title: Response of the hypothalamo-pituitary-adrenal axis to nicotine.
abstract: Nicotine has been shown to be a potent stimulus for the secretion of the stress-responsive hormones, adrenocorticotropin (ACTH) and prolactin. This paper reviews the findings by our laboratory and others that demonstrate the polysynaptic pathways involved in the neuroendocrine responses to systemic nicotine. It will focus primarily on the hypothalamo-pituitary-adrenal (HPA) axis and the effect of nicotine on ACTH secretion, with supplementary information on prolactin secretion, where relevant. Data are presented demonstrating that nicotine acts via a central mechanism to stimulate indirectly the release of ACTH from the anterior pituitary corticotropes. Nicotine does not appear to act directly at the hypothalamic paraventricular nucleus (PVN), the site of the corticotropin-releasing hormone (CRH) neurons crucial to the regulation of ACTH. However, brainstem catecholaminergic regions projecting to the PVN showed a regionally selective and dose-dependent sensitivity to nicotine, particularly the noradrenergic/adrenergic nucleus tractus solitarius (NTS). A reduction in the modulatory effect of these catecholamines (by neurotoxic lesion, synthetic enzyme inhibitors or adrenergic receptor antagonists) resulted in an inhibition of nicotine-stimulated ACTH secretion. In addition, blockade of nicotinic cholinergic receptors (NAchRs) in the brainstem by the antagonist, mecamylamine, resulted in a dose-dependent reduction in norepinephrine (NE) release from terminals in the PVN, and a concomitant reduction in plasma ACTH. The differential sensitivity of these receptors to the nicotinic agonists, cytisine and nicotine, reflects the heterogeneity of the NAchR subtypes involved. The desensitization characteristics of the neuroendocrine responses to both acute and chronic nicotine exposure are indicative of an alteration in these NAchRs.
authors.affiliation: Endocrine Neuroscience Laboratory, Minneapolis Medical Research Foundation, MN 55404, USA. matta001@maroon.tc.umn.edu
authors.forename: S G
authors.initials: SG
authors.lastname: Matta
authors.forename: Y
authors.initials: Y
authors.lastname: Fu
authors.forename: J D
authors.initials: JD
authors.lastname: Valentine
authors.forename: B M
authors.initials: BM
authors.lastname: Sharp
mesh_terms: D000818:Animals; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*
chemical_list: D018722:Nicotinic Agonists; D009538:Nicotine