Impact of isotype-selective estrogen receptor agonists on ovarian function
Impact of isotype-selective estrogen receptor agonists on ovarian function
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DOI：
10.1073/pnas.0306720101
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发表时间：
2004-04-06
影响因子：
11.1
通讯作者：
Fritzemeier, KH
中科院分区：
文献类型：
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作者：
Hegele-Hartung, C;Siebel, P;Fritzemeier, KH
其他同型选择性雌激素受体 (ER) 激动剂，选择性 ERα 激动剂 3,17-二羟基-19-nor-17α-pregna-1,3,5 (10)triene-21,16α-内酯和选择性 ERbeta 激动剂 8-vinylestra-1,3,5 (10)-triene-3,17beta-diol，用于垂体切除术大鼠、促性腺激素释放激素拮抗剂治疗的小鼠以及完整大鼠，以阐明同型选择性雌激素对卵泡发生和排卵生理学的影响。在垂体切除的大鼠和促性腺激素释放激素拮抗剂治疗的小鼠中，ERβ激动剂引起早期卵泡发生的刺激、卵泡闭锁的减少、卵巢基因表达的诱导以及晚期卵泡生长的刺激，同时伴随着类似于17β-雌二醇(E2)的排卵卵母细胞数量的增加。相反，ERα 激动剂对这些参数影响很小或没有影响，这意味着雌激素对卵泡发育的直接影响是由 ERβ 介导的。在完整大鼠中，E2 和 ERalpha 激动剂剂量依赖性地抑制排卵，与 ERbeta 激动剂相反。另一方面，与 E2 和 ERα 激动剂相比，ERbeta 激动剂不会刺激完整大鼠的子宫重量。这一发现符合以下假设：雌激素介导的排卵抑制和子宫生长刺激是由 ERα 介导的，而不是由 ERβ 介导的。
Other isotype-selective estrogen receptor (ER) agonists, the selective ERalpha agonist 3,17-dihydroxy-19-nor-17alpha-pregna-1,3,5 (10)triene-21,16alpha-lactone and the selective ERbeta agonist 8-vinylestra-1,3,5 (10)-triene-3,17beta-diol, were used in hypophysectomized rats, gonadotropin-releasing hormone antagonist-treated mice, as well as intact rats to elucidate the effects of isotype-selective estrogens on the physiology of folliculogenesis and ovulation. in hypophysectomized rats and gonadotropin-releasing hormone antagonist-treated mice, the ERbeta agonist caused stimulation of early folliculogenesis, a decrease in follicular atresia, induction of ovarian gene expression, and stimulation of late follicular growth, accompanied by an increase in the number of ovulated oocytes similar to 17beta-estradiol (E2). In contrast, the ERalpha agonist had little or no effect on these parameters, implying that direct estrogen effects on ovarian follicular development are mediated by ERbeta. In intact rats, E2 and the ERalpha agonist dose-dependently inhibited ovulation, in contrast to the ERbeta agonist. On the other hand, the ERbeta agonist did not stimulate uterine weight in intact rats, in contrast to E2 and the ERalpha agonist. This finding is in line with the assumption that estrogen mediated ovulation inhibition and stimulation of uterine growth are mediated by ERalpha but not by ERbeta.