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
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References
[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.
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