食欲素-A在下丘脑-垂体-性腺轴启动中的作用

doi:10.11852/zgetbjzz2020-0917

中国儿童保健杂志 ›› 2021, Vol. 29 ›› Issue (7): 730-733.DOI: 10.11852/zgetbjzz2020-0917

食欲素-A在下丘脑-垂体-性腺轴启动中的作用

杨眉¹, 李海艳¹, 侯会丹¹, 韩敬¹, 陶月红²

1.大连医科大学,辽宁大连 116000;
2.扬州大学附属苏北人民医院儿科

收稿日期:2020-05-17 修回日期:2020-07-24 发布日期:2021-07-28 出版日期:2021-07-10
通讯作者: 陶月红,E-mail:ektyh520@163.com
作者简介:杨眉(1993-),女,四川人,住院医师,硕士研究生在读,主要研究方向为儿童内分泌。
基金资助:
江苏省“333工程”科研项目(BRA2017167)

Role of Orexin-A in the initiation of hypothalamic-pituitary-gonadal axis

YANG Mei^*, LI Hai-yan, HOU Hui-dan, HAN Jing, TAO Yue-hong

^*Dalian Medical University, Dalian, Liaoning 116000, China

Received:2020-05-17 Revised:2020-07-24 Online:2021-07-10 Published:2021-07-28
Contact: TAO Yue-hong, E-mail: ektyh520@163.com

摘要/Abstract

摘要： 目的观察食欲素-A(Orexin-A)对大鼠性发育和血清黄体生成素(LH)、卵泡刺激素(FSH)、雌二醇(E2)、瘦素(Leptin)、吻肽(Kisspeptin)水平的影响,探讨能量代谢在下丘脑-垂体-性腺轴(HPGA)启动中的作用。方法 2018年6月将100只5日龄的SPF级SD仔鼠随机分成4组(每组25只):对照组,性早熟组,Orexin-A组,Orexin-A+食欲素受体1(OX1R)拮抗剂组。后三组皮下注射25μl的含达那唑(300μg/只)的乙醇与乙二醇的混合液1次,建立大鼠性早熟模型。对照组注射同体积的不含达那唑的乙醇与乙二醇的混合液1次。15日龄后,Orexin-A组、Orexin-A+OX1R拮抗剂组分别每天侧脑室注射1次0.5 nmol/L的Orexin-A 5μl和同浓度的Orexin-A 5 μl+30 nmol/L的OX1R拮抗剂5 μl。比较各组大鼠首次阴道开口时间和青春前期、青春期及青春后期3个时间段的血清性激素、Kisspeptin、Leptin水平。结果 1)性早熟组大鼠首次阴道开口时间明显早于对照组(H＝3.092,P=0.012);2)青春前期:Orexin-A组LH、雌二醇(E2)、Kisspeptin、Leptin水平低于性早熟组(t=-3.082、-2.476、-3.732、-3.289,P＜0.05);而Orexin-A+OX1R拮抗剂组与性早熟组相比较,除Kisspeptin水平差异有统计学意义(t=-4.486,P<0.05),其余各指标组间差异均无统计学意义(P>0.05)。青春期:Orexin-A组LH、Leptin水平低于性早熟组(t=-2.469,H=-2.771,P＜0.05);而Orexin-A+OX1R拮抗剂组与性早熟组相比较,各指标组差异均无统计学意义(P>0.05)。青春后期:Orexin-A组Leptin水平低于性早熟组(t=3.674,P＜0.05)。结论 Orexin-A可能通过抑制下丘脑Kisspeptin的表达来抑制HPGA的启动和进展。能量代谢与HPGA的启动具有相关性。

关键词: 性早熟, 食欲素-A, 瘦素, 吻肽, 能量代谢

Abstract: Objective To analyze the effects of Orexin-A on sexual development, serum levels of luteinizing hormone(LH), follicle stimulating hormone(FSH), estradiol(E2), Leptin and Kisspeptin, in order to explore the role of energy metabolism in the initiation of hypothalamic- pituitary-gonadal axis (HPGA). Methods In June 2018, 100 five-days-old female SPF SD rats were randomly divided into 4 groups: the control group, the precocious puberty group, the Orexin-A group, the Orexin-A+Orexin-1 receptor (OX1R) antagonist group, with 25 rats in each group. Each rat in the later three groups was subcutaneously injected with a mixture (25μl) of ethanol and ethylene glycol with 300μg of danazol to establish the precocious puberty model, while rats in the control group were injected with the same volume of danazol-free ethanol and ethylene glycol. Rats in the Orexin-A group were injected with 0.5 nmol/L Orexin-A 5μl once daily via lateral ventricle at 15 days old, and rats in the Orexin-A+OX1R antagonist group were injected with 0.5 nmol/L Orexin-A 5μl and 30 nmol/L OX1R antagonist 5μl once daily via lateral ventricle at 15 days old. The levels of serum sex hormones, Kisspeptin and Leptin at prepuberty, onset puberty and post puberty stage were tested. The vaginal opening time in different groups was compared, and the levels of serum sex hormones, Kisspeptin and Leptin were compared in different groups and periods. Results 1) The first vaginal opening time in the precocious puberty group was earlier than that in the control group (H=3.092,P=0.012,P＜0.05). 2) It was found that the LH, E2, Kisspeptin and Leptin levels of the Orexin-A group were lower than those of the precocious puberty group at prepuberty stage (t=-3.082,-2.476,-3.732,-3.289,P＜0.05). However, there were no significant differences on other hormone level except Kisspeptin(t=-4.486,P<0.05) between the precocious puberty group and the Orexin-A+OX1R antagonist group((t=-2.469,-2.771,P＞0.05). During puberty onset stage, the LH and Leptin levels in the Orexin-A group was lower than those in the precocious puberty group(P＜0.05). However, there were no significant differences between the precocious puberty group and the Orexin-A+OX1R antagonist group(P＞0.05). At post puberty stage, the leptin level in the Orexin-A group was lower than that in the precocious puberty group(t=3.674,P＜0.05). Conclusion Orexin-A can inhibit the initiation and progress of the HPGA by inhibiting Kisspeptin expression in the hypothalamus. Energy metabolism is related to the initiation of HPGA.

