미성숙 암컷 흰쥐 시상하부-뇌하수체 축 상의 유전자 발현에 미치는 Vinclozolin 투여 효과
Effect of Vinclozolin Administration on the Gene Expressions in Hypothalamus-Pituitary Axis of Immature Female Rats
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Vinclozolin(VCZ) is a systemic fungicide commonly used in fruits, vegetables and the wine industry. VCZ and its metabolites, butenoic acid(M1) and enanilide(M2) derivatives, act as anti-androgens through actions on the androgen receptor. Although there is growing body of evidence that VCZ's action as an endocrine disrupting chemical(EDC) in male reproductive physiology and pathphysiology, no evidence on the VCZ's EDC action in female is available yet. Previously we found that the prepubertal VCZ exposures could effectively delay the onset of puberty in female rats, suggesting the postponed or weakened activities of hypothalamus-pituitary-ovary(H-P-O) reproductive hormonal axis. The present study was performed to examine whether the VCZ administration affects the transcriptional activities of reproductive hormone-related genes in the same animal model. VCZ(10mg/kg/day) was administered daily from postnatal day 21(PND 21) through the day when the first vaginal opening(V.O.) was observed. To determine the transcriptional changes of reproductive hormone-related genes in hypothalamus and pituitary, total RNAs were extracted and applied to the semi-quantitative reverse transcription polymerase chain reaction(RT-PCR). As a result, treatment with VCZ significantly lowered the transcriptional activity of nitric oxide synthase-2(NOS-2) which is known to adjust gonadotropin-releasing hormone(GnRH) secretion in the hypothalamus(p<0.01). Similarly, the mRNA levels of KiSS-1, G protein-coupled receptor54(GPR54) and GnRH were significantly decreased in hypothalamus(p<0.01) from VCZ-treated group. As expected, the transcriptional activities of luteinizing hormone-β(LH-β) and follicle stimulating hormone-β(FSH-β) in the anterior pituitary from VCZ-treated group were also significantly lower than those from the control group. The present study indicates that (i) the inhibitory effect of VCZ exposure on the onset of puberty in immature female rats could be derived from the reduced transcriptional activities of gonadotropin subunits and their upstream modulators such as GnRH and KiSS-1 in hypothalamus-pituitary neuroendocrine axis, and (ii) these inhibitory effects could be mediated by NO signaling pathway
Abstract
Vinclozolin(VCZ) is a systemic fungicide commonly used in fruits, vegetables and the wine industry. VCZ and its metabolites, butenoic acid(M1) and enanilide(M2) derivatives, act as anti-androgens through actions on the androgen receptor. Although there is growing body of evidence that VCZ's action as an endocrine disrupting chemical(EDC) in male reproductive physiology and pathphysiology, no evidence on the VCZ's EDC action in female is available yet. Previously we found that the prepubertal VCZ exposures could effectively delay the onset of puberty in female rats, suggesting the postponed or weakened activities of hypothalamus-pituitary-ovary(H-P-O) reproductive hormonal axis. The present study was performed to examine whether the VCZ administration affects the transcriptional activities of reproductive hormone-related genes in the same animal model. VCZ(10mg/kg/day) was administered daily from postnatal day 21(PND 21) through the day when the first vaginal opening(V.O.) was observed. To determine the transcriptional changes of reproductive hormone-related genes in hypothalamus and pituitary, total RNAs were extracted and applied to the semi-quantitative reverse transcription polymerase chain reaction(RT-PCR). As a result, treatment with VCZ significantly lowered the transcriptional activity of nitric oxide synthase-2(NOS-2) which is known to adjust gonadotropin-releasing hormone(GnRH) secretion in the hypothalamus(p<0.01). Similarly, the mRNA levels of KiSS-1, G protein-coupled receptor54(GPR54) and GnRH were significantly decreased in hypothalamus(p<0.01) from VCZ-treated group. As expected, the transcriptional activities of luteinizing hormone-β(LH-β) and follicle stimulating hormone-β(FSH-β) in the anterior pituitary from VCZ-treated group were also significantly lower than those from the control group. The present study indicates that (i) the inhibitory effect of VCZ exposure on the onset of puberty in immature female rats could be derived from the reduced transcriptional activities of gonadotropin subunits and their upstream modulators such as GnRH and KiSS-1 in hypothalamus-pituitary neuroendocrine axis, and (ii) these inhibitory effects could be mediated by NO signaling pathway
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