[an error occurred while processing this directive]

Journal of Chinese Integrative Medicine ›› 2006, Vol. 4 ›› Issue (2): 166-174.doi: 10.3736/jcim20060212

• Original Experimental Research • Previous Articles     Next Articles

Effects of Chinese herbal medicine on modulating the course of puberty development in children with precocious puberty

De-pei Cai1, Bo-ying Chen2, Wei Zhang3, Pin Li1   

  1. 1. Department of Integrated Chinese and Western Medicine, Pediatric Hospital, Fudan University, Shanghai 200032, China
    2. Department of Neurobiology, Medical College, Fudan University, Shanghai 200032, China
    3. Department of Molecular Biology, Shanghai PASIC Bioengineer Institute, Shanghai 200032, China
  • Online:2006-03-20 Published:2006-03-15

RichHTML

3

PDF (PC)

414

Cited

47

Like

Objective

To explore the therapeutic effects of Ziyin Xiehuo Recipe (ZYXHR) for nourishing yin and lowering fire and Yishen Tianjing Recipe (YSTJR) for nourishing kidney and replenishing essence on regulating the gonadotrophic and somatotrophic functions of hypothalamic-pituitary axis, and to reveal the mechanisms of ZYXHR and YSTJR in modulating the course of pubertal development of children with precocious puberty.

Methods

The pubertal rats were fed with ZYXHR or YSTJR for 30 days, and the parameters of rats were monitored as the followings: The content of gonadotropin-releasing hormone（GnRH）, the frequency and amplitude of GnRH impulse releasing, the releasing amounts of aminoacid neurotransmitters, and neuropeptide Y (NPY) and β-endorphin (β-END) in the gonadotrophic area of the hypothalamus were detected with neurobiological methods (push-pull perfusion, homogenate, incubation of brain slices, and immunohistochemical staining). The levels of gene and protein expressions of GnRH, growth hormone releasing hormone (GHRH) and somatostatin (SS) in hypothalamus, and follicular stimulating hormone (FSH), luteinizing hormone (LH) and growth hormone (GH) in adenohypophysis as well as insulin-like growth factorⅠ (IGF-Ⅰ) in metaphysis were determined with real time reverse transcription-polymerase chain reaction (RT-PCR).

Results

The ZYXHR could reduce the activity of GnRH neurons in hypothalamus through inhibiting the release of central exciting aminoacid neurotransmitters, whereas promoting the release of central inhibiting aminoacid neurotransmitters, NPY and β-END in gonadotrophic area of hypothalamus. The expression levels of GnRH, FSH and LH mRNAs were down-regulated while the expression level of SS mRNA in hypothalamus was up-regulated in the ZYXHR-treated group. The GH mRNA in hypophysis and the IGF-Ⅰ mRNA in metaphysis were both down-regulated by ZYXHR. The YSTJR could promote the activity of GnRH neurons in hypothalamus through inhibiting the release of NPY in gonadotrophic area of hypothalamus, up-regulating the expression levels of GnRH, FSH, LH and GH mRNAs in hypophysis, and IGF-Ⅰ mRNA in metaphysis, while down-regulating the expression level of SS mRNA in hypothalamus.

Conclusion

The ZYXHR and YSTJR could both regulate the gonadotrophic and somatotrophic functions of hypothalamic-pituitary axis through modulating the neuroendocrine regulation and the gene expressions of GnRH and SS in hypothalamus, GH, FSH and LH in hypophysis, and IGF-Ⅰ in metaphysis. These may be the chief mechanisms of ZYXHR and YSTJR in modulating the course of pubertal development and ameliorating the skeletal development in children with precocious puberty.

