Somatostatin and the Syndrome of Acromegaly

Abstract

Regulation of pituitary growth hormone (GH) secretion by the hypothalamus was first suspected when it was clear that rodents who had lesions of the hypothalamus grew abnormally. That these lesions, which were designed to create “hypothalamic obesity,” were resulting in a decrease in pituitary GH secretion was first suggested by Bogdanove and Lipner (1) in 1952. This possibility was directly confirmed by Reichlin (2) who demonstrated that full replacement of thyroid, gonadal, adrenal, and posterior pituitary hormones did not prevent the growth retardation induced by large medial basal hypothalamic lesions. After Franz and co-workers (3) reported that acetone/acetic acid extracts of porcine hypothalamus contained somatotrophic hormone releasing activity, a number of laboratories including those of Guillemin, McCann, Meites, Saffran, Schally, and Reichlin began an intensive search for this GH-releasing factor (GRF). During the search for this factor, Krulich et al. (4) noted that hypothalamic extracts also contained a GH release-inhibiting factor (Fig. 1), an observation later confirmed by Knobil et al. (5). In a similar fashion, Brazeau, Vale, and colleagues in the laboratory of Roger Guillemin, found a GH inhibitory activity inside fractions of ovine hypothalamic extracts (6,7) which were prepared for the search for GRF and which were used to isolate and identify the first hypothalamic releasing factor, TRH. The somatotropin release-inhibiting factor (SRIF) was isolated, sequenced, and found to be a tetradecapeptide which was named “somatostatin” (SS).