Growth hormone (GH) suppresses its own secretion by stimulating somatostatin (SRIF) release. Thus, the possible regulation of GH-releasing factor (GRF) and SRIF release and SRIF messenger ribonucleic acid (mRNA) by GH was studied in the hypothalamus of male rats in vitro. The median eminences (ME's) were incubated in buffer containing 10(-7)-10(-11) M GH for 30 min. SRIF and GRF released into the medium were quantitated by RIA. The release of SRIF from ME fragments was significantly increased (P < 0.001) by 10(-9) M GH; however, 10(-9) M GH also inhibited (P < 0.01) GRF release from the ME. To determine the effect of GH on SRIF mRNA levels, periventricular nucleus (PeN) explants were cultured during 6 h in medium with 10(-7)-10(-11) M GH. Levels of SRIF mRNA (determined by an S1 nuclease protection assay) were significantly elevated in the presence of 10(-10)-10(-7) M GH. Likewise, 10(-9) M GH significantly stimulated SRIF release from PeN explants at 30 min and at 6 h. Surprisingly, 10(-9) M GH also significantly increased GRF release from the PeN explants at these times as well. This GRF was not responsible for the increased SRIF release or SRIF mRNA induced by GH since GRF antibody did not modify the GH-induced increases in SRIF release and mRNA levels. These results demonstrate a negative short-loop feedback of GH mediated at the ME by suppression of GRF and stimulation of SRIF release, whereas in the PeN GH increased both SRIF release and SRIF mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)