Concentration of plasminogen activators and inhibitor in the human endometrium at different phases of the menstrual cycle

Koh, Sau; Wong, Philip Ching Yat; Yuen, R.; Chua, S.; Ng, B. L.; Ratnam, S. S.

doi:10.1530/jrf.0.0960407

Cited by 30 publications

(19 citation statements)

References 14 publications

(14 reference statements)

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“…We also found that the SERPINE2 protein is present in the uterine fluid. PA activity was also demonstrated to be present in the uterine fluid [4-6]. Thus, the SERPINE2 protein may exert an inhibitory role of modulating PA activity in the uterine milieu.…”

Section: Discussionmentioning

confidence: 99%

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SERPINE2, an inhibitor of plasminogen activators, is highly expressed in the human endometrium during the secretory phase

Lee

Fan

Hwu

et al. 2011

Reprod Biol Endocrinol

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Background: SERPINE2, also known as protease nexin-1, belongs to the serine protease inhibitor (SERPIN) superfamily. It is one of the potent SERPINs that modulates the activity of plasminogen activators (PAs). PAs and their SERPIN inhibitors, such as SERPINB2 and SERPINE1, were expressed in the human endometrium and were implicated in implantation. However, expression data about SERPINE2 in the human endometrium is still unknown. Thus, we conducted an investigation to reveal the spatiotemporal and cellular expression of SERPINE2 in the human uterus during the menstrual cycle. Methods: Seven patients who underwent a hysterectomy and samples of 120 archived patients' endometrial curettage or parts of the uterus that were formalin-fixed and embedded in paraffin. Western blotting was performed to evaluate the specificity and sensitivity of the antibody. Immunohistochemistry was conducted to localize the SERPINE2 expression site. Quantitative analysis was conducted to evaluate expression levels of SERPINE2 in various sub-phases of the menstrual cycle. Results: The SERPINE2 protein was primarily detected in the uterine fluid during the mid-and late-secretory phases of the menstrual cycle. It was predominantly expressed in the luminal and glandular epithelium, less in the myometrium, and only dispersedly in certain stromal cells throughout the menstrual cycle. A quantitative analysis of expression levels of SERPINE2 in the glandular epithelium revealed that it was highly expressed in the endometrium during the secretory phase compared to the proliferative phase. Conclusions: The SERPINE2 protein is highly expressed in the endometrium during the secretory phase, indicating that it may participate in tissue remodeling involved in implantation.

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Section: Discussionmentioning

confidence: 99%

“…The expression and activity of PLAT and PLAU were detected in the human uterus, including the uterine fluid [4-6], and the endometrium during cycling [5-9] and implantation [10]. SERPINB2 [8] and SERPINE1 [7,8] were demonstrated to be present in the human endometrium.…”

Section: Introductionmentioning

confidence: 99%

SERPINE2, an inhibitor of plasminogen activators, is highly expressed in the human endometrium during the secretory phase

Lee

Fan

Hwu

et al. 2011

Reprod Biol Endocrinol

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“…The choice to use Tris–buffered saline (pH 8.5) for tissue homogenization was in agreement with the indications in the kits for the enzyme‐linked immunmosorbent assays (ELISAs) for PAI‐1, u‐PA and u‐PAR, supplied by American Diagnostics Inc., USA. In our preliminary studies of endometrial t‐PA, u‐PA and PAI‐1 at different phases of the menstrual cycle, normal saline alone was used for tissue homogenization [16]. However, in t‐PA activity determinations, 0.1 m HCl was used for activation in both plasma and tissue extracts and then neutralized with 0.1 m NaOH; the acid‐treated aliquots were then used for assays [22].…”

Section: Methodsmentioning

confidence: 99%

“…Fibrinolysis in the endometrium plays an important role in menstruation. Levels of plasminogen activators, especially tissue‐type plasminogen activator (t‐PA) and its inhibitor, plasminogen activator inhibitor‐1 (PAI‐1), were found to be significantly increased in the late secretory endometrium [16]. They are influenced by the cyclic variation of the sex hormone concentration at different phases of the menstrual cycle.…”

Section: Introductionmentioning

confidence: 99%

The effect of levonorgestrel‐releasing intrauterine system use on menstrual blood loss and the hemostatic, fibrinolytic/inhibitor systems in women with menorrhagia

