Effects of Intraventricular Growth Hormone-Releasing Factor on Growth Hormone Release: Further Evidence for Ultrashort Loop Feedback*

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Abstract
The effects of cerebroventricular injection of synthetic human GH [growth hormone] releasing factor [hGRF-(1-44)] on regulation of GH release in conscious male rats were examined. These results were compared with the direct effects of hGRF on hormone released from dispersed anterior pituitary cells. Administration of 2 higher doses of hGRF (200 and 2000 ng) into the third ventricle (3V) produced a dose-related increase in plasma GH levels (P < 0.001). Injection of hGRF into the 3V at 2 lower doses actually reduced GH release. Infusion of 20 ng (5 pmol) hGRF reduced plasma GH from 5-60 min (P < 0.005), with a maximum suppression of 66%. The 2-ng (0.5-pmol) dose decreased GH secretion by 45% (P < 0.05). hGRF stimulated a significant and dose-dependent release of GH from dispersed pituitary cells at concentrations of 10-10 and 10-9 M (P < 0.025). The specificity of GRF for GH control, whether stimulatory or inhibitory, was seen by the failure of GRF to modify PRL, TSH, or LH [luteinizing hormone] release. Apparently, injection of larger doses of GRF into the 3V produce GH release, but at lower doses, 3V GRF may exert an action centrally to inhibit GH release. Evidently, hypothalamic GRF may decrease its own neurosecretion by negative ultrashort loop feedback.