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|Title:||Efeito do uso contínuo de hormônios esteróides sexuais na mama de ratas wistar|
|Keywords:||Anticoncepcional hormonal; Terapia hormonal; Tibolona; Estradiol; Progesterona; Ooforectomia; Mama; Ratas; Hormonal contraceptive; Hormone therapy; Tibolone; Estradiol; Progesterone; Ovariectomy; Mammary gland; Rats|
|Abstract:||There is no consensus about the effect of cumulative use of sex steroids on mammary tumors development. The aim of this study is to verify the effect of hormone therapy (HT) using tibolone (T), estradiol (E2) or conjugated estradiol / progesterone (E2Pg) after hormonal contraceptive (HC) use during the reproductive life on the mammary gland of ovariectomized rats. Fifty Wistar female rats, weighing 172.7 ± 2.3 g were used. Rats were randomly divided into 10 groups (n = 5/group): HC+OVX+T, HC+OVX+E2, HC+OVX+E2Pg, HC+OVX+pl, HC+SHAM+pl, pl+OVX+T, pl+OVX+E2, pl+OVX+E2Pg, pl+OVX+pl, pl+SHAM+pl. Each animal received weekly treatment with HC (Mesigyna ®) or placebo (pl) via s.c. (0.02 ml) for 21 days. Subsequently, the animals were ovariectomized or sham operated and, after 28 days, rats received 0.5 mL of E2 (1 mg/mL), E2Pg (1 mg/ml +0.5 mg/mL), T (2 mg/ml) or pl for 35 days by gavage. Vaginal cytology, control of body weight and feed consumption to feed efficiency calculation, uterine weight, measurements of serum estradiol and progesterone, mammary gland histopathology and histomorphometry for area percentage of mamma structures and expression of c-myc, IGFII, Bcl2, Bax, alpha and beta ER, PR, and AR genes by RT-PCR in real time were performed. Mean and standard deviation were calculated for each group. Appropriate statistical analysis tests were applied, with significance level at P<0.05. HC use determined full development of mammary glands, ducts and acini with dilated lumen containing fat secretion (lactation aspect). Typical hyperplasia of alveolar buds was observed in 12 abdominal glands (three in HC+OVX+T, two in HC+OVX+E2, two in HC+OVX+E2Pg, one in HC+OVX+pl and four HC+SHAM+pl) and three in thoracic glands (two in HC+OVX+pl and one in HC+SHAM+pl). Rats treated only with HT and pl+SHAM+pl, showed ducts and acini without secretion in most cases. In pl+OVX+pl group, the gland appearance was atrophied. Depending on the intensity of ductoacinar development, differences were seen in glandular luminal and ductoacinar percentage areas of mamma and lobules. The use of HC determined highest mean values of these components compared to the respective groups without HC. Gene expression of hormone receptors and cell proliferation-related genes c-myc and IGFII, and apoptosis-related genes bax and Bcl2 was not significantly altered by experimental treatments compared to the atrophied gland (pl+OVX+pl). C-myc expression was significantly higher in HC+OVX+pl vs. pl+SHAM+pl since the expression of IGFII and ER alpha and beta was numerically higher while Bax and PR was lower. The use of any HT increased significantly the expression of proliferation-related genes and ER alpha vs. pl+SHAM+pl. The gene expression pattern was altered by T use, with or without HC. The hormonal contraceptive use during reproductive life may increase the risk of developing mammary gland cancer since it causes hyperplasia of alveolar buds, regardless of the use of hormone therapy in post-menopause|
|Appears in Collections:||TEDE sem arquivo|
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