Estradiol administration suppresses body temperature elevation induced by application of menthol to ovariectomized rats

doi:10.1016/j.jtherbio.2018.10.016

Journal of Thermal Biology

Volume 78, December 2018, Pages 281-289

https://doi.org/10.1016/j.jtherbio.2018.10.016 Get rights and content

Highlights

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The effect of estradiol on thermoregulation induced by menthol was examined.
•
Menthol increased body temperature and estradiol suppressed it in female rats.
•
Menthol increased cFos expression in the paraventricular nucleus in female rats.

Abstract

The aim of the present study was to investigate the effect of estradiol (E₂) on thermoregulatory responses induced by menthol in ovariectomized rats. Wistar rats were ovariectomized, and implanted with a silastic tube with or without E₂ (E₂(+) and E₂(−) groups). L-menthol (10%) or vehicle was applied to the skin of the whole trunk in selected animals, which were then exposed to 27 °C or 16 °C for 2 h. Continuous body temperature (T_b), tail skin temperature (T_tail), and treatment-associated behaviors were measured. cFos immunoreactive (cFos-IR) cells in the median preoptic area, paraventricular nucleus (PVN), medial preoptic area, posterior hypothalamus, and dorsomedial hypothalamus were counted. At 27 °C, in the E₂(+) and E₂(−) groups, the T_b and T_tail were greater in rats applied menthol than that in rats applied vehicle. In rats applied menthol, the T_b in the E₂(+) group was lower than that in the E₂(−) group. In the E₂(+) and E₂(−) groups, the number of cFos-IR cells in the PVN was greater in rats applied menthol than that in rats applied vehicle. These results suggested that menthol treatment increased T_b in ovariectomized rats with or without E₂ at 27 °C, and that activation of the PVN might be involved in this response. E₂ administration suppresses T_b 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 (T_b) and decreased tail skin temperature (T_tail) at 10 °C (Uchida et al., 2010a). These results indicated that E₂ directly affected the MPO and contributed to the maintenance of T_b 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 T_b. 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 T_b, 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. T_b, T_tail, 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 (T_a) 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 (∆T_b) and change in tail skin temperature (∆T_tail)

Fig. 1 showed that the ∆T_b and ∆T_tail from the baseline at 27 °C (A and C) and 16 °C (B and D). At 27 °C, the baseline of T_b 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 ∆T_b [F(8,65) = 45.20, p < 0.01] at 27 °C. No significant difference was

