts dissipated—suggesting that local biochemical environments, cellular scaffolding, or native physiological signaling within intact skin tissue are required to sustain the channel tuning.
The research team plans to engineer localized genetic knockdowns restricted to the peripheral nerve endings of the paws to evaluate whether site-specific sensor tuning alters behavior. Because both TRPM2 and TRPM8 are heavily conserved in human sensory physiology and have been implicated in neuropathic pain, fibromyalgia, and thermal hyperalgesia, mapping their sex-specific operational ranges may provide new insights into why chronic pain syndromes disproportionately affect women.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this neuroscience Research:
- Media Contact: Francesca Greenstreet
- Source: King’s College London
- Image Credit: Image credited to Neuroscience News
- Original Research is Open Access: Journal of Physiology (Oct 1, 2026). “TRPM8 and TRPM2 ion channels determine sex differences in thermal preference in mice.” Authors: Bruno Vilar, Peter A. McNaughton.
- DOI: 10.1113/JP288076
Abstract
TRPM8 and TRPM2 ion channels determine sex differences in thermal preference in mice
Several ion channels belonging to the large TRP family are activated either by increases or decreases in temperature, but it is unclear which of these potential thermosensors actually determine the sensation of temperature in the non-noxious thermal range, from approximately 20°C to approximately 40°C.
Here we show that below 33°C, male cool preference is determined by TRPM8, whereas warm preference is mainly influenced by TRPM2. Female thermal preference is shifted to warmer temperatures by around 4°C when compared to males, consistent with warm shifts in the female activation ranges of both TRPM8 and TRPM2. Removal of testosterone causes a shift in male thermal preference towards female preference; conversely, female thermal preference is shifted towards male by injection of testosterone.
Removing or injecting female hormones had no effect on thermal preference. We conclude that TRPM8 and TRPM2 are the main thermal detectors in the non-noxious range, and that testosterone is an important determinant of the difference in preference between males and females.
