title: Glucocorticoids provoke a shift from alpha2- to alpha1-adrenoreceptor activities in cultured hypothalamic slices leading to opposite noradrenaline effect on corticotropin-releasing hormone release.
abstract: We have shown previously that noradrenaline (NA) stimulated or inhibited the release of corticotropin-releasing hormone (CRH) according to the availability of adrenal steroids. The aim of the present work was to examine whether the changes in the NA modulation of CRH release from hypothalamic neurons result from a steroid-induced plasticity of the adrenergic transduction pathways. From anterior hypothalamic slices cultured in standard medium (i.e., containing adrenal steroids at a final dilution of 61 +/- 9 ng/ml), (a) the stimulatory effect of NA on CRH release was reversed in a dose-dependent manner by increasing concentrations of the alpha1-adrenoreceptor antagonist prazosin, (b) activation of protein kinase C by acute treatment with phorbol 12-myristate 13-acetate (0.5 microM, 1 h) mimicked NA stimulation of CRH secretion, and (c) the activation of L-type Ca2+ channels by Bay K 8644 also produce an increased CRH secretion. In contrast, the inhibitory effect of NA on CRH secretion from slices cultured in steroid-free medium was markedly reversed by the alpha2-adrenoreceptor antagonist yohimbine, by pretreatment with pertussin toxin, or by the addition of 4-aminopyridine, a K+-channel blocker. Acute treatment with phorbol 12-myristate 13-acetate did not change the inhibitory NA effect. Moreover, all these effects were reversed by daily corticosterone supplementation, for as long as they were tested. These results are consistent with a steroid-dependent change in the nature of adrenergic receptors and its associated transduction pathways involved in the regulation of CRH secretion in the hypothalamus.
authors.affiliation: Cerebral Plasticity Laboratory, EP 628 CNRS, University of Montpellier 2, France.
authors.forename: E
authors.initials: E
authors.lastname: Feuvrier
authors.forename: M
authors.initials: M
authors.lastname: Aubert
authors.forename: A L
authors.initials: AL
authors.lastname: Mausset
authors.forename: G
authors.initials: G
authors.lastname: Alonso
authors.forename: S
authors.initials: S
authors.lastname: Gaillet
authors.forename: F
authors.initials: F
authors.lastname: Malaval
authors.forename: A
authors.initials: A
authors.lastname: Szafarczyk
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000378:metabolism / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D003470:Culture Media / Q000494:pharmacology; D007031:Hypothalamus / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D009473:Neuronal Plasticity / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology*; D009924:Organ Culture Techniques; D026902:Potassium Channel Blockers; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000893:Anti-Inflammatory Agents; D002273:Carcinogens; D003470:Culture Media; D026902:Potassium Channel Blockers; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D010566:Virulence Factors, Bordetella; D003346:Corticotropin-Releasing Hormone; D015761:4-Aminopyridine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D003345:Corticosterone; D009638:Norepinephrine