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KMID : 0894520110150020179
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Development & Reproduction
2011 Volume.15 No. 2 p.179 ~ p.185
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Direct Action of Genistein on the Hypothalamic Neuronal Circuits in Prepubertal Female Rats : Estrogen Receptor Beta(ERβ) Pathway?
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Heo Hyun-Jin
Lee Sung-Ho
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Abstract
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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 /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: AU, p<0.001) but increased that of GAD67 (1: 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: AU, p<0.001), and exerted no effect on the mRNA level of kisspeptin receptor GPR-54 (1: AU). GnRH gene expression was significantly decreased in GS-treated group compared to control group (1: AU, p<0.05). There was no difference in the mRNA level of in the GS-treated group compare to control group (1: AU, Fig. 3A). However, icv infusion of GS significantly increased the transcriptional activities of (1: 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 pathway in GS’s hypothalamus-specific action, and this idea is consistent with the GS’s well-known -mediated protective action in breast cancer.
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KEYWORD
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Genistein (GS), Intracerebroventricular injection, Prepubertal female rat, GnRH system,
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