The effect of ovarian function on insulin-like growth factor I plasma levels and hepatic IGF-I mRNA levels in diabetic rats treated with insulin.

When insulin was administered to streptozotocin-induced diabetic female rats, the percentage of glycohemoglobin, growth rate, ovulatory cycle, uterus to body weight ratio, and insulin-like growth factor (IGF-I) level returned to near normal. In untreated diabetic rats there were no normal estrous cycles, and hepatic IGF-I mRNA (7.94 +/- 1.02 O.D. units per micrograms total RNA) levels were significantly lower than the control or insulin-treated groups in proestrus (16.47 +/- 0.91 and 17.15 +/- 1.84, respectively). Insulin therapy restored the hypothalamic-pituitary-ovarian axis with the reinstitution of normal estrous cycles. Plasma IGF-I levels were highest in non-diabetic proestrous animals (277 +/- 36.9 ng/ml), significantly higher than IGF-I levels in insulin-treated diabetic rats in diestrus (174 +/- 23.1 ng/ml), non-diabetic diestrus rats (165 +/- 18.4 ng/ml) and untreated diabetic rats (135 +/- 19.7 ng/ml). Plasma IGF-I levels were elevated in insulin-treated diabetic rats in proestrus (221 +/- 78.3 ng/ml), however this was not significantly different from any other group. The increases observed in plasma IGF-I and hepatic IGF-I mRNA after insulin therapy correlate with the normalization of sex hormone secretion. Though this study does not prove a causal relationship between restoration of ovarian function and normalization of circulating IGF-I levels, a relationship has been established, as evidenced by higher levels of IGF-I in both the control and insulin-treated diabetic proestrous groups when compared to the diestrus groups.