Adverse effect of environmental endocrine disruptors on gonadal development of prepubertal male rats and therapeutic effect of bushen tianjing recipe on it / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To verify the antagonistic effect of Bushen Tianjing Recipe (BTR) on environmental endocrine disruptors (EEDs) induced gonadal dysgenesis (GD) Sprague-Dawley (SD) male rat model.</p><p><b>METHODS</b>Totally 70 3-week-old male SD rats were randomly divided into seven groups, i.e., the control group (fed with corn oil), the model A group [di-2-ethylhexyl-phthalate (DEHP) 500 mg/kg], the CM A group (fed with DEHP 500 mg/kg + BTR 40 mL/kg), the exposed group B (fed with CYP 80 mg/kg), the CM B group (fed with CYP 80 mg/kg + BTR 40 mL/kg), the model C group [fed with DEHP 500 mg/kg + CYP 80 mL/kg], the CM C group (DEHP 500 mg/kg + CYP 80 mg/kg + BTR 40 mL/kg), respectively, 10 in each group. All were administered with corresponding medication by gastrogavage, once daily, for total 30 days. Rats were killed 24 h after the last administration, and their body weight and wet testis weight were weighed. The coefficient of testis was calculated. The serum testosterone (T) level was measured by chemiluminescent immunoassay. The histopathologic tissue was prepared. The ultrastructural changes of genital cells were observed by electron microscope.</p><p><b>RESULTS</b>Compared with the control group, there was no statistical difference in the body weight increase among all groups (P > 0.05). The time of testicular descent and preputial separation were significantly delayed in each exposed group (P < 0.01). In the exposed group A and the exposed group C, the wet weight of the testes was reduced and serum T level decreased (P < 0.01). The coefficient of testis significantly decreased in the exposed group A (P < 0.01). Compared with corresponding model group, the time of testicular descent and preputial separation were significantly fore-laid in each corresponding CM group (P < 0.01). The weight of the testes, the coefficient of testis, and the serum T level increased in the CM A group (P < 0.01). The serum T level obviously increased in the CM B group (P < 0.05).</p><p><b>CONCLUSIONS</b>The GD rat model was successfully duplicated by using DEHP. EEDs were proved to have significant anti-androgen activities. BTR was verified to have significant antagonistic to its anti-androgen effect.</p>

The establishment of environmental endocrine disruptors induced precocious puberty Macaca fascicularis model and the intervention of yin nourishing fire purging Chinese materia medica / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To establish the environmental endocrine disruptors (EEDs) induced precocious puberty macaca fascicularis model, thus verifying the antagonism of yin nourishing fire purging Chinese materia medica (YNFPCMM) against the estrogenic effects.</p><p><b>METHODS</b>(1) The female prepubescent monkeys at different months old were fed with high dose and low dose EEDs. By observing EEDs' estrogenic effects, the optimal age, the optimal exposure dose, and the optimal exposure time were determined. (2) Fifteen female prepubescent monkeys were randomly divided into the exposure group, the treatment group, and the control group, 5 in each group. Those in the exposure group were fed with EEDs such as nonylphenol (4-NP) and bisphenol A (BPA). Those in the treatment group were fed with EEDs and YNFPCMM. Those in the control group were fed with dissolvent such as corn oil. The therapeutic course was 4 weeks. By the end of the treatment, the serum estrogen level was measured and the maturation index of the vaginal keratinocytes was calculated. The uterus was extracted to measure the wet weight, the endometrial thickness, the ring-shaped myometrium thickness, the endometrial epithelial cells, and the glandular epithelium height.</p><p><b>RESULTS</b>(1) Twenty month was the optimal exposure age. The low dose EEDs was the best exposure dose, and 4 weeks was the optimal exposure time. (2) Compared with the control group, the serum estrogen level obviously increased, the maturation index of the vaginal keratinocytes significantly increased, the wet uterus weight, the endometrial thickness, the ring-shaped myometrium thickness, the endometrial epithelial cells, and the glandular epithelium height significantly increased in the exposure group (P<0.05). Compared with the exposure group, the aforesaid indices significantly decreased in the treatment group (P<0.05).</p><p><b>CONCLUSIONS</b>The EEDs induced precocious puberty macaca fascicularis model was successfully established in this study. The EEDs were proved to have estrogenic-like activities. YNFPC-MM was proved to have significant antagonism like estrogenic activities.</p>