Key words: Chinese materia medica, Puberty, Precocious, Neurotransmitters, Neuropeptide Y, β-endorphin, Hypothalamic-pituitary-gonadal axis,

CLC Number: 

  • R585

Table 1

Effects of ZYXHR on releasing contents of aminoacid transmitters and β-END in preoptic area of hypothalamus (ヌ±S, nmol/L)"

Group n Asp Glu GABA β-END
Normal control 6 120.29±117.01 161.53±101.75 104.74±71.81 372.57±156.24
ZYXHR-treated 6 33.10±13.34* 76.15±46.10* 238.79±104.13** 619.51±195.20*

Table 2

Effects of ZYXHR and YSTJR on NPY contents in hypothalamus (ヌ±S)"

Group n NPY (integrated optic density)
MPOA ARC ME
Normal control 5 0.26±0.09 0.57±0.31 0.63±0.10
ZYXHR-treated 5 0.45±0.16* 0.93±0.46* 0.97±0.51*
YSTJR-treated 5 0.34±0.05 0.32±0.08* 0.43±0.22*

Table 3

Effects of ZYXHR on impulse releasing of GnRH in preoptic area of hypothalamus (ヌ±S)"

Group n Pulse interval（min) Pulse amplitude(ng/L)
Normal control 5 104.00±22.80 40.36±10.05
ZYXHR-treated 5 ≥180** 28.31±5.88*

Table 4

Effects of ZYXHR and YSTJR on GnRH contents in homogenate of preoptic area of hypothalamus (ヌ±S, pg/mg)"

Group n GnRH
Normal control 5 42.77±13.39
ZYXHR-treated 8 30.77±8.57
YSTJR-treated 7 152.28±113.07*

Table 5

Effects of ZYXHR on GnRH releasing in medial basal hypothalamus (ヌ±S,ng/L)"

Group n GnRH contents in incubating solution
Basic level Activated release
Normal control 10 34.82±18.09 83.44±14.38
ZYXHR-treated 10 36.10±21.23 65.21±30.40*

Table 6

Effects of ZYXHR and YSTJR on GnRH contents in hypothalamus (ヌ±S)"

Group n GnRH (integrated optic density)
MPOA ARC ME
Normal control 5 0.97±0.60 0.84±0.08 0.86±0.14
ZYXHR-treated 5 0.19±0.04** 0.41±0.13** 0.49±0.11**
YSTJR-treated 5 1.96±0.64* 1.98±0.36** 3.14±0.27**

Figure 1

Effects of ZYXHR and YSTJR on GnRH contents in hypothalamusA: Positive expression of GnRH in MPOA in normal control group (×100); B: Positive expression of GnRH in ARC in normal control group (×200); C: Positive expression of GnRH in ME in normal control group (×200); D: Positive expression of GnRH in MPOA in ZYXHR-treated group (×100); E: Positive expression of GnRH in ARC in ZYXHR-treated group (×200); F: Positive expression of GnRH in ME in ZYXHR-treated group (×200); G: Positive expression of GnRH in MPOA in YSTJR-treated group (×100); H: Positive expression of GnRH in ARC in YSTJR-treated group (×200); I: Positive expression of GnRH in ME in YSTJR-treated group (×200)."

Table 7

Effects of ZYXHR and YSTJR on expressions of GnRH gene in hypothalamus, and FSH and LH genes in hypophysis (ヌ±S)"

Group n Integrated optic density
GnRH cDNA FSH cDNA LH cDNA
Normal control 10 0.045±0.008 0.566±0.008 0.406±0.019
ZYXHR-treated 10 0.416±0.013** 0.518±0.012** 0.375±0.009**
YSTJR-treated 10 0.534±0.011** 0.629±0.011** 0.434±0.022**

Table 8

Effects of ZYXHR and YSTJR on expression level of SS mRNA in periventricular nucleus of hypothalamus (ヌ±S)"

Group n SS mRNA
Amount of positive Amount of positive neurons Areal optic density of
neurons per unit area （/mm2） positive neurons
Normal control 6 124.28±14.19 55.23±5.75 4 688.72±786.60
ZYXHR-treated 6 165.22±36.44* 73.43±15.64* 6 813.60±889.18*
YSTJR-treated 6 91.61±10.91* 40.72±7.41* 2 912.33±132.47*

Table 9

Effects of ZYXHR and YSTJR on expression level of SS protein in periventricular nucleus of hypothalamus (ヌ±S)"

Group n SS protein
Amount of positive Amount of positive neurons Areal density of
neurons per unit area （/mm2） positive neurons
Normal control 6 98.11±15.50 43.60±6.34 4 651.72±607.33
ZYXHR-treated 6 143.83±23.24* 62.82±10.13* 8 321.22±1041.40*
YSTJR-treated 6 61.39±9.51* 25.80±4.27* 3 424.94±884.56*

Figure 2

Positive neurons of SS mRNA in periventricular nucleus of hypothalamus in three groupsA: Normal control group; B： ZYXHR-treated group; C: YSTJR-treated group."

