NEUROKININ-B GENE-EXPRESSION IS INCREASED IN THE ARCUATE NUCLEUS OF OVARIECTOMIZED RATS

Hypertrophy and increased gene expression of tachykinin neurons occur in the infundibular (arcuate) nucleus of postmenopausal women. We have hypothesized that the alterations in tachykinin gene expression in the hypothalami of postmenopausal women are secondary to ovarian failure and not due to age per se. In this study, in situ hybridization and computer-assisted microscopy were used to determine whether ovariectomy modulates neurokinin B (NKB), substance P (SP) or proopiomelanocortin (POMC) gene expression in the rat arcuate nucleus. Four groups were examined: proestrus; diestrous day 1; ovariectomized, and constant estrus induced by a single injection of 20 mg/kg estradiol valerate. Rats were sacrificed 2 months after treatment. Computer-assisted microscopy was used to determine the number of tachykinin neurons, cell areas, and the autoradiographic grain density of labeled neurons. We report marked changes in NKB gene expression in ovariectomized rats. The number of neurons containing NKB gene transcripts was significantly greater in ovariectomized rats (16.9 +/- 1.0 neurons/arcuate section) than all other groups. There was also a significant difference in the number of NKB neurons/arcuate section between proestrous (8.9 +/- 1.8 neurons) and diestrous (4.8 +/- 1.0 neurons) rats. The lowest number of neurons was detected in the estradiol valerate-injected rats (2.9 +/- 0.6 NKB neurons/arcuate section). Furthermore, the autoradiographic grain density of NKB neurons was doubled in the ovariectomized group compared to all other groups. In contrast, few SP neurons were identified in the rat arcuate nucleus and no changes were detected during the estrous cycle or in response to ovariectomy. However, the mean cell area of SP neurons was decreased in the estradiol valerate rats. The only change detected in POMC arcuate neurons was a decreased number of cells in the estradiol valerate rat. These data indicate that NKB neurons in the rat arcuate nucleus are modulated by ovarian hormones and support the hypothesis that increased NKB gene expression in the hypothalamus of postmenopausal women is due to ovarian failure.