INHERENT GLUCOCORTICOID RESPONSE POTENTIAL OF ISOLATED HYPOTHALAMIC NEUROENDOCRINE NEURONS

Within the broader framework of facilitating investigations into the i nherent responses of restricted neuronal phenotypes devoid of their in vivo afferents, serum- and steroid-free cultures enriched in corticot ropin-releasing hormone (CRH), arginine vasopressin (AVP), and beta-en dorphin (beta-END) peptidergic neurons were prepared from the hypothal amic paraventricular (PVN: CRH and AVP) and/or arcuate (ARC: beta-END) nuclei of juvenile male rats, The functional viability of these ARC/P VN cultures was verified by their ability to synthesize and secrete CR H, AVP, and beta-END under basal and depolarizing (veratridine) condit ions in vitro. Peptide secretion was shown to be Ca2+ and Na+ dependen t in that it was blocked in the presence of veraspamil and tetrodotoxi n, respectively. Exposure of ARC/PVN cocultures to the glucocorticoid dexamethasone (DEX) resulted in a dose-dependent increase of CRH secre tion and an inhibition of AVP and beta-END; the CRH responses deviated strikingly from predictions based on in vivo experiments. Steroid wit hdrawal or treatment with the glucocorticoid receptor antagonist RU384 86 reversed these trends. Opposite effects of DEX on CRH secretion wer e observed in cultures consisting of PVN cells only. Supported by stud ies using an opioid receptor agonist (morphine) and antagonist (naloxo ne), these observations demonstrate that ARC-derived (beta-END) neuron s modulate the responses of PVN neurons to DEX.