Gonadotropin-releasing hormone agonist in premenopausal women does not alter hypothalamic-pituitary-adrenal axis response to corticotropin-releasing hormone
Gonadotropin-releasing hormone agonist in premenopausal women does not alter hypothalamic-pituitary-adrenal axis response to corticotropin-releasing hormone
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DOI：
10.1152/ajpendo.00221.2017
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发表时间：
2018-08-01
影响因子：
5.1
通讯作者：
Kohrt, Wendy M.
中科院分区：
文献类型：
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作者：
Gavin, Kathleen M.;Shea, Karen L.;Kohrt, Wendy M.
性激素似乎在调节下丘脑-垂体-肾上腺(HPA)轴的活动中起作用。目的是分离雌二醇(E-2)对HPA轴中枢激活的影响。我们假设，在地塞米松(Dex)抑制下，HPA轴对促肾上腺皮质激素释放激素(CRH)的反应在慢性卵巢激素抑制时会被夸大，而生理性的E-2添加将减轻这种反应。30名绝经前妇女接受促性腺激素释放激素激动剂(GnRH(AG))和透皮剂[E-2，每天0.075 mg，GnRH(AG)，+E-2，n=15]或安慰剂(GnRH(AG)+PL，n=15)治疗20wk。GnRH(AG)+PL组和GnRH(AG)+E-2组的年龄(38(SD 5)岁比36(SD 7)岁)和体重指数(27(SD 6)kg/m(2)比27(SD 6)kg/m(2))相似。血清E-2随GnRH(AG)+PL的升高而降低(P=0.008)，GnRH(AG)+E-2无明显变化(P=0.36)。血清促肾上腺皮质激素(ACTH)与总皮质醇(P=0.03)和皮质醇(P=0.04)对CRH的曲线下面积(AUC(Inc))不同。在检查组内更改时。GnRH(AG)+PL不改变HPA轴对Dex/CRH的反应，但GnRH(AG)+E-2使ACTH的AUC(INC)降低(AUC(Inc)，1,623+/-257至1,211+/-236pg/ml中心点，P=0.004)。皮质醇(1.795+/-367~1.090+/-281 ng/ml中心点最小值，P=0.009)和总皮质醇(7.008+/-1.387~3,893+/-1,090 ng/ml中心点最小值，P=0.02)。应用促性腺激素释放激素(GnRH，AG)治疗20wk后，HPA轴对CRH的反应并未增加，但生理性E-2加法降低了HPA轴的活性。
Sex honnones appear to play a role in the regulation of hypothalamic-pituitary-adrenal (HPA) axis activity. The objective was to isolate the effects of estradiol (E-2) on central activation of the HPA axis. We hypothesized that the HPA axis response to corticotropin-releasing hormone (CRH) under dexamethasone (Dex) suppression would be exaggerated in response to chronic ovarian hormone suppression and that physiologic E-2 add-back would mitigate this response. Thirty premenopausal women underwent 20 wk of gonadotropin-releasing hormone agonist therapy (GnRH(AG)) and transderma] E-2 (0.075 mg per day, GnRH(AG), + E-2, n = 15) or placebo (PL) patch (GnRH(AG) + PL, n = 15). Women in the GnRH(AG) + PL and GnRH(AG) + E-2 groups were of similar age (38 (SD 5) yr vs. 36 (SD 7) yr) and body mass index (27 (SD 6) kg/m(2) vs. 27 (SD 6) kg/m(2)). Serum E-2 changed differently between the groups (P = 0.01); it decreased in response to GnRH(AG) + PL (77.9 +/- 17.4 to 23.2 +/- 2.6 pg/ml; P = 0.008) and did not change in response to GnRH(AG) + E-2 (70.6 +/- 12.4 to 105 +/- 30.4 pg/ml; P = 0.36). The incremental area under the curve (AUC(INC)) responses to CRH were different between the groups for total cortisol (P = 0.03) and cortisone (P = 0.04) but not serum adrenocorticotropic hormone (ACTH) (P = 0.28). When examining within-group changes. GnRH(AG) + PL did not alter the HPA axis response to Dex/CRH, but GnRH(AG) + E-2 decreased the AUC(INC) for ACTH (AUC(INC), 1,623 +/- 257 to 1,211 +/- 236 pg/ml center dot min, P = 0.004). cortisone (1.795 +/- 367 to 1.090 +/- 281 ng/ml center dot min, P = 0.009), and total cortisol (7.008 +/- 1.387 to 3,893 +/- 1,090 ng/ml center dot min, P = 0.02). Suppression of ovarian hormones by GnRH(AG) therapy for 20 wk did not exaggerate the HPA axis response to CRH, but physiologic E-2 add-back reduced HPA axis activity compared with preintervention levels.