Gallo Daniela, Zannoni Gian Franco, Martinelli Enrica, Ferlini Cristiano, Fabrizi Manuela, Riva Antonella, Morazzoni Paolo, Bombardelli Ezio, Scambia Giovanni
Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
Menopause. 2006 Jan-Feb;13(1):72-9. doi: 10.1097/01.gme.0000191208.05491.94.
In the following study, we investigated treatment-related changes in mammary gland histomorphology and structure after the administration of soy to adult virgin ovariectomized (OVX) female rats. Additionally, mammary receptor regulation was extensively evaluated by immunohistochemical analysis, and tissue proliferative activity analyzed by cell nuclear proliferating antigen expression (Ki67).
OVX rats were treated, for 6 weeks, with either the vehicle, the soy extract (SSE 100 mg/kg/d PO), or 17beta-estradiol (0.5 mg/kg/d PO); a sham control group (SHAM) was also included in the study. When killed, mammary glands were collected and subsequently processed for light microscopy or immunohistochemistry. Immunoreactivity was quantified by a scoring system that took into account both the percentage of positive cells and the intensity of the staining.
The 17beta-estradiol--treated rats had stimulated mammary glands compared with OVX rats, with an average lobulo-alveolar development not different from the SHAM controls. Only a partial regression of the glandular atrophy was observed in OVX rats receiving 100 mg/kg/d SSE, with a histological appearance between that of the OVX and SHAM controls. No significant changes were observed among experimental groups in the median ERalpha scores of the epithelial compartment (score of 3 in all groups); in the stromal compartment, a tendency toward decreased expression was seen with 17beta-estradiol rats compared with OVX controls (scores of 2 and 5, respectively). A significant reduction in ERbeta immunostaining was observed in the mammary glands of SSE-treated rats, in both epithelium and stroma (scores of 4 and 3, respectively), compared with those of OVX controls (score of 8 in both compartments). The ERbeta receptor status was not significantly affected by 17beta-estradiol. Compared with OVX rats (score of 1), PR expression was up-regulated by 17beta-estradiol (score of 6), whereas an ovariectomy-like pattern was observed after the administration of SSE (score of 0). Ki67 immunoreactivity in the epithelium and stroma was increased by the administration of 17beta-estradiol (scores of 4 and 5, respectively) and was unchanged after SSE treatment (scores of 0 and 2, respectively), compared with OVX controls (scores of 1 and 2, respectively).
The differences observed in the histological pattern, hormonal receptor status regulation, and Ki67 modulation suggest a different role for phytoestrogens and 17beta-estradiol in postmenopausal rodent mammary glands.
在以下研究中，我们调查了给成年未交配的去卵巢（OVX）雌性大鼠喂食大豆后乳腺组织形态学和结构的治疗相关变化。此外，通过免疫组织化学分析广泛评估了乳腺受体调节，并通过细胞核增殖抗原表达（Ki67）分析了组织增殖活性。
将OVX大鼠用赋形剂、大豆提取物（100mg/kg/d口服）或17β-雌二醇（0.5mg/kg/d口服）治疗6周；研究中还包括一个假手术对照组（SHAM）。处死大鼠后，收集乳腺并随后进行光学显微镜检查或免疫组织化学检查。通过一个评分系统对免疫反应性进行量化，该系统同时考虑阳性细胞的百分比和染色强度。
与OVX大鼠相比，17β-雌二醇治疗的大鼠乳腺受到刺激，平均小叶-腺泡发育与SHAM对照组无差异。在接受100mg/kg/d SSE的OVX大鼠中，仅观察到腺体萎缩部分消退，其组织学外观介于OVX和SHAM对照组之间。实验组上皮区室的中位ERα评分在各实验组之间未观察到显著变化（所有组均为3分）；在基质区室中，与OVX对照组相比，17β-雌二醇处理的大鼠有表达降低的趋势（分别为2分和5分）。与OVX对照组（两个区室均为8分）相比，SSE处理的大鼠乳腺上皮和基质中ERβ免疫染色均显著降低（分别为4分和3分）。ERβ受体状态未受到17β-雌二醇的显著影响。与OVX大鼠（1分）相比，PR表达被17β-雌二醇上调（6分），而给予SSE后观察到类似去卵巢的模式（0分）。与OVX对照组（分别为1分和2分）相比，给予17β-雌二醇后上皮和基质中的Ki67免疫反应性增加（分别为4分和5分），SSE处理后未发生变化（分别为0分和2分）。
在组织学模式、激素受体状态调节和Ki67调节方面观察到的差异表明，植物雌激素和17β-雌二醇在绝经后啮齿动物乳腺中具有不同作用。