Effect of Chinese herbs for nourishing shen-yin and removing xiang-fire on estrogen receptor expression in reproductive organ of rats contaminated with environmental endocrine disruptor / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effect of Chinese herbs for nourishing Shen-yin and removing Xiang-fire (NYRF) on estrogen receptor (ER) expression in uterus and ovary of rats contaminated with nonylphenol (NP) or its bisphenol A (BPA) mixture, for exploring the action mechanism of NYRF in antagonizing the estrogen-mimetic activity of environmental endocrine disruptors (EEDs).</p><p><b>METHODS</b>EEDs contaminated female SD rats, 3-week old, were divided into two groups, the treated group fed with NYRF and the control group with corn oil during the same period of contaminating for 15 days. The wet weight (WW) and organ coefficient (OC) of uterus in rats, as well as the ER protein and mRNA expressions in rat's uterus and ovary were detected and compared.</p><p><b>RESULTS</b>As compared with normal range, WW and OC increased significantly in the contaminated rats of the control group, with significantly down-regulated ER protein expression in uterus, and expressions of ER alpha and ER beta gene and protein in ovary (P<0.05). While in the treated group, the above-mentioned abnormalities of various indicators were markedly reversed to a certain extent (P<0.05).</p><p><b>CONCLUSION</b>EEDs show estrogenic-mimetic action on productive organs, which could be antagonized by NYRF, resulting in the down-regulated mRNA and protein expressions of ER in reproductive organs, so as to reduce the sensibility of reproductive organs to EEDs, which is probably one of the acting mechanisms of NYRF.</p>

Regulative effects of Chinese herbs for nourishing yin and removing fire on gene expressions of estrogen receptor alpha, insulin-like growth factor-1 receptor, epithelial growth factor receptor and protein synthesis in epiphyseal growth plate of female pubertal rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effect of Chinese herbs for nourishing yin and removing fire (NYRF) on gene expressions of estrogen receptor alpha (ER alpha), insulin-like growth factor-1 receptor (IGF-1R) and epithelial growth factor receptor (EGFR) in the epiphyseal growth plate of the female pubertal rats.</p><p><b>METHODS</b>The rats were randomly divided into the control group and the intervened group. Immunohistochemistry and realtime-PCR methods were used to measure the gene expression of ER alpha, IGF-1R and EGFR and their protein synthesis in epiphyseal growth plate.</p><p><b>RESULTS</b>After being intervened with NYRF, the gene expressions of ER alpha and IGF-1R were down-regulated and their protein synthesis markedly reduced, while those of EGFR were unchanged.</p><p><b>CONCLUSION</b>NYRF can modulate the development and maturation of bone by regulating the expressions of ER alpha and IGF-1R in the epiphyseal growth plate.</p>

