LONG-TERM INHIBITORY EFFECTS OF SOMATOSTATIN AND INSULIN-LIKE-GROWTH-FACTOR-1 ON GROWTH-HORMONE RELEASE BY SERUM-FREE PRIMARY CULTURE OF PITUITARY-CELLS FROM EUROPEAN EEL (ANGUILLA-ANGUILLA)

To investigate the ability of hypothalamic and peripheral factors to d irectly regulate growth hormone (GH) release in a primitive teleost, t he European eel (Anguilla anguilla L.), we used primary cultures of di spersed pituitary cells. When cultured for 12 days in a serum-free med ium, pituitary cells continuously released large amounts of GH, which exceeded the initial cellular content. Somatotropin-release inhibiting hormone (SRIH-14) dose-dependently inhibited GH release (EC50 0.75 nM ) up to a maximal inhibitory effect of 95%. No desensitization of soma totropes to SRIH was observed over the 12 days of culture. Use of rece ptor subtype-selective SRIH agonists suggests the existence on eel som atotropes of SRIH receptor(s) related to the mammalian sst(2)/sst(3)/s st(5) class rather than to the sst(1)/sst(4) class. Insulin-like growt h factor 1 (IGF1) dose-dependently inhibited GH release (EC50 0.03 nM) up to a maximal inhibitory effect of 85%, without desensitization. IG F1 and IGF2 were equipotent in inhibiting GH release, whereas insulin was 1,000 times less active, suggesting the implication of a receptor related to the mammalian IGF type 1 receptor. These results indicate t hat eel somatotropes are active in vitro without any specific addition al factors, and suggest the existence of a dominant inhibitory control of GH release in vivo. Two potential candidates for this chronic nega tive regulation are a neurohormone, SRIH and a circulating factor, IGF 1. These data underline the early evolutionary origin of the molecular and functional SRIH-GH-IGF1 neuroendocrine axis in vertebrates.