CENTRALLY ADMINISTERED INSULIN-LIKE GROWTH FACTOR-II FAILS TO ALTER PULSATILE GROWTH-HORMONE SECRETION OR FOOD-INTAKE

Insulin-like growth factor II (IGF-II) peptide, mRNA, and receptors are widely distributed in the central nervous system, yet the physiological role of IGF-II in brain remains largely unknown. In the present study, we examined the in vivo effects of central administration of recombinant human IGF-II on pulsatile GH secretion and food intake. The IGF-II preparation used was shown to stimulate H-3-thymidine incorporation in MG-63 human osteosarcoma cells in vitro. Free-moving adult male rats bearing chronic intracerebroventricular (icv) and intracardiac venous cannulae were icv administered 10-mu-l of either IGF-II (in doses of 300 ng and 1-mu-g) or the vehicle solution, and blood samples were obtained every 15 min for 6 h. Vehicle-injected control animals exhibited the typical pulsatile pattern of GH secretion with most peak GH values greater than 100 ng/ml and trough levels less than 1.2 ng/ml. Central administration of IGF-II, at both doses, failed to alter the spontaneous 6-hour GH secretory profile; there were no significant differences in either GH peak amplitude, GH trough level, GH interpeak interval, or mean 6-hour plasma GH level, compared to vehicle-injected controls. There was also no effect of icv administered IGF-II on mean plasma glucose or insulin levels. Compared to vehicle-injected control rats, the icv injection of IGF-II (at doses of 300 ng and 1-mu-g) did not significantly alter 24-h food intake or body weight gain in normal feeding rats. Furthermore, IGF-II icv, at both doses, had no effect on short-term food consumption in rats exposed to a 17-h period of food deprivation. Taken together, these findings do not provide evidence to support a physiological role for IGF-II in feedback regulation of pulsatile GH secretion at the level of the brain, or in the central control of food intake.