Is. Currie et al., MODULATION OF ARGININE-VASOPRESSIN SECRETION FROM CULTURED OVINE HYPOTHALAMIC CELLS BY GLUCOCORTICOIDS AND OPIOID-PEPTIDES, Neuroendocrinology, 60(4), 1994, pp. 360-367
In sheep, arginine vasopressin (AVP) appears to be a more potent ACTH-
releasing factor than ovine corticotrophin-releasing hormone. In order
to investigate the neuroendocrine regulation of AVP secretion we have
developed a novel system for maintaining fetal ovine hypothalamic neu
rones in serum-free culture. Hypothalamic neurones derived from fetal
sheep at day 70 gestation (term = 145 days) secreted AVP under basal c
onditions and in response to repeated potassium-induced depolarization
s, for up to 35 days in vitro. AVP secretion was time- and calcium-dep
endent. AVP secreted from ovine hypothalamic cells co-eluted with synt
hetic AVP on a Sephadex chromatography column and diluted in parallel
with AVP standard in the radioimmunoassay. The addition of coritisol (
150 nM) to medium bathing ovine hypothalamic cells significantly inhib
ited basal, and potassium-induced AVP secretion without altering the A
VP content of the cell cultures. Furthermore, the opioid peptide [D-Pr
o(10)]Dynorphin(1-11) which acts via the kappa opioid receptor, signif
icantly inhibited basal and potassium-stimulated AVP secretion, an eff
ect which was abolished when cells were cultured in the presence of co
rtisol. These data show that hypothalamic AVP is a site for negative f
eedback regulation within the ovine hypothalamic-pituitary-adrenal axi
s. Furthermore, these data suggest that the kappa opioid system inhibi
ts AVP secretion from ovine hypothalamic neurones, a response which is
modulated by glucocorticoids.