Cycle modulation of insulin-like growth factor-binding protein 1 in human endometrium

Abstract

Endometrium is one of the fastest growing human tissues. Sex hormones, estrogen and progesterone, in interaction with several growth factors, control its growth and differentiation. Insulin-like growth factor 1 (IGF-1) interacts with cell surface receptors and also with specific soluble binding proteins. IGF-binding proteins (IGF-BP) have been shown to modulate IGF-1 action. Of six known isoforms, IGF-BP-1 has been characterized as a marker produced by endometrial stromal cells in the late secretory phase and in the decidua. In the current study, IGF-1-BP concentration and affinity in the proliferative and secretory phase of the menstrual cycle were measured. Endometrial samples were from patients of reproductive age with regular menstrual cycles and taking no steroid hormones. Cytosolic fractions were prepared and binding of 125 I-labeled IGF-1 performed. Crosslinking reaction products were analyzed by SDS-polyacrylamide gel electrophoresis (7.5%) followed by autoradiography. 125 I-IGF-1 affinity to cytosolic proteins was not statistically different between the proliferative and secretory endometrium. An approximately 35-kDa binding protein was identified when 125 I-IGF-1 was cross-linked to cytosol proteins. Secretory endometrium had significantly more IGF-1-BP when compared to proliferative endometrium. The specificity of the cross-linking process was evaluated by the addition of 100 nM unlabeled IGF-1 or insulin. Unlabeled IGF-1 totally abolished the radioactivity from the band, indicating specific binding. Insulin had no apparent effect on the intensity of the labeled band. These results suggest that IGF-BP could modulate the action of IGF-1 throughout the menstrual cycle. It would be interesting to study this binding protein in other pathologic conditions of the endometrium such as adenocarcinomas and hyperplasia.

Gene induction and categorical reprogramming during in vitro human endometrial fibroblast decidualization

“…IGFBP-1 stimulates human extravillous trophoblast cell migration by signaling through integrin-␣5␤1 and the mitogen-activated protein kinase pathway (16). This supports a role for decidual IGFBP-1 in trophoblast invasion as well as during the menstrual cycle since secretory endometrium has significantly more IGFBP-1 than proliferative endometrium (12). IGFBP-5, the major binding protein in bone tissue, inhibits IGF binding to its receptor (25).…”

Progesterone receptors A and B and estrogen receptor alpha expression in normal breast tissue and fibroadenomas

“…The mechanisms controlling development and growth of FAs are little understood [8]. La Rosa and co-workers [6,9] have suggested that multiple receptor signaling pathways, including the pathways of estrogen and progesterone receptors (PRs) as well as those of growth factors and their receptors, could be involved in the growth and differentiation of benign breast lesions.…”

Influence of the menstrual cycle on aminolevulinic acid induced protoporphyrin IX fluorescence in the endometrium: In vivo study

“…Its cycle of proliferation, differentiation, and cell death is repeated in every menstrual cycle covering a unique dynamic process. Sex hormones, estrogen and progesterone, in interaction with several growth and other factors, control endometrial growth and differentiation [6]. Estrogen, i.e., affects the relaxin-like factor (RLF) gene activity.…”