更年期におけるHot flashと骨代謝の変化の機序に関する研究 : calcitonin関連物質の関与 (<シンポジウム>2. 中高年女性の加齢による変化)

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Hot flash occurs following the decline of estrogen levels in females during menopause or in males after estrogen therapy. Because prepubertal girls are not reported of hot flash, withdrawal from estrogen or aging process might be a significant factor for the onset of hot flash, however, the precise mechanism of it has not been fully understood. Since hot flash initiated through vasodilatation and increased of blood flow, we investigated to see the changes of vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP) ; the neuropeptides which were known to cause vasodilatation, in relation to hot flash. The plasma CGRP levels were significantly elevated at the flash compared to before and after the flash (p = 0.0002 by ANOVA), however, no significant change was observed in serum VIP level, nor FSH, LH, TSH, cortisol and ACTH levels during the flash. The cold load test was performed to see the relation between the sensory nerve function and CGRP level in postmenopasual women with or without hot flash, we found the immediate significant increase of CGRP level after the cold load in women with flash compared to without it (p < 0.05). It was indicated that elevated secretion or hypersensitivity of CGRP to stimuli after estrogen deficiency has an important role for the occurrence of hot flash. To study whether or not CGRP does elevate body temperature after estrogen deficiency, we monitored the tail skin and rectal temperature in ovariectomized (OVX) rat. The tail skin temperature was significantly elevated compared to sham operated rat at 2 to 6 weeks after ovariectomy, but no significant change was observed thereafter. By the venous injection of CGRP in OVX rat, skin tail temperature was significantly and dose dependently (3 to 30 μg/kg) elevated at 30 minutes after it (p < 0.05), however, no significant change was observed in rectal temperature. These data suggest that the augmented skin temperature response to CGRP and the elevation of skin temperature in OVX rat may occur in menopausal women and contribute to their hot flash. Estradiol replacement (30 μg/kg) in OVX rat decreased the skin temperature to sham operated level, but this treatment did not significantly decreased the skin temperature after venous injection of CGRP by 10 μg/kg, suggesting estrogen replacement can not always well control the flash as we experience in clinical settings. By the three hours-monitoring of CGRP, LH, FSH and estradiol level in postmenopausal women with flash, we found that pulsatile pattern of CGRP did not always reveal a close association with LH pulse, however, interestingly, CGRP pulse had closely associated with estradiol pulse in some instances. To investigate the association of CGRP and estradiol, we monitored CGRP, LH, FSH and estradiol level in women with normal menstruation cycles, and it was shown that a peak secretion of CGRP was observed just two to three days after the estradiol or LH surge, suggesting the close association between CGRP and estradiol level. Since the CGRP containing sensory nerve fibers were distributed not only in uterine or ovarian vessels but in ovarian stroma or around follicles in rat, these observations in postmenopausal women were likely to suggest that pulsatile CGRP release at hot flash might at least increase the ovarian blood flow or stimulate the ovarian function after estrogen deficiency. In conclusion, it was speculated that hyperrelease of CGRP at sensory nerve end might occur after estrogen deficiency, which contributes to increase the peripheral blood flow, and to generate hot flash. On the other hand, pulsatile CGRP release at hot flash might at least increase the ovarian blood flow or stimulate the ovarian function because CGRP containing sensory nerve fibers were possible to distribute in ovarian vessels or stroma.
社団法人日本産科婦人科学会の論文
1997-08-01

更年期におけるHot flashと骨代謝の変化の機序に関する研究 : calcitonin関連物質の関与 (<シンポジウム>2. 中高年女性の加齢による変化)

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