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Exercise training prevents endometrial hyperplasia and biomarkers for endometrial cancer in rat model of type 1 diabetes.

Al-Jarrah M, Matalka I, Aseri HA, Mohtaseb A, Smirnova IV, Novikova L, Stehno-Bittel L, Alkhateeb A - J Clin Med Res (2010)

Bottom Line: A 4-week treadmill training program was initiated with the development of diabetes.The expression of ERα increased significantly (p < 0.02) while the expression level of p16 decreased significantly (p < 0.04) in the diabetic sedentary group compared to the non-diabetic groups.Exercise training led to a reversal in the percentage of p16 and ERα positive cells in diabetic rats.

View Article: PubMed Central - PubMed

Affiliation: Department of Allied Medical Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Jordan.

ABSTRACT

Background: Endometrial cancer is one of the most common types of gynecologic cancers. The ability of exercise to reduce the risk of endometrial cancer in women with type 2 diabetes has been established, but no studies have examined this link in type 1 diabetes.A randomized, controlled animal study was designed using a standard rat model of type 1 diabetes. The goal of this study was to investigate the ability of exercise to prevent increased levels of endometrial cancer biomarkers, estrogen receptor (ERα) and p16, and endometrial hyperplasia associated with diabetes.

Methods: FORTY FEMALE RATS WERE RANDOMIZED INTO FOUR GROUPS: sedentary control, exercise control, sedentary or exercised diabetic. Diabetes was induced by alloxan injection. A 4-week treadmill training program was initiated with the development of diabetes. Endometrial tissues were evaluated for hyperplasia and ERα and p16 levels and subcellular localization using microscopy.

Results: Severe diabetes lead to hyperplasia in the endometrial tissue in 70% of sedentary diabetic rats. Exercise-trained diabetic rats and the non-diabetic rats displayed no hyperplasia. The expression of ERα increased significantly (p < 0.02) while the expression level of p16 decreased significantly (p < 0.04) in the diabetic sedentary group compared to the non-diabetic groups. Exercise training led to a reversal in the percentage of p16 and ERα positive cells in diabetic rats.

Conclusions: Severe diabetes leads to hyperplasia of the endometrial tissue and increased ERα levels and decreased p16 levels in rats, which can be prevented with aerobic exercise.

Keywords: Diabetes; Estrogen receptor alpha; P16; Endometrial hyperplasia; Endometrial cancer; Exercise.

No MeSH data available.


Related in: MedlinePlus

Comparison of estrogen receptor (ERα positive staining in four groups of rats. Tissue from sedentary control (SC) and exercised control (EC) rats illustrated less than 10% of the total area that was positive for ERα per region analyzed. Sedentary diabetic (SD) animals showed a marked increase in ERα immunostaining (* indicates difference from the three other groups, p < 0.02), with exercise training (ED) showing a trend towards reversal.
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Figure 2: Comparison of estrogen receptor (ERα positive staining in four groups of rats. Tissue from sedentary control (SC) and exercised control (EC) rats illustrated less than 10% of the total area that was positive for ERα per region analyzed. Sedentary diabetic (SD) animals showed a marked increase in ERα immunostaining (* indicates difference from the three other groups, p < 0.02), with exercise training (ED) showing a trend towards reversal.

Mentions: Estrogen receptor (ERα) levels have been shown to be highly correlated with gynecological cancers, and have been suggested as simple screening mechanism for high risk patients [24]. In the rats with diabetes from this study, there was a significant increase in the expression of ERα in the endometrium. Figure 1 shows two representative fields from control sedentary and diabetic sedentary animals. ERα levels were analyzed in stromal cells during the mid-secretory phase of the cycle when baseline ERα levels are at their lowest [25]. Control tissue had limited ERα staining in the nuclei of stromal cells, while sections from diabetic animals showed staining in both the cytoplasmic and nuclear regions of the cells, along with other indications of proliferation. Since both the amount of immune-reactive tissue and the number of ERα-positive cells are important indicators of protein levels, two quantization methods were utilized. First, the total area of ERα staining within each micrograph was calculated as a percentage. Figure 2 demonstrates a robust increase in the total ERα-stained area in the sedentary diabetic (SD) group of animals, which was statistically different from the two control groups (p < 0.02). There was greater variation in the area of ERα staining in the samples from the sedentary diabetic group with some stromal regions reaching as high as 82%. Treadmill exercise induced no change in the level of ERα in the control groups (comparing sedentary and exercised controls). The exercise protocol did reduce the area stained positive for ERα in the diabetic group, but not to a statistically significant level.