Koh

Singh

2007

Journal of Thrombosis and Haemostasis

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To cite this article: Koh SCL, Singh K. The effect of levonorgestrel-releasing intrauterine system use on menstrual blood loss and the hemostatic, fibrinolytic/inhibitor systems in women with menorrhagia. J Thromb Haemost 2007; 5: 133-8.Summary. Background: Menorrhagia is known to be associated with uterine fibroids, adenomyosis, pelvic infections, endometrial polyps and clotting defects. A viable alternative therapy to hysterectomy should alleviate heavy menstrual blood flow and consequently improve the quality-of-life measures in women presenting with menorrhagia. The levonorgestrelreleasing intrauterine system (LNG-IUS) ranks higher than medical treatments in terms of efficacy, comparable improvements in quality of life and psychological well-being. Objective: The purpose of the study was to determine the effects of 6 months of LNG-IUS use on menstrual blood loss and the hemostatic, fibrinolytic/inhibitor systems in blood and the endometrium in women with menorrhagia with known pathologic causes. Patients and methods: Samples from 41 women were analyzed. Hemoglobin, hematocrit, thrombelastography, tissue-type plasminogen activator (t-PA), urokinase plasminogen activator (u-PA), u-PA receptor (u-PAR), plasminogen activator inhibitor-1/2 (PAI-1/2), D-dimer and von Willebrand factor (VWF) were determined, and t-PA, u-PA and PAI-1/2 were also determined in endometrial tissue extracts. Results: Menorrhagia was reduced in 89% of women by 3 months; by 6 months all women had no menorrhagia, and 39% of women had become amenorrhoeic. Hemoglobin and hematocrit levels showed improvement, and reached normal reference levels by 6 months. There were no systemic changes in the fibrinolytic/ inhibitor systems and VWF, except for a decreased u-PAR level. However, in the endometrium, significant elevations in PAI-1/2 together with u-PAR levels were seen at 6 months. Conclusions: The slow levonorgestrel-release intrauterine device use results in high expression of fibrinolytic inhibitors (PAI-1/2) and upregulated u-PAR expression in the endometrium. Systemic hemostasis was not significantly altered. The study demonstrated that LNG-IUS is highly effective in the treatment of menorrhagia with known pathologic causes.

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“…Plasminogen activator (PA) system is an important regulator mainly produced by Sertoli cells and involved in many biological processes as a general proteolytic system, such as spermatogenesis, oogenesis, embryo implantation, fibrinolysis, angiogenesis, inflammation, and tumor metastasis [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. There are two forms of PA, tissue type PA (tPA) and urokinase type PA (uPA) characterized in mammals.…”

Section: Introductionmentioning

confidence: 99%

Testosterone upregulation of tissue type plasminogen activator expression in Sertoli cells

Guo

Shi

Yang

et al. 2007

Endocr

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Our previous studies have demonstrated that tissue type plasminogen activator (tPA) might be involved in matrix degradation of blood-testis barrier in rat. In this study, we have further investigated the effect of testosterone (T) on tPA production in rat Sertoli cells. Our results showed that Sertoli cells isolated from rat testes at various ages in vitro secreted tPA in an age-dependent manner. The tPA activity was detected on day 20 after birth, and reached maximum on day 60. The Sertoli cells isolated from the testes on day 20 were then cultured in the presence or absence of testosterone, FSH, and forskolin, the tPA activities were upregulated by T, FSH and forskolin. Addition of H89 or U0126, both inhibited the testosterone-, FSH-, and forskolin-induced tPA expression. It is suggested that FSH- and testosterone-stimulated tPA expression in Sertoli cells may be via PKA and ERK signal transduction. Furthermore, we have observed that testosterone stimulated tPA secretion at all the stages of spermatogenesis (II-VI, VII-VIII, IX-XII and XIII-I), the highest stimulation of tPA activity was observed at stages VII-VIII. This study further suggests that testosterone-induced tPA activity in the Sertoli cells might be related to the function of blood-testis barrier opening and/or closing.

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Concentration of plasminogen activators and inhibitor in the human endometrium at different phases of the menstrual cycle

Cited by 30 publications

References 14 publications

SERPINE2, an inhibitor of plasminogen activators, is highly expressed in the human endometrium during the secretory phase

SERPINE2, an inhibitor of plasminogen activators, is highly expressed in the human endometrium during the secretory phase

The effect of levonorgestrel‐releasing intrauterine system use on menstrual blood loss and the hemostatic, fibrinolytic/inhibitor systems in women with menorrhagia

Testosterone upregulation of tissue type plasminogen activator expression in Sertoli cells

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