ON THE NEUROENDOCRINE ROLE OF INSULIN-LIKE GROWTH-FACTOR-1 AND FACTOR-II IN THE REGULATION OF GROWTH-HORMONE SECRETION

It has been suggested that insulin-like growth factor-1 (IGF-1) may play a role in the regulation of growth hormone (GH) secretion. However, recent studies using recombinant IGF-1 contradict this. A possible role for IGF-2 has also been postulated, but data for this are fewer. In the present study we have sought to elucidate the role of IGFs in the control of GH secretion by central administration of both IGFs at near physiological doses. Further investigation of their physiological role in GH release has been studied using specific immunoneutralization of IGFs. Sheep with indwelling intracerebroventricular (icv) cannulae were given either IGF-1 (10 μg), IGF- 2 (1 or 10 μg), or a combination of IGF-1 and IGF-2 (10 μg of each). Centrally administered IGF-1 had no effect on plasma GH, but IGF-2 caused a sustained decrease (P < 0.01) in plasma GH between 45 and 105 min after injection. The combination of IGF-1 and -2 resulted in a similar decrease in GH levels (P < 0.01). A potent immunoneutralizing antiserum against IGF-1 failed to have any effect on GH levels when administered icv, but administration of antiserum against IGF-2 stimulated GH release (P < 0.01) either alone or when administered together with anti-IGF-1 serum. These results indicate that central IGF-1 does not play a role in GH regulation. In contrast, central levels of IGF-2 may be physiologically important in regulating plasma GH levels. © 1993 Academic Press, Inc.