Estradiol administration suppresses body temperature elevation induced by application of menthol to ovariectomized rats
Introduction
Menthol that is one of ingredients in mint of herbs is used in the anhidrotics, antithermic sheets, and lip balm for the purposes of a cold sensation and refreshing feeling. Regardless of gender, we use the products in the daily life. A cold sensation from the skin is transmitted to brain via the peripheral cold receptors, for example, transient receptor potential melastatin-8 (TRPM8) which is normally expressed in sensory nerves of the skin. TRPM8 is activated cooling or substances such as menthol. The concentrations of female sex hormones (i.e., estradiol (E2) and progesterone) in the blood fluctuate in menstrual cycle in women. The menstrual cycle affected a cold sensation assessed by the dressing behavior in young women (Kim and Tokura, 1995). However, the effect of female hormones on menthol-mediated thermoregulatory responses in the cold is not revealed.
The central administration of E2 (0.1 mg) to the medial preoptic area (MPO) in ovariectomized rats maintained body temperature (Tb) and decreased tail skin temperature (Ttail) at 10 °C (Uchida et al., 2010a). These results indicated that E2 directly affected the MPO and contributed to the maintenance of Tb by vasoconstriction in the cold in female rats. E2 affects central autonomic thermoregulation in the cold. On the other hand, behavioral thermoregulation is important for maintaining Tb. The tail-hiding behavior, the behavior which rats place their tails underneath their bodies, which we reported (Uchida et al., 2012), is thought to be useful indicator of behavioral thermoregulation in rats in the cold. E2 administration facilitated the tail-hiding behavior in ovariectomized rats at 16 °C (Uchida et al., 2017). Our results indicated that E2 affects behavioral thermoregulation in female rats in the cold; however, the underlying mechanisms by which E2 affects the responses via peripheral cold receptors are currently unknown.
L-menthol (10%) application to body trunk of mice increased oxygen consumption and Tb, and changed the preferred floor temperature (Tajino et al., 2007). TRPM8 is usually activated at temperatures at 16 °C (Peier et al., 2002). Animal studies using TRPM8 knockout mice showed that TRPM8 is necessary for cold sensation in mice (Colburn et al., 2007, Dhaka et al., 2007). Menthol is one of agonists of TRPM8. The results indicated that menthol stimulation induced thermogenic responses by autonomic and behavioral thermoregulation; however, the effect of menthol on the responses in female animals and the effect of E2 on the responses induced by menthol have not be clarified.
The aim of the present study was to validate the hypothesis that E2 affects thermoregulatory responses induced by menthol in ovariectomized rats. Tb, Ttail, the duration of tail-hiding behavior, and the brain region related to thermoregulation were assessed.
Section snippets
Animals
Virgin female Wistar rats (n = 70; body weight 158 ± 1.3 g; age, 9 weeks; Japan SLC, Hamamatsu, Japan) were used. They were individually housed in cages (37 × 21 × 19 cm) at ambient temperature (Ta) of 26 ± 1 °C in 12:12-h light-dark cycle (light on at 07:00 h) and allowed free access to food and water. The institutional Animal Care and use Committee of Nara Women's University (Nara, Japan) approved all experimental protocols.
Surgery
The rats underwent surgery under inhalation anesthesia with
Change in body temperature (∆Tb) and change in tail skin temperature (∆Ttail)
Fig. 1 showed that the ∆Tb and ∆Ttail from the baseline at 27 °C (A and C) and 16 °C (B and D). At 27 °C, the baseline of Tb was not different among the groups (Vehicle/E2(−), 37.6 ± 0.1 °C; Vehicle/E2(+), 37.5 ± 0.1 °C; Menthol/E2(−), 37.6 ± 0.1 °C; Menthol/E2(+), 37.7 ± 0.1 °C). Two-way ANOVA indicated a significant main effect of time [F(2,65) = 123.32, p < 0.01] and a significant interaction between time and group on ∆Tb [F(8,65) = 45.20, p < 0.01] at 27 °C. No significant difference was
Discussion
The present study revealed that menthol application increased Tb at 27 °C and 16 °C, and increased Ttail at 27 °C in ovariectomized rats with and without E2. In addition, menthol application increased cFos-IR expression in the PVN in ovariectomized rats with and without E2 at 27 °C. These results suggested that the activation of PVN might be involved in the responses at 27 °C. E2 did not affect the duration of the tail-hiding behavior in ovariectomized rats applied menthol. E2 suppressed the
Acknowledgements
We are grateful to Prof. Keiko Morimoto, Prof. Akira Takamata (Nara Women's University), Prof. Kei Nagashima (Waseda University), and Prof. Kazunari Yuri (Kochi University) for their support of this research. The present research was partly supported by the Japan Society for the Promotion of Science; Grant-in-Aid for Young Scientists (B), No. 17K17882, No. 26350117; Nara Women's University; Intramural and Mental and Physical Health Project Research Grants, Grant for Mental and Physical Health
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2021, Journal of Thermal BiologyCitation Excerpt :These results suggested that E2 may decrease cold sensitivity via a decrease in TRPM8 expression. We reported that E2 suppressed the elevation of body temperature by the application of L-menthol, an agonist of TRPM8, to the body trunk (Uchida et al., 2018). In addition, the skin temperature in the second, third, and fifth toes to which 0.5% L-menthol was applied decreased during the preovulatory phase compared with that in the luteal and menstrual phases in young women (Uchida et al., 2019).
Effect of the menstrual cycle phase on foot skin temperature during menthol application in young women
2019, Journal of Thermal BiologyCitation Excerpt :Thus, it is not clear whether the effect of the menstrual cycle on the thermoregulatory responses was induced by menthol application and whether menthol application itself had an effect on the Tsk of the foot. In animal study, systemic E2 administration suppressed core temperature during the application of menthol, but not cinnamaldehyde that was an agonist of TRPA1 to body trunk in ovariectomized rat (Uchida et al., 2018a; Uchida and Atsumi, 2019). The results indicated that E2 which fluctuated in menstrual cycle might affect the thermoregulatory responses via TRPM8, not TRPA1 in female rats.
Cinnamaldehyde application decreases tail temperature in ovariectomized rats with and without estradiol administration
2019, Journal of Thermal BiologyCitation Excerpt :Tail placement classification was performed in accordance with a previous study (Uchida et al., 2018). At 27 °C and 16 °C, E2 did not affect the duration of tail-hiding behavior in ovariectomized rats treated with vehicle, which was consistent with the results obtained from the same experimental protocol in the previous study (Uchida et al., 2018). In contrast, E2 facilitated tail-hiding behavior in ovariectomized rats in the cold (Uchida et al., 2017).
UCP1 and TRPM8 expression in the brown fat did not affect the restriction of menthol-induced hyperthermia by estradiol in ovariectomized rats
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