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A Possible Mechanism for the Action of Adrenomedullin in Brain to Stimulate Stress Hormone Secretion

Department of Pharmacological and Physiological Science, Saint Louis University, St. Louis, Missouri 63104

Address all correspondence and requests for reprints to: Meghan M. Taylor, Saint Louis University, Department of Pharmacological and Physiological Science, 1402 South Grand Boulevard, St. Louis, Missouri 63104. E-mail: taylormm{at}slu.edu.

Adrenomedullin (AM) has been reported to have actions at each level of the hypothalamo-pituitary-adrenal (HPA) axis, suggesting that the peptide plays a role in the organization of the neuroendocrine responses to stress. We examined the mechanism by which AM regulates the central nervous system branch of the HPA axis as well as the possible role of AM in the modulation of the releases of two other hormones, prolactin and GH, whose secretions also are altered by stress. Intracerebroventricular administration of AM led to elevated plasma corticosterone levels in unrestrained, conscious male rats. This effect was abrogated by pretreatment with a CRH antagonist, suggesting that AM activates the HPA axis by causing the release of CRH into hypophyseal portal vessels. In addition, AM given intracerebroventricularly stimulated the release of prolactin but did not alter the secretion of GH. We propose that AM produced in the brain may be an important neuromodulator of the hormonal stress response.

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