mRNA expression of insulin-like growth factor-I (IGF-I) is suppressed and those of IGF-II and IGF-binding protein-1 are constantly expressed in the endometrium during use of an intrauterine levonorgestrel system

Insulin-like growth factors (IGF-I and IGF-II) are believed to mediate and modulate steroid hormone actions in the endometrium. In this study we determined the effects of an intrauterine system (IUS), releasing 20 mu g levonorgestrel (LNG) daily, on endometrial expression of mRNAs encoding IGFs and insulin-like growth factor binding protein (IGFBP)-1. In Northern blotting, IGF-I mRNA was undetectable in all endometrial specimens from women with an LNG-IUS (n = 11) and in pregnancy decidua, whereas several transcripts of 0.6-7.6 kb were detected in proliferative and secretory phase endometria. In contrast, mRNAs encoding lGF-II and IGFBP-1 were strongly expressed in pregnancy and in all endometrial samples from women with an LNG-IUS, but were undetectable in proliferative or early to mid-secretory phase endometria. Using the more sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) method, IGF-I and IGF-II mRNAs were detectable in all cycling endometria, in early pregnancy decidua and in LNG-exposed endometrium. IGFBP-1 mRNA was constantly expressed in LNG-exposed endometrium, in early pregnancy decidua and in premenstrual endometrium, but was undetectable! in all specimens from proliferative or early to mid-secretory endometrium. Our data demonstrate that progestin treatment can affect the gene expression of endometrial growth factors in vivo. The consistent expression of mRNAs encoding IGF-II and IGFBP-1, with suppression of IGF-I mRNA in endometria exposed to LNG, suggests that this mode of hormone treatment can inhibit IGF-I action in the endometrium. If IGF-I mediates and modulates oestrogen action, suppression of IGF-I mRNA may be one of the molecular mechanisms which;accounts for the antiproliferative effects of progestogens on oestrogen-primed endometrium and the atrophy of endometrial epithelium resulting from use of an LNG-IUS.