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The Journal of Neuroscience, July 1, 1999, 19(13):5464-5472

Differential Regulation of Corticotropin-Releasing Hormone and Vasopressin Gene Transcription in the Hypothalamus by Norepinephrine

Keiichi Itoi^{1, 2}, Dana L. Helmreich¹, Manuel O. Lopez-Figueroa¹, and Stanley J. Watson¹

¹ Mental Health Research Institute, University of Michigan, Ann Arbor, Michigan 48109, and ² The Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai 980-8574, Japan

All stress-related inputs are conveyed to the hypothalamus via several brain areas and integrated in the parvocellular division of the paraventricular nucleus (PVN) where corticotropin-releasing hormone (CRH) is synthesized. Arginine vasopressin (AVP) is present in both magnocellular and parvocellular divisions of the PVN, and the latter population of AVP is colocalized with CRH. CRH and AVP are co-secreted in the face of certain stressful stimuli, and synthesis of both peptides is suppressed by glucocorticoid. CRH and AVP stimulate corticotropin (ACTH) secretion synergistically, but the physiological relevance of the dual corticotroph regulation is not understood. Norepinephrine (NE) is a well known neurotransmitter that regulates CRH neurons in the PVN. We explored the mode of action of NE on CRH and AVP gene transcription in the PVN to examine the effect of the neurotransmitter on multiple genes that are responsible for a common physiological function. After NE injection into the PVN of conscious rats, CRH heteronuclear (hn) RNA increased rapidly and markedly in the parvocellular division of the PVN. AVP hnRNA did not change significantly in either the parvocellular or magnocellular division of the PVN after NE injection. The present results show that the transcription of CRH and AVP genes is differentially regulated by NE, indicating the complexity of neurotransmitter regulation of multiple releasing hormone genes in a discrete hypothalamic neuronal population.

Key words: rat; paraventricular nucleus; parvocellular division; magnocellular division; catecholamines; messenger RNA; in situ hybridization; corticotropin

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Copyright © 1999 Society for Neuroscience  0270-6474/99/19135464-09$05.00/0

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