Chronic hyperestrogenemia: lack of positive feedback action on gonadotropin-releasing hormone-induced luteinizing hormone release and dual site of negative feedback action.
Chronic hyperestrogenemia: lack of positive feedback action on gonadotropin-releasing hormone-induced luteinizing hormone release and dual site of negative feedback action.
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慢性高雌激素血症：对促性腺激素释放激素诱导的黄体生成激素释放缺乏正反馈作用和负反馈作用的双重位点。
DOI：
10.1210/endo.130.3.1537275
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发表时间：
1992
期刊：
影响因子：
4.8
通讯作者：
A. Little
中科院分区：
文献类型：
--
作者：
D. Richardson;K. Gordon;R. Billiar;A. Little
为了测试在持续存在GnRH刺激的情况下，持续的卵泡中期雌激素浓度是否会使垂体对GnRH的反应敏感，6只有规律月经周期的雌性猴子在有或没有雌酮植入的情况下每小时一次地给予GnRH脉冲。其中三组分别为1)对照组，2)外源性GnRH每小时脉冲(6微克/1分钟)，3)每小时GnRH脉冲加雌酮(E1)植入，以及4)单独E1，按2-8周的顺序进行研究。在其他三种动物中，顺序是1)对照组，2)E1，3)E1植入+每小时GnRH脉冲，以及4)仅GnRH脉冲。雌二醇平均浓度从55pg/ml增加到100pg/ml，相应的雌二醇浓度从95pg/ml增加到160pg/ml。除周期中期峰外，对照组、GnRH组、GnRH加E1期和E1期的LH值分别为10.9+/-2.2(SEM)ng/ml、12.6+/-1.5 ng/ml、11.7+/-1.5 ng/ml和检测不到(<6 ng/ml)。值得注意的是，在E1单独治疗期间，卵泡中期雌激素浓度将黄体生成素浓度抑制到无法检测到的水平，并通过应用外源性促性腺激素释放激素支持使黄体生成素浓度恢复到正常卵泡期水平。这提示雌激素负反馈信号可以抑制内源性GnRH。为了进一步验证这一假设，我们对两只性腺功能低下的雌性猴子进行了同样的实验。将雌二醇平均浓度从22 pg/ml增加到61 pg/ml，并将促黄体生成素和卵泡刺激素抑制到检测不到的水平。当每小时给予GnRH(6微克/1min)脉冲时，平均促黄体生成素和促卵泡刺激素分别增加到29.8和14.9 ng/ml。这些研究表明，将雌激素浓度提高到卵泡中期水平不会使垂体对GnRH刺激敏感，因此，在无排卵状态下，垂体敏化不太可能是导致黄体生成素分泌增加的重要原因，如多囊卵巢综合征。在性腺功能低下的猴子中，尽管完全支持外源性GnRH，促性腺激素浓度还是下降了5倍，这与雌激素负反馈作用在脑垂体部的作用是一致的。然而，当只使用雌激素时，GnRH钳确实阻止了对黄体生成素和卵泡刺激素的完全抑制，这与对下丘脑的额外负反馈效应是一致的。虽然在真性腺猴中也观察到了同样的现象，但雌激素抑制的下丘脑部位似乎不太可能在月经周期中发挥重要作用，否则卵泡期雌激素浓度的进行性上升将通过抑制GnRH的分泌而中止卵泡发生。
To test whether sustained midfollicular estrogen concentrations sensitize the pituitary response to GnRH in the continued presence of a GnRH stimulus, six female monkeys with regular menstrual cycles were administered hourly pulses of GnRH in the presence or absence of an sc estrone implant. Three were studied in a sequence of 2- to 8-week blocks of 1) control, 2) hourly pulses of exogenous GnRH (6 micrograms/1 min), 3) hourly GnRH pulses plus an estrone (E1) implant, and 4) the E1 alone. In the other three animals the sequence was 1) control, 2) E1, 3) E1 implant plus hourly GnRH pulses, and 4) GnRH pulses only. E1 increased mean estradiol concentrations from 55 pg/ml to 100 pg/ml and the corresponding E1 concentrations from 95 pg/ml to 160 pg/ml. LH concentrations, excluding midcycle surges, were 10.9 +/- 2.2 (SEM) ng/ml, 12.6 +/- 1.5 ng/ml, 11.7 +/- 1.5 ng/ml, and undetectable (less than 6 ng/ml) for the control, GnRH, GnRH plus E1, and E1-treatment periods, respectively. Of note was the suppression of LH concentrations to undetectable levels by midfollicular concentrations of estrogen during the E1-alone treatment period, and the return of LH concentrations to normal follicular phase levels by the application of exogenous GnRH support. This observation suggested that an estrogen negative feedback signal can suppress endogenous GnRH. To further examine this hypothesis we applied the same protocol to two hypogonadal female monkeys. E1 capsule placement increased the mean estradiol concentration from 22 to 61 pg/ml and suppressed LH and FSH to undetectable levels. When hourly pulses of GnRH (6 micrograms/1 min) were supplied, mean LH and FSH increased to 29.8 and 14.9 ng/ml, respectively. These studies demonstrate that elevation of estrogen concentrations to midfollicular levels does not sensitize the pituitary to GnRH stimulation, and pituitary sensitization is therefore unlikely to be important as a cause of elevated LH secretion in anovulatory states, such as the polycystic ovaries syndrome. In the hypogonadal monkeys, a 5-fold decrease in gonadotropin concentrations occurred in spite of full exogenons GnRH support, consistent with a hypophyseal site of estrogen negative feedback action. However, the GnRH clamp did prevent the complete suppression of LH and FSH noted when only estrogen was applied, consistent with an additional negative feedback effect on the hypothalamus. Although this same phenomenon is observed in the eugonadal monkeys, it appears unlikely that a hypothalamic site of estrogen inhibition plays a significant role during the menstrual cycle, otherwise the progressive rise in follicular phase estrogen concentrations would, by arresting GnRH secretion, abort folliculogenesis.
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成年恒河猴摆脱卵巢功能的慢性雌激素抑制：改变促性腺激素分泌对雌激素抑制的敏感性的证据。
影响因子：
4.8
作者：
Billiar,RB;Richardson,DW;Little,B
通讯作者：
Little,B
影响因子：
3.6
作者：
KARSCH, FJ;CUMMINS, JT;CLARKE, IJ
通讯作者：
CLARKE, IJ
卵巢类固醇对兔子下丘脑-垂体轴的反馈作用。
影响因子：
3.6
作者：
Pau,KY;Orstead,KM;Hess,DL;Spies,HG
通讯作者：
Spies,HG
幼年灵长类动物的卵泡刺激与排卵诱导：促性腺激素释放激素剂量的重要性。
DOI：
10.1210/jcem-62-3-557
发表时间：
1986
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
Sopelak,VM;Collins,RL;Hodgen,GD
通讯作者：
Hodgen,GD