(1)中枢神経関連生理活性物質のゴナドトロピン分泌へのかかわり(<特集>第61回学術講演会シンポジウム2「中枢神経関連生理活性物質の生殖機能へのかかわり」)
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It has been established that several hypothalamic factors are involved in the control of gonadotrophin release. Some orexigenic and stress-related factors suppress GnRH release. On the other hand, kisspeptin, which have direct neural contacts with GnRH neurons, stimulates GnRH release. Expression of kisspeptin is influenced from the state of nutrition and metabolism. In this study, we examined the action of orexigenic factors (orexin A, ghrelin) and stress-related factors (CRH, UCN, UCN2, CRH receptors) on GnRH/gonadotrophin release, and whether starvation and stress altered the expression of kisspeptin. In addition, we examined the functional mechanism of GnIH/RFRP-3, which have identified as a negative regulator of gonadotrophin release. Intracerebroventricular (i.c.v.) injections of orexin A and ghrelin suppressed the pulsatile LH release in female rats. From the experiments of co-administration with the blockers, it was clarified that orexin A-induced suppression of pulsatile LH release was mediated by β-endorphin, NPY, CRH and UCN 2, and that ghrelin-induced suppression of pulsatle LH release was mediated by β-endorphin. 72hr fasting reduced bogy weight and disrupted the estrous cycle in female rats. In this condition, serum leptin concentration was decreased and KiSS-1 mRNA expression was suppressed in the hypothalamic block containing arcuate nucleus, which was involved in pulsatile GnRH release, but not in the hypothalamic block containing anteroventral periventricular nucleus, which was involved in GnRH surge. Intravenous (i.v.) injection of LPS, which was one of the immune stress factors, suppressed the serum LH concentration and hypothalamic KiSS-1 mRNA expression in female rats. These suppressive effects were blocked by concomitant administration of indomethacin. I.v. injection of RFRP-3 significantly reduced serum LH concentrations. However, i.c.v. RFRP-3 injections did not affect the pulsatile LH secretion. When using cultured pituitary cells, in the absence of GnRH, the suppressive effect of RFRP-3 on LH secretion was not clear, but when GnRH was present, RFRP-3 significantly suppressed LH secretion. These results suggest that gonadotrophin secretion was regulated by a lot of hypothalamic peptides, and that both activation of gonadotrophin suppressive factors (orexigenic and stress-related factors) and inactivation of gonadotrophin stimulate factor (kisspeptin) are involved in suppression of the reproductive function in starved and stressful conditions.
- 社団法人日本産科婦人科学会の論文
- 2009-10-01
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