Characterization of the steroid-dependence of insulin-like growth factor-binding protein-2 synthesis and mRNA expression in cultured human endometrial stromal cells

Giudice, Linda C.; Milkowski, Deborah A.; Fielder, Paul J.; Irwin, Juan C.

doi:10.1093/oxfordjournals.humrep.a137396

Cited by 26 publications

(8 citation statements)

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“…In the cyclic cow IGFBP-2 mRNA levels increased during the luteal phase, concomitant with the highest levels of plasma progesterone [19]. Other studies have shown that human endometrial cells constitutively synthesise and secrete IGFBP-2 in vitro [45] and in response to estradiol [46]. In the bovine mammary gland [47], IGF-I may stimulate IGFBP-2 expression and protein secretion, whereas in fetal visceral glomerular epithelial cells isolated from human kidneys IGFBP-2 production was stimulated by IGF-II [48].…”

Section: Discussionmentioning

confidence: 91%

Endometrial expression of the insulin-like growth factor system during uterine involution in the postpartum dairy cow

Llewellyn

Fitzpatrick²,

Kenny

et al. 2008

Domestic Animal Endocrinology

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Rapid uterine involution in the postpartum period of dairy cows is important to achieve a short interval to conception. Expression patterns for members of the insulin-like growth factor (IGF) family were determined by in situ hybridisation at day 14 ± 0.4 postpartum (n = 12 cows) to investigate a potential role for IGFs in modulating uterine involution. Expression in each uterine tissue region was measured as optical density units and data were analysed according to region and horn. IGF-I mRNA was localized to the sub-epithelial stroma (SES) of inter-caruncular and caruncular endometrium. Both IGF-II and IGF-1R expression was detected in the deep endometrial stroma (DES), the caruncular stroma and myometrium. IGFBP-2, IGFBP-4 and IGFBP-6 mRNAs were all localised to the SES of inter-caruncular and caruncular uterine tissue, and in the DES and caruncular stroma, with IGFBP-4 mRNA additionally expressed in myometrium. IGFBP-3 mRNA was only detectable in luminal epithelium. IGFBP-5 mRNA was found in myometrium, inter-caruncular and caruncular SES and caruncular stroma. These data support a role for IGF-I and IGF-II in the extensive tissue remodelling and repair which the postpartum uterus undergoes to return to its non-pregnant state. The differential expression of binding proteins between tissues (IGFBP-3 in epithelium, IGFBP-2, -4, -5 and -6 in stroma and IGFBP-4 and -5 in myometrium) suggest tight control of IGF activity within each compartment. Differential expression of many members of the IGF family between the significantly larger previously gravid horn and the previously non-gravid horn may relate to differences in their rate of tissue remodelling.

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Section: Discussionmentioning

confidence: 91%

Endometrial expression of the insulin-like growth factor system during uterine involution in the postpartum dairy cow

Llewellyn

Fitzpatrick²,

Kenny

et al. 2008

Domestic Animal Endocrinology

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“…IGFBP2, having been widely accepted as one of the estrogen-responsive genes, appears to be involved in the maintenance of ERα and is regulated by E 2 administration in ERα-positive breast carcinoma cell lines [34], rat hippocampus [35] and adult articular cartilage [36]. The transcriptional and protein synthesis levels of IGFBP2 are steroid-dependent, being regulated by steroid hormones, including estradiol and progesterone, in cultured human endometrial stromal cells [37]. Importantly, studies also demonstrated that knockdown endogenous IGFBP2 decreases the expression of ERα and, conversely, that the addition of exogenous IGFBP2 increases the protein levels of ERα.…”

Section: Discussionmentioning

confidence: 99%

Insulin growth factor binding protein 2 mediates the progression of lymphangioleiomyomatosis

Zhang

et al. 2017

Oncotarget

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Lymphangioleiomyomatosis (LAM) is a progressive pulmonary disease that almost exclusively affects women. LAM cells migrate to the lungs, where they cause cystic destruction of lung parenchyma. Mutations in TSC1 or TSC2 lead to the activation of the mammalian target of rapamycin complex-1, a kinase that regulates growth factor-dependent protein translation, cell growth, and metabolism. Insulin-like growth factor binding protein 2 (IGFBP2) binds insulin, IGF1 and IGF2 in circulation, thereby modulating cell survival, migration, and invasion in neoplasms. In this study, we identified that IGFBP2 primarily localized in the nucleus of TSC2-null LAM patient-derived cells in vitro and in vivo. We also showed that nuclear accumulation of IGFBP2 is closely associated with estrogen receptor alpha (ERa) expression. Furthermore, estrogen treatment induced IGFBP2 nuclear translocation in TSC2-null LAM patient-derived cells. Importantly, depletion of IGFBP2 by siRNA reduced cell proliferation, enhanced apoptosis, and decreased migration and invasion of TSC2-null LAM patient-derived cells. More interestingly, depletion of IGFBP2 markedly decreased the phosphorylation of MAPK in LAM patient-derived TSC2-null cells. Collectively, these results suggest that IGFBP2 plays an important role in promoting tumorigenesis, through estrogen and ERalpha signaling pathway. Thus, targeting IGFBP2 may serve as a potential therapeutic strategy for women with LAM and other female gender specific neoplasms.

