The growth factors with mitogenic activity, such as transforming growth factor-β3, fibroblast growth factor, epidermal growth factor, and insulin-like growth factor-I are elevated in fibroids and may have a role as effectors of the tumor promotion.
The progesterone may down-regulate IGF-I expression through PRB, and PRA appears to inhibit this function of progesterone by inhibiting the transcription of PRB; thus, the action of progesterone on leiomyoma growth may depend on different ratios of PRA and PRB.
The expression of IGF-I mRNA increases in leiomyoma and ER alpha mRNA is positively correlated with IGF-I mRNA, which implies that estrogen upregulates the gene encoding IGF-I through ER alpha in leiomyoma; ER beta may also be involved in the IGF-I signaling pathway in leiomyoma.
The IGF-I protein concentrations in fibroids and myometrium from GnRH agonist-treated and post-menopausal women were similar to those from premenopausal non-treated women.
Low-grade leiomyosarcomas contained more IGF-II mRNAs than myometrium and leiomyoma, fewer type II IGF/mannose 6-phosphate receptors and less IGFBP-3 than myometrium and, in addition, fewer IGF-I mRNAs and type I IGF receptors than leiomyoma.
We evaluated the presence of growth hormone receptor messenger ribonucleic acid in the human uterus and leiomyomas to investigate whether growth hormone might act directly rather than by hepatic generation of insulin-like growth factor-I.
The data showed that in fibroids compared to myometrium, 1) the relative abundance of IGF-I mRNA was not different, but there was an increase in the relative abundance 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 was an increase in the relative abundance of IGFBP-3 mRNA in myometrium (P < 0.05).
The objective of this study was to examine the possible steroid dependence of IGF, IGFBP and IGF receptor gene expression and IGFBP synthesis in uterine leiomyomata, using tissues from women cycling normally and made hypo-oestrogenic by a gonadtrophin-releasing hormone agonist (GnRHa).