Figure 3

Positive neurons of SS protein in periventricular nucleus of hypothalamus in three groupsA: Normal control group; B： ZYXHR-treated group; C: YSTJR-treated group."

Table 10

Effects of ZYXHR and YSTJR on expression level of GHRH mRNA in ARC of hypothalamus (ヌ±S)"

Group n GHRH mRNA
Amount of positive neurons Areal optic density of positive neurons
Normal control 6 27.17±4.4 0.125±0.026
ZYXHR-treated 6 27.44±5.0 0.120±0.027
YSTJR-treated 6 28.06±3.5 0.127±0.028

Figure 4

Positive neurons of GHRH mRNA in ARC of hypothalamus in three groupsA: Normal control group： B; ZYXHR-treated group; C: YSTJR-treated group."

Table 11

Effects of ZYXHR and YSTJR on gene copy number of GH cDNA in hypophysis and IGF-Ⅰ cDNA in liver and metaphysis (ヌ±S, ×107 copy)"

Group n GH IGF-Ⅰ in liver IGF-Ⅰ in metaphysis
Normal control 10 19.38±6.69 16.80±6.57 2 141.0±585.38
ZYXHR-treated 10 7.08±1.20* 6.39±1.61* 228.5±65.73*
YSTJR-treated 10 44.69±9.14* 40.50±16.27* 3 860.43±673.00*

Table 12

Effects of ZYXHR and YSTJR on GH cells in adenohypophysis (ヌ±S)"

Group n Single cell area (μm2) Amount of positive cell (/field of vision) Positive cell area (μm2)
Normal control 10 47.66±5.53 557.08±62.74 25 776.85±2110.37
ZYXHR-treated 10 34.21±3.06* 455.09±35.96* 20 806.55±1784.75*
YSTJR-treated 10 43.43±4.29 704.80±55.66* 298 99.60±4014.45*

Figure 5

GH-positive cells in adenohypophysis in three groupsA: Normal control group; B：ZYXHR-treated group; C: YSTJR-treated group."

