Combined Autoradiographic and Immunohistochemical Evidence for an Association of Somatostatin Binding Sites with Growth Hormone‐Releasing Factor‐Containing Nerve Cell Bodies in the Rat Arcuate Nucleus

Abstract

Abstract The regulation of growth hormone secretion depends upon the complex interplay between two hypothalamic hypophysiotropic factors: growth hormone-releasing factor and somatotropin release inhibiting factor or somatostatin. Interactions between these two neurohormones appear to be exerted both distally, at the level of pituitary somatotropes, and proximally, within the hypothalamus. In an attempt to detect a possible anatomical substrate for central interactions between the two neurohormones, we compared the autoradiographic distribution of specifically labeled somatostatin binding sites with the immunohistochemical distribution of growth hormone-releasing factor-containing neurons in the hypothalamus of adult rats. Somatostatin binding sites were labeled in vitro by incubating serial brain sections with [(125)l]TyrO-DTrp8-somatostatin. Growth hormone-releasing factor-immunoreactive neurons were visualized in a second set of animals, using an antiserum raised against synthetic rat growth hormone-releasing factor (1-29) NH(2). In light microscopic autoradiograms of sections incubated with [(125)l]somatostatin the label was found to be concentrated over small, round or oval neuronal perikarya clustered within the ventrolateral aspect of the arcuate nucleus. The topographic distribution of these [(125)l]somatostatin-labeled cells was similar to that of growth hormone-releasing factor-immunoreactive neurons detected within the same region. Moreover, the number of [(125)l]somatostatin-labeled cells was found to vary in parallel with that of growth hormone-releasing factor-immunoreactive neurons throughout the rostro-caudal extent of the arcuate nucleus (coefficient of correlation r = 0.80). These results suggest that somatostatin binding sites may be directly associated with the perikarya of arcuate growth hormone-releasing factor neurons. Such an association would provide an anatomical substrate for a direct regulation of growth hormone-releasing factor secretion by somatostatin at the hypothalamic level.