Differential modulation of gonadotropin secretion by selective estrogen receptor 1 and estrogen receptor 2 agonists in ovariectomized ewes
Differential modulation of gonadotropin secretion by selective estrogen receptor 1 and estrogen receptor 2 agonists in ovariectomized ewes
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DOI：
10.1095/biolreprod.107.060046
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发表时间：
2007-08-01
影响因子：
3.6
通讯作者：
Nett, Terry M.
中科院分区：
文献类型：
--
作者：
Arreguin-Arevalo, J. Alejandro;Davis, Tracy L.;Nett, Terry M.
本研究的目的是确定雌激素受体1（ESR 1;也称为ER α）或雌激素受体2（ESR 2;也称为ER β）或两者的激活是否需要：1）急性抑制LH分泌，2）诱导排卵前LH样峰，3）抑制卵巢切除（OVX）母羊的FSH分泌。OVX母羊（n = 6）肌内注射25 μ g雌二醇（E-2）、12 mg丙基吡唑三醇（PPT;亚型选择性ESR 1激动剂）、21 mg二辛基丙腈（DPN;亚型选择性ESR 2激动剂）或PPT + DPN。与E-2一样，PPT、DPN或两者联合使用可迅速降低LH分泌（P < 0.05）。每种激动剂诱导的LH分泌的初始抑制后，一个渐进的，长期的上升，但无论是单独的激动剂，也没有联合激动剂能够诱导一个“正常的”排卵前LH样激增类似于E-2诱导。与E-2处理的母羊相比，DPN处理的母羊LH分泌开始增加的时间较早（P < 0.01），PPT处理的母羊较晚（P < 0.05），而接受联合激动剂处理的母羊的时间间隔相似。与E-2一样，PPT抑制FSH分泌（P < 0.05），但抑制持续时间较长。在本研究中，DPN不改变FSH的分泌。在原代培养的绵羊垂体细胞中，研究了PPT和DPN对GnRH受体数量的调节作用。在我们的研究中，PPT和DPN都增加了GnRH受体的数量，但刺激GnRH受体合成所需的DPN剂量比PPT高10倍。结果表明：1）ESR 1和ESR 2在垂体水平介导了E-2对LH分泌的负反馈作用; 2）ESR 1和ESR 2之间既不协同也不拮抗;然而，它们确实相互作用以同步E-2对LH分泌的刺激作用的开始，（3）ESR 1和ESR 2可能通过增加GnRH受体的数量，至少部分地介导了E2对LH分泌的正反馈作用;（4）只有ESR 1参与了E2对FSH分泌的负反馈作用。
The objectives of this study were to determine whether activation of estrogen receptor 1 (ESR1; also known as ERalpha), or estrogen receptor 2 (ESR2; also known as ERbeta), or both are required to: 1) acutely inhibit secretion of LH, 2) induce the preovulatory-like surge of LH, and 3) inhibit secretion of FSH in ovariectomized (OVX) ewes. OVX ewes (n = 6) were administered intramuscularly 25 micrograms estradiol (E-2), 12 mg propylpyrazoletriol (PPT; a subtype-selective ESR1 agonist), 21 mg diaprylpropionitrile (DPN; a subtype-selective ESR2 agonist), or PPT + DPN. Like E-2, administration of PPT, DPN, or combination of the two rapidly decreased (P < 0.05) secretion of LH. Each agonist induced a gradual, prolonged rise in secretion of LH after the initial inhibition, but neither agonist alone nor the combined agonists was able to induce a "normal" preovulatory-like surge of LH similar to that induced by E-2. Compared with E-2-treated ewes, the beginning of the increase in secretion of LH occurred earlier (P < 0.01) in DPN-treated ewes, later (P < 0.05) in PPT-treated ewes, and at a similar interval in ewes receiving the combined agonist treatment. Like E-2, PPT decreased (P < 0.05) secretion of FSH, but the duration of suppression was much longer in PPT-treated ewes. DPN did not alter secretion of FSH in this study. Modulation of the number of GnRH receptors by PPT and DPN was examined in primary cultures of ovine pituitary cells. In our hands, both PPT and DPN increased the number of GnRH receptors, but the dose of DPN required to stimulate synthesis of GnRH receptors was 10 times higher than that of PPT. We conclude that in OVX ewes: 1) ESR1 and ESR2 mediate the negative feedback of E-2 on secretion of LH at the level of the pituitary gland, 2) ESR1 and ESR2 do not synergize or antagonize the effects of each other; however, they do interact to synchronize the beginning of the stimulatory effect of E-2 on secretion of LH, 3) ESR1 and ESR2 may mediate at least partially the positive feedback of E2 on LH secretion by increasing the number of GnRH receptors, and 4) only ESR1 appears to be involved in the negative feedback of E-2 on secretion of FSH.