| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
Estrogen plays critical role in sexual differentiation of the developing brain and sex-specific regulation of reproductive neuroendocrinology in adult. Cellular estrogen signaling is conveyed by nuclear estrogen receptors (ERs) which include the classical ERa as well as the recently cloned ERβ. Both ERs are expressed in the preoptic area (POA), hypothalamus, limbic structures, which have been implicated in the regulation of reproduction. It is unclear, however, whether ERβ, like ERa is expressed in sex-specific manner. Furthermore, the presence of both ERs in the same neurons could alter the specificity of the transcription by forming heterodimers and might produce different responses to estrogen in different cells, depending on the ratios of ERa and ERβ. In our preivous study, we detected sex difference in the ERβ expression both in the anteroventral periventricular nucleus (AVPV) and the ventromedial nucleus of the hypothalamus (VMH), were reversed by altering neonatal steroid enviro
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nment. We also studied the influence of estrogen in the adult in the expression of ERβ of the VMH, AVPV and the medial amygdala by using non-isotopic, digoxigenin-labeled in situ hybridization histochemistry. Our results suggest that sex specific expression of ERβ is patterned by perinatal hormone exposure, down-regulation of ERβ by estrogen is selected in a region specific manner in the adult.
We also found the normal development and gonadal steroid modulation of a sex difference expression of somatostain mRNA positive cells within the sexually dimorphic nucleus of the preoptic area (SDN-POA). In the juvenile rat on day 8 and extending through day 15 analyzed, the volume of somatostain mRNA expressed nucleus was larger in males than in females. Orchidectomy of males on the day of birth decreased the volume of the somatostain mRNA-positive nucleus by day 15 and administraton of estradiol benzoate (10μg/0.02 ml in sesame oil) from days 1-5 to female increased the volume of somatostain mRNA-positive nucleus in the SDN-POA by day 15. Despite estrogen facilitates apoptotic cell death in the developing anteroventral periventricular nucleus of the preoptic area, estrogen prevents apoptotic cell death in the SDN-POA of female pups. Apoptosis prevention regulated by estrogen is a possible major role in regulating final volume of the SDN-POA. In the SDN-POA, however, we demonstrated here no estrogen receptor β in this nucleus as likely estrogen receptor a. Therefore, we propose that the sexual dimorphism and gonadal steroid modulation of somatostain is a possible involvement of regulating final volume of the SDN-POA. Less
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