The Endocrinology of Uterine Decidualization

Osteen, Kevin G.

doi:10.1007/978-1-4612-1804-3_19

Cited by 6 publications

(7 citation statements)

References 66 publications

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“…Our laboratory has focused considerable attention toward better understanding the role of progesterone in the regulation of MMPs in the normal endometrium as well as in the disease endometriosis. By studying the process of decidualization in vitro [Osteen, unpublished data, 1999] we find that the local synthesis of retinoic acid may be an important component of progesterone action during the establishment of pregnancy [14]. In the current study, we have determined that retinoic acid can act in a fashion similar to progesterone in the regulation of endometrial MMPs.…”

Section: Discussionmentioning

confidence: 58%

“…Specifically, ovarian synthesis of estradiol induces growth and associated MMP expression, whereas ovarian progesterone serves as a potent inhibitor of MMP expression [7,8]. In vitro observations have confirmed that progesterone exposure of isolated endometrial cells or organ cultures inhibits expression of MMP-3, MMP-7, and MMP-11 [13,14].…”

Section: Endometrial Remodeling During the Menstrual Cyclementioning

confidence: 99%

“…The local expression of cytokines precisely regulate endometrial function, including cell-specific MMP expression during the cycle [14,25,26]. For example, both in vivo and in vitro findings have shown that progesterone-mediated suppression of endometrial MMPs involves both direct cellular effects and indirect effects mediated by secondary paracrine pathways [7,8,13,27,28].…”

Section: Cytokine Regulation Of Mmp Expressionmentioning

confidence: 99%

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Paracrine Regulation of Matrix Metalloproteinase Expression in the Normal Human Endometrium

Osteen

Keller²,

Feltus³

et al. 1999

Gynecol Obstet Invest

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Endometrial expression of matrix metalloproteinase (MMP)-3, MMP-7 and MMP-11 occurs during menstrual breakdown and subsequent estrogen-mediated growth, but not during the secretory phase. These enzymes are suppressed by progesterone treatment. Paracrine factors, including transforming growth factor-β (TGF-β) and retinoic acid, are also critical for MMP regulation in the endometrium. In contrast, inflammatory cytokines such as interleukin-1α may block or interfere with steroid-mediated MMP regulation at ectopic sites of growth. Using in vitro models, our laboratory has investigated the complex interactions between progesterone and locally produced cytokines that may affect MMP expression during the development of endometriosis. Our results indicate that targeting the regulation of MMPs may represent an appropriate therapeutic strategy for the treatment of endometriosis.

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Section: Discussionmentioning

confidence: 58%

Section: Endometrial Remodeling During the Menstrual Cyclementioning

confidence: 99%

Section: Cytokine Regulation Of Mmp Expressionmentioning

confidence: 99%

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Paracrine Regulation of Matrix Metalloproteinase Expression in the Normal Human Endometrium

Osteen

Keller²,

Feltus³

et al. 1999

Gynecol Obstet Invest

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“…Development of this transient organ, however, involves invasive events that are facilitated by potentially destructive proteolytic enzymes (9). However, maintaining uterine tissue integrity during the disruptive events of implantation and placentation requires that the expression of MMPs by maternal cells be limited (12)(13)(14). However, maintaining uterine tissue integrity during the disruptive events of implantation and placentation requires that the expression of MMPs by maternal cells be limited (12)(13)(14).…”

mentioning

confidence: 99%

“…Clinical observations have demonstrated the importance of adequate progesterone levels for normal maturation of the endometrial stroma in forming the decidua of pregnancy (4,14,30,31). And, although the IL-1 family appears to play a positive role in implantation (7,26), these cytokines are also elevated in association with endometrial breakdown during menstruation (18 -20, 32, 33) and at the time of parturition (34 -37).…”

mentioning

confidence: 99%

Progesterone Exposure Prevents Matrix Metalloproteinase-3 (MMP-3) Stimulation by Interleukin-1α in Human Endometrial Stromal Cells1

Keller

Sierra-Rivera

Eisenberg

et al. 2000

The Journal of Clinical Endocrinology &Amp; Metabolism

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Suppression of endometrial matrix metalloproteinases (MMPs) is necessary to maintain tissue stability during the invasive events of implantation and placental development. Several laboratories have shown that inflammatory cytokines, including interleukin-lalpha (IL-1alpha), can oppose progesterone suppression of MMPs in the human endometrium. Furthermore, we have recently demonstrated colocalization of epithelial cell IL-1alpha and MMP-7 expression at sites of ectopic pregnancy. The current study extends these findings, revealing a previously unrecognized interrelationship between progesterone and IL-1alpha in regulation of MMP-3. Although IL-1alpha is a potent stimulator of MMP-3 in proliferative phase endometrium in organ culture, we demonstrate that progesterone exposure in vivo reduces IL-1alpha stimulation of MMP-3 in secretory phase tissue. This loss of sensitivity to IL-1alpha was duplicated in isolated stromal cells treated with progesterone in vitro, and IL-1alpha stimulation of MMP-3 returned in a dose-dependent manner with progesterone withdrawal. The antiprogestin, onapristone, partially blocked the ability of progesterone to prevent stimulation of MMP-3 by IL-1alpha. These data suggest a novel mechanism by which progesterone may preserve tissue integrity during the establishment and maintenance of pregnancy by limiting stimulation of MMPs by inflammatory cytokines such as IL-1a.

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