| Budget Amount *help |
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
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| Research Abstract |
Hypothalamic-pituitary-adrenal axis (HPA-axis) plays a pivotal role in maintaining the homeostatic balance of organisms. Corticotropin-releasing hormone (CRH) plays the most important role in the regulation of the HPA-axis. We demonstrated recently that norepinephrine (NE), one of the major transmitters in the brain, stimulates CRH gene expression in the hypothalamus. Vasopressin (AVP) colocalizes with CRH in an identical neuron. It has not been clear whether NE regulates CRH and/or AVP gene expression at the transcriptional level. In this experiment, we quantitated CRH and AVP hnRNA in the PVN by in situ hybridization histochemistry using cRNA probes corresponding to the intronic sequences of the genes. NE stimulated CRH gene transcription. The time course showed very rapid action of NE, reaching the peak within 15 min, and returning to the baseline within an hour. In contrast, AVP hnRNA did not change significantly after NE injection. In the next series of experiments, rats were adrenalectomized and supplemented with a low- dose corticosterone (CORT), thereby plasma CORT concentration was clamped at a low concentration. In this experimental condition, rats were given intrahypothalamic NE, and the time course of CRH/AVP hnRNA was compared to that of the sham-operated controls. The time course of CRH hnRNA in the ADX/CORT group was not greatly different from that of the sham-operated group. AVP hnRNA increased more prominently in the ADX/CORT group. These results suggest that the AVP gene transcription may be more sensitively regulated by circulating glucocorticoid than the CRH gene transcription in the physiological conditions.
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