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本文引用的文献

1
Hypothalamic-pituitary-gonadal axis in two men with aromatase deficiency: evidence that circulating estrogens are required at the hypothalamic level for the integrity of gonadotropin negative feedback.两名芳香化酶缺乏男性的下丘脑 - 垂体 - 性腺轴：有证据表明，在下丘脑水平维持促性腺激素负反馈的完整性需要循环雌激素。
Eur J Endocrinol. 2006 Oct;155(4):513-22. doi: 10.1530/eje.1.02254.
2
In men, peripheral estradiol levels directly reflect the action of estrogens at the hypothalamo-pituitary level to inhibit gonadotropin secretion.在男性中，外周雌二醇水平直接反映雌激素在下丘脑 - 垂体水平抑制促性腺激素分泌的作用。
J Clin Endocrinol Metab. 2006 Sep;91(9):3324-8. doi: 10.1210/jc.2006-0462. Epub 2006 Jun 20.
3
Importance of inhibin B in the regulation of FSH secretion in the human male.抑制素B在男性促卵泡激素分泌调节中的重要性。
J Clin Endocrinol Metab. 2001 Nov;86(11):5541-6. doi: 10.1210/jcem.86.11.8031.
4
Aromatization mediates testosterone's short-term feedback restraint of 24-hour endogenously driven and acute exogenous gonadotropin-releasing hormone-stimulated luteinizing hormone and follicle-stimulating hormone secretion in young men.芳香化作用介导了睾酮对年轻男性24小时内源性驱动及外源性促性腺激素释放激素急性刺激下的促黄体生成素和促卵泡激素分泌的短期反馈抑制。
J Clin Endocrinol Metab. 2001 Jun;86(6):2600-6. doi: 10.1210/jcem.86.6.7520.
5
Differential regulation of gonadotropin secretion by testosterone in the human male: absence of a negative feedback effect of testosterone on follicle-stimulating hormone secretion.睾酮对男性促性腺激素分泌的差异性调节：睾酮对促卵泡激素分泌无负反馈作用。
J Clin Endocrinol Metab. 2001 Jan;86(1):53-8. doi: 10.1210/jcem.86.1.7101.
6
Aromatase inhibition in the human male reveals a hypothalamic site of estrogen feedback.对男性进行芳香化酶抑制研究揭示了雌激素反馈的下丘脑位点。
J Clin Endocrinol Metab. 2000 Sep;85(9):3027-35. doi: 10.1210/jcem.85.9.6795.
7
Free alpha-subunit is superior to luteinizing hormone as a marker of gonadotropin-releasing hormone despite desensitization at fast pulse frequencies.尽管在快速脉冲频率下会出现脱敏现象，但游离α亚基作为促性腺激素释放激素的标志物优于促黄体生成素。
J Clin Endocrinol Metab. 1999 Mar;84(3):1028-36. doi: 10.1210/jcem.84.3.5579.
8
The direct pituitary effect of testosterone to inhibit gonadotropin secretion in men is partially mediated by aromatization to estradiol.睾酮对男性促性腺激素分泌的直接垂体抑制作用部分是由其芳香化转化为雌二醇介导的。
J Androl. 1994 Jan-Feb;15(1):15-21.
9
The antiandrogenic effects of delta 1-testolactone (Teslac) in vivo in rats and in vitro in human cultured fibroblasts, rat mammary carcinoma cells, and rat prostate cytosol.δ1-睾酮内酯（Teslac）在大鼠体内以及在人培养成纤维细胞、大鼠乳腺癌细胞和大鼠前列腺胞质溶胶中的抗雄激素作用。
Endocrinology. 1982 Jan;110(1):214-9. doi: 10.1210/endo-110-1-214.
10
Induction of puberty in men by long-term pulsatile administration of low-dose gonadotropin-releasing hormone.通过长期脉冲式给予低剂量促性腺激素释放激素诱导男性青春期。
N Engl J Med. 1982 Nov 11;307(20):1237-41. doi: 10.1056/NEJM198211113072003.

睾酮对男性促黄体生成素分泌的抑制作用，其垂体效应需要芳香化作用，而下丘脑效应则不需要：来自正常男性和促性腺激素释放激素缺乏男性的串联研究证据。

Inhibition of luteinizing hormone secretion by testosterone in men requires aromatization for its pituitary but not its hypothalamic effects: evidence from the tandem study of normal and gonadotropin-releasing hormone-deficient men.

作者信息

Pitteloud Nelly, Dwyer Andrew A, DeCruz Suzzunne, Lee Hang, Boepple Paul A, Crowley William F, Hayes Frances J

机构信息

Reproductive Endocrine Unit, Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA.

