Molecular and Cellular Endocrinology, 71 (1991) 175-180 0 1991 Elsevier Scientific Publishers Ireland, Ltd. 0303-7207/91/$03.50 175 MOLCEL 02492 Insulin-like growth factor-I gene expression during development and estrous cycle in the rat uterus BjBrn Carlsson and HAkan Billig Department of Physiology, University of Giitehorg, S-400 33 Giitehorg, Sweden (Received 20 September 1990; accepted 9 January 1991) Kqv waordst Insulin-like growth factor-l mRNA; Estradiol; (Rat uterus) zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIH Summary 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 < 0.01). The levels of IGF-I transcripts changed markedly during the estrous cycle with the highest levels at proestrus ( p < 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 < 0.01). A low dose of estradiol (0.1 pg/lOO g) increased the levels of IGF-I transcripts but progesterone in higher doses (5 pg/lOO 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. The present study provides further support for estrogen as a major regulator of IGF-I gene expression in the uterus in vivo. Introduction Estrogen is a major stimulator of uterine growth in vivo. The proliferative effects have been dif- ficult to achieve on cultured uterine epithelial, myometrial, and endometrial cells (Chen et al., Address for correspondence: Dr. BjGrn Carlsson, Depart- ment of Physiology, University of Giiteborg, P.O. Box 33031, S-400 33 GGteborg, Sweden. 1973; Gerschenson et al., 1977; Pavlic et al., 1978; Tomooka et al., 1986). This has led to the sugges- tion that the effects of estrogen are mediated by other factors. Murphy et al. have suggested that insulin-like growth factor-I (IGF-I) is an autocrine and paracrine mediator of estrogen action in the uterus. This is supported by the demonstration of local production of IGF-I in the uterus (Murphy et al., 1988) the presence of IGF-I receptors (Ghahary and Murphy, 1989), the uterus having the highest extrahepatic steady-state levels of