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a Neuroadaptations Group, Department of Neuroendocrinology, Max Planck Institute of Psychiatry,D-80804 Munich, Germany
Within the broader framework of facilitating investigations into the inherent responses of restricted neuronal phenotypes devoid of their in vivo afferents, serum- and steroid-free cultures enriched in corticotropin-releasing hormone (CRH), arginine vasopressin (AVP), and ß-endorphin (ß-END) peptidergic neurons were prepared from the hypothalamic paraventricular (PVN: CRH and AVP) and/or arcuate (ARC: ß-END) nuclei of juvenile male rats. The functional viability of these ARC/PVN cultures was verified by their ability to synthesize and secrete CRH, AVP, and ß-END under basal and depolarizing (veratridine) conditions in vitro. Peptide secretion was shown to be Ca2+ and Na+ dependent in that it was blocked in the presence of veraspamil and tetrodotoxin, respectively. Exposure of ARC/PVN cocultures to the glucocorticoid dexamethasone (DEX) resulted in a dose-dependent increase of CRH secretion and an inhibition of AVP and ß-END; the CRH responses deviated strikingly from predictions based on in vivo experiments. Steroid withdrawal or treatment with the glucocorticoid receptor antagonist RU38486 reversed these trends. Opposite effects of DEX on CRH secretion were observed in cultures consisting of PVN cells only. Supported by studies using an opioid receptor agonist (morphine) and antagonist (naloxone), these observations demonstrate that ARC-derived (ß-END) neurons modulate the responses of PVN neurons to DEX.Hellbach, S., Gärtner, P., Deicke, J., Fischer, D., Hassan, A. H. S., Almeida, O. F. X. Inherent glucocorticoid response potential of isolated hypothalamic neuroendocrine neurons. FASEB J. 12, 199207 (1998)
Key Words: corticotropin-releasing hormone arginine vasopressin ß-endorphin dexamethasone glucocorticoid feedback
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