Effects of Growth Hormone Excess and Deficiency on Hypothalamic Somatostatin Content and Release and on Tissue Somatostatin Distribution*

Abstract

Considerable indirect evidence now exists to suggest that hypothalamic somatostatin (SRIF) is the physiological inhibitory regulator of pituitary GH release. To support this relationship further, we studied the effect of in vivo modifications of GH homeostasis on hypothalamic SRIF content and in vitro release in an attempt to document a feedback relationship between the two peptides. GH administration to normal rats resulted in increased hypothalamic SRIF concentration and release. GH deficiency, in contrast, resulted in decreased hypothalamic SRIF concentration and release. This effect appears to be, at least in part, a direct action of GH, since a dose-related stimulation of hypothalamic SRIF release was demonstrated in the presence of GH concentrations ranging from 10(-9)-10(-5) M. The lowest dose causing stimulation (10(-9) M) is well within the normal concentration range of plasma GH in the rat, suggesting that the effect may be physiological. Specificity of the effect is suggested by a much greater sensitivity of the medial basal hypothalamus than the septum and preoptic area to the effects of GH. The perturbations of GH homeostasis studied had no effect on extrahypothalamic neural or gastrointestinal SRIF concentrations, suggesting a different regulatory mechanism in these areas.