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“…The expression of IGFBP-1 mRNA and protein in endometrial epithelial and stromal cells [24][25][26][27][28][29][30], and of immunoreactive pregnancy-associated endometrial al-globulin (PEG) in endometrial tissue during the menstrual cycle and in decidual cells throughout pregnancy [32] has been demonstrated. IGFBP-1 is first detected during the mid-secretory phase (Days 19-23), with the highest intensity associated with stromal cells during the late luteal phase in humans and baboons [31][32][33][34]; not all the endometrial tissues were found to be immunostained for al-PEG [32].…”

Section: Discussionmentioning

confidence: 99%

“…Six distinct forms of IGFBPs have been identified and are synthesized and secreted by a variety of cell types [23]. In the uterus, the expression of mRNA and protein for IGFBP-1 has been demonstrated and immunohistochemically localized in human endometrial epithelial and stromal cells during the late luteal phase of the menstrual cycle, in human decidual cells during early pregnancy, and in baboon decidual cells throughout pregnancy [24][25][26][27][28][29][30][31][32][33][34]. Relaxin and progesterone (P 4 ) have been shown to stimulate IGFBP-1 production in stromal cells and endometrial explant culture [24,35].…”

Section: Introductionmentioning

confidence: 99%

Insulin-Like Growth Factor I (IGF-I), IGF-I Receptors, and IGF Binding Proteins 1–4 in Human Uterine Tissue: Tissue Localization and IGF-I Action in Endometrial Stromal and Myometrial Smooth Muscle Cells in Vitro

Tang

Rossi

Masterson

et al. 1994

Biology of Reproduction

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The objective of the present study was to elucidate the presence and cellular distribution of insulin-like growth factor I (IGF-I), IGF-I receptor (IGF-IR), and IGF binding proteins (IGFBPs) in human uterine tissue at various reproductive stages, and to determine the effect of IGF-I and its interaction with epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) in endometrial stromal and myometrial smooth muscle cells in primary culture. Using specific antibodies, immunohistochemical observations indicated that luminal and glandular epithelial cells were the major sites of immunoreactive IGF-I, IGF-IR, and IGFBPs 1-4, followed by myometrial smooth muscle and endometrial stromal cells. The immunostaining intensity of IGF-I, IGF-IR, and IGFBPs in endometrial but not myometrial tissue was cycle-dependent and higher in the late proliferative and early/mid-secretory periods than in the late secretory and postmenopausal periods, with little immunostaining at the early proliferative phase of the menstrual cycle. Stromal and smooth cells in primary cell culture also contained immunoreactive IGF-I, IGF-IR, and IGFBPs. IGF-I at 10-100 ng/ml stimulated 3H-thymidine incorporation in quiescent stromal and smooth muscle cells with maximal effect at 100 ng/ml (p < 0.05). However, in the presence of 2% serum, which induces half-maximal stimulation, IGF-I (100 ng/ml) further increased the rate of 3H-thymidine incorporation in stromal but not smooth muscle cells (p < 0.05). The effect of IGF-I was significantly lower than that induced by EGF (10 ng/ml), PDGF-BB (10 ng/ml) and their combination (p < 0.005), and higher in stromal cells from proliferative, than secretory phase of the cycle in the presence of 2% fetal bovine serum, but not serum-free condition (p < 0.005). The effect of IGF-I on myometrial smooth muscle cells was significantly higher than that induced by EGF, but lower than that induced by PDGF-BB or by EGF+PDGF-BB, without the cycle specificity seen with stromal cells. EGF, PDGF-BB, and their combination with IGF-I, but not IGF-I alone, stimulated stromal and smooth muscle cell growth as determined by a cell proliferation assay. The results indicate that human uterine tissue at various reproductive stages contains immunoreactive IGF-I, IGF-IR, and IGFBPs 1-4. Although IGF-I alone was found to be a weak mitogenic factor for stromal and smooth muscle cells, by interacting with EGF and PDGF-BB in a cycle-dependent manner it may regulate the growth and differentiation of these and other uterine cell types.

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Characterization of the steroid-dependence of insulin-like growth factor-binding protein-2 synthesis and mRNA expression in cultured human endometrial stromal cells

Cited by 26 publications

References 0 publications

Endometrial expression of the insulin-like growth factor system during uterine involution in the postpartum dairy cow

Endometrial expression of the insulin-like growth factor system during uterine involution in the postpartum dairy cow

Insulin growth factor binding protein 2 mediates the progression of lymphangioleiomyomatosis

Insulin-Like Growth Factor I (IGF-I), IGF-I Receptors, and IGF Binding Proteins 1–4 in Human Uterine Tissue: Tissue Localization and IGF-I Action in Endometrial Stromal and Myometrial Smooth Muscle Cells in Vitro

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