Study on the level of environmental endocrine disruptors in serum of precocious puberty patients / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the role of environmental endocrine disruptors (EEDs) in causing the precocious puberty.</p><p><b>METHODS</b>The blood samples were collected from 79 cases of precocious puberty patients and 42 cases of normal children. The concentrations of 4-nonylphenol (4-NP), 1, 1-dichloro-2, 2, bis (p-chlorophenyl) ethylene (p, p'-DDE) and di-2-ethylhexyl phthalate (DEHP) in blood serum samples were measured by using reversed-phase high performance liquid chromatography (HPLC). The volume of uterus and ovary, the bone density, and the content of estradiol (E(2)) in serum were determined at the same time. The contents of EEDs in blood serums of precocious puberty and the indices of the target organs were analyzed by using of correlation and regression.</p><p><b>RESULTS</b>In normal control group, p, p'-DDE was detected in all the blood samples (14.93 - 40.39 ng/ml), but 4-NP and DEHP were detected in some samples (ND -6.77 ng/ml, ND -17.61 ng/ml). The levels of 4-NP, p, p'-DDE and DEHP in blood serum in precocious puberty group were notably increased than that in control group (P < 0.01). In precocious puberty group, there was a positive correlations between the 4-NP in volume of uterus and the volume of ovary and the density of bone (r = 0.394, 0.286, 0.237, P < 0.01); p, p'-DDE and volume of uterus also showed a the positive correlation (r = 0.306, P < 0.01). The influencing extent of 4-NP was 1.3 times to that of the p, p'-DDE.</p><p><b>CONCLUSION</b>The normal children and the children with precocious puberty should be all contaminated by EEDs, and the later be exposured to more EEDs. There might exist a close relationship between EEDs and the precocious puberty, and EEDs should be an important factor in causing the disease. Different kinds of EEDs might have different influencing extents to the target organs.</p>

Study on the regulative rule of reinforcing shen principle on sexual precocity and senescence at the molecular level / 中国中西医结合杂志

The imbalance of Shen-yin and Shen-yang is a common pathological basis of sexual precocity and senescence. Senescence can be regarded as physiological Shen-deficiency, which is mainly the deficiency of Shen-Yang, while the essence of sexual precocity is hyperactivity of Fire due to Yin-deficiency, and deficiency of Shen-Yin is the predominance in the imbalance. The process of growth, development, maturing and aging led by Shen-qi, is mainly involving the hypothalamus-pituitary-growth hormone axis and sexual gland axis. Early initiation of these two axes appears in sexual premature children, manifesting syndrome of Fire hyperactivity due to Yin-deficiency, while in senescence, the decline of the axes appears ahead of time and manifests syndrome of Yang qi consumption. It has been shown in experimental and clinical researches that significantly good effects could be obtained by applying Chinese recipe for warmly reinforcing Shen-Yang to postpone senescence and recipe for nourishing Yin and removing Fire to inhibit sexual precocity. It also been proved by determining syndrome and speculating the damaged site according to the effects of drug that the pathologic damage of sexual precocity and senescence is sited on the hypothalamus or higher center.

Pattern of abnormal skeletal development in girls with idiopathic precocious puberty and therapeutic effect of Chinese herbs for nourishing yin and purging fire / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the pattern of abnormal skeletal development in girls with idiopathic precocious puberty (IPP) and the therapeutic effect of Chinese herbs for nourishing yin and purging fire (CH).</p><p><b>METHODS</b>Measurement of bone age, bone mineral content (BMC) and bone density (BD) were performed and levels of serum gla-protein (BGP), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP3) were determined in girls with IPP at various stages of pubertal development. Data were compared with those collected from matched girls, and the correlativity between various parameters and the extent of the disease were analyzed to explore the pattern. Thirty-eight girls out of them were treated with CH and the therapeutic effect was observed.</p><p><b>RESULTS</b>The bone age of the IPP girls was ahead of time obviously (P < 0.05), levels of BMC, BD and serum BGP, IGF-1 were significantly higher than the levels in the healthy girls of matched age (P < 0.05). And the degree of these changes were markedly positive correlated with the severity of disease (P < 0.05). After being remitted with CH treatment, the advanced bone age was apparently alleviated, and above-mentioned abnormal criteria were lowered significantly (P < 0.05).</p><p><b>CONCLUSION</b>The skeletal development of the girls with IPP was accelerated and the skeletal maturity were ahead of time, the more serious the condition of disease, the more obvious the acceleration and the advanced bone age. CH could decelerate skeletal development and delay the skeletal maturity of IPP patients.</p>