合成estrogenの下垂体gonadotropin分泌調節について

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Effects of mestranol, one of the synthetic estrogens, on the pituitary responses to a synthetic LH-RH were investigated. <BR>Seven normal women with regular menstrual cycles were used as controls in the late proliferative phase. Thirteen healthy volunteers with normal ovulating cycles were devided into 2 groups. Five women received orally 20μg per day (Group I) and other 8 women were administered 40μg per day (Group II) of mestranol, beginning from the 5th day of the cycle for a period of 10 days. Volunteers in each group were kept fasting overnight and 5ml of blood was drawn at 9 to 10 am on the day of the experiment. Ten minutes after drawing blood, 200μg of synthetic LH-RH was injected subcutaneously in the late proliferative phase in the normal women with regular menstrual cycles. According to the same procedure, women taking mestranol were administered LH-RH on the 8th to 10th day after the beginning of taking the first administration. Three ml of blood was taken at 15, 30, 60,120 minutes and 24 hours after injection of synthetic LH-RH. Serum levels of LH and FSH were determined by the double antibody radioimmunoassay. The 2nd IRP-HMG was used as the standard materials and expressed as mIU/ml of serum. <BR>Mean baseline serum LH and FSH concentrations were not significantly changed by doses of mestranol used in this experiment. In Group I and Group II, mean LH levels were not significantly altered within 60 minutes after the subcutaneous administration of LH-RH. Thereafter, mean LH levels continued to rise and reached a peak at 120 minutes after injection of LH-RH in contrast with the control. A significant delay in the LH peak was observed in treatments with 20μg and 40μg of mestranol. In Group II, mean LH level at 120 minutes after LH-RH was significantly elevated as compared with those seen in the late proliferative phase of the cycle and in the Group I. Concerning the FSH response to LH-RH, 20μg mestranol did not induce a significant rise. On the other hand, mean FSH level in Group II at 120 minutes after injection of LH-RH was significantly elevated as compared with that seen in the late prolijerative phase. As expected, mean net increases of LH and FSH above each baseline level at 120 minutes after LH-RH in Group II were significantly greater than those of the control, but at all other points in both treated groups the mean net increases following LH-RH were not markedly changed. Moreover, the maximum LH increase in the treatment of 2 doses of mestranol occurred later than that seen in the control. However, in terms of percent changes from baseline levels LH and FSH releases to LH-RH at 120 minutes were not significant. <BR>From these results, it was suggested that mestranol at a dose of 40μg exerted a direct action on the pituitary gonadotropin response to LH-RH. The prolonged response of LH following administration of LH-RH in the mestranol-treated women was seemed to be related to the increased sensitivity of the pituitary. The time-course of changes in serum LH and FSH with LH-RH may reflect a dual role of LH-RH in regulating releases and repletions of pituitary gonadotropins in the treatment of 40μg mestranol. The initial responses of LH and FSH within 60 minutes after injection of LH-RH revealed appearently the release of readily releasable components. On the other hand, the repletion at 120 minutes was presumably stimulated in addition and in consequence newly synthesized LH and FSH, subsequently released. Thus, mestranol enhanced the sensitivity of pituitary gonadotrophs to LH-RH in normal women with regular menstrual cycles. Moreover, the nature of the modulating effect of estrogen on pituitary responsiveness to LH-RH was dependent on the dosage and the duration of the exposure.
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合成estrogenの下垂体gonadotropin分泌調節について

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