Exercise training prevents endometrial hyperplasia and biomarkers for endometrial cancer in rat model of type 1 diabetes.

Al-Jarrah M, Matalka I, Aseri HA, Mohtaseb A, Smirnova IV, Novikova L, Stehno-Bittel L, Alkhateeb A - J Clin Med Res (2010)

Comparison of estrogen receptor (ERα positive staining in four groups of rats. Tissue from sedentary control (SC) and exercised control (EC) rats illustrated less than 10% of the total area that was positive for ERα per region analyzed. Sedentary diabetic (SD) animals showed a marked increase in ERα immunostaining (* indicates difference from the three other groups, p < 0.02), with exercise training (ED) showing a trend towards reversal.
© Copyright Policy - open access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3104659&req=5

Figure 2: Comparison of estrogen receptor (ERα positive staining in four groups of rats. Tissue from sedentary control (SC) and exercised control (EC) rats illustrated less than 10% of the total area that was positive for ERα per region analyzed. Sedentary diabetic (SD) animals showed a marked increase in ERα immunostaining (* indicates difference from the three other groups, p < 0.02), with exercise training (ED) showing a trend towards reversal.
Mentions: Estrogen receptor (ERα) levels have been shown to be highly correlated with gynecological cancers, and have been suggested as simple screening mechanism for high risk patients [24]. In the rats with diabetes from this study, there was a significant increase in the expression of ERα in the endometrium. Figure 1 shows two representative fields from control sedentary and diabetic sedentary animals. ERα levels were analyzed in stromal cells during the mid-secretory phase of the cycle when baseline ERα levels are at their lowest [25]. Control tissue had limited ERα staining in the nuclei of stromal cells, while sections from diabetic animals showed staining in both the cytoplasmic and nuclear regions of the cells, along with other indications of proliferation. Since both the amount of immune-reactive tissue and the number of ERα-positive cells are important indicators of protein levels, two quantization methods were utilized. First, the total area of ERα staining within each micrograph was calculated as a percentage. Figure 2 demonstrates a robust increase in the total ERα-stained area in the sedentary diabetic (SD) group of animals, which was statistically different from the two control groups (p < 0.02). There was greater variation in the area of ERα staining in the samples from the sedentary diabetic group with some stromal regions reaching as high as 82%. Treadmill exercise induced no change in the level of ERα in the control groups (comparing sedentary and exercised controls). The exercise protocol did reduce the area stained positive for ERα in the diabetic group, but not to a statistically significant level.

Bottom Line: A 4-week treadmill training program was initiated with the development of diabetes.The expression of ERα increased significantly (p < 0.02) while the expression level of p16 decreased significantly (p < 0.04) in the diabetic sedentary group compared to the non-diabetic groups.Exercise training led to a reversal in the percentage of p16 and ERα positive cells in diabetic rats.

View Article: PubMed Central - PubMed

Affiliation: Department of Allied Medical Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Jordan.

ABSTRACT

Background: Endometrial cancer is one of the most common types of gynecologic cancers. The ability of exercise to reduce the risk of endometrial cancer in women with type 2 diabetes has been established, but no studies have examined this link in type 1 diabetes.A randomized, controlled animal study was designed using a standard rat model of type 1 diabetes. The goal of this study was to investigate the ability of exercise to prevent increased levels of endometrial cancer biomarkers, estrogen receptor (ERα) and p16, and endometrial hyperplasia associated with diabetes.

Methods: FORTY FEMALE RATS WERE RANDOMIZED INTO FOUR GROUPS: sedentary control, exercise control, sedentary or exercised diabetic. Diabetes was induced by alloxan injection. A 4-week treadmill training program was initiated with the development of diabetes. Endometrial tissues were evaluated for hyperplasia and ERα and p16 levels and subcellular localization using microscopy.

Results: Severe diabetes lead to hyperplasia in the endometrial tissue in 70% of sedentary diabetic rats. Exercise-trained diabetic rats and the non-diabetic rats displayed no hyperplasia. The expression of ERα increased significantly (p < 0.02) while the expression level of p16 decreased significantly (p < 0.04) in the diabetic sedentary group compared to the non-diabetic groups. Exercise training led to a reversal in the percentage of p16 and ERα positive cells in diabetic rats.

Conclusions: Severe diabetes leads to hyperplasia of the endometrial tissue and increased ERα levels and decreased p16 levels in rats, which can be prevented with aerobic exercise.

Keywords: Diabetes; Estrogen receptor alpha; P16; Endometrial hyperplasia; Endometrial cancer; Exercise.

No MeSH data available.


Related in: MedlinePlus