ROLE OF ENDOGENOUS SOMATOSTATIN IN THE GH RESPONSE TO EXOGENOUS GHRH

The role of endogenous hypothalamic somatostatin (SRIH) in the pituita ry somatotrophs responsiveness to growth hormone-releasing hormone (GH RH) administration was investigated in the sheep. First, SRIH was meas ured in hypophysial portal blood (HPB) following two consecutive injec tions of GHRH; as expected, CH response was significantly reduced afte r the second injection. The first dose of GHRH induced a significant, but short-lasting increase in SRIH release (143.3 +/- 28 pg/ml at 30 m in vs 90.5 +/- 18 at 0 min; P<0.05). However, the role of endogenous S RIH in the refractoriness of pituitary somatotrophs to repeated GHRH i njections is not proven since SRIH levels had returned to initial valu es at the time of the second injection. Second, to study whether SRIH is necessary for the maintenance of somatotroph function including res ponsiveness to GHRH in the sheep, animals were actively immunized agai nst the peptide. Long-term immunoneutralization of SRIH caused a signi ficant reduction of the CH response to an acute GHRH injection suggest ing that endogenous SRIH is necessary for the maintenance of GHRH resp onsiveness.