Basal tail skin temperature elevation and augmented response to calcitonin gene-related peptide in ovariectomized rats
Abstract
Hyper-release of calcitonin gene-related peptide (CGRP) plays a direct and pivotal role in the induction of menopausal hot flushes (HFs), in which a drastic increase in skin temperature occurs. However, it is not possible to investigate whether CGRP induces skin temperature increase and whether skin temperature response to CGRP changes and contributes to the occurrence of HFs in postmenopausal women who are in oestrogen deficiency. By using rats' tail skin temperature (TST), a good marker to evaluate skin temperature regulation, we examined the effects of CGRP and calcitonin (3, 10 and 30 micrograms/kg, i.v.) on TST in female rats and further investigated the TST change induced by CGRP (10 micrograms/kg, i.v.) in ovariectomized (OVX) rats compared with that in sham-operated (Sham) rats. We found that CGRP, but not calcitonin, induced a TST increase in a dose-dependent manner and that the TST change induced by CGRP (0.6 +/- 0.2 degrees C for OVX rats vs 0.3 +/- 0.1 degree C for Sham rats, P < 0.05) and also the basal TST (26.0 +/- 0.2 degrees C for OVX rats vs 25.5 +/- 0.1 degree C for Sham rats) were significantly greater in OVX rats (P < 0.05). Furthermore, treatment with oestradiol (30 micrograms/kg, s.c.) for 8 days partially inhibited the augmented TST response to CGRP in OVX rats and almost completely inhibited (P < 0.05) the basal TST elevation, with the concomitant recovery of the serum oestradiol level to that in Sham rats. These results suggest that the augmented skin temperature response to CGRP and the elevation of basal skin temperature that are found in OVX rats, animals which are oestradiol deficient, may also occur in menopausal women and contribute to their HFs.
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Tail skin temperature is increased by ovariectomy and reduced by estrogen treatment of ovariectomized rats.
“Tail skin temperature is increased by ovariectomy (Berendsen et al., 2001; Kobayashi et al., 1995; Opas et al., 2004) and reduced by estrogen treatment of ovariectomized rats (Berendsen et al., 2001; Bowe et al., 2006; Dacks and Rance, 2010; Hosono et al., 2001; Kobayashi et al., 1995).”
From Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes (2013) · cites this paper as Kobayashi et al., 1995
Cited by
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Rance, N. E., Dacks, P. A., Mittelman-Smith, M. A., Romanovsky, A. A., & Krajewski-Hall, S. J. (2013) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2013.07.003 · Cited by 380 · see citing works
“7), but this effect is smaller in magnitude than during the dark phase, delayed until 7–8 days after treatment and dependent on the ambient temperature (Dacks and Rance, 2010; Hosono et al., 2001; Kobayashi et al., 1995; Williams et al., 2010).”
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Ognjanovic, S., & Bryant‐Greenwood, G. D. (2002) · American Journal of Obstetrics and Gynecology · doi:10.1067/mob.2002.126295 · Cited by 191 · see citing works
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Bansal, R., & Aggarwal, N. (2019) · Journal of Mid-life Health · doi:10.4103/jmh.jmh_7_19 · Cited by 108 · see citing works
“Intravenous CGRP causes greater increase in skin temperature of ovariectomized rats compared to controls.[30,31]”
BackgroundThe menopausal hot flush: a review
Sturdee, D. W., Hunter, M. S., Maki, P. M., Gupta, P., Sassarini, J., Stevenson, J. C., & Lumsden, M. A. (2017) · Climacteric · doi:10.1080/13697137.2017.1306507 · Cited by 79 · see citing works
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Elevation of tail skin temperature in ovariectomized rats in relation to menopausal hot flushes
Kobayashi, T., Tamura, M., Hayashi, M., Katsuura, Y., Tanabe, H., Ohta, T., & Komoriya, K. (2000) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2000.278.4.r863 · Cited by 61 · see citing works
“In the previous study (14), we measured the basal level of TST (before testing the effects of drugs) as a mean value of three recordings for a total of 30 min and evaluated the effects of E2 on this parameter.”
BackgroundMethodInfluentialSelf-citationEffects of Estradiol on the Thermoneutral Zone and Core Temperature in Ovariectomized Rats
Dacks, P. A., & Rance, N. E. (2010) · Endocrinology · doi:10.1210/en.2009-1112 · Cited by 60 · see citing works
“After ovariectomy, tail skin temperature increases, and this effect can be abolished by treatment with estrogens (13–18).”
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Jt, C., & Shiraki, M. (2003) · Maturitas · doi:10.1016/s0378-5122(03)00128-2 · Cited by 45 · see citing works
“As we previously reported that rats’ tail skin temperature was a good marker to evaluate skin temperature regulation, tail skin temperature was increased in a dose dependent manner after CGRP injection and was revealed to have greater response in OVX rats than in Sham rats [18].”
BackgroundSelf-citationThe neuroendocrinology of the preoptic area in menopause: Symptoms and therapeutic strategies
Modi, M., & Dhillo, W. S. (2021) · Handbook of clinical neurology · doi:10.1016/b978-0-12-819975-6.00029-7 · Cited by 40 · see citing works
Hosono, T., Chen, X.-M., Miyatsuji, A., Yoda, T., Yoshida, K., Yanase-Fujiwara, M., & Kanosue, K. (2001) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2001.280.5.r1341 · Cited by 32 · see citing works
“Several investigators hypothesize that the tail vasodilation seen in ovariectomized rats can be regarded as a model of the human hot flush although their experiments used retrained animals only at a few ambient temperatures (11, 12, 19).”