Key words: precocious puberty, orexin-A, leptin, kisspeptin, energy metabolism

中图分类号:

R338

杨眉, 李海艳, 侯会丹, 韩敬, 陶月红. 食欲素-A在下丘脑-垂体-性腺轴启动中的作用[J]. 中国儿童保健杂志, 2021, 29(7): 730-733.

YANG Mei, LI Hai-yan, HOU Hui-dan, HAN Jing, TAO Yue-hong. Role of Orexin-A in the initiation of hypothalamic-pituitary-gonadal axis[J]. Chinese Journal of Child Health Care, 2021, 29(7): 730-733.

参考文献

[1] Boss C,Roch C. Recent trends in orexin research--2010 to 2015[J]. Bioorg Med Chem Lett, 2015, 25(15): 2875-2887.
[2] Tomasik PJ, Spodaryk M, Sztefko K. Plasma concentrations of orexins in children[J]. Ann Nutr Metab, 2004, 48(4): 215-220.
[3] Russell SH, Small CJ, Kennedy AR, et al. Orexin A interactions in the hypothalamo-pituitary gonadal axis[J]. Endocrinology, 2001, 142(12):5294-5302.
[4] Furuta M, Funabashi T, Kimura F. Suppressive action of orexin A on pulsatile luteinizing hormone secretion is potentiated by a low dose of estrogen in ovariectomized rats[J]. Neuroendocrinology, 2002, 75(3):151-157.
[5] Zhao Y, Singh C, Prober DA, et al. Morphological and physiological interactions between GnRH3 and hypocretin/orexin neuronal nystems in zebrafish (danio rerio)[J]. Endocrinology, 2016, 157(10): 4012-4020.
[6] Liguori G, Squillacioti C, Assisi L, et al. Potential role of orexin A binding the receptor 1 for orexins in normal and cryptorchid dogs[J]. BMC Vet Res, 2018, 14(1): 55.
[7] Liu L, Wang Q, Liu A, et al. Physiological implications of orexins/hypocretins on energy metabolism and adipose tissue development[J]. ACS Omega, 2019, 5(1): 547-555.
[8] Ch'ng SS, Lawrence AJ. Distribution of the orexin-1 receptor (OX1R) in the mouse forebrain and rostral brainstem: a characterisation of OX1R-eGFP mice[J]. J Chem Neuroanat, 2015, 66-67: 1-9.
[9] Chen M, Eugster EA. Central precocious puberty: update on diagnosis and treatment[J]. Paediatr Drugs, 2015, 17(4): 273-281.
[10] Avendaño MS, Vazquez MJ, Tena-Sempere M. Disentangling puberty: novel neuroendocrine pathways and mechanisms for the control of mammalian puberty[J]. Hum Reprod Update, 2017, 23(6):737-763.
[11] Hosseini A, Khazali H. Central orexin A affects reproductive axis by modulation of hypothalamic kisspeptin/neurokinin B/dynorphin secreting neurons in the male wistar rats[J]. Neuromolecular Med, 2018, 20(4): 525-536.
[12] Louis GW, Greenwald-Yarnell M, Phillips R, et al. Molecular mapping of the neural pathways linking leptin to the neuroendocrine reproductive axis[J]. Endocrinology, 2011, 152(6):2302-2310.
[13] Radwańska P, Kosior-Korzecka U. Relationships between leptin, Kiss-1/GPR54 expression and TSH secretion from pituitary cells of pubertal ewes in vitro[J]. Res Vet Sci, 2016, 105: 180-187.
[14] Cortés ME, Carrera B, Rioseco H, et al. The role of kisspeptin in the onset of puberty and in the ovulatory mechanism: a mini-review[J]. J Pediatr Adolesc Gynecol, 2015, 28(5):286-291.
[15] Kang MJ, Oh YJ, Shim YS, et al. The usefulness of circulating levels of leptin, kisspeptin, and neurokinin B in obese girls with precocious puberty[J]. Gynecol Endocrinol, 2018, 34(7):627- 630.
[16] 李素娟.不同青春发育阶段儿童青少年血清leptin、kisspeptin水平的变化[D]. 北京:北京协和医学院, 2015: 9-11.
[17] Kelly Y, Zilanawala A, Sacker A, et al. Early puberty in 11-year-old girls: millennium cohort study findings[J]. Arch Dis Child, 2017, 102(3): 232-237.
[18] Flom JD, Cohn BA, Tehranifar P, et al. Earlier age at menarche in girls with rapid early life growth: cohort and within sibling analyses[J]. Ann Epidemiol, 2017, 27(3): 187-193.
[19] Lian Q, Mao Y, Luo S, et al. Puberty timing associated with obesity and central obesity in Chinese Han girls[J]. BMC Pediatr, 2019, 19(1): 1.
[20] He F, Guan P, Liu Q, et al. The relationship between obesity and body compositions with respect to the timing of puberty in Chongqing adolescents: a cross-sectional study[J]. BMC Public Health, 2017, 17(1): 664.

食欲素-A在下丘脑-垂体-性腺轴启动中的作用

Role of Orexin-A in the initiation of hypothalamic-pituitary-gonadal axis

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