DIFFERENTIAL EXPRESSION OF MESSENGER RIBONUCLEIC-ACIDS ENCODING INSULIN-LIKE GROWTH-FACTORS AND THEIR RECEPTORS IN HUMAN UTERINE ENDOMETRIUM AND DECIDUA

During the menstrual cycle, the endometrium undergoes characteristic c hanges in response to circulating sex steroids. Intense mitotic activi ty of glands and stroma occurs in the proliferative (estradiol-dominan t) phase, and glandular secretion and stromal differentiation in the s ecretory (progesterone-dominant) phase. The insulin-like growth factor s (IGF-I and IGF-II) promote cellular growth and differentiation and h ave been proposed to participate in these cyclic endometrial events, a cting as mediators of steroid hormones. The objective of this study wa s to determine whether the messenger RNAs (mRNAs) encoding the IGF pep tides and the type I and type II IGF receptors are differentially expr essed in human endometrium during the menstrual cycle and in early pre gnancy. A solution hybridization ribonuclease protection assay, using P-32-labeled riboprobes for IGF-I, IGF-II, and beta-actin (control), r evealed IGF-I gene expression primarily in proliferative and early sec retory endometrium and abundant IGF-II gene expression in mid-late sec retory endometrium and early pregnancy decidua. Northern analysis, usi ng IGF-I and IGF-II complementary DNA probes, revealed multiple IGF-I mRNAs [2-7.6 kilobase (kb)], expressed primarily in proliferative and early secretory endometrium, and IGF-II mRNAs (1.4-6.0 kb), expressed primarily in secretory endometrium and in early pregnancy decidua. The 7.6-kb IGF-I mRNA and the 6.0-kb IGF-IL mRNA were most abundantly exp ressed. IGF-IE(a) and IGF-IE(b) mRNA splicing variants were present in a ratio of about 9:1, respectively. Type I and type II IGF receptor g ene expression in endometrium was investigated using specific riboprob es and the ribonuclease protection assay. Messenger RNAs encoding both receptors were more abundantly expressed in the secretory phase and d uring early pregnancy, compared to the proliferative phase. These resu lts show that mRNAs encoding the IGF peptides and their receptors are differentially expressed in human endometrium, depending on the steroi d hormone milieu. The preferential expression of IGF-I mRNA in the pro liferative phase supports the hypothesis that IGF-I is an estromedin i n human endometrium. The expression of endometrial IGF-II mRNA in the mid to late secretory phase and in early pregnancy supports a role for IGF-II in differentiative functions of the endometrium, perhaps inclu ding endometrial tissue shedding in the menstrual cycle or remodeling during early pregnancy.