Effects of Simvastatin on Retinoic Acid System in Primary Human Endometrial Stromal Cells and in a Chimeric Model of Human Endometriosis

Anna Sokalska, MariaPia Anderson, Jesus A. Villanueva, Jesus Villanueva, Israel Ortega, Kaylon L Bruner-Tran, Kaylon L. Bruner‐Tran, Kevin G Osteen, Antoni J Duleba, Antoni J. Dulęba
The Journal of clinical endocrinology and metabolism · 2013 · vol. 98(3) , pp. E463–E471 · doi:10.1210/jc.2012-3402 · PMID:23337719 · PMC3590479 · W2018699561
article OA: bronze CC0 ⤵ 19 in-corpus citations
📄 Open PDF View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

Simvastatin enhances retinoic acid's growth inhibition of human endometrial stromal cells and endometriotic implants by increasing STRA6 and CRABP2 expression.

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

Abstract

CONTEXT: Retinoic acid (RA) may promote survival or apoptosis of cells, depending on the levels of binding proteins: apoptosis-inducing cellular RA binding protein 2 (CRABP2), and cell survival-promoting fatty acid binding protein 5 (FABP5). Increased cellular uptake of retinol and altered actions of RA related to reduced expression of CRABP2 may contribute to the development of endometriosis. Recently statins have been shown to inhibit growth of human endometrial stromal (HES) cells and to reduce the number and size of endometriotic implants in experimental models of this disorder. OBJECTIVE: The objective of the study was to determine whether effects of simvastatin on HES cells and experimental endometriotic implants are related to the modulation of the RA system. METHODS: Effects of simvastatin and RA on proliferation and apoptosis of HES cells were evaluated. Expression of stimulated by RA 6 (STRA6), CRABP2, and FABP5 was determined by real-time PCR and Western blotting. Effects of simvastatin were also evaluated in a nude mouse model of human endometriosis. RESULTS: Simvastatin potentiated an inhibitory effect of RA on growth of HES cells. In HES cells, simvastatin induced expression of STRA6 and CRABP2 but not FABP5. Similarly, simvastatin treatment of nude mice bearing human endometrial xenografts led to an increased expression of CRABP2 and STRA6 proteins in ectopic lesions. CONCLUSIONS: Simvastatin interacts with the RA system, inducing the expression of the key protein regulating the uptake of retinol (STRA6) and the expression of apoptosis-promoting CRABP2. These effects may contribute to cooperative apoptosis-inducing effects of simvastatin and RA and support the examination of these compounds in the treatment of endometriosis.

My notes (saved in your browser only)

Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometrium Simvastatin Stromal Cells Tretinoin Adult Animals Apoptosis Apoptosis Apoptosis Cell Proliferation Cell Proliferation Cell Survival Cell Survival Cell Survival Chimera Disease Models, Animal Endometriosis Endometriosis

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 (37)

Cited by (19)

Source provenance

europepmc
last seen: 2026-06-13T06:22:48.782012+00:00
openalex
last seen: 2026-06-04T00:00:01.174412+00:00
pubmed
last seen: 2026-05-13T22:19:12.052662+00:00
License: CC0 · commercial use OK