Effects of ethanol on the intraovarian insulin-like growth factor-1 system in the prepubertal rat.
Insulin-like growth factor-1 (IGF-1) is considered to play an important role during ovarian development and function. Because ethanol (ETOH) is a gonadal toxin in men, as well as male and female rats, we hypothesized that this drug may be having detrimental effects in the ovary by altering the intraovarian actions of IGF-1. In support of this notion, the present study was undertaken to examine the chronic effects of ETOH on the ovarian IGF-1 system in prepubertal female rats. Each rat was implanted with a gastric cannula on day 24 and began receiving either a control or ETOH liquid diet on day 29. The animals were killed on day 34, confirmed to be in the late juvenile stage of development, and their ovaries and blood were collected. Using an RNase protection assay, we determined the expression of mRNAs encoding IGF-1 and the Type 1 IGF receptor in the ovaries of control and ETOH-treated rats. Results indicate that the ETOH-treated rats showed an increase in the ovarian expression of IGF-1a (p < 0.0001) and IGF-1b (p < 0.001) mRNA, the two alternatively spliced forms of the IGF-1 gene. Conversely, ovarian IGF-1 protein levels were depressed (p < 0.05) in ETOH-treated rats as determined by radioimmunoassay. Furthermore, ETOH-treated rats showed a decrease (p < 0.01) in the expression of Type-1 IGF receptor mRNA with a subsequent decrease (p < 0.05) in the ovarian levels of IGF-1 receptor protein, as determined by Western blot analysis. Also, using Western immunoblotting, we determined increases in immunoreactive IGF-binding proteins-3 (p < 0.05) and 5 (p < 0.01), but not 4, in ETOH-treated rats as compared with controls. Furthermore, we observed a concomitant decrease (p < 0.01) in the serum levels of estradiol. These results demonstrate for the first time that chronic ETOH administration is capable of altering the prepubertal intraovarian IGF-1 signaling system. We suggest that, at least in part, these effects contribute to altered prepubertal ovarian function after chronic exposure to ETOH.