• The Journal of Korean Obstetrics and Gynecology
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• v.24 no.3
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• pp.28-47
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• 2011

Objectives: This study was performed to investigate the effects of Angelicae gigantis Radix (AGR) which is one of the most useful herbal-drug to treat patients with Polycystic Ovary Syndrome (PCOS) in Oriental medicine on gene expression of ovary tissue. Methods: The effects of AGR on gene expression of ovary tissue resected from PCOS induced rats using single injection of $\ss$-Estradiol 17-valerate (EV) was measured using microarray technique, and the functional analysis on these genes was conducted. Results: Total 2,812 genes were up-regulated or down-regulated, 1,421 genes were up-regulated, 1,391 genes were down-regulated by induction of PCOS. Up-regulated genes were mainly involved in biological function such as cell signalling pathways and inflammatory response. Expression levels of 1,442 genes were restored to those of naive animals by administration of AGR. 558 genes were restored to those of naive animals, which were lowered by induction of PCOS. 884 genes were lowered to naive levels, which were elevated by induction of PCOS. The functions of restored genes were partially involved in the restoration of expression levels, which were changed by induction of PCOS. Especially, up-regulated gene by induction of PCOS were mainly involved in these changes. These results mean restorative effects of AGR on damaged functions by induction of PCOS. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as IRS2, MCM10, ORC2L related in up-regulated genes, CTBP2, CD44, RHOA, related in down-regulated genes that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: Restored genes by AGR were thought to have common pathways related in regulation of gene expressions. Especially, genes in restored expression levels by AGR, which were up-regulated by induction of PCOS, were regulated by 9 of common transcription factors, genes in restored expression levels by AGR, which were down-regulated by induction of PCOS, were involved in 25 of common transcription factors.

• Development and Reproduction
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• v.15 no.2
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• pp.179-185
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• 2011

Some phytoestrogens in soy and red wine, for example, might have beneficiary rather than adverse effects. In particular, dietary soy intake seems to be highly correlated with protection of breast cancer, osteoporosis and cardiovascular disorders. However, questions persist on the potential adverse effects of the main soy constituent genistein (GS) on female reproductive physiology. Previously we found that prepubertal exposure to GS could activate the reproductive system of immature female rats leading to precocious puberty onset, and intracerebroventricularly (ICV) injected GS could directly activate hypothalamic kisspeptin-GnRH neuronal circuits in adult female rats. The present study was performed to examine the hypothalamus-specific GS effects in prepubertal female rats and which subtype of estrogen receptor is mediated in this GS effect. Prepubertal female rats (PND 30) were anaesthetized, treated with single dose of GS (3.4 ${\mu}g$/animal), and sacrificed at 2 hrs post-injection. To determine the transcriptional changes of reproductive hormone-related genes in hypothalamus, total RNAs were extracted and applied to the semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). ICV infusion of GS significantly lowered the transcriptional activities of mTOR (1:$0.361{\pm}0.058$ AU, p<0.001) but increased that of GAD67 (1:$1.285{\pm}0.099$ AU, p<0.05), which are known to act as an upstream modulator of kisspeptin and GnRH neuronal activities in the hypothalamus, respectively. GS administration enhanced significantly the mRNA levels of KiSS-1(1:$1.458{\pm}0.078$ AU, p<0.001), and exerted no effect on the mRNA level of kisspeptin receptor GPR-54 (1:$1.29{\pm}0.08$ AU). GnRH gene expression was significantly decreased in GS-treated group compared to control group (1:$0.379{\pm}0.196$ AU, p<0.05). There was no difference in the mRNA level of $ER{\alpha}$ in the GS-treated group compare to control group (1:$1.180{\pm}0.390$ AU, Fig. 3A). However, icv infusion of GS significantly increased the transcriptional activities of $ER{\beta}$ (1:$4.209{\pm}0.796$ AU, p<0.01, Fig. 3B). Taken together, the present study indicated that the acute exposure to GS could directly alter the hypothalamic GnRH modulating system in prepubertal female rats. Our study strongly suggested the involvement of $ER{\beta}$ pathway in GS's hypothalamus-specific action, and this idea is consistent with the GS's well-known $ER{\beta}$-mediated protective action in breast cancer.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.21 no.2
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• pp.116-122
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• 2011

