Elsevier

Maturitas

Volume 31, Issue 2, 4 January 1999, Pages 179-184
Maturitas

TGF-beta 1 and IGF-1 expression in atrophic post-menopausal endometrium

https://doi.org/10.1016/S0378-5122(98)00095-4Get rights and content

Abstract

Objectives: Endometrial cells may synthetize cytokines and growth factors which may modulate some of the molecular mechanisms of endometrial proliferation and differentiation. Patients and Methods: We investigated the role of transforming growth factor beta-1 (TGF-β1), insulin-like growth factor-1 (IGF-1) and relative receptors in five tissue samples from atrophic post-menopausal endometria. The control group was represented by proliferative and secretory endometria from 10 healthy, normally-menstratued women. TGF-β1 and IGF-1 m-RNA expression was evaluated by Northern hybridization analysis, while TGF-β1 and IGF-1 receptors distribution was studied by immunohistochemistry. Results: In atrophic endometria Northern hybridization analysis showed a significant decrease of IGF-1 expression, and an increase of TGF-β1 expression compared to proliferative and secretory endometria. By immunohistochemistry it was demonstrated that TGF-β1 and IGF-1 receptors were both localized in cell cytoplasm, mainly in the stromal compartment. Conclusions: The results of our study would suggest a possible role of IGF-1 and TGF-β1 in maintaining the quiescent differentiative state of atrophic post-menopausal endometrium. The persistence of IGF-1 and TGF-β1 receptors in epithelial compartment could play a key role in proliferative response of atrophic endometrium to exogenous hormone replacement therapy (HRT) or endogenous intervening high estrogens levels.

Introduction

The morphological aspects of atrophic post-menopausal endometrium have been described many years ago 1, 2, but the majority of molecular mechanisms which regulate endometrial differentiation and proliferation are still unknown [3].

While the role of steroid hormones in endometrial biology are well-established [4], the action of other peptides such as cytokines and growth factors remains to be elucidated in atrophic endometrium [5].

Transforming growth factor beta-1 (TGF-β1) is a potent inhibitor of epithelial cell proliferation in-vitro and is overexpressed in several different solid tumors [6], while insulin-like growth factor-1 (IGF-1) promotes cellular mitosis in human endometrium 7, 8. The role of these growth factors in endometrial atrophy are largerly unknown at present.

We investigated the expression of TGF-β1, IGF-1 and their receptors using Northern hybridization and immunohistochemistry in atrophic postmenopausal endometrium and discuss the possible biological role of these growth factors in a system usually considered as in a `resting phase'.

Section snippets

Patients and methods

Atrophic endometrial specimens were collected from five healthy, asymptomatic, post-menopausal women, admitted to our Unit for surgical treatment of uterine prolapse. Mean age of the patients was 61 years (range 55–63); menopausal age was comprised between 5 and 15 years. None of these women had received hormonal treatment or had complained of episodes of abnormal uterine bleeding. Body mass index was in normal range. Pelvic examination, hysteroscopy and ultrasonography excluded other

TGF-β1 gene expression

The level of the 2.5 kb TGF-β1 mRNA transcript resulted in an increase in all the post-menopausal patients, when compared to the expression of the TGF-β1 measured in the endometrial tissue isolated from the patients in the proliferative phase used as normal controls The increase of the TGF-β1 expression, ranged from approximately 195% up to 550% (percentile expression), with an average value of 315% compared to normal proliferative endometria. This difference was statistically significant (P

Discussion

Atrophic postmenopausal endometrium is characterized by a simple and well spaced cubical epithelium with a dense, cellular and compact stromal compartment. Mitotic activity is absent and cell thickness and volume decreases with the age 1, 2.

The observation of a pronounced protein expression in glandular epithelium and stromal cells [15]and a persistence of proliferative activity in epithelial cells [3], however, question the concept of inactive state of postmenopausal endometrium. Moreover, a

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