Kobayashi T, Ushijima O, Chen J T, Shiraki M, Ohta T, Kiyoki M
Pharmacological Research Department, Teijin Institute for Bio-Medical Research, Hino City, Tokyo, Japan.
J Endocrinol. 1995 Sep;146(3):431-7. doi: 10.1677/joe.0.1460431.
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.
降钙素基因相关肽（CGRP）的过度释放在绝经潮热（HFs）的诱发过程中起直接且关键的作用，绝经潮热时皮肤温度会急剧升高。然而，对于处于雌激素缺乏状态的绝经后女性，无法探究CGRP是否会导致皮肤温度升高，以及皮肤对CGRP的温度反应是否发生变化并促使潮热的出现。通过利用大鼠的尾皮肤温度（TST）这一评估皮肤温度调节的良好指标，我们检测了CGRP和降钙素（静脉注射，剂量分别为3、10和30微克/千克）对雌性大鼠TST的影响，并进一步研究了与假手术（Sham）大鼠相比，CGRP（静脉注射，剂量为10微克/千克）对去卵巢（OVX）大鼠TST的影响。我们发现，CGRP而非降钙素能以剂量依赖的方式使TST升高，且CGRP诱导的TST变化（OVX大鼠为0.6±0.2℃，Sham大鼠为0.3±0.1℃，P<0.05）以及基础TST（OVX大鼠为26.0±0.2℃，Sham大鼠为25.5±0.1℃）在OVX大鼠中均显著更高（P<0.05）。此外，皮下注射雌二醇（剂量为30微克/千克）持续8天可部分抑制OVX大鼠对CGRP增强的TST反应，并几乎完全抑制（P<0.05）基础TST升高，同时血清雌二醇水平恢复至Sham大鼠的水平。这些结果表明，在雌激素缺乏的OVX大鼠中发现的对CGRP增强的皮肤温度反应以及基础皮肤温度升高，在绝经女性中可能也会出现，并促使她们发生潮热。
