Effects of ethanol on the intraovarian insulin-like growth factor-1 systemin the prepubertal rat

Insulin-like growth factor-1 (IGF-1) is considered to play an important rol e during ovarian development and function. Because ethanol (ETOH) is a gona dal toxin in men, as well as male and female rats, we hypothesized that thi s drug may be having detrimental effects in the ovary by altering the intra ovarian 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 syst em in prepubertal female rats, Each rat was implanted with a gastric cannul a on day 24 and began receiving either a control or ETCH liquid diet on day 29. The animals were killed on day 34, confirmed to be in the late juvenil e stage of development, and their ovaries and blood were collected, Using a n RNase protection assay, we determined the expression of mRNAs encoding IG F-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 determi ned by radioimmunoassay. Furthermore, ETCH-treated rats showed a decrease ( p < 0.01) in the expression of Type-1 IGF receptor mRNA with a subsequent d ecrease (p < 0.05) in the ovarian levels of IGF-1 receptor protein, as dete rmined by Western blot analysis. Also, using Western immunoblotting, we det ermined 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, Fur thermore, we observed a concomitant decrease (p < 0.01) in the serum levels of estradiol. These results demonstrate for the first time that chronic ET OH administration is capable of altering the prepubertal intraovarian IGF-1 signaling system. We suggest that, at least in part, these effects contrib ute to altered prepubertal ovarian function after chronic exposure to ETOH.