Discussion

The present study revealed that menthol application increased T_b at 27 °C and 16 °C, and increased T_tail 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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Effect of menstrual cycle and female hormones on TRP and TREK channels in modifying thermosensitivity and physiological functions in women
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Citation 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).
Thermoregulation is crucial for human survival at various ambient temperatures. Transient receptor potential (TRP) and TWIK-related K⁺ (TREK) channels expressed in sensory neurons play a role in peripheral thermosensitivity for temperature detection. In addition, these channels have various physiological roles in the skeletal, nervous, immune, vascular, digestive, and urinary systems. In women, the female hormones estradiol (E2) and progesterone (P4), which fluctuate during the menstrual cycle, affect various physiological functions, such as thermoregulation in hot and cold environments. The present review describes the effect of female hormones on TRP and TREK channels and related physiological functions. The P4 decreased thermosensitivity via TRPV1. E2 facilitates temporomandibular joint disease (TRPV1), breast cancer (TRPM8), and calcium absorption in the digestive system (TRPV5 and TRPV6), inhibits the facilitation of vasoconstriction (TRPM3), nerve inflammation (TRPM4), sweetness sensitivity (TRPM5), and menstrual disorders (TRPC1), and prevents insulin resistance (TRPC5) via each channel. P4 inhibits vasoconstriction (TRPM3), sweetness sensitivity (TRPM5), ciliary motility in the lungs (TRPV4), menstrual disorder (TRPC1), and immunity (TRPC3), and facilitates breast cancer (TRPV6) via each channel as indicated. The effects of female hormones on TREK channels and physiological functions are still under investigation. In summary, female hormones influence physiological functions via some TRP channels; however, the literature is not comprehensive and future studies are needed, especially those related to thermoregulation in women.
Systemic acyl-ghrelin increases tail skin temperature in rats without affecting their thermoregulatory behavior in a cold environment
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Fasting increases ghrelin that is a peptide hormone with two circulating isoforms, acyl and des-acyl ghrelin. We reported that fasting or des-acyl ghrelin facilitates behavioral thermoregulation in the cold in rats assessed by tail-hiding behavior that was the indicator of rats’ thermoregulatory behavior in the cold; however, the effect of acyl-ghrelin on the same process remains to be elucidated. We investigated the effect of acyl-ghrelin on thermoregulatory behavior in the cold in rats. The animals received an intraperitoneal saline or 24 μg acyl-ghrelin injection and were exposed to 27 °C or 15 °C for 2 h, while their body temperature, tail skin temperature, and tail-hiding behavior were constantly monitored. cFos immunoreactive (cFos-IR) cells in the median preoptic area, medial preoptic area, paraventricular nucleus (PVN), and arcuate nucleus were counted. Body temperature and the duration of thermoregulatory behavior did not show a significant difference between the acyl-ghrelin-treated and control groups at 15 °C; however, tail skin temperature in the acyl-ghrelin-treated group was higher than that in the control group. The number of cFos-IR cells in the PVN was greater in the control group than that in the acyl-ghrelin-treated group at 27 °C. These results indicate that acyl-ghrelin did not affect behavioral thermoregulation but might affect tail skin temperature in rats in the cold.
Effect of the menstrual cycle phase on foot skin temperature during menthol application in young women
2019, Journal of Thermal Biology
Citation 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.
According to the literature, the arteriovenous anastomoses in the peripheral parts (ex. hands and feet) respond thermal stimulation susceptibly. Thus, the feet are sensitive to cold stimulation. The aim of the present study was to investigate the effect of menstrual cycle on skin temperature (T_sk) of the foot during menthol application in young women. T_sk and partial cutaneous blood flow in the foot, tympanic temperature, blood pressure, heart rate, thermal sensation and pleasantness during the preovulatory (P), luteal (L), and menstrual (M) phases during menthol application in young women using thermography, laser Doppler flowmetry, a digital blood pressure monitor, and VAS scale were examined at 25 °C. After application of the 0.5% menthol solution to the right foot, the measurements were continued for 20 min. The T_sk of the second and third right toes in the P phase were lower than that in the L phase. The T_sk of the little right toe in the P phase was lower than that in the L and M phases. No significant differences were observed in the T_sk of the dorsum of right foot, cutaneous Laser-Doppler flow in the right great toe, tympanic temperature, blood pressure, heart rate, thermal sensation and pleasantness among the phases. The menstrual cycle phase did not affect T_sk in the dorsum of the foot, but it affected T_sk in some toes during menthol application.
Cinnamaldehyde application decreases tail temperature in ovariectomized rats with and without estradiol administration
2019, Journal of Thermal Biology
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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).
The aim of this study was to examine the effect of estradiol (E₂) on the thermoregulatory responses induced by cinnamaldehyde, a component extracted from cinnamon at 16 °C or 27 °C. The thermoneutral and subneutral experiments were performed to evaluate the augmented effect of cinnamaldehyde by cold exposure and the effect of cinnamaldehyde itself. Ovariectomized rats were implanted with a silastic tube with or without E₂ (E₂(+) and E₂(−) groups), and data loggers into the peritoneal cavity. After the application of 30% cinnamaldehyde or vehicle into the skin of the whole trunk of rats, the rats were exposed to 16 °C or 27 °C for 2 h. Body temperature (T_b) and tail temperature (T_tail) were measured using a data logger and thermography. After exposure, blood samples were obtained, and plasma catecholamine concentration were measured by high-performance liquid chromatography. In the E₂(−) group exposed to 27 °C, the change in T_b in rats applied cinnamaldehyde was significantly lower than that of rats applied vehicle. The change in T_tail in rats applied cinnamaldehyde was significantly lower than that of rats applied vehicle in both E₂(−) and E₂(+) groups at 27 °C and 16 °C. Plasma catecholamine concentration at 27 °C was not different among the groups. E₂ might not affect thermoregulatory responses induced by cinnamaldehyde application; however, it decreased T_tail in female rats.
Progesterone Did Not Affect Thermoregulatory Responses in Ovariectomized Rats Administered Ostruthin
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Estradiol administration suppresses body temperature elevation induced by application of menthol to ovariectomized rats

Highlights

Abstract

Introduction

Section snippets

Animals

Surgery

Change in body temperature (∆Tb) and change in tail skin temperature (∆Ttail)

Discussion

Acknowledgements

Brain Res.

Brain Res.

iScience

Neurosci. Lett.

Neuron

Neuron

Physiol. Behav.

J. Urol.

Mol. Cells

Cell

Brain Res.

Brain Res.

Plasma concentration of LH, FSH, prolactin, progesterone and estradiol-17beta throughout the 4-day estrous cycle of the rat

Endocrinology

Change in body temperature (∆T_b) and change in tail skin temperature (∆T_tail)