DISCORDANT EFFECTS OF ENDOGENOUS AND EXOGENOUS SOMATOSTATIN ON GROWTHHORMONE-RELEASING HORMONE-SECRETION FROM PERIFUSED MOUSE HYPOTHALAMI

The role of somatostatin (SRIF) on growth hormone-releasing hormone (G RH) secretion has been controversial because of discordant findings th at may be model dependent. We have examined possible explanations for these findings by altering endogenous and exogenous SRIF tone in a mou se hypothalamic perifusion system, Four mediobasal hypothalamic fragme nts were perifused in a single chamber for 6 h. After a 2-hour equilib ration period, test substances were introduced and maintained througho ut the perifusion. After an additional 2 h, fragments were submaximall y stimulated with 30 mM K+. Depletion of tissue SRIF by 10(-3) M cyste amine increased K+-stimulated GRH release 2-fold without altering basa l GRH secretion. Removal of endogenous SRIF tone by anti-SRIF serum al so augmented the GRH response to K+. Perifusion of SRIF at concentrati ons ranging from 10(-12) to 10(-8) M significantly increased the GRH r esponse to K+ in a dose-dependent manner, A significant increase was a lso observed during the perifusion of 10(-9) M octreotide, Simultaneou s perifusion with anti-SRIF serum and 10(-9) M octreotide (to which th e antibody does not bind) resulted in a response of GRH to K+ that was similar to that observed with anti-SRIF serum alone. Combined perifus ion with cysteamine and 10(-9) M SRIF also resulted in a GRH response to K+ that did not differ from the response observed during cysteamine alone, The enhancement of GRH secretion by reduction of endogenous SR IF tone or tissue content implies an inhibitory role of endogenous SRI F on GRH secretion, The seemingly paradoxical increase in GRH response s induced by exogenous SRIF and octreotide may be explained by an inhi bitory effect on a yet unidentified interneuron which exerts a suppres sive action on GRH secretion, The latter possibility could also explai n the previously reported elevation of plasma GH after central adminis tration of SRIF.