Centrally Administered Insulin-Like Growth Factor II Fails to Alter Pulsatile Growth Hormone Secretion or Food Intake

Abstract

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 3H-thymidine incorporation in MG-63 human osteosar-coma cells in vitro. Free-moving adult male rats bearing chronic intracerebroventricular (icv) and intracardiac venous cannulae were icv administered 10 µl of either IGF-II (in doses of 300 ng and 1 µg) or the vehicle solution, and blood samples were obtained every 15 mm 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 µg) 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.

Insulin-like growth factor-I feedback regulation of growth hormone and luteinizing hormone secretion in the pig: evidence for a pituitary site of action

“…These findings support the observation of Spencer et al (1991 and and Tannenbaum (1992a and1992b), who were unable to demonstrate a central effect of IGF-I on GH secretion and suggested that IGF-I does not play a role in the negative feedback regulation of GH at the level of the brain. To that extent, Fletcher et al (1995) was unable to demonstrate an inhibitory response to IGF-I following either lateral or third ventricle administration or infusion of 5 mg of IGF-I into the third ventricle over a 2 h period.…”

Effect of high-protein feed supplements on concentrations of growth hormone (GH), insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in plasma and on the amounts of GH and messenger RNA for GH in the pituitary glands of adult rams

“…Subse¬ quent studies showed that i.c.v. administration of human recombinant IGF-I (Harel & Tannenbaum, 19926) and IGF-II (Harel & Tannenbaum, 1992 ) in rats, did not affect pulsatile GH release, while a mixture was effective (Harel & Tannenbaum, 1992 ). The differences between early and recent studies on feedback effects on GH of IGF-I when administered centrally might be due to the IGF-I/somatomedin-C preparations being a mixture of IGF-I and IGF-II, while the recent development of recombinant technol¬ ogy has made large amounts of pure IGF-I and -II available.…”

Effect of insulin‐like growth factor I on anterior pituitary function

“…Neither intracerebroventricular recombinant IGF-I (in doses up to 10 pg) nor IGF-I1 (at doses up to 1 Fg) affected GH secretion. Intriguingly, however, a dose of 1 pg IGF-I administered in conjunction with 1 pg IGF-I1 completely inhibited G H secretion (10,11). The synergy of centrally administered IGF-I and IGF-I1 in inhibiting G H secretion in rats supports the belief that the somatomedin-C preparations contained both IGF-I and IGF-I1 and emphasizes the importance of the hypothalamus in the regulation of G H secretion, possibly via somatostatin.…”