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Tristan Free
Across the animal kingdom, females are more sensitive to the cold than males. It’s a phenomenon that’s observed in most mammals, including humans, and even in birds – but we didn’t understand why until now.
The molecular basis of sex differences in temperature preference may have finally been explained – in mice at least – thanks to a new study from scientists at King’s College London (UK). The researchers have pinpointed two thermal sensors, both of which are also present in humans, tuned to activate at warmer temperatures in female mice. Together, the findings help to answer the long-standing question of why many female animals feel the cold more acutely than their male counterparts.
In many mammals and most birds, females show a preference for warmer temperatures than males. The same is also true of humans: women, in general, prefer an environmental temperature of 25°C, whereas men prefer 22°C. Previous research on this discrepancy has largely focused on morphology, such as the fact that females, on average, have a higher body fat percentage and surface-area-to-weight ratio than males. However, the molecular basis of sex differences in thermal preference has never been fully realized.
To address this, the team behind the recent work decided to study two ion channels belonging to the Transient receptor potential (TRP) family: TRPM2 and TRPM8. Both proteins are expressed in sensory neurons and respond to changes in temperature; TRPM2 is known to detect warmth, while TRPM8 is activated at cooler temperatures.
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First, they placed mice on two heated plates; one was maintained at 33°C, which previous research has revealed is the preferred temperature of male mice, and the other’s temperature was varied. After recording the movements of the mice between the two plates for an hour, the researchers confirmed that male mice spent most of their time at a temperature of around 32°C, whereas females preferred to be slightly warmer, at 36°C.
In a series of knockout experiments, they demonstrated that deletion of the trpm2 gene, coding for the warmth sensor, in male mice shifted preference to hotter temperatures. Meanwhile, deleting trpm8, the gene for the cold sensor, in both males and females shifted preference to cooler temperatures.
The same results were seen when the ion channels were blocked using a drug, leading the scientists to conclude that the sensors themselves determine thermal preference, rather than off-target effects. In addition, there were no differences in core body temperature or surface temperature between male and female mice at any plate temperature, ruling this out as a factor too. Taken together, the authors deduced that this must imply that there is a sex-dependent shift of input from both TRPM8 and TRPM2 towards warmer temperatures in females compared to males.
Testosterone also plays a part, the study went on to reveal. When the researchers gave the mice a hormone blocker to prevent production of testosterone, they noticed a shift toward female warm preference. Conversely, administering testosterone to female mice changed their thermal preference toward male, with the mice becoming more averse to heat. Altering female sex hormones had no such effect.
Ultimately, the team concluded that TRPM2 and TRPM8, alongside testosterone, play an important role in the differing temperature sensitivity of male and female mice – and potentially other species too.
“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,” corresponding author Peter McNaughton summarized.
A definitive demonstration of male and female receptors being activated at different temperatures is lacking from the paper, making this conclusion a deduction of the most likely cause, rather than a demonstrated fact. McNaughton commented on further limitations of this paper in relation to humans, but posited the relevance, stating that “[the] 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 post Women feel the cold more keenly than men – and we may finally know why appeared first on BioTechniques.
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