The ontogeny and estrous cycle-dependent variation of insulin-like growth factor-I (IGF-I) gene expression was analyzed in the rat uterus. RNA extracted from rat uteri contained transcripts with estimated sizes of 7.0, 1.7, and 1.2-0.8 kb that were recognized by a 32P-labelled mouse IGF-I RNA probe. A solution hybridization RNase protection assay was used to measure the abundance of IGF-I mRNAs in uteri from rats of different ages. The highest levels were found in adult rats (p less than 0.01). The levels of IGF-I transcripts changed markedly during the estrous cycle with the highest levels at proestrus (p less than 0.01). There was an 8-fold increase in the abundance of IGF-I mRNA between diestrus-2 and proestrus. The corresponding livers had no significant variation of IGF-I gene expression during the estrous cycle, demonstrating a tissue-specific regulation of the IGF-I gene. The time and dose dependency of estrogen regulation of IGF-I gene expression was studied in hypophysectomized rats. The levels of IGF-I mRNA in the uterus decreased after hypophysectomy. A single s.c. injection of estradiol significantly increased the levels of IGF-I transcripts after 3 h (p less than 0.01). A low dose of estradiol (0.1 micrograms/100 g) increased the levels of IGF-I transcripts but progesterone in higher doses (5 micrograms/100 g) was without effect, indicating that the effect was specific for estradiol. However, the present study provides no information regarding whether this regulation is at the level of transcription or mRNA stability.(ABSTRACT TRUNCATED AT 250 WORDS)