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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

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."

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