Discordant effects of endogenous and exogenous somatostatin on growth hormone-releasing hormone secretion from perifused mouse hypothalami

The role of somatostatin (SRIF) on growth hormone-releasing hormone (GRH) secretion has been controversial because of discordant findings that may be model dependent. We have examined possible explanations for these findings by altering endogenous and exogenous SRIF tone in a mouse hypothalamic perifusion system, Four mediobasal hypothalamic fragments were perifused in a single chamber for 6 h. After a 2-hour equilibration period, test substances were introduced and maintained throughout the perifusion. After an additional 2 h, fragments were submaximally stimulated with 30 mM K+. Depletion of tissue SRIF by 10(-3) M cysteamine increased K+-stimulated GRH release 2-fold without altering basal GRH secretion. Removal of endogenous SRIF tone by anti-SRIF serum also augmented the GRH response to K+. Perifusion of SRIF at concentrations ranging from 10(-12) to 10(-8) M significantly increased the GRH response to K+ in a dose-dependent manner, A significant increase was also observed during the perifusion of 10(-9) M octreotide, Simultaneous perifusion with anti-SRIF serum and 10(-9) M octreotide (to which the antibody does not bind) resulted in a response of GRH to K+ that was similar to that observed with anti-SRIF serum alone. Combined perifusion 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 SRIF tone or tissue content implies an inhibitory role of endogenous SRIF on GRH secretion, The seemingly paradoxical increase in GRH responses induced by exogenous SRIF and octreotide may be explained by an inhibitory effect on a yet unidentified interneuron which exerts a suppressive action on GRH secretion, The latter possibility could also explain the previously reported elevation of plasma GH after central administration of SRIF