Rapid and opposite effects of dexamethasone on in vivo and in vitro hypothalamic somatostatin release.
We have previously reported the rapid response of hypothalamic somatostatin (SS) neurons to acute stress. Since it is well known that glucocorticoids (GC) are involved in neuroendocrinal stress regulation, we investigate in this study the effects of acute administration of dexamethasone (Dex) on both in vivo and in vitro SS release. Freely moving animals received stereotaxic implant of a push-pull cannula into the median eminence for 10 days, and then they were perfused with artificial cerebrospinal fluid for 120-150 min. An i.p. injection of Dex (200 or 300 micrograms/100 g) induced, 15-30 min later, a mean increase in SS hypothalamic output of 62.6 +/- 6.2% of basal secretion. By contrast, after 15 min incubation of hypothalamic fragments with either 10(-7) or 10(-6) M Dex, SS release decreased abruptly to 57.3 +/- 3.3% (n = 16; P < 0.001 compared with basal release) and 78.0 +/- 9.5% (n = 13; P < 0.05 compared with basal release) of basal release, respectively. Other Dex concentrations induced no variations, giving the dose-effect curve an abrupt "on-off" effect. The inhibitory effect was blocked by picrotoxin (10(-4) M) and was immediately reversed when Dex was removed from the medium. Specificity was tested by using another steroid, estradiol, and another tissue, cortex. The rapid action of GC whatever the model used and in particular the blocking in vitro effect of picrotoxin could suggest that GCs act at the level of the membrane and could operate physiologically in response to stress. In addition, the opposite in vivo and in vitro effects on SS release would indicate that GCs exert two different controls on SS neurons.
Estupina
C
C
Laboratoire Plasticité et Adaptation Cellulaires, Université Montpellier 2, France.
Belmar
J
J
Tapia-Arancibia
L
L
Astier
H
H
Arancibia
S
S
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000378:metabolism*; D013997:Time Factors
D013004:Somatostatin; D003907:Dexamethasone