Galanin has been reported to stimulate secretion of GH in humans and rats. Thus, to investigate whether the effect of galanin on GH release is the result of either a stimulation of GH-releasing factor (GRF) and/or an inhibition of somatostatin (SRIF) release, we have evaluated the action of galanin on the release of SRIF and GRF from median eminence (ME) fragments in vitro. The MEs from adult male rats were incubated in Krebs-Ringer bicarbonate-glucose buffer, pH 7.4, at 37°C, in an atmosphere of 95% O2, 5% CO2 with constant shaking for 30 min. Medium was discarded and replaced by medium containing various concentrations of galanin (10–10–10–7M). Galanin stimulated SRIF and GRF release in a dose-related manner. This effect was significant at concentrations varying from 10–8 to 10–7M. To determine the mechanism by which galanin stimulated SRIF and GRF release, MEs were incubated with pimozide (dopaminergic blocker), phentolamine (α-ad-renergic blocker) or naloxone (opioid blocker), at concentrations of 10–6M, and the effect of galanin was then evaluated. Phentolamine and naloxone did not alter the stimulatory effect of galanin, but when galanin was tested with pimozide, the galanin-induced release of SRIF and GRF was blocked. To determine whether the effect of galanin is mediated through D-1 and/or D-2 dopamine receptors, selective antagonists of D-l (SCH 23390) and D-2 receptors (domperidone) were used (10–7M) in the presence of galanin (10–7M). The stimulatory effect of galanin on SRIF release was unaffected by domperidone, although SCH 23390 inhibited galanin-evoked SRIF release. However, galanin-evoked GRF release was completely abolished by either domperidone or SCH 23390. Since GRF stimulates SRIF release in vitro, we hypothesized that the SRIF-stimulating action of galanin might be mediated by GRF accumulating in the static incubation system; however GRF antiserum (1:100) failed to alter this effect. These results demonstrate that galanin stimulates GRF and SRIF from ME fragments in vitro by a dopaminergic mechanism. In vivo, this GRF activates release of GH from the somatotropes. Thus, the stimulation of GRF release by galanin will increase GH release. Since galanin stimulates GH release in vivo, its stimulatory effect on SRIF release via a dopaminergic mechanism was puzzling. Since this effect was not blocked by GRF antiserum, the mediation of the effect by accumulated GRF appears to be ruled out. Therefore, we hypothesize that the effect is mediated by galanin itself acting as a negative feedback, when present in high concentration intrahypothalamically, to stimulate SRIF release. This effect would not be manifest in vivo except at very high secretion rates of galanin since the released galanin would enter the portal vessels instead of remaining in the tissue as in this static incubation system employed here

Keywords:
Median eminence, In vitro incubation, Growth hormone-releasing factor, Somatotrophin release-inhibiting factor
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© 1992 S. Karger AG, Basel
1992
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