MESSENGER-RIBONUCLEIC-ACID EXPRESSION OF THE INSULIN-LIKE GROWTH-FACTORS AND THEIR BINDING-PROTEINS IN UTERINE FIBROIDS AND MYOMETRIUM

Fibroids (leiomyomata) are the most common tumors in women, but their etiology is unknown. The insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) may be important in the growth of these beni gn neoplasms. We have examined the presence of mRNA encoding both IGF- I and IGF-II and IGFBP-1, -2, and -3 in fibroids and corresponding myo metrium from 20 women undergoing hysterectomy for symptomatic uterine fibroids. Northern blots of total cellular RNA were probed with oligon ucleotides for IGF-I, IGF-II, IGFBP-2, and IGFBP-3 and a human IGFBP-1 cDNA. Western ligand blotting was also used to detect the presence of IGFBP proteins in both fibroid and myometrium. The data showed that i n fibroids compared to myometrium, 1) the relative abundance of IGF-I mRNA was not different, but there was an increase in the relative abun dance of IGF-II mRNA (P < 0.001); 2) IGFBP-1 mRNA was undetectable in fibroids and detectable in only 1 specimen of myometrium; 3) there was no difference in the relative abundance of IGFBP-2 mRNA, but there wa s an increase in the relative abundance of IGFBP-3 mRNA in myometrium (P < 0.05). By Western ligand blotting, both IGFBP-2 and -3 proteins w ere present. Our data show that the mRNAs encoding IGF-I, IGF-II, IGFB P-2, and IGFBP-3 are expressed in both fibroids and myometrium and tha t fibroids express more IGF-II and less IGFBP-3 mRNA than myometrium. We postulate that the net effect of the changes seen is to increase th e bioavailability of free (bioactive) IGF, which may then play a major role in promoting fibroid tumor growth.