EFFECTS OF ESTROGEN ON RAT UTERINE EXPRESSION OF INSULIN-LIKE GROWTH FACTOR-BINDING PROTEINS

Previous studies have established that the IGFs are involved in oestrogen-induced uterine proliferation. IGF-binding proteins (IGFBPs) are present in most biological fluids and tissues and may modulate the actions of the IGFs. We examined uterine, hepatic and renal expression of the IGFBPs throughout the oestrous cycle and investigated the effects of oestradiol (OE(2)) on IGFBP expression in ovariectomized (ovx) rats. Uterine expression of IGFBPs-1 and -3 showed a definite variation throughout the oestrous cycle with highest levels during dioestrus. In the liver and kidney the changes in IGFBP-1 and IGFBP-3 mRNA abundance were the opposite of those observed in the uterus, with the highest levels observed during oestrus. Administration of OE(2) to ovx rats decreased uterine IGFBP-3 mRNA and increased IGFBP-4 mRNA levels. In these rats there were no consistent changes in renal IGFBP-1 or IGFBP-3 mRNAs; however, a significant increase in IGFBP-4 mRNA was observed in this tissue, as in the uterus. In the liver an increase in IGFBP-1 mRNA and a decrease in IGFBP-3 mRNA levels were observed in rats treated with OE(2). Despite changes in uterine, hepatic and renal IGFBP mRNA levels, no significant variation was seen in serum IGFBPs as determined by ligand blotting of sera. These data demonstrate that there is a cyclical variation in the expression of the IGFBPs in the uterus, kidney and liver, and that OE(2) is able to modulate differentially IGFBP expression in these tissues.