出版信息

J Clin Endocrinol Metab. 2008 Mar;93(3):784-91. doi: 10.1210/jc.2007-2156. Epub 2007 Dec 11.

DOI:10.1210/jc.2007-2156
PMID:18073301
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2266963/
Abstract

CONTEXT

Studies on the regulation of LH secretion by sex steroids in men are conflicting.

OBJECTIVE

Our aims were to determine the relative contributions of testosterone (T) and estradiol (E2) to LH regulation and localize their sites of negative feedback.

DESIGN

This was a prospective study with three arms.

SETTING

The study was conducted at a General Clinical Research Center.

PATIENTS OR OTHER PARTICIPANTS

Twenty-two normal (NL) men and 11 men with GnRH deficiency due to idiopathic hypogonadotropic hypogonadism (IHH) participated.

INTERVENTION

Medical castration and inhibition of aromatase were achieved using high-dose ketoconazole (KC) for 7 d with 1) no sex steroid add-back; 2) T enanthate 125 mg im starting on d 4; or 3) E2 patch 37.5 microg/d starting on d 4. Blood sampling was performed every 10 min for 12 h at baseline, overnight on d 3-4 and d 6-7.

MAIN OUTCOME MEASURES

Mean LH levels, LH pulse amplitude, and GnRH pulse frequency were assessed at baseline, d 3-4, and d 6-7.

RESULTS

In NL men, KC caused a 3-fold increase in mean LH on d 3-4, which was stable on d 6-7 with no add-back. Addition of T reduced LH levels (34.6+/-3.9 to 17.4+/-3.6 IU/liter, P<0.05) by slowing GnRH pulse frequency (13.3+/-0.4 to 6.7+/-1.0 pulses/12 h, P<0.005). LH amplitude increased (6.9+/-1.0 to 12.1+/-1.4 IU/liter, P<0.005). E2 add-back suppressed LH levels (36.4+/-5.6 to 19.0+/-2.4 IU/liter, P<0.005), by slowing GnRH pulse frequency (11.4+/-0.2 to 8.6+/-0.4 pulses/12 h, P<0.05) and had no impact on LH pulse amplitude. In IHH men, restoring normal T levels caused no suppression of mean LH levels or LH amplitude. E2 add-back normalized mean LH levels and decreased LH amplitude from 14.7+/-1.7 to 12+/-1.5 IU/liter (P<0.05).

CONCLUSIONS

  1. T and E2 have independent effects on LH. 2) Inhibition of LH by T requires aromatization for its pituitary, but not hypothalamic effects. 3) E2 negative feedback on LH occurs at the hypothalamus.
摘要

背景

关于性类固醇对男性促黄体生成素（LH）分泌调节的研究结果相互矛盾。

目的

我们的目的是确定睾酮（T）和雌二醇（E2）对LH调节的相对贡献，并定位它们负反馈的部位。

设计

这是一项有三个分支的前瞻性研究。

地点

该研究在一个综合临床研究中心进行。

患者或其他参与者

22名正常（NL）男性和11名因特发性低促性腺激素性性腺功能减退（IHH）导致GnRH缺乏的男性参与了研究。

干预

使用高剂量酮康唑（KC）进行7天的药物去势和芳香化酶抑制，具体如下：1）不补充性类固醇；2）从第4天开始，肌肉注射庚酸睾酮125mg；或3）从第4天开始，使用37.5μg/d的E2贴片。在基线、第3 - 4天和第6 - 7天的夜间，每10分钟采集一次血样，共采集12小时。

主要观察指标

在基线、第3 - 4天和第6 - 7天评估平均LH水平、LH脉冲幅度和GnRH脉冲频率。

结果

在NL男性中，KC使第3 - 4天的平均LH增加了3倍，在第6 - 7天不补充时保持稳定。添加T可降低LH水平（从34.6±3.9降至17.4±3.6IU/L，P<0.05），通过减慢GnRH脉冲频率（从13.3±0.4降至6.7±1.0脉冲/12小时，P<0.005）。LH幅度增加（从6.9±1.0升至12.1±1.4IU/L，P<0.005）。添加E2可抑制LH水平（从36.4±5.6降至19.0±2.4IU/L，P<0.005），通过减慢GnRH脉冲频率（从11.4±0.2降至8.6±0.4脉冲/12小时，P<0.05），且对LH脉冲幅度无影响。在IHH男性中，恢复正常T水平不会抑制平均LH水平或LH幅度。添加E2可使平均LH水平正常化，并使LH幅度从14.7±1.7降至12±1.5IU/L（P<0.05）。

结论

1）T和E2对LH有独立作用。2）T对LH的抑制作用在垂体需要芳香化，但在下丘脑不需要。3）E2对LH的负反馈发生在下丘脑。