[1] Cai DP, Ji ZY, Chen BY , et al. Pathogenetic regularity of female precocious puberty and the mechanism of therapy with TCM[J]. Chin J Integr Med, 2001,7(2):132-134
doi: 10.1007/BF02935023
[2] 李嫔, 向正华, 蔡德培 . 中药对大鼠下丘脑生长抑素及垂体生长激素基因表达与蛋白表达的调节作用[J]. 中国中西医结合杂志, 2003,23(3):207-210
doi: 10.7661/CJIM.2003.3.207
[3] 沈皓, 蔡德培, 陈伯英 . 补肾中药对下丘脑-垂体促性腺机能的影响[J]. 中西医结合学报, 2004,2(1):53-57
[4] Wetsel WC, Valenca MM, Mercanthaler I , et al. Intrinsic pulsatile secretory activity of immortalized luteinizing hormone-releasing hormone-secreting neurons[J]. Proc Nact Acad Sci U S A, 1992,89(9):4149-4153
[5] Wu FC, Butler GE, Kelnar CJ , et al. Ontogeny of pulsatile gonadotropin releasing hormone secretion from midchildhood, through puberty, to adulthood in the human male: a study using deconvolution analysis and an ultrasensitive immunofluorometric assay[J]. J Clin Endocrinol Metab, 1996,81(5):1798-1805
[6] Bourguignon JP, Franchimont P . Puberty-related increase in episodic LHRH release from rat hypothalamus in vitro[J]. Endocrinology, 1984,114(5):1941-1943
doi: 10.1210/endo-114-5-1941 pmid: 6370671
[7] Spergel DJ, Krsmanoric LZ, Stojilkovic SS , et al. Glutamate modulates [Ca2+]i and gonadotropin-releasing hormone secretion in immortalized hypothalamic GT1-7 neurons[J]. Neuroendocrinology, 1994,59(4):309-317
[8] Jarry H, Hirsch B, Leonhardt S , et al. Amino acid neurotransmitter release in the preoptic area of rats during the positive feedback actions of estradiol on LH release[J]. Neuroendocrinology, 1992,56(2):133-140
[9] Kawano H, Daikoku S . Somatostatin-containing neuron systems in the rat hypothalamus: retrograde tracing and immunohistochemical studies[J]. J Comp Neurol, 1988,271(2):293-299
[10] McCarthy GF, Beaudet A, Tannenbaum GS . Colocalization of somatostatin receptors and growth hormone-releasing factor immunoreactivity in neurons of the rat arcuate nucleus[J]. Neuroendocrinology, 1992,56(1):18-24
[1] Na Wu , Lu Song , Xin-xin Yang, Jiang-lei Wei , Zhen-guo Liu. Effects of Chinese herbal medicine Tianqi Pingchan Granule on G protein-coupled receptor kinase 6 involved in the prevention of levodopa-induced dyskinesia in rats with Parkinson disease. Journal of Chinese Integrative Medicine, 2012, 10(9): 1018-1024.
[2] Xin-min Li, Hui Chen, Yan-yan Ren, Yan-li Lu. Effects of Chinese herbal medicine Xifeng Capsule on multidrug resistance-associated protein 1 expression in hippocampus and cortex of rats with lithium-pilocarpine-induced epilepsy. Journal of Chinese Integrative Medicine, 2012, 10(8): 911-917.
[3] Yong Zhang, Xiao-wen Sun, Jian-hua Xu, Hai Lu, Zhong-ze Fan, Jue Sun, Xiao-xiao Zhang. Effects of medicated serum prepared with Chinese herbal medicine Changweiqing on pharmacokinetics of oxaliplatin in colon cancer cells. Journal of Chinese Integrative Medicine, 2012, 10(8): 901-910.
[4] Wei-hua Xu, Ze-huai Wen, Wei-xiong Liang, Qi Wang. A review of research on the development of instruments for therapeutic efficacy evaluation of traditional Chinese medicine. Journal of Chinese Integrative Medicine, 2012, 10(7): 726-737.
[5] Lin Wang, Guan-liang Wang, Jia-han Liu, Di Li, De-zeng Zhu, Liang-neng Wu . Effects of ursolic acid in ameliorating insulin resistance in liver of KKAy mice via peroxisome proliferator-activated receptors α and γ. Journal of Chinese Integrative Medicine, 2012, 10(7): 793-799.
[6] Yu-ting Yin, Xiao-wan Li , Yang Dong , Jian-rong Shi. Research progress in biological basis of cold and heat essence of Chinese medicine. Journal of Chinese Integrative Medicine, 2012, 10(12): 1328-1335.
[7] Rui Jin , Bing Zhang . A complexity analysis of Chinese herbal property theory: The multiple expressions of herbal property (Part 2). Journal of Chinese Integrative Medicine, 2012, 10(12): 1321-1327.
[8] Rui Jin, Bing Zhang. A complexity analysis of Chinese herbal property theory: the multiple formations of herbal property (Part 1). Journal of Chinese Integrative Medicine, 2012, 10(11): 1198-1205.
[9] Jie-ning Wang, Sheng Ye, Dong-hai Yu, Hui Zhao, Le-yi Du. Practice and exploration on clinical evaluations of hospital-made Chinese herbal formulas in the Pudong New Area of Shanghai. Journal of Chinese Integrative Medicine, 2012, 10(10): 1084-1087.