Human occupational exposure to n-hexane has been associated with neurobehavioral symptoms such as depression, irritablity, acute irritation symptom, concentration disturbance and fatigue. Effects of monoamine oxidase (MAO) B and serotonin transporter receptor (5-HTTR) polymorphisms on the neurobehavioral symptoms were investigated in 70 male workers from TV and computer monitor manufacturing plants exposed to n-hexane. Neurobehavioral symptoms were assessed through a self-reported questionnaire and ambient level of n-hexane was measured by NIOSH method. Blood and urine were collected from each workers to determine the MAO(B), 5-HTTR and urinary 2,5-hexanedione(2,5-HD). The mean concentration of volatile n-hexane was $18.8{\pm}28.8ppm$ and that of urinary 2,5-HD was $1.07{\pm}1.47mg/g$ creatinine. Statistically significant associations with sexual disturbance were age and smoking. The frequencies of MAO(B) AA, AG and GG were 18.6%, 45.7% and 35.7%, respectively, and the frequencies of 5-HTTR ll, ls and ss genotype were 82.9%, 15.7% and 1.4%, respectively. MAO (B) gene polymorphisms had susceptibility to the neurobehavioral symptoms such as fatigue, concentration disturbance, irritability and acute irritation symptom and 5-HTTR gene polymorphism had susceptibility to the sleep disturbance and acute irritation symptom. On multiple logistic regression analysis for the neurobehavioral symptoms, memory disturbance was significantly associated with smoking(OR=6.752, 95% CI=37.46) and drinking(OR=4.033, 95% CI=1.252-12.98), emotional lability was MAO(B) genotype(OR=0.412, 95% CI=0.170-0.996), fatigue (OR=1.011, 95% CI=1.000-1.021) and acute irritation(OR=0.990, 95% CI=0.981-1.000) were working duration and sexual disturbance were significantly associated with age(OR=1.208, 95% CI=1.042-1.399), ambient n-hexane(OR=1.077, 95% CI=1.005-1.154) and 2,5-HD(OR=0.186, 95% CI=0.041-0.841). This finding implies that the MAO (B) and 5-HTTR polymorphisms may affect susceptibility for specific neurobehavioral symptoms associated with n-hexane exposure in workers.

• Asian-Australasian Journal of Animal Sciences
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• v.28 no.11
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• pp.1573-1582
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• 2015

This study was to investigate the effect of soyabean isoflavones (SIF) on onset of puberty, serum hormone concentration, and gene expression in hypothalamus, pituitary and ovary of female Bama miniature pigs. Fifty five, 35-days old pigs were randomly assigned into 5 treatment groups consisting of 11 pigs per treatment. Results showed that dietary supplementation of varying dosage (0, 250, 500, and 1,250 mg/kg) of SIF induced puberty delay of the pigs with the age of puberty of pigs fed basal diet supplemented with 1,250 mg/kg SIF was significantly higher (p<0.05) compared to control. Supplementation of SIF or estradiol valerate (EV) reduced (p<0.05) serum gonadotrophin releasing hormone and luteinizing hormone concentration, but increased follicle-stimulating hormone concentration in pigs at 4 months of age. The expression of KiSS-1 metastasis-suppressor (KISS1), steroidogenic acute regulatory protein (StAR) and 3-beta-hydroxysteroid dehydrogenase/delta-5-delta-4 isomerase ($3{\beta}-HSD$) was reduced (p<0.01) in SIF-supplemented groups. Expression of gonadotropin-releasing hormone receptor in the pituitary of miniature pigs was reduced (p<0.05) compared to the control when exposed to 250, 1,250 mg/kg SIF and EV. Pigs on 250 mg/kg SIF and EV also showed reduced (p<0.05) expression of cytochrome P450 19A1 compared to the control. Our results indicated that dietary supplementation of SIF induced puberty delay, which may be due to down-regulation of key genes that play vital roles in the synthesis of steroid hormones.