Analysis of hypothalamic neuronal system controlling the secretion of gonadotropin and prolactin

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In the present study, hypothalamic neuronal mechanisms controlling the secretion of gonadotropin and prolactin were investigated. First, the role of glucocorticoid in the suppression of hypothalamic GnRH pulse generator activity by cytokines was studied in the rat. TNF suppressed pulse generator activity, which was enhanced by adrenalectomy. Injection of corticosterone restored excessive suppression observed in the adrenalectomized animals, suggesting that activation of h hypothalamo-pitui tary-adrenal axis supports hypothalamo-pituitary-gonadal function even under stress conditions. In the goat, it was found that male pheromones increased the electrical activity of the hypothalamic GnRH pulse generator. In the mouse, the excitability of tuberoinfundibular dopaminergic neurons were found to be increased by male pheromones with a resultant decrease in prolactin secretion. In addition, as a estrogen inducible gene in rat hypothalamus during the critical period, we identified the gene of granulin (grn). To elucidate the involvement of gin in sexual differentiation of the brain, the antisense oligodeoxynucleotide (ODN) of gin precursor gene was i*sed into the third ventricle of male rats at 2 day-old. After maturation, animals treated with antisense ODN of gin displayed significantly lower scores than control males on various parameters assessing sexual behavior, suggesting that gin gene plays a crucial role in the process of masculinization of rat brain.