Interaction between malnutrition and ovarian hormones on the systemic IGF-I axis

Institute of Biochemistry, CSIC-Universidad Complutense, Madrid, Spain.

OBJECTIVE: In malnutrition both the GH-IGF and reproductive axes are greatly affected. Because the actions of IGF and sex steroids are inter-dependent in many tissues, we have examined how ovariectomy modulates the response of the systemic IGF system to undernutrition. DESIGN AND METHODS: Peripubertal (30 days of age) female rats were either sham operated or ovariectomized. Five days later half of each group was submitted to a protein-caloric restriction diet. All rats were killed at 60 days of age. RESULTS: Growth was decreased in all rats submitted to calorie restriction and this was consistent with a decrease in circulating IGF-I concentrations and liver IGF-I mRNA expression. While in normally fed rats ovariectomy had no significant effect on serum IGF-I concentrations, ovariectomized and underfed rats had significantly higher levels than intact underfed rats. In undernourished rats, serum IGF-binding proteins (IGFBP)-1, -2 and -3 concentrations were significantly reduced and this was not modified by ovariectomy. In contrast, liver mRNA concentrations of IGFBP-1 and -2 were increased and IGFBP-3 unchanged in intact undernourished animals, suggesting that undernutrition could be affecting the proteolysis of these binding proteins, and this response was significantly modulated by ovariectomy. CONCLUSION: These results indicate that the presence of circulating ovarian hormones significantly affects the response of the IGF system to undernutrition.