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Gynecol Endocrinol. 1998 Dec;12(6):399-406.

Insulin-like growth factors in endometrial function.

Author information

1
Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Finland.

Abstract

Growth factors and related peptides are believed to mediate and modulate the actions of hormones at their target tissues through autocrine/paracrine mechanisms. Endometrial stromal cells produce insulin-like growth factors I and II (IGF-I and IGF-II) as well as the high-affinity IGF binding proteins (IGFBPs), whereas epithelial cells and, in a lesser amount, also stromal cells contain cell membrane receptors for IGFs. IGFs have proliferative, differentiative and metabolic effects. Estrogen stimulates IGF-I gene expression in the endometrium, and IGF-I is assumed to mediate estrogen action. IGF-II gene expression is associated with endometrial differentiation. All six high-affinity IGFBPs are expressed in human endometrium, the most abundant being IGFBP-1. This is secreted by predecidualized/decidualized endometrial stromal cells in late secretory phase endometrium and pregnancy decidua, i.e. under the action of progesterone. The primary negative regulator of IGFBP-1 expression is insulin, by inhibiting IGFBP-1 transcription. IGFBP-1 inhibits the receptor binding and biological actions of IGF-I in the endometrium and in cultured human trophoblastic cells. These findings support the view that the IGF system has autocrine and paracrine functions in the regulation of endometrial proliferation and differentiation. After implantation, decidual IGFBP-1 may regulate IGF actions at the embryo-endometrial interface, since trophoblast cells contain IGF receptors and express IGF-II, but do not express IGFBP-1. Clinical conditions that are known to increase the risk of endometrial cancer are all characterized by the absence of IGFBP-1. Thus, like unopposed estrogen, unopposed IGF-I action may also lead to uncontrolled endometrial proliferation and favor the development of endometrial cancer. The measurement of mRNAs encoding the IGF system might provide a novel tool to evaluate the endometrial response to endogenous and exogenous estrogens and progestins at the molecular level.

PMID:
10065165
DOI:
10.3109/09513599809012842
[Indexed for MEDLINE]

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