BackgroundFleischer, A., Schalk, J. C., Wetzel, E. A., Hanson, A. M., Sem, D., Donaldson, W. A., & Frick, K. (2021) · Hormones and Behavior · doi:10.1016/j.yhbeh.2021.104948 · Cited by 20 · see citing works
“, 2011), and long-term treatment with estrogenic compounds often prevents this elevation in temperature in both mice and rats (Berendsen et al., 2001; Bowe et al., 2006; Kobayashi et al., 1995; Opas et al., 2004, 2006; Zhao et al., 2011).”
Role of calcitonin gene-related peptide in energy metabolism
Lima, W. G., Marques‐Oliveira, G. H., da Silva, T. M., & Chaves, V. E. (2017) · Endocrine · doi:10.1007/s12020-017-1404-4 · Cited by 27 · see citing works
“Similar results are found in ovariectomized rats [73].”
BackgroundResultDacks, P. A., Krajewski, S. J., & Rance, N. E. (2011) · Endocrinology · doi:10.1210/en.2010-1230 · Cited by 19 · see citing works
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“This agrees with the results of a previous study reported by Kobayashi et al. (1995). In addition, we demonstrated that the CGRP-induced elevation of skin temperature was inhibited by human CGRP8–37 in both OVX and sham-operated rats.”
InfluentialSelf-citationNoguchi, M., Ikarashi, Y., Yuzurihara, M., Kase, Y., Watanabe, K., Plotnikoff, G. A., Takeda, S., & Aburada, M. (2005) · Life Sciences · doi:10.1016/j.lfs.2004.09.032 · Cited by 13 · see citing works
Braasch, D. C., Deegan, E. M., Grimm, E. R., & Griffin, J. D. (2008) · BMC Neuroscience · doi:10.1186/1471-2202-9-64 · Cited by 13 · see citing works
“Experimentally, several studies have demonstrated similar increases in sympathetic activation and skin temperature when CGRP is elevated through intravenous injection [8,9,11].”
BackgroundIs calcitonin gene-related peptide a modulator of menopausal vasomotor symptoms?
de Oliveira, M. A., Lima, W. G., Schettini, D. A., Tilelli, C. Q., & Chaves, V. E. (2018) · Endocrine · doi:10.1007/s12020-018-1777-z · Cited by 11 · see citing works
Noguchi, M., Ikarashi, Y., Yuzurihara, M., Kase, Y., Takeda, S., & Aburada, M. (2003) · Journal of Pharmacy and Pharmacology · doi:10.1211/0022357022142 · Cited by 10 · see citing works
“Most studies in which tail skin temperatures were recorded have required restraint devices to prevent the rats from removing the probes that monitor skin temperature (Kobayashi et al 1995).”
BackgroundInfluentialNoguchi, M., Yuzurihara, M., & Ikarashi, Y. (2002) · Neuropeptides · doi:10.1016/s0143-4179(02)00090-2 · Cited by 10 · see citing works
Effects of Aqueous Extracts of Cynanchum wilfordii in Rat Models for Postmenopausal Hot Flush
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“After ovariectomy, TST increases, and this effect can be reduced by supplying estrogen (19-23).”
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Sun, C., Chen, M., Mao, J., et al. (2001) · Neuroreport · doi:10.1097/00001756-200111160-00025 · Cited by 6 · see citing works
Erten, F., Er, B., Ozmen, R., Tokmak, M., Gökdere, E., Orhan, C., Morde, A. A., Padigaru, M., & Şahin, K. (2025) · Antioxidants · doi:10.3390/antiox14030355 · Cited by 8 · see citing works
“Similar thermoregulatory changes have been documented in rodent models, such as OVX rats, where elevated skin and body temperatures were reported approximately two weeks post-ovariectomy, mirroring the thermoregulatory disruptions observed in humans [56].”
Morimoto, Y., Aozuka, Y., & Shibata, Y. (2011) · YAKUGAKU ZASSHI · doi:10.1248/yakushi.131.1241 · Cited by 5 · see citing works
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Prelle, K., Igl, B., Obendorf, M., Girbig, D., Lehmann, T., & Patchev, V. K. (2012) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0b013e318245533f · Cited by 5 · see citing works
Effects of Progesterone on the Elevation of Tail Skin Temperature in Ovariectomized Rats.
Kobayashi, T., Tamura, M., Hayashi, M., Itano, Y., Tanabe, H., Katsuura, Y., Ohta, T., & Komoriya, K. (2000) · The Japanese Journal of Physiology · doi:10.2170/jjphysiol.50.651 · Cited by 2 · see citing works
Self-citationYuzurihara, M., Noguchi, M., Igarashi, Y., et al. (2003) · 日本東洋醫學雜誌 · doi:10.3937/kampomed.54.791
Approach to Hot Flashes: A Narrative Review
Nayan, A., Teja, S., Nareddy, S., Mahesh, K. V., Goyal, M., & Bansal, R. (2026) · Journal of Postgraduate Medicine Education and Research · doi:10.5005/jp-journals-10028-1760
- Authors
- Kobayashi, T., Ushijima, O., Chen, J.-T., Shiraki, M., Ohta, T., & Kiyoki, M.
- Affiliations
- Teijin (Japan) (JP)
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 1995-09-01
- Volume
- 146
- Issue
- 3
- Pages
- 431-437
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2169259278
- Cited by
- 29
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2021: 3 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 1 · 2013: 1 · 2012: 1
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- calcitonin gene-related peptide, menopausal hot flushes, tail skin temperature, ovariectomy, calcitonin, skin temperature regulation, postmenopausal women, estrogen deficiency
- MeSH terms
- Animals, Calcitonin, Climacteric, Dose-Response Relationship, Drug, Estradiol, Female, Humans, Ovariectomy, Skin Temperature, Tail, Vasodilation, Calcitonin Gene-Related Peptide, Rats, Sprague-Dawley, Rats
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