Neurokinin B and the Hypothalamic Regulation

10 The morphology and gene expression of neurokinin B (NKB) neurons is altered in the human infundibular (arcuate) nucleus in association with the ovarian failure of menopause. Also, gonadotropin releasing-hormone (GnRH) mRNA is elevated and proopiomelanocortin (POMC) mRNA decreased. To determine if loss of ovarian steroids could produce comparable changes in gene expression in primates, we measured the effects of ovariectomy on NKB and GnRH in young cynomolgus monkeys. We also measured POMC gene expression, serum leptin and body weight to examine the consequences of ovariectomy on energy balance. Neurokinin B neurons in the infundibular nucleus of ovariectomized monkeys were larger, more numerous and displayed increased levels of NKB mRNA than the intact controls. Ovariectomy increased the number of neurons expressing GnRH gene transcripts. In contrast, the energy balance parameters were unchanged by ovariectomy. This study provides strong support for the hypothesis that ovarian failure contributes to the mophological changes and increased NKB and GnRH gene expression observed in postmenopausal women. We hypothesized that hypothalamic NKB neurons participate in the hypothalamic circuitry regulating LH. We determined if intracerebral infusion of a NK3 receptor agonist alters serum LH in the ovariectomized estrogen-treated rat. A significant inhibition of serum LH was observed after senktide injection, accompanied by changes in Fos expression in medial preoptic area, arcuate, paraventricular and supraoptic nuclei.