Mullerian Inhibiting Substance Induces Apoptosis of Human Endometrial Stromal Cells in Endometriosis

Overview

Journal J Clin Endocrinol Metab

Publisher Oxford University Press

Specialty Endocrinology

Date 2012 Jul 5

PMID 22761458

Citations 16

Authors

Jeong Namkung

Jae Yen Song

Hyun Hee Jo

Mee Ran Kim

Young Oak Lew

Patricia K Donahoe

David T MacLaughlin

Jang Heub Kim

Affiliations

Soon will be listed here.

Abstract

Context: Müllerian inhibiting substance (MIS) is produced in Sertoli cells of fetal testis and causes regression of müllerian ducts in male embryos. MIS also can induce the cell cycle arrest and apoptosis in müllerian duct-derived tumors in vivo and in vitro.

Objective: Our objective was to investigate the expression of MIS type II receptor (MISR II) and whether MIS can inhibit the proliferation and induce apoptosis in primary cultures of endometrial stromal cells (ESC) of endometriosis.

Design And Settings: In vitro experiments were performed in the university research laboratory.

Participants: Tissue samples from 12 patients who had undergone evisceration for ovarian endometrial cysts were included in this study.

Interventions And Main Outcome Measures: The expression of MISR II in ESC was investigated by immunohistochemistry. The cell viability and apoptosis in ESC treated with MIS was measured by methylthiazoletetrazolium assay and annexin V analysis. The expression of regulatory proteins in ESC treated with MIS was shown by Western blotting.

Results: ESC showed specific immunostaining for the MISR II. ESC treated with MIS exhibited 32% growth inhibition (P = 0.0001). The changes in cell cycle distribution after MIS exposure at 72 h demonstrated that S and G(2)M phases were decreased; G(0)G(1) and sub-G(0)G(1) phases were increased. ESC treated with MIS showed 13.72% annexin V-fluorescein isothiocyanate positivity. In the ESCs, which contain defective p16, MIS increased the expression of pocket proteins p107 and p130 and decreased E2F transcription factor 1.

Conclusions: The results support a central role for MIS in endometriosis. Although the precise mechanism of MIS-mediated inhibition of ESC growth has not been fully defined, these data suggest that MIS has activity against ESC in vitro and may also be an effective targeted therapy for endometriosis.

Citing Articles

Anti-Müllerian hormone: biology and role in endocrinology and cancers.

Gowkielewicz M, Lipka A, Zdanowski W, Wasniewski T, Majewska M, Carlberg C Front Endocrinol (Lausanne). 2024; 15:1468364.

PMID: 39351532 PMC: 11439669. DOI: 10.3389/fendo.2024.1468364.

High anti-Müllerian hormone (AMH) is associated with increased risks of ectopic pregnancy in women undergoing fresh embryo transfer cycle, a cohort study.

Hu K, Li S, Hunt S, Yang R, Xu H, Li R Reprod Biol Endocrinol. 2023; 21(1):18.

PMID: 36737777 PMC: 9896741. DOI: 10.1186/s12958-022-01038-6.

Functional profiles of Müllerian inhibiting substance/anti-Müllerian hormone (MIS/AMH) in primarily cultured endometrial cancer cells.

Kim S, Yoon J, Hur S J Cancer. 2021; 12(20):6289-6300.

PMID: 34539902 PMC: 8425195. DOI: 10.7150/jca.60700.

Hormonal treatments for endometriosis: The endocrine background.

Vannuccini S, Clemenza S, Rossi M, Petraglia F Rev Endocr Metab Disord. 2021; 23(3):333-355.

PMID: 34405378 PMC: 9156507. DOI: 10.1007/s11154-021-09666-w.

AMH Concentrations in Peritoneal Fluids of Women With and Without Endometriosis.

Kitajima M, Matsumoto K, Murakami N, Kajimura I, Harada A, Kitajima Y Front Surg. 2020; 7:600202.

PMID: 33263001 PMC: 7686136. DOI: 10.3389/fsurg.2020.600202.

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