[10] Xiao-ping Huang , Xiao-dan Liu , Chang-qing Deng . Effects of the combination of active component extracts from Astragalus membranaceus and Panax notoginseng on apoptosis, reactive oxygen species and mitochondrial membrane potential of PC12 cells with oxidative injury. Journal of Chinese Integrative Medicine, 2012, 10(10): 1127-1134.
[11] Rui Jin, Bing Zhang , Xiao-qing Liu , Chun-miao Xue , Qian Zhang, Lian-zhen Li, Qian Zhao, Kang Li . A theoretical and experimental study on the Fuzzy evaluation model of biological performance of Chinese materia medica with an either cold or hot herbal property. Journal of Chinese Integrative Medicine, 2012, 10(10): 1106-1119.
[12] Han Xiang-hui, Ye Yi-yi, Guo Bao-feng, Liu Sheng. Effects of platycodin D in combination with different active ingredients of Chinese herbs on proliferation and invasion of 4T1 and MDA-MB-231 breast cancer cell lines. Journal of Chinese Integrative Medicine, 2012, 10(1): 67-75.
[13] Ng Cui-shan, Wang Shan-ping, Cheong Jun-long, Wu Yu-dan, Jia Yong-liang, Leung Siu-wai. Systematic review and meta-analysis of randomized controlled trials comparing Chinese patent medicines Compound Danshen Dripping Pills and Di’ao Xinxuekang in treating angina pectoris. Journal of Chinese Integrative Medicine, 2012, 10(1): 25-34.
[14] Qian Zhang, Bing Zhang, Rui Jin, Lian-zhen Li, Qian Zhao, Xiao-qing Liu. Pharmacological effects of Oleum Cinnamomi and water extract of Cortex Cinnamomi in rats with yang-deficiency cold syndrome and the mathematical analysis. Journal of Chinese Integrative Medicine, 2011, 9(9): 983-990.
[15] Li-li Yang, Miao Wang, Tao Liu, Hai-yan Song, Dong-fei Li, Pei-yong Zheng, Ping Liu, Guang Ji. Effects of Chinese herbal medicine Jiangzhi Granule on expressions of liver X receptor α and sterol regulatory element-binding protein-1c in a rat model of non-alcoholic fatty liver disease. Journal of Chinese Integrative Medicine, 2011, 9(9): 998-1004.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] Jin-rong Fu. Establishment of multivariate diagnosis and treatment system of modern gynecology of traditional Chinese medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 22-24
[2] Hao Li, Ming-jiang Yao, Wen-ming Zhao, Jie Guan, Lin-lin Cai, Ling Cui. A randomized, controlled, double-blind trial of Huannao Yicong capsule in senile patients with mild cognitive impairment. Journal of Chinese Integrative Medicine, 2008, 6(1): 25-31
[3] Zhi-chun Jin. Problems in establishing clinical guideline for integrated traditional Chinese and Western medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 5-8
[4] SUN Ming-yu, ZUO Jian, DUAN Ji-feng, HAN Jun, FAN Shi-ming, ZHANG Wei, ZHU Li-fang, YAO Ming-hui. Antitumor activities of kushen flavonoids in vivo and in vitro. Journal of Chinese Integrative Medicine, 2008, 6(1): 51-59
[5] Min Cheng, Qiong Feng, Shu-wen Qian, Hui Gao, Cui-qing Zhu. Preliminary assay of p-amyloid binding elements in heart-beneficial recipe. Journal of Chinese Integrative Medicine, 2008, 6(1): 68-72
[6] Ning-qun Wang, Liang-duo Jiang, Zong-xing Li. Research progress in asthma-related quality of life. Journal of Chinese Integrative Medicine, 2008, 6(1): 93-97
[7] Jing-yuan Mao, Chang-xiao Liu, Heng-he Wang, Guang-li Wei , Zhen-peng Zhang, Jie Xing, Wang Xian liang , Ying-fei Bi . Effects of Shenmai Injection on serum concentration and pharmacokinetics of digoxin in dogs with heart failure. Journal of Chinese Integrative Medicine, 2010, 8(11): 1070-1074
[8] Zhi-mei Wang, Bin Zhang. A study on translation of ellipses in Huangdi Neijing from perspective of hermeneutic theory. Journal of Chinese Integrative Medicine, 2010, 8(11): 1097-1100
[9] Gui Yu, Jie Wang. Thinking on building the network cardiovasology of Chinese medicine. Journal of Chinese Integrative Medicine, 2012, 10(11): 1206-1210
[10] Pedro Saganha João, Doenitz Christoph, Greten Tobias, Efferth Thomas, J. Greten Henry. Qigong therapy for physiotherapists suffering from burnout: a preliminary study. Journal of Chinese Integrative Medicine, 2012, 10(11): 1233-1239
[an error occurred while processing this directive]