Dose-Dependent Insulin Regulation of Insulin-Like Growth Factor Binding Protein-1 in Human Endometrial Stromal Cells Is Mediated by Distinct Signaling Pathways

Ruth B. Lathi, A.P. Hess, Suzana Tulač, Nihar R. Nayak, Marco Conti, Linda C. Giudice
In: The Journal of Clinical Endocrinology & Metabolism · 2005 · vol. 90(3) , pp. 1599–1606 · doi:10.1210/jc.2004-1676 · PMID:15613433 · W2060712358
article OA: closed CC0 ⤵ 5 in-corpus citations
View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

Insulin inhibits IGFBP-1 in human endometrial cells via PI3-kinase at low doses and additionally MAPK at higher doses.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

Abstract

IGF binding protein-1 (IGFBP-1) is a major product of decidualized human endometrial stromal cells and decidua, and as a modulator of IGF action and/or by independent mechanisms, it regulates cell growth and differentiation and embryonic implantation in these tissues. IGFBP-1 secretion is primarily stimulated by progesterone and cAMP and is inhibited by insulin and IGFs. The signaling pathways mediating the latter are not well defined, and the current study was conducted to determine which pathways mediate the effects of insulin on IGFBP-1 mRNA and protein expression by human endometrial stromal cells decidualized in vitro by progesterone. Cells were cultured and treated with different combinations of insulin; wortmannin, an inhibitor of the phosphatidylinositide-3-kinase (PI3-kinase) pathway; and PD98059, an inhibitor of the MAPK pathway. IGFBP-1 mRNA was determined by real-time PCR, and protein secretion in the conditioned medium was measured by ELISA. Activation of the PI3-kinase and the MAPK pathways was assessed by the detection of phosphorylated AKT and ERK in Western blots, respectively. Insulin inhibited IGFBP-1 mRNA and protein secretion in a dose-dependent fashion, with an ED(50) for the latter 0.127 ng/ml (21.6 pm). Inhibitor studies revealed that at low doses, insulin acts through the PI3-kinase pathway, whereas at higher levels it also activates the MAPK pathway in the inhibition of IGFBP-1. The data demonstrate that human endometrium is a target for insulin action in the regulation of IGFBP-1. At physiological levels insulin likely plays a homeostatic role for energy metabolism in the endometrium, and in hyperinsulinemic states, insulin action on the endometrium may activate cellular mitosis via the MAPK pathway and perhaps predispose this tissue to hyperplasia and/or cancer.

My notes (saved in your browser only)

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (25)

Cited by (5)

Source provenance

openalex
last seen: 2026-06-04T00:00:01.174412+00:00
License: CC0 · commercial use OK