Establishment and comparison of two methods to produce a rat model of mammary gland hyperplasia with hyperprolactinemia

Abstract This study aimed to establish and compare models of mammary gland hyperplasia (MGH) with hyperprolactinemia (HPRL) using two different methods. The models provide information on the relationship between mammary gland hyperplasia and associated hormones. Model A was constructed using intramuscular injections of estradiol benzoate injection (EBI), followed by progesterone (P), and then metoclopramide dihydrochloride (MDI). Model B was designed by administering MDI, follow by EBI, and then P intramuscularly. Model B showed higher MGH progression compared with model A. Notably, increase in estradiol (E2) was negatively correlated with prolactin (PRL) secretion. However, PRL levels in model B were significantly higher compared with the levels in model A. Estrogen (ER), prolactin receptor (PRLR), and progesterone receptor (PR) mRNA and protein expression levels in model B rats were positively correlated with changes in the corresponding hormone levels. However, E2, P, and PRL levels in model A showed no direct relationship with levels of the mRNAs of related hormones and protein expression levels. Our results suggest that model B is an appropriate model of MGH with HPRL that can be used to perform further studies about the interactions of the E2, P, and PRL hormones in this disorder.

摘要 本研究旨在通过两种不同方法构建并对比伴高泌乳素血症（hyperprolactinemia, HPRL）的乳腺增生（mammary gland hyperplasia, MGH）模型，以探究该疾病与相关激素之间的关联机制。模型A通过肌内注射苯甲酸雌二醇注射液（estradiol benzoate injection, EBI）、随后注射孕酮（progesterone, P），再注射盐酸甲氧氯普胺（metoclopramide dihydrochloride, MDI）构建而成。模型B则先肌内注射盐酸甲氧氯普胺，再依次注射苯甲酸雌二醇与孕酮。相较模型A，模型B的乳腺增生进展程度更高。值得注意的是，雌二醇（estradiol, E2）水平升高与泌乳素（prolactin, PRL）的分泌呈负相关；而模型B的泌乳素水平显著高于模型A。模型B大鼠体内的雌激素受体（estrogen receptor, ER）、泌乳素受体（prolactin receptor, PRLR）以及孕酮受体（progesterone receptor, PR）的mRNA与蛋白表达水平，均与对应激素水平的变化呈正相关。但模型A大鼠的雌二醇、孕酮及泌乳素水平，与相关激素的mRNA及蛋白表达水平并无直接关联。本研究结果表明，模型B是一种适用于伴高泌乳素血症乳腺增生的理想模型，可用于后续开展该疾病中雌二醇、孕酮与泌乳素三者相